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[ "11736743", "1776437", "10981524", "9062633", "8831855", "15858965", "7971447", "11345180", "1447641", "8346868", "12642834", "9279143", "8888916", "11429516", "8350218", "1586005", "10452771" ]

[ "Cow's milk-specific cellular and humoral immune responses and atopy skin symptoms in infants from atopic families fed a partially (pHF) or extensively (eHF) hydrolyzed infant formula.", "The effect of hypoallergenic formula on the occurrence of allergic diseases in high risk infants.", "Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention: a prospective, randomized study.", "Immunogenicity and antigenicity of a partially hydrolyzed cow's milk infant formula.", "Effects of a dietary and environmental prevention programme on the incidence of allergic symptoms in high atopic risk infants: three years' follow-up.", "Higher urinary excretion of essential amino acids in preterm infants fed protein hydrolysates.", "[The prevention of allergic diseases with a hypoallergenic formula: a follow-up at 24 months. The preliminary results].", "Extensive and partial protein hydrolysate preterm formulas: the effect on growth rate, protein metabolism indices, and plasma amino acid concentrations.", "Long-term prevention of allergic diseases by using protein hydrolysate formula in at-risk infants.", "Influence of hypoallergenic milk formula on the incidence of early allergic manifestations in infants predisposed to atopic diseases.", "The effect of hydrolyzed cow's milk formula for allergy prevention in the first year of life: the German Infant Nutritional Intervention Study, a randomized double-blind trial.", "Extensively and partially hydrolysed infant formulas for allergy prophylaxis.", "Allergy development and macromolecular absorption in infants with different feeding regimens during the first three days of life. A three-year prospective follow-up.", "Nutritional efficacy of preterm formula with a partially hydrolyzed protein source: a randomized pilot study.", "The nutritional value of a whey hydrolysate formula compared with a whey-predominant formula in healthy infants.", "Effect of a whey hydrolysate prophylaxis of atopic disease.", "Supplementary feeding in maternity hospitals and the risk of cow's milk allergy: A prospective study of 6209 infants." ]

[ "Hydrolyzed milk formulas are recommended to feed infants at high risk of atopy if breast-feeding is not possible. We studied the specific cellular and humoral immune response to cow's milk proteins and occurrence of atopic dermatitis under different feeding regimens: two hydrolyzed infant milk formulas (partially [pHF] and extensively hydrolyzed [eHF]) and under exclusive breast-feeding (BF).\n Seventy-two infants from families with atopic symptoms were randomized in the pHF and eHF groups, respectively. At 6 and 12 months of age, peripheral blood mononuclear cell proliferation along with specific IgG and IgE to cow's milk proteins was determined in infants fed pHF or eHF, respectively, and those who had not yet received any formula at 6 months of age (BF). Cases of atopic dermatitis were recorded throughout the first 12 months of life, and their severity was evaluated with SCORAD points.\n A significantly decreased proliferation to cow's milk caseins was found in the pHF group compared to the exclusively breast-fed group. Medians of stimulation indexes for CAS at 6 months were as follows: pHF 1.18; n=24; BF 1.70; n=24 (P=0.033, Mann-Whitney U-test). Higher levels of plasma IgG antibodies to BCAS were found in infants fed pHF than in those fed eHF at 12 months. Optical density (OD): (25th percentile; median; 75th percentile): pHF: 0.00; 0.14; 0.38; n=30; eHF: 0.00; 0.03; 0.14; n=28; P=0,089, Mann-Whitney U-test. Cow's milk-specific IgE was detected at 6 months as follows: BF: 3 of 24; eHF: 2 of 21; pHF: 0 of 23. The number of cases of atopic dermatitis and their severity did not differ among the groups during the first 12 months.\n Feeding pHF appears to suppress cow's milk-specific cellular responses and stimulate specific IgG production. Specific IgE sensitization can occur also with breast-feeding.", "To study the influence of hypoallergenic milk on the occurrence of allergic diseases, thirty-three high risk, normal full-term newborns were divided into two groups with comparable family allergy score (FAS) and cord serum IgE. Group A consisted of 18 babies fed since birth with regular formula, while group B included 15 babies fed breast milk and/or NAN H.A. (Hypoallergenic infant formula) for the first 6 months of life. Close clinical observations for the appearance of atopic dermatitis, allergic rhinitis and wheezing as well as serial examination of total serum IgE and milk-specific IgE antibodies were done during the first year of life. The results showed: 1) Infants fed regular formula had a higher incidence of moderate to severe atopic dermatitis (AD) and allergic rhinitis (AR) than those fed NAN H.A. (39% vs 13% for AD; and 33% vs 13% for AR), but the difference was not significant. There was no difference in the incidence of wheezing between these two groups; 2) There was no relationship between cord blood IgE and FAS; 3) Neither the cord blood IgE nor FAS influenced the occurrence of allergic diseases and total serum IgE at one year of age; 4) Hypoallergenic milk (NAN H.A.) could support normal growth and development. In conclusion, a higher incidence of moderate to severe AD and AR was found in high risk infants fed regular formula than in those fed hypoallergenic milk. However, a study with a larger number of babies and a longer period of follow-up is needed to obtain a solid conclusion.", "The aim of this study was to compare the allergy-preventive effect of a partially hydrolyzed formula with two extensively hydrolyzed formulas, in infants with a high risk for development of allergic disease. High-risk infants from four Danish centres were included in the period from June 1994 to July 1995. Five-hundred and ninety-five high-risk infants were identified. High-risk infants were defined as having biparental atopy, or a single atopic first-degree relative combined with cord blood immunoglobulin E (IgE)> or =0.3 kU/l. At birth all infants were randomized to one of three different blinded formulas. All mothers had unrestricted diets during pregnancy and lactation and were encouraged to breast-feed exclusively. If breast-feeding was insufficient, one of the three formulas, according to randomization, was given during the first 4 months. It was recommended not to introduce cow's milk, cow's milk products. and solid foods until the age of 4 months. After the age of 4 months a normal unrestricted diet and conventional cow's milk-based formula were given when needed. All infants were followed-up prospectively with interview and physical examination at the age of 6, 12, and 18 months, and if any possible atopic symptoms were reported. If food allergy was suspected, controlled elimination/challenge procedures were performed in a hospital setting. Of 550 infants included in the study, 514 were seen at all visits and 36 were excluded owing to noncompliance. Of 478 infants who completed the study, 232 were exclusively breast-fed, 79 received an extensively hydrolyzed casein formula (Nutramigen), 82 an extensively hydrolyzed whey formula (Profylac), and 85 a partially hydrolyzed whey formula (Nan HA), during the first 4 months of life. These four groups were identical in regard to atopic predisposition, cord blood IgE, birthplace, and gender. Exclusively breast-fed children were exposed less to tobacco smoke and pets at home and belonged to higher social classes, whereas the three formula groups were identical concerning environmental factors. The frequency of breast-feeding was high; only eight (2%) children were not breast-fed at all. The three formula groups were identical in regard to duration of breast-feeding and age at introduction of formula and solid foods. No significant differences were found in the three groups of infants receiving formula milk regarding the cumulative incidence of atopic dermatitis or respiratory symptoms. The cumulative incidence of parental-reported cow's milk allergy was significantly higher in children fed partially hydrolyzed formula (Nan HA) compared with extensively hydrolyzed formula (Nutramigen or Profylac) at 12 and 18 months (NanHA, 7.1%; Nutramigen, 2.5%; Profylac, 0%; p=0.033). The cumulative incidence of confirmed cow's milk allergy was 1.3% (three of 232) in exclusively breast-fed infants, 0.6% (one of 161) in infants fed extensively hydrolyzed formula (Nutramigen or Profylac), and 4.7%(four of 85) in infants fed partially hydrolyzed formula (Nan HA). Partially hydrolyzed formula was found to be less effective than extensively hydrolyzed formula in preventing cow's milk allergy, 0.6% vs. 4.7% (p=0.05), but because of the small number of cases the results should be interpreted with caution. Compared with other similar studies the frequency ofatopic symptoms was low, even though the dietetic intervention did not include either maternal diet during lactation or dietary restrictions to the children after the age of 4 months.", "We evaluated the immunogenicity and antigenicity of a formula based on partially hydrolyzed cow's milk whey protein in infants at risk of atopy and in controls. Total IgE and specific IgE, IgG, and IgG4 subclass antibodies against egg albumin and cow's milk alpha-lactalbumin, casein, and beta-lactoglobulin were measured by radioimmunoassay of cord blood and of peripheral blood at 5 days and 6 months of life in five groups of infants: 16 breast-fed infants at risk of atopy (group 1), 21 partially hydrolyzed whey formula-fed infants at risk of atopy (group 2), 14 formula-fed infants at risk of atopy (group 3), 10 breast-fed control infants (group 4), and 13 formula-fed control infants (group 5). Total IgE concentration was significantly lower in group 2 at 6 months than in groups 3 and 5 infants and similar to that observed in groups 1 and 4 infants. The concentration of specific antiegg and anti-cow's milk protein IgG and of specific anti-cow's milk alpha-lactalbumin and beta-lactoglobulin IgG4 subclass antibodies was significantly reduced in group 2 as compared to group 3 infants and similar to that found in breast-fed infants. In conclusion, the partially hydrolyzed formula was less immunogenic and antigenic than a traditional formula and was as immunogenic and antigenic as breast milk.", "A prospective case-control study is presented to assess an allergy prevention programme in children up to 36 months of age. Infants born at three maternity hospitals were followed from birth: 279 infants with high atopic risk (intervention group) were compared with 80 infants with similar atopic risk but no intervention (non-intervention group). The intervention programme included dietary measures (exclusive and prolonged milk feeding diet followed by a hypoantigenic weaning diet) and environmental measures (avoidance of parental smoking in the presence of the babies, day care > 2 years of life). Mothers in this group who had insufficient breast milk were randomly assigned to one of two coded formulas: either a hydrolysed milk formula (Nidina HA, Nestlé) or a conventional adapted formula (Nan, Nestlé). Other environmental measures remained the same as for the breastfeeding mothers. The non-intervention group were either breastfed or received the usual Italian milk feeding and weaning diet, without environmental advice. The main outcome measures were anthropometric measurements and allergic disease manifestations. Normal anthropometric data were observed both in the intervention group and in the non-intervention group. The incidence of allergic manifestations was much lower in the intervention group than in the non-intervention group at 1 year (11.5 versus 54.4%, respectively) and at 2 years (14.9 versus 65.6%) and 3 years (20.6 versus 74.1%). Atopic dermatitis and recurrent wheezing were found in both the intervention group and the non-intervention group from birth up to the second year of life, while urticaria and gastrointestinal disorders were only present in the non-intervention group in the first year of life. Conjunctivitis and rhinitis were present after the second year in both the intervention group and the non-intervention group. Relapse of the same allergic symptom was less in the intervention group (13.0%) than in the non-intervention group (36.9%). In comparison to the non-intervention group, there were fewer intervention group cases with two or more different allergic symptoms (8.7 versus 32.6%), and they were more likely to avoid steroid treatment (0 versus 10.8%) and hospital admission (0 versus 6.5%). Babies in the non-intervention group fed with adapted formula were more likely to develop allergies than breastfed babies in the same group. In the intervention group the breastfed infants had the lowest incidence of allergic symptoms, followed by the infants fed the hydrolysed formula (ns). Infants in the intervention group fed the adapted formula had significantly more allergies than the breastfed and hydrolysed milk fed infants, although less than their counterparts in the non-intervention group. Of the affected subjects in the intervention group, 80.4% were RAST and/or Prick positive to food or inhalant allergens. Total serum IgE values detected at birth in the intervention group were not predictive, but at 1 and 2 years of age, IgE values more than 2 SD above the mean in asymptomatic babies were found to predictive for later allergy. In breastfed babies the total IgE level at 1 and 2 years of age was lower than in the other two feeding groups. Of the various factors tested in the non-intervention group, the following were the most important in the pathogenesis of allergic symptoms: (i) formula implementation begun in the first week of life; (ii) early weaning (< 4 months); (iii) feeding beef (< 6 months); (iv) early introduction of cow's milk (< 6 months); and (v) parental smoking in the presence of the babies and early day care admission (< 2 years of life). All the preventive measures used in this study (exclusive breastfeeding and/or hydrolysed milk feeding, delayed and selective introduction of solid foods, and environmental advice) were effective at the third year of follow-up, greatly reducing allergic manifestations in high atopic risk babies in comparison with those not receiving these interventions", "Protein hydrolysates have been introduced in preterm formulae, but it is not clear whether they are needed for the feeding of preterm infants. We designed a randomized, controlled trial to test the effects of a preterm formula with hydrolysed cow's milk proteins on short-term growth and urinary and plasma amino acids levels.\n Infants with a birthweight < or = 1750 g and gestational age < or = 34 wk fed a conventional preterm infant formula (formula B) or a hydrolysed formula (formula A). Weight was measured daily; length, head circumference, mid-arm circumference and total skinfold thickness were measured weekly. Blood and urine were analysed for amino acid concentrations at start, 14 and 28 d.\n Twenty-one infants met the criteria for randomization. The daily feeding volumes were: formula A 172.8 +/- 5.6 vs formula B 170.1 +/- 2.8 ml/kg/d. Infants fed with formula A showed slower weight gain (17.4 +/- 3.4 vs 20.5 +/- 3.3 g/kg/d; p = 0.045) and lower mean change in Z-scores for weight (-0.18 +/- 0.16 vs 0.00 +/- 0.09; p = 0.009) and for head circumference (-0.06 +/- 0.13 vs 0.06 +/- 0.13; p = 0.049). After 14 d, infants receiving formula A had statistically significant higher urinary levels of essential amino acids compared to infants receiving formula B.\n Our results support the hypothesis of less nutritional value of hydrolysed versus conventional preterm formulae. Higher renal excretion of essential amino acids may be one of the mechanisms involved. These findings must be confirmed by further studies with larger sample sizes and protein hydrolysates with different degrees of hydrolysis.", "One hundred-eight infants from atopic families were admitted to the study. Each had at least one first-degree relative affected by asthma or rhinitis, conjunctivitis, eczema, cow's milk protein intolerance. All infants not breast fed were hypoallergenic formula. 46 infants were breast fed, 39 were bottle fed by the ordinary formula and 23 received the hypoallergenic one. No other food was introduced up to 6 months. Cow's milk proteins, egg, poultry and fish were introduced after 6 months. All infants were followed up to 24 months. Incidence of allergic diseases up to 24 months was not significantly different among the 3 groups.", "The use of protein hydrolysate preterm formulas is restricted because data on their nutritional adequacy are scarce. The authors evaluated the rate of growth and indices of protein metabolism in low-birth weight infants fed extensive and partial protein hydrolysate preterm formula followed for 12 weeks.\n A total of 61 low-birth weight infants were assigned randomly to receive extensive protein hydrolysate preterm formula (EH: n = 16), partial protein hydrolysate preterm formula (PH: n = 15), and standard preterm formula (SF; n = 15), or were fed their own mother's fortified breast milk (FBM; n = 15). The infants were investigated at study entry, and at 4, 8, and 12 weeks after study entry.\n There were no differences with respect to growth rate (weight gain, increments in length and head circumference), urea, albumin, prealbumin, transferrin, and plasma amino acid concentrations (except for tyrosine on a single occasion) according to the degree of hydrolysis. There were also no differences between groups fed hydrolyzed formulas and SF. However, several differences were found when EH and PH were compared with FBM. Weight gain from the entry to 12 weeks, serum urea at 12 weeks, and total plasma essential amino acids at 8 weeks were significantly higher in groups fed EH and PH than in those fed FBM. In addition, valine was significantly higher in groups fed PH (P < 0.05) than in the group fed FBM at 8 and 12 weeks, tyrosine was higher in EH and PH in comparison with FBM at 4 weeks, and in PH versus FBM at 12 weeks after study entry.\n This study suggests that experimental EH and PH are at least nutritionally equivalent to SFs.", "This prospective, long-term study assessed the effects of a protein hydrolysate formula on allergy prevention in infants with a family history of allergy. Infants were randomly assigned to receive either the hydrolysate formula (n = 92) or an adapted cow milk formula (n = 85) alone or with breast-feeding for 4 months. The groups did not differ in family allergy history scores or cord blood IgE levels. After 4 months, total IgE levels and allergic reactions did not differ significantly between groups, although the hydrolysate group had a lower prevalence of eczema. At 12 months of age, neither IgE levels nor allergic reactions were significantly different. At 2 years of age, however, 18 allergic reactions had occurred in the hydrolysate group and 31 had occurred in the control group; the differences were significant for eczema (p < 0.001) but not for asthma. At 4 years of age, allergic signs were found in 11 children in the hydrolysate group and in 17 children in the control group; the difference was significant only for eczema (p < 0.01). These results suggest that early feeding of a protein hydrolysate formula to infants at risk for allergies had a long-term preventive effect on the prevalence of eczema but not of asthma.", "One hundred twenty-two infants at risk of atopy on the basis of IgE screening at birth and family history of atopy were studied. The occurrence of atopic manifestations was analyzed in relation to their diets during the first 3 months of age. Only the infants receiving hypoallergenic milk were protected effectively; all other regimens (humanized cow milk, hypoallergenic milk or humanized cow milk + supplements) increased the frequency of allergic symptoms (P < .07). After a 1-year follow-up, the infants fed strictly on hypoallergenic milk during their 3 first months presented allergic symptoms less frequently than other infants (P < .007).", "The potential of extensively or partially hydrolyzed formulas to reduce the risks for allergies is controversial.\n We sought to assess the preventive effect of differently hydrolyzed formulas compared with cow's milk formula (CMF) in high-risk infants.\n Between 1995 and 1998, 2252 infants with a hereditary risk for atopy were enrolled in the German Infant Nutritional Intervention Study and randomly assigned at birth to one of 4 blinded formulas: CMF, partially hydrolyzed whey formula, extensively hydrolyzed whey formula, and extensively hydrolyzed casein formula (eHF-C). The primary end point at 1 year of age was the presence of allergic manifestation, which was defined as atopic dermatitis (AD), gastrointestinal manifestation of food allergy, allergic urticaria, or a combination of these factors.\n At 12 months per protocol, analysis was performed on 945 infants exposed to study formula: 304 (13.5%) infants had left the study, 138 (6.1%) infants were excluded because of noncompliance, and 865 infants were exclusively breast-fed the first 4 months of life. The incidence of allergic manifestation was significantly reduced by using eHF-C compared with CMF (9% vs 16%; adjusted OR, 0.51; 95% CI, 0.28-0.92), and the incidence of AD was significantly reduced by using eHF-C (OR, 0.42; 95% CI, 0.22-0.79) and partially hydrolyzed whey formula (OR, 0.56; 95% CI, 0.32-0.99). Family history of AD was a significant risk factor and modified the preventive effect of the hydrolysates.\n Prevention of allergic diseases in the first year of life is feasible by means of dietary intervention but influenced by family history of AD. The preventive effect of each hydrolyzed formula needs to be clinically evaluated.", "The allergy preventive effect of extensively (N) and partially (PH) hydrolysed cows' milk formulas compared with a regular formula (RM) was assessed in 155 infants with a family history of allergy. No cows' milk was given during the first nine months of life and no egg and fish up to 12 months of age. Breast feeding mothers avoided the same foods. At weaning the infants were randomised to one of the formula groups. The cumulative incidence of atopic symptoms at 18 months was 51, 64, and 84% in the N, PH, and RM groups, respectively. From 6 to 18 months there were significantly less cumulative atopic symptoms in the N group compared with the RM group, and significantly less than the PH group up to 6 (N = 25%; PH = 46%) and 9 months (N = 34%, PH = 58%). At 9 months significantly fewer infants in the N group (10%) than in the PH group (33%) had a positive skin prick test to eggs. The findings support an allergy preventive effect of an extensively hydrolysed formula, but not of a partially hydrolysed formula, during the first 18 months of life of high risk infants.", "A group of 129 infants were randomly assigned at birth to one of three feeding regimens: human milk (HM), cow's milk formula (CMF) or a casein hydrolysate formula (CHF) during the first 3 days of life. Blood samples were taken on at 4 days and at 2, 4, 8, 12 and 24 months of age. Macromolecular absorption was analysed by measuring the serum concentration of human alpha-lactalbumin (S-alpha-LA) with a competitive radioimmunoassay (RIA). Total serum IgE was measured by RIA. A family history of allergy correlated to the proportion of infants with allergic symptoms both at 24 and 36 months of age (p = 0.03 and p = 0.04 respectively). In none of the three groups did correlation exist between the duration of breastfeeding and serum alpha-LA, serum IgE, family history of allergy, frequency of allergic symptoms and proportion of infants with infections.", "Decreased nitrogen levels, calcium intestinal absorption rates, and plasma amino acid imbalances were reported for preterm infants who were fed partially hydrolyzed preterm formulas. In this pilot study, we evaluated a new formula with modified nitrogen and calcium sources.\n During their second week of life, 16 preterm infants were randomly assigned to one of two groups: 9 were fed the new partially hydrolyzed formula and 7 were fed a conventional formula. Nutrient balance was performed at the end of the first month of life. Amino acid concentrations and anthropometric parameters were measured at theoretical term.\n Birth weight and gestational age (mean +/- SD) were similar in the two groups (28.9 +/- 7.0 weeks and 1183 +/- 242 g vs. 27.7 +/- 1.0 weeks and 1139 +/- 162 g). Median nitrogen absorption rates (85% vs. 89%; P = 0.03) and biological values (59% vs. 69%; P = 0.13) were lower for infants who were fed the new formula than for those fed the conventional formula. After correction for difference in nitrogen intake, there was no significant difference in nitrogen retained between the two groups (P = 0.11). Plasma amino acid concentrations were also similar in the two groups. Median calcium absorption tended to be higher in the new-formula group than in the conventional-formula group (54% vs. 45%, P = 0.19). At theoretical term, infants fed the conventional formula were heavier than infants fed the new formula (3559 +/- 362 g vs. 3193 +/- 384 g, P = 0.04).\n Because nitrogen content is 10% higher in hydrolyzed-protein formula than in entire-protein formula, appropriate nitrogen retention, plasma amino acid profile, and mineral use can be achieved with the new partially hydrolyzed formula. Further studies with larger groups are needed to evaluate the effect on growth.", "Forty-five healthy infants were included in a double-blind randomized prospective study comparing the nutritional value of two formulas. One group received a whey-predominant formula (n = 20); the other group received a whey hydrolysate formula (n = 25). Four infants of the whey hydrolysate group were dropped because they refused the formula. Although the mean daily volume intake was smaller with the whey hydrolysate formula compared with the whey-predominant formula (p < 0.001), the weight gain in the two groups after 13 weeks was identical (27.2 g/day in both groups; the mean difference in weight gain between the groups after 13 weeks was only 8 g). Length gain at 13 weeks was 10.4 cm in the whey-predominant formula group and 10.8 cm in the whey hydrolysate formula group (p = NS). After 13 weeks, blood was sampled for hemoglobin, hematocrit, red blood cell count, white blood cell count, lymphocytes, glycemia, proteins, albumin, prealbumin, calcium, phosphorus, urea, creatinine, iron, iron-binding capacity, zinc, and vitamins A and E. Except for the iron-binding capacity, zinc, urea (in plasma as well as in urine) (all three were higher in the whey hydrolysate group), no significant differences were found. According to these results, exclusive feeding of the whey hydrolysate formula from birth to 3 months of age to healthy infants appears to result in an adequate nutritional status, as assessed at 3 months of age.", "The incidence of atopic manifestations was analyzed in infants \"at risk\" because of histories of atopy in first degree relatives. The incidence of atopic manifestations was significantly reduced (P = .0011) during the first 6 months of life when only the whey hydrolysate was administered (2/32 infants, 6.3%) compared with the incidence when an adapted formula was given (14/35 infants, 40%). This beneficial effect continued during the 6 to 12-month period, after diversification of the diet at 6 months. At the age of 1 year, 7/32 (21.8%) of the infants in the whey hydrolysate group had presented with manifestations of probable atopic disease compared with 17/35 (48.6%) infants in the adapted formula group (P = .021). The incidence of cow milk protein sensitivity was evaluated at 5/32 (15.6%) in the hydrolysate group and 15/35 (42.8%) in the adapted formula group (P = .014). Other foods such as egg and fish may be responsible for manifestations in three infants in hydrolysate group and in five infants of the adapted group (9.4% and 14.3%, respectively NS). These preliminary data show that the administration of a whey hydrolysate during the first 6 months of life to babies \"at risk\" decreased the incidence of atopic disease up to the age of 12 months. The incidence of cow milk protein sensitivity appeared to be decreased, whereas the incidence of sensitivities to other food proteins was comparable in both groups.", "Early feeding with cow's milk (CM) may increase the risk of cow's milk allergy (CMA).\n We sought to examine prospectively whether supplementary feeding of CM at the maternity hospital would increase the risk when compared with feeding with pasteurized human milk or hydrolyzed formula.\n We studied 6209 unselected healthy, full-term infants, of whom 5385 (87%) required supplementary milk while in the hospital. The infants were randomly assigned to receive CM formula (1789 infants), pasteurized human milk (1859 infants), or whey hydrolysate formula (1737 infants). The comparison group (824 infants) was composed of infants who were exclusively breast-fed. The infants were followed for 18 to 34 months for symptoms suggestive of CMA. The primary endpoint was a challenge-proven adverse reaction to CM after a successful CM elimination diet.\n The cumulative incidence of CMA in the infants fed CM was 2.4% compared with 1.7% in the pasteurized human milk group (odds ratio [OR], 0.70; 95% confidence interval [CI], 0. 44-1.12) and 1.5% in the whey hydrolysate group (OR, 0.61; 95% CI, 0. 38-1.00). In the comparison group, CMA developed in 2.1% of the infants. Among the infants who required supplementary feeding at hospital, both exposure to CM while in the hospital (OR, 1.54; 95% CI, 1.04-2.30; P =.03) and obvious parental atopy (OR, 2.32; 95% CI, 1.53-3.52; P <.001) increased the risk of CMA.\n Our data indicate that feeding of CM at maternity hospitals increases the risk of CMA when compared with feeding of other supplements, but exclusive breast-feeding does not eliminate the risk." ]

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[ "Evaluation of the dose-effect relationship of a new ace inhibitor (perindopril) by an automatic blood pressure recorder.", "Evaluation of the antihypertensive efficacy and tolerability of moexipril, a new ACE inhibitor, compared to hydrochlorothiazide in elderly patients.", "Cilazapril plus hydrochlorothiazide: improved efficacy without reduced safety in mild to moderate hypertension. A double-blind placebo-controlled multicenter study of factorial design.", "Effects of moderate salt restriction alone and in combination with cilazapril on office and ambulatory blood pressure.", "[2.5 and 5 mg cilazapril once daily in comparison with placebo in hypertension. A comparative study with ambulatory 24-hour monitoring].", "The effects of benazepril, a new angiotensin-converting enzyme inhibitor, in mild to moderate essential hypertension: a multicenter study.", "Dose finding studies with imidapril--a new ACE inhibitor.", "A dose-response study of perindopril in hypertension: effects on blood pressure 6 and 24 h after dosing. Perindopril Multicentre Dose-Response Study Group.", "Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy, tolerability and safety compared to an angiotensin-converting enzyme inhibitor, lisinopril.", "Steady-state pharmacokinetics and pharmacodynamics of cilazapril in the presence and absence of cyclopenthiazide.", "Comparison of the fixed combination of enalapril/diltiazem ER and their monotherapies in stage 1 to 3 essential hypertension.", "The effect of an endothelin-receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. Bosentan Hypertension Investigators.", "A randomized, placebo-controlled, double-blind, parallel study of various doses of losartan potassium compared with enalapril maleate in patients with essential hypertension.", "The effect of perindopril and hydrochlorothiazide alone and in combination on blood pressure and on the renin-angiotensin system in hypertensive subjects.", "Combined enalapril and felodipine extended release (ER) for systemic hypertension. Enalapril-Felodipine ER Factorial Study Group.", "Low-dose captopril for the treatment of mild to moderate hypertension. I. Results of a 14-week trial. Veterans Administration Cooperative Study Group on Antihypertensive Agents.", "Antihypertensive efficacy and tolerability of captopril in the elderly: comparison with hydrochlorothiazide and placebo in a multicentre, double-blind study.", "Antihypertensive duration of action of cilazapril in patients with mild to moderate essential hypertension.", "Once-daily treatment of patients with hypertension: a placebo-controlled study of amlodipine and benazepril vs amlodipine or benazepril alone.", "Efficacy and tolerance of trandolapril (0.5-2 mg) administered for 4 weeks in patients with mild-to-moderate hypertension. Investigator Study Group.", "Usefulness of piretanide plus ramipril for systemic hypertension: a multicenter trial.", "Lisinopril dose-response relationship in essential hypertension.", "Placebo-controlled comparison of spirapril at 6, 12 and 24 mg/day in mild to severe essential hypertension.", "Placebo-controlled comparison of the efficacy and tolerability of once-daily moxonidine and enalapril in mild to moderate essential hypertension.", "Efficacy of combination therapy with trandolapril and verapamil sr in primary hypertension: a 4 x 4 trial design. The Trandolapril Study Group.", "Effects of nitrendipine and enalapril on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension.", "Antihypertensive efficacy of cilazapril 2.5 and 5.0 mg once-daily versus placebo on office blood pressure and 24-hour blood pressure profile.", "Insulin sensitivity in hypertensive Type 2 diabetic patients after 1 and 19 days' treatment with trandolapril.", "Diurnal blood pressure in patients with mild-to-moderate hypertension treated with once-daily benazepril hydrochloride.", "Differing mechanisms of action of angiotensin-converting enzyme inhibition in black and white hypertensive patients. The Trandolapril Multicenter Study Group.", "Twenty-four hour blood pressure effect of once-daily lisinopril, enalapril, and placebo in patients with mild to moderate hypertension.", "A multicentre multidose study of the efficacy and safety of spirapril in mild-to-moderate essential hypertension. UK Study Group of Spirapril in Hypertension.", "A double-blind study to compare the efficacy, tolerance and safety of two doses of the angiotensin converting enzyme inhibitor ramipril with placebo.", "Antihypertensive profiles with ascending dose combinations of ramipril and felodipine ER.", "The use of benazepril in hypertensive patients age 55 and over.", "Effects of the converting enzyme inhibitor quinapril (CI-906) on blood pressure, renin-angiotensin system, and prostanoids in essential hypertension.", "Brazilian multicenter study on efficacy and tolerability of trandolapril in mild-to-moderate essential arterial hypertension. EMBATHE substudy with ambulatory blood pressure monitoring.", "The effects of the long-acting angiotensin-converting enzyme inhibitor cilazapril on casual, exercise, and ambulatory blood pressure.", "Evaluation of the efficacy and tolerability of a low-dose combination of isradipine and spirapril in the first-line treatment of mild to moderate essential hypertension.", "Cardiac and hormonal effects of enalapril in hypertension.", "Effect of low-dose ramipril on microalbuminuria in normotensive or mild hypertensive non-insulin-dependent diabetic patients. North-East Italy Microalbuminuria Study Group.", "Nitrendipine and enalapril combination therapy in mild to moderate hypertension: assessment of dose-response relationship by a clinical trial of factorial design.", "Once-daily treatment of essential hypertension with captopril.", "Verapamil SR and trandolapril combination therapy in hypertension--a clinical trial of factorial design. German Hypertension Study Group.", "Quinapril: a double-blind, placebo-controlled trial in essential hypertension.", "Felodipine-metoprolol combination tablet: a valuable option to initiate antihypertensive therapy?", "[Cilazapril in essential hypertension. A placebo-controlled double-blind study to establish the dosage].", "Additive effects of verapamil and enalapril in the treatment of mild to moderate hypertension.", "Effects of verapamil and trandolapril in the treatment of hypertension. Trandolapril Study Group.", "Tricenter assessment of the efficacy of the ACE inhibitor, moexipril, by ambulatory blood pressure monitoring.", "Fosinopril monotherapy: relationship between blood pressure reduction and time of administration.", "Evaluation of the antihypertensive effect of once-a-day trandolapril by 24-hour ambulatory blood pressure monitoring. The Italian Trandolapril Study Group.", "The 24 h blood pressure responses of hypertensives to a once-a-day cilazapril regimen.", "Combined versus single effect of fosinopril and hydrochlorothiazide in hypertensive patients.", "Use of the factorial design and quadratic response surface models to evaluate the fosinopril and hydrochlorothiazide combination therapy in hypertension.", "Antihypertensive effect of fosinopril, a new angiotensin converting enzyme inhibitor: findings of the Fosinopril Study Group II.", "Comparative study of once-daily administration of captopril 50 mg, hydrochlorothiazide 25 mg and their combination in mild to moderate hypertension.", "Superiority of home blood pressure measurements over office measurements for testing antihypertensive drugs.", "Comparison of efficacy of spirapril and enalapril in control of mild-to-moderate hypertension.", "Dose response and safety of telmisartan in patients with mild to moderate hypertension.", "Evaluation of blood pressure response to the combination of enalapril (single dose) and diltiazem ER (four different doses) in systemic hypertension.", "Metabolic effects of temocapril in hypertensive patients with diabetes mellitus type 2.", "Co-administration of an ACE-inhibitor (moexipril) and hormonal replacement therapy in postmenopausal women.", "Preventing increases in early-morning blood pressure, heart rate, and the rate-pressure product with controlled onset extended release verapamil at bedtime versus enalapril, losartan, and placebo on arising.", "Antihypertensive effect of enalapril as first-step treatment of mild and moderate uncomplicated essential hypertension. Evaluation by two methods of blood pressure measurement.", "Placebo-controlled comparison of the efficacy and tolerability of once-daily moxonidine and enalapril in mild-to-moderate essential hypertension.", "The effect of cilazapril, a new angiotensin converting enzyme inhibitor, on peak and trough blood pressure measurements in hypertensive patients.", "Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy and safety compared with placebo and enalapril.", "Dose-finding study of cilazapril (Inhibace) in patients with uncomplicated essential hypertension.", "Antihypertensive effectiveness of low-dose lisinopril-hydrochlorothiazide combination. A large multicenter study. Lisinopril-Hydrochlorothiazide Group.", "Effects of benazepril and hydrochlorothiazide, given alone and in low- and high-dose combinations, on blood pressure in patients with hypertension.", "[Antihypertensive effect of fosinopril in mild hypertension].", "Perindopril as monotherapy in hypertension: a multicenter comparison of two dosing regimens. The Perindopril Study Group.", "Additive effects of diltiazem and lisinopril in the treatment of elderly patients with mild-to-moderate hypertension.", "ACE-inhibition with perindopril in essential hypertensive patients with concomitant diseases. The Perindopril Therapeutic Safety Collaborative Research Group.", "Monotherapy of essential hypertension with a converting-enzyme inhibitor.", "Treatment of patients with essential hypertension: amlodipine 5 mg/benazepril 20 mg compared with amlodipine 5 mg, benazepril 20 mg, and placebo.", "Discrepancies between clinic and ambulatory blood pressure responses to cilazapril therapy.", "Effects of verapamil SR, trandolapril, and their fixed combination on 24-h blood pressure: the Veratran Study." ]

[ "Repeated blood pressure recordings by non-invasive devices are of better predictive value than single measurements in the evaluation of antihypertensive treatment. Such a method has been used to establish the dose-effect relationship of perindopril. After a two-week placebo run-in period, 40 patients with essential hypertension (age 56.6 +/- 1.5 years, 31 males, nine females) were treated with placebo or 2, 4 or 8 mg of perindopril once daily for one month following a randomized double-blind design. They were included if at least 75% of diastolic blood pressure recordings, made over an 8 h diurnal period using an automatic blood pressure recorder, were greater than 95 mmHg on placebo. Values (mean +/- SEM) before and after treatment were assessed using analysis of variance. These data showed a significantly greater reduction of blood pressure with 4 mg and 8 mg daily doses compared to placebo and the 2 mg daily dose. Such results were not obtained with blood pressure levels recorded by a mercury sphygmomanometer, confirming the value of an automatic blood pressure recorder as a tool in therapeutic trials.", "To compare the antihypertensive efficacy of moexipril, a new angiotensin-converting enzyme (ACE) inhibitor, to treatment with hydrochlorothiazide (HCTZ).\n Two hundred and one non-hospitalized male and female patients between 65 and 80 years of age with essential hypertension.\n This was a multicentre, placebo-controlled, double-blind study with a parallel group design. Subjects with a sitting diastolic blood pressure (DBP) > or = 95 mmHg were randomized to monotherapy with placebo, moexipiril 7.5 mg o.d., moexipril 15 mg o.d. or HCTZ 25 mg o.d. for 8 weeks.\n Throughout the study period treatment with moexipril and HCTZ resulted in significant reductions of DBP compared with placebo, but there were no significant differences between the active treatment groups. At end point the adjusted mean reductions were 10.5, 8.7 and 10.1 mmHg in the HCTZ, moexipril 7.5 mg and moexipril 15 mg groups, respectively, compared to 3.9 mmHg in the placebo group. Treatment with moexipril was associated with two cases of first dose hypotension and two cases of moderate and reversible increases in serum creatinine levels. Otherwise, both dosages of moexipril were well tolerated and the overall percentages of patients who had adverse experiences were smaller than in the placebo group.\n Moexipril is well tolerated and is at least as effective as HCTZ in elderly patients with essential hypertension.", "In this multicenter, placebo-controlled, double-blind, 4 x 3 factorial design study, 1,162 patients randomized into 12 parallel groups received either placebo (n = 97), cilazapril (CLZ 0.5, 5, or 10 mg; n = 288 total), hydrochlorothiazide (HCTZ 12.5 or 25 mg; n = 198 total), or one of the six possible combinations of the two drugs (n = 579 total) given orally once daily for 4 weeks. The mean decrease from baseline in predose (i.e., 24 h postdose) sitting diastolic blood pressure (SDBP) was statistically significantly (p < 0.01) greater for all combinations studied compared to placebo, as well as to their respective monotherapy components. Synergistic antihypertensive effects were noted for the 5/12.5 mg CLZ/HCTZ combination therapy. The normalization (SDBP < or = 90 mm Hg) rate of the 5/12.5 mg CLZ/HCTZ combination was essentially additive with respect to the component monotherapies. The tolerability profile of the CLZ/HCTZ combination was similar to its respective components and comparable to placebo. The CLZ/HCTZ group reported low serum potassium (K+) and high serum uric acid less frequently than the HCTZ group. Therefore, the CLZ/HCTZ combination (5 mg/12.5 mg) is an option for hypertensive patients not responding to single drug CLZ therapy.", "The purpose of the present study was to examine the effects of salt-restriction alone and in combination with an angiotensin-converting enzyme (ACE) inhibitor (cilazapril) on both office and ambulatory blood pressure (BP) levels in free living subjects with elevated BP. The study was carried out in an out-patient setting with subjects recruited from occupational health care system mainly. After exclusions, 39 subjects (24 men, 15 women, aged 28-65 years) with mildly to moderately elevated BP completed the study. After 3 months run-in period with placebo (first month on normal-salt and the next 2 months on sodium-restricted diet) the subjects were randomised into either salt-restriction placebo or salt-restriction cilazapril (2.5 mg daily) groups for 3 months. In the whole group, 24-h urinary sodium excretion decreased (mean +/- s.d.) from 198 +/- 60 to 112 +/- 59 mmol (4 weeks vs 24 weeks, P < 0.001). Systolic and diastolic office BP decreased during the placebo-sodium-restriction phase (-7.1 [95% Cl -11.2; -3.0] and -4.2 [95% Cl -6.6; -1.8] mm Hg for systolic and diastolic BP), and similarly the daytime ambulatory BP (ABP) was reduced during this period (-2.8 [95% Cl -5.2; -0.5] and -2.8 [95% Cl -4.5; -1.2] mm Hg, systolic (SBP) and diastolic blood pressure (DBP) respectively). No changes were observed in the night time ABP. Addition of cilazapril to sodium-restriction enhanced significantly the office BP (-13.2, [95% Cl -20.2; -6.2], and -9.1 [95% Cl -13.5; -4.7]) and daytime ABP (-5.9, [95% Cl -10.1; -1.8] and -5.3, [95% Cl -8.8; -1.9]) reduction. Blood glucose, plasma insulin or serum lipids did not change during the study. Moderate sodium restriction seems to lower the office and daytime ABP levels in subjects with mild-to-moderate hypertension. The antihypertensive effect of cilazapril could be enhanced by sodium restriction.", "nan", "Benazepril hydrochloride is a new angiotensin-converting enzyme inhibitor. In a multicenter study, 206 patients with mild to moderate hypertension were randomized to receive benazepril at a dose of 2, 5, 10, or 20 mg, hydrochlorothiazide, 25 mg, or placebo once daily for 4 weeks. The 20 mg dosage of benazepril lowered blood pressure to a degree equal to that of 25 mg hydrochlorothiazide: -12.2/7.7 mm Hg and -13.4/-7.5 mm Hg, respectively. Hydrochlorothiazide proved to be more effective in black subjects. At lower dosage levels of benazepril (2, 5, and 10 mg), blood pressure reduction was not significantly different from that with placebo. In those patients who failed to achieve goal diastolic blood pressure of less than 90 mm Hg with monotherapy after 4 weeks, the addition of open-label hydrochlorothiazide (25 mg/day) to benazepril, hydrochlorothiazide, or placebo produced a substantial additional decrease in blood pressure over a 2-week period. No definite adverse effects on hematologic measurements, serum biochemistry test results, or urinalyses were noted. Subjective adverse experiences were common in all groups but except in three or possibly four instances were not considered causally related to the study drug.", "1. We describe an approach involving a smaller, shorter study, leading onto a longer, larger study in which the antihypertensive effects of ascending doses of imidapril, a new ACE inhibitor, were investigated. Both studies were planned prospectively, assuming a clinically useful fall in BP to be 8 mm Hg (s.d. = 9). The studies included patients with mild to moderate essential hypertension (baseline sitting diastolic blood pressure (SDBP) 95-115 mm Hg). After a placebo run-in of 2-3 weeks patients received either placebo or imidapril 2.5, 5, 10 or 20 mg in the 2 week study (n = 91) or imidapril 5, 10, 20 or 40 mg in the 4 week study (n = 162). 2. The overall mean baseline SDBP was 103.4 mm Hg (s.d. 0.62) in the initial study and 101.5 mm Hg (s.d. 0.41) in the 4 week study. 3. Compared with placebo, imidapril 10, 20 and 40 mg significantly reduced SDBP. There was no significant difference between these doses, suggesting that 10 mg achieved maximal ACE inhibition in most patients. The 2.5 mg dose showed no significant effect. The 5 mg dose gave an intermediate effect. In both studies the overall incidence of adverse events was similar in the imidapril and placebo groups, and was not worrying.", "To examine the dose-response characteristics of perindopril at the time of its peak and trough antihypertensive effects, with the primary outcome measure being changes in diastolic blood pressure.\n After a four-week, single-blind placebo run-in, patients were randomly allocated to four doses of perindopril or placebo using a parallel group design.\n Sixteen specialist centres in the United States.\n Of 483 patients entered into the run-in phase, 293 were eligible for randomization to perindopril or placebo therapy, with 260 patients included in the final efficacy analysis.\n Eligible patients were randomized to 12 weeks of therapy with perindopril 2, 4, 8 or 16 mg or placebo.\n At the final visit, all doses of perindopril significantly (P < 0.05) lowered diastolic blood pressure compared with placebo. The ratio of changes in placebo-corrected diastolic blood pressure at 24 versus 6 h for perindopril 2, 4 and 8 mg was 1.0, 1.0 and 0.97, respectively. The maximum antihypertensive effect was seen with perindopril 8 mg, with the 16 mg dose providing no additional response. Changes in systolic and diastolic blood pressure were similar.\n Perindopril is most effective at doses of 4 and 8 mg once daily, with similar reductions in diastolic blood pressure present at 6 and 24 h after dosing.", "To compare the efficacy, safety and tolerability of valsartan to an angiotensin-converting enzyme (ACE) inhibitor, lisinopril, and placebo in patients with mild-to-moderate essential hypertension.\n A total of 734 men and women were randomised in this multicentre, double-blind, optional titration, parallel group trial. Volunteers received valsartan 80 mg (n = 364), lisinopril 10 mg (n = 187) or placebo (n = 183) daily for 4 weeks, with subsequent titration of dose depending on response to treatment (valsartan 80 mg titrated to valsartan 160 mg once daily or valsartan 80 mg twice daily, lisinopril 10 mg titrated to lisonopril 20 mg once daily). Patients were assessed at 4, 8 and 12 weeks.\n The primary variable was change from baseline in mean sitting diastolic blood pressure (SDBP). Other efficacy variables included sitting systolic blood pressure (SSBP) and percentage of 'successful' responders (SDBP <90 mm Hg or > or =10 mm Hg reduction from baseline).\n All active treatment groups were shown to demonstrate significant reductions in SDBP compared to placebo at endpoint of therapy (least mean square reduction from baseline: valsartan 80/160 mg: -5.25 mm Hg (Cl -7.17, -3.34, P< 0.001); valsartan 80/80 mg twice daily: -5.63 mm Hg (Cl -7.51, -3.75, P< 0.001); lisinopril 10/20 mg: -6.93 mm Hg, (Cl -8.81, -5.05, P< 0.001). There were no statistically significant differences between the active treatment groups at endpoint of therapy. In patients requiring titration to a higher dose (placebo n = 142, valsartan 80/80 twice daily n = 124, valsartan 80/160 n = 114, lisinopril 10/20 n = 120), there were no significant treatment differences between valsartan 160 mg given as a single daily dose or as 80 mg twice daily (P = 0.658). Both valsartan and lisinopril produced similarly high percentages of 'successful' responders at endpoint of therapy. A somewhat higher frequency of drug related cough was observed in lisinopril treated patients (8%) compared to valsartan (1.1%) or placebo (0.5%).\n Valsartan 80 mg daily, with titration to 160 mg daily as required, provides similar antihypertensive efficacy to lisinopril 10 mg daily with titration to 20 mg daily. Valsartan provides a new antihypertensive agent with comparable efficacy to lisinopril and appears to be associated with a reduced incidence of cough.", "Twenty-two patients with essential hypertension received a single dose of 2.5 mg cilazapril and were then randomised into a double-blind parallel group study to receive either placebo, 1.25 mg cilazapril + 0.5 mg cyclopenthiazide (CPTZ), 2.5 mg cilazapril + 0.5 mg CPTZ, or 2.5 mg cilazapril alone for 1 month. After oral administration of a single dose of 2.5 mg cilazapril, the active diacid cilazaprilat appeared rapidly in the plasma (Tmax 2.0 +/- 0.2 h). With the radioinhibitor assay used in this study, a single elimination phase of cilazaprilat was evident, with a half-life (t1/2) of 2-3 h. At steady state, the pharmacokinetics of cilazaprilat were similar to single-dose administration and were not altered by CPTZ. The Cmax and area under the curve (AUC) of cilazaprilat were directly proportional to dose. Cilazapril administration in the dose range of 1.25-2.5 mg produced a dose-proportional inhibition of angiotensin-converting enzyme (ACE) activity that was maximum 2 h after drug administration. The degree of ACE inhibition correlated with the plasma concentration-time profile of cilazaprilat and the maximum decrease in blood pressure (BP). The EC50 for ACE inhibition by cilazaprilat was 7.7 ng/ml after acute treatment and was not significantly altered during chronic administration or by concomitant administration of CPTZ. There was no evidence of a dose-related antihypertensive effect of cilazapril at steady state and, with the small numbers of subjects used in this study, there was no evidence of 24-h BP control with monotherapy.", "The safety and efficacy of two fixed dose combinations of enalapril and diltiazem extended release formation (ER) (E/D) were compared with their monotherapies and placebo in patients with stage 1 to 3 hypertension. The trial design was a multicenter, randomized, double blind, placebo controlled, parallel group, 12 week treatment phase, followed by a 36 week, open label phase. A total of 891 patients with sitting diastolic blood pressure (SiDBP) between 95 and 115 mm Hg were randomly assigned to enalapril 5 mg, diltiazem ER 120 mg, diltiazem ER 180 mg, enalapril 5 mg/diltiazem ER 120 mg (E5/D120), enalapril 5 mg/ diltiazem ER 180 mg (E5/D180), or placebo. In the open label phase, 562 patients received the fixed combination, titrated as needed to control SiDBP < 90 mm Hg. Efficacy was determined with trough (24 +/- 2 h postdose) sitting blood pressure measurements at week 12 and at the end of the open label part of the study. Safety was evaluated based on patient symptoms, clinical laboratories, and electrocardiograms (ECG). E5/D120 and E5/D180 significantly reduced trough SiDBP (-7.6 and -8.3 mm Hg, respectively; P < .05) versus their monotherapies. E5/D120 and E5/D180 significantly reduced trough sitting systolic blood pressure (-7.9 and -9.0, respectively; P < .05) versus both diltiazem ER monotherapies. All active treatments significantly decreased SiDBP and SiSBP versus placebo. E/D effectively lowered SiDBP and SiSBP during the open label extension. No significant difference was seen among treatment groups for the overall incidence of adverse events. The most common drug related adverse events were headache, edema/swelling, dizziness, asthenia/fatigue, cough, rash, and impotence. The event frequency for the combinations were similar to those seen with the monotherapies. Fixed combinations of E/D were generally well tolerated, with an increased blood pressure lowering effect as compared with the individual components in patients with stage I to III hypertension.", "Endothelin is a powerful vasoconstrictor peptide derived from the endothelium. We evaluated the contribution of endothelin to blood-pressure regulation in patients with essential hypertension by studying the effect of an endothelin-receptor antagonist, bosentan.\n We studied 293 patients with mild-to-moderate essential hypertension. After a placebo run-in period of four to six weeks, patients were randomly assigned to receive one of four oral doses of bosentan (100, 500, or 1000 mg once daily or 1000 mg twice daily), placebo, or the angiotensin-converting-enzyme inhibitor enalapril (20 mg once daily) for four weeks. Blood pressure was measured before and after treatment.\n As compared with placebo, bosentan resulted in a significant reduction in diastolic pressure with a daily dose of 500 or 2000 mg (an absolute reduction of 5.7 mm Hg at each dose), which was similar to the reduction with enalapril (5.8 mm Hg). There were no significant changes in heart rate. Bosentan did not result in activation of the sympathetic nervous system (as determined by measurement of the plasma norepinephrine level) or the renin-angiotensin system (as determined by measurements of plasma renin activity and angiotensin II levels).\n An endothelin-receptor antagonist, bosentan, significantly lowered blood pressure in patients with essential hypertension, suggesting that endothelin may contribute to elevated blood pressure in such patients. The favorable effect of treatment with bosentan on blood pressure occurred without reflexive neurohormonal activation.", "The efficacy and safety of various doses of losartan potassium, a specific and selective angiotensin II receptor antagonist, were compared with those of placebo and enalapril maleate 20 mg in patients with mild to moderate essential hypertension in a randomized, double-blind, parallel study. We randomly allocated 576 patients at the end of a 4-week placebo baseline period to 8 weeks of once-daily double-blind treatment with losartan potassium 10, 25, 50, 100, or 150 mg, enalapril maleate 20 mg, or placebo. After 8 weeks of treatment, mean reductions from baseline in supine systolic/diastolic pressure 24 hours after dosing (trough) for losartan potassium 10, 25, 50, 100, and 150 mg, enalapril maleate 20 mg, and placebo were 7.6/7.9, 7.8/6.8, 13.0/10.1, 8.9/9.9, 10.5/9.7, 14.7/11.2, and 3.8/5.6 mm Hg, respectively. Compared with mean changes in supine diastolic pressure in the placebo group, losartan potassium 50 to 150 mg and enalapril maleate 20 mg produced clinically important and statistically significant reductions (P < or = .01) in blood pressure. At 24 hours after dosing, the blood pressure changes obtained with losartan potassium 50 mg were essentially identical to those obtained with enalapril maleate 20 mg. While there was a dose-related effect with losartan potassium from 10 to 50 mg at peak (6 hours after dosing), doses of 10 and 25 mg were not consistently different from placebo 24 hours after dosing. To assess the once-daily effect of losartan potassium, trough-to-peak ratios of the mean changes in supine diastolic pressure after 8 weeks of treatment were calculated.(ABSTRACT TRUNCATED AT 250 WORDS)", "The pharmacodynamic effects and acceptability of perindopril (4 mg daily) and hydrochlorothiazide (25 mg daily) given alone or in combination for 1 month were investigated in a double-blind, placebo controlled, parallel group study. The pharmacokinetics of perindopril and its active metabolite perindoprilat and the time course of angiotensin converting enzyme inhibition were studied for 72 h following the last dose of treatment in the two appropriate groups. Similar decreases in blood pressure were seen 24 h after the last dose of perindopril or hydrochlorothiazide (11/7 mm Hg supine) given alone at these doses. The effect of these drugs given together was additive on diastolic blood pressure and synergistic on systolic blood pressure (24.5/12.6 mm Hg supine) taking into account the placebo response. The significant increase in plasma renin activity produced by perindopril alone was potentiated by concurrent administration of hydrochlorothiazide. The formation of perindoprilat was slightly reduced in the group also receiving hydrochlorothiazide and there was a very small reduction in ACE inhibition in this group. Perindopril, whether given alone or in combination with hydrochlorothiazide, was well tolerated and produced no clinically significant change in routine haematology or serum biochemistry. The additive or synergistic effects of perindopril and hydrochlorothiazide on blood pressure must be due to their complementary physiological actions and not to a pharmacokinetic interaction.", "This multicenter, placebo-controlled, double-blind trial of factorial design evaluated the safety and efficacy of combination treatment with the angiotensin-converting enzyme inhibitor, enalapril, and the vascular selective calcium antagonist felodipine extended release (ER) in patients with essential hypertension. After a 4-week, single-blind placebo baseline period, 707 patients with sitting diastolic blood pressures (BPs) in the range of 95 to 115 mm Hg received placebo, enalapril (5 or 20 mg), felodipine ER (2.5, 5, or 10 mg), or their combinations for an 8-week double-blind treatment period. All doses of enalapril and felodipine ER had a statistically significant (p < 0.05) additive effect in reducing both systolic and diastolic BP. The trough to peak ratios for the combinations ranged from 0.63 (enalapril 5 mg-felodipine ER 2.5 mg) to 0.79 (enalapril 20 mg-felodipine ER 10 mg) and were consistent with effective BP control with 1 dose/day. Patients aged > or = 65 years demonstrated a greater reduction in diastolic BP. Combinations of enalapril-felodipine ER were associated with less drug-induced peripheral edema (4.1%) compared to felodipine ER monotherapy (10.8%). There were no serious drug-related adverse effects observed during the study. In this trial, the combination of enalapril and felodipine ER effectively lowered BP and was generally well tolerated with an excellent safety profile when used in the treatment of hypertension.", "We randomized 495 men with uncomplicated hypertension (diastolic BP, 92 to 109 mm Hg) to one of five captopril regimens at the following dosages: 12.5 mg three times a day, 25 mg three times a day, 37.5 mg twice daily, 50 mg three times a day, or placebo three times a day. After seven weeks, BP reduction with each captopril dose was greater than in the placebo group, averaging 10.2 to 14.2/8.6 to 10.5 mm Hg. Captopril, 37.5 mg/day, was as effective as 150 mg/day. Hydrochlorothiazide, 25 mg twice daily, was added for seven more weeks to all patients receiving placebo and to two thirds of those randomized to captopril therapy. Blood pressure reduction averaged 12.0/8.7 mm Hg in those receiving hydrochlorothiazide alone and 24.9 to 26.4/14.4 to 17.3 mm Hg in those receiving a combination of hydrochlorothiazide and captopril. Added hydrochlorothiazide greatly enhanced the antihypertensive response. The 15 terminations (4.3%) related to captopril were not life threatening. Conclusion: Captopril treatment of uncomplicated hypertension may be initiated with 37.5 mg/day--half the currently recommended dose.", "In this study we compared the antihypertensive efficacy and tolerability of captopril at 25 mg twice daily, hydrochlorothiazide (HCTZ), 12.5 mg twice daily and placebo in a multicentre, double-blind, randomized study that included 152 essential hypertensive patients (77 males, 75 females, 87 WHO stage I, 65 WHO stage II, aged 69 +/- 4 years, mean +/- s.d.). Supine and standing blood pressure were similarly reduced by captopril and HCTZ (P less than 0.01 for both compared with placebo). The heart rate did not change. Captopril (25-30 mg twice daily) and HCTZ (12.5 mg twice daily), alone or in combination, maintained their antihypertensive effect during a 24-week single-blind follow-up study. During the follow-up, diastolic blood pressure remained less than 100 mmHg in seven essential hypertensives on placebo, in 45 on captopril and in 25 on HCTZ. Side effects were observed in seven essential hypertensives during placebo (treatment withdrawn in two), in eight during HCTZ and in three during captopril. Serum potassium was reduced (P less than 0.05) and uric acid was increased (P less than 0.01) only during HCTZ. We conclude that captopril and HCTZ have similar antihypertensive efficacy in the elderly; however, captopril appears to be better tolerated.", "The efficacy of cilazapril monotherapy was evaluated in 2 multicentre double-blind dose-response trials. After 4 weeks of a single-blind placebo run-in period, patients with uncomplicated mild to moderate essential hypertension and a sitting diastolic blood pressure of 100 to 115 mm Hg, 24 hours after the last placebo dose (trough), were randomised to take either placebo or cilazapril 2.5 mg or 5 mg for 4 weeks (study 1, 86 patients) or 8 weeks (study 2, 78 patients). Sitting diastolic blood pressure was checked every 2 weeks at trough in both studies and at peak in study 2. The reductions in sitting diastolic blood pressure from baseline at trough, and the difference from placebo, were clinically and statistically significant for both cilazapril groups in the 2 studies. The reduction in blood pressure in both active treatment groups was similar, but the response rate with cilazapril 5 mg was greater than that with 2.5 mg. More than 50% of the peak effect was still present at trough for both cilazapril groups. It is concluded that both dosages of cilazapril are effective and reduce blood pressure compared with placebo over a 24-hour period.", "To compare the efficacy, tolerability, and safety of once-daily therapy with amlodipine 5 mg/benazepril 10 mg vs amlodipine 5 mg, benazepril 10 mg, and placebo.\n Randomised, double-blind, placebo-controlled, parallel-group, multicentre trial.\n Twenty-two clinical centres, including private practice groups and academic research clinics.Patients: A total of 530 patients between 21 and 80 years of age with essential hypertension were screened for the study, and 454 were randomised to treatment with amlodipine 5 mg/benazepril 10 mg, amlodipine 5 mg, benazepril 10 mg, or placebo for 8 weeks.\n Amlodipine 5 mg/benazepril 10 mg produced greater reductions from baseline in sitting diastolic blood pressure than amlodipine 5 mg (P < 0.03), benazepril 10 mg (P < 0.001), and placebo (P < 0.001). The response rate in the amlodipine 5-mg/benazepril 10-mg treatment group (66.4%) was better than that observed in the amlodipine 5-mg (50.0% P < 0.02), benazepril 10-mg (38.3% P < 0.001), and placebo (24.4% P < 0.001) groups. There was no significant difference in heart rate among the four groups. The incidence of oedema in the amlodipine 5-mg/benazepril 10-mg (1.7%) group was somewhat less than that in the amlodipine 5-mg (4.5%) group.\n Therapy with amlodipine 5 mg/benazepril 10 mg was well tolerated and was superior to amlodipine 5 mg, benazepril 10 mg, and placebo in reducing sitting diastolic blood pressure in patients with essential hypertension.", "This double-blind, placebo-controlled, dose-ranging study recruited 170 patients with mild-to-moderate hypertension from nine centers. After a 4-week, single-blind, placebo run-in phase, patients were randomized in a double-blind fashion to four parallel groups that received either placebo or 0.5, 1, or 2 mg trandolapril for 4 weeks. Treatment was administered as a once-daily dose in the morning and blood pressure was measured 24 h after drug intake. The primary criterion of efficacy was a decrease in supine diastolic blood pressure. At the end of the study, the lowest dose of trandolapril that consistently produced a significant difference from placebo in reducing blood pressure was 1 mg (-6.6 mm Hg for supine diastolic blood pressure). It was effective from around 2 weeks onward; the 2-mg dose differed significantly from placebo from around 1 week onward. At the end of the study, the 1- and 2-mg doses were equally effective. The lowest dose tested, 0.5 mg, showed some evidence of an effect on systolic blood pressure and may well prove to be a useful dose in patients who are highly sensitive to the effect of ACE inhibition. Tolerance throughout the study was good for all doses tested.", "To test the dose responses of piretanide, ramipril, and their combination in patients with essential hypertension, a prospective, randomized, double-blind, placebo-controlled trial was conducted in 480 patients. Twelve separate groups were studied: placebo, piretanide 3 mg, piretanide 6 mg, ramipril 2.5 mg, ramipril 5 mg, ramipril 10 mg, and their combinations, as single daily morning doses. Patients were randomized after a 2-week run-in period without drugs; treatment was given for 6 weeks. A dose response compared with placebo was found for both drugs; the combination was more effective than either drug alone. Piretanide 6 mg, combined with ramipril 5 mg, provided optimal blood pressure reduction. Self-reported adverse effects of both drugs and their combinations did not exceed those reported for placebo. A surface analysis suggested that piretanide primarily reduced systolic blood pressure, whereas ramipril was more effective in reducing diastolic blood pressure. The data attest to a combined efficacy of piretanide and ramipril in decreasing arterial blood pressure.", "1. This was a multicentre, double-blind, parallel study in 216 patients with mild to moderate (supine diastolic blood pressure = 95-115 mm Hg) essential hypertension. 2. After a 4-week placebo washout, patients were randomized to placebo or lisinopril 1.25, 5.20 or 80 mg once daily for 6 consecutive weeks. Supine and erect blood pressure was measured 24 h postdose at the end of weeks -2, 0, 2, 4, and 6. 3. There was a linear dose-response relationship for both supine and erect blood pressure. Diastolic blood pressure reductions in the lisinopril 20 and 80 mg day-1 groups were significantly greater than in the placebo or lisinopril 1.25 and 5 mg day-1 groups. 4. Lisinopril, at doses up to 80 mg day-1, was well tolerated.", "In a double-blind, parallel-group study, 260 patients with mild to severe essential hypertension were randomized to treatment with placebo or spirapril at 6, 12 or 24 mg once daily for 6 weeks. When blood pressures were measured at the end of the dosing interval (trough), all spirapril regimens had produced similar reductions in sitting systolic and diastolic blood pressures (siSBP/siDBP) which were significantly greater than those observed in placebo-treated patients. There were no relevant changes in resting heart rate in any of the study groups. At the study endpoint, the mean reductions in siSBP/siDBP were 14.9/11.5 mmHg with spirapril at 6 mg, 15.4/12.0 mmHg with spirapril at 12 mg and 17.8/12.4 mmHg with spirapril at 24 mg/day vs. 3.1/3.6 mmHg with placebo. In a subgroup of 122 patients, blood pressure was recorded at the end of the dosing interval and during the 8 hours immediately postdose to monitor the peak effects on blood pressure. All spirapril dosages produced similar reductions at peak with a mean decrease of siDBP of approximately 20 mmHg in comparison to baseline values vs 6-7 mmHg with placebo. The trough:peak ratios for 6, 12 and 24 mg all lay between 60% and 90% for siSBP and siDBP, indicating that most of the peak effect was maintained at trough. Spirapril was well tolerated; the adverse event profile was not different from that with placebo, and no dose-related adverse events were observed.(ABSTRACT TRUNCATED AT 250 WORDS)", "To compare the antihypertensive efficacy and tolerability of the imidazoline I1-receptor agonist moxonidine, administered as a single daily dose of 0.6 mg, with the angiotensin-converting enzyme inhibitor enalapril (20 mg o.d.) in patients with mild to moderate essential hypertension.\n A total of 154 patients were enrolled and randomized to placebo (n = 50), moxonidine (0.2 mg o.d.; n = 51) or enalapril (5 mg o.d.; n = 53) for 2 weeks. Dosages were then increased to moxonidine 0.6 mg o.d. or enalapril 20 mg o.d. for a further 6 weeks. Blood pressure responses to therapy were measured using conventional office techniques and by 24-h ambulatory blood pressure monitoring.\n The average reduction in sitting blood pressure with moxonidine was similar to that achieved with enalapril (24.9 +/- 20.7/13.2 +/- 8.4 mmHg vs 21.9 +/- 17.1/11.9 +/- 7.5 mmHg, respectively) and significantly superior to that seen with placebo (1.2 +/- 14.4/2.3 +/- 7.0 mmHg; p < 0.001). Reductions in blood pressure after 8 weeks of treatment were as follows: moxonidine, from 166.2 +/- 15.5/101.3 +/- 4.0 to 141.2 +/- 15.7/88.1 +/- 7.7mmHg; enalapril, from 165.4 +/- 14.3/101.1 +/- 4.4 to 143.5 +/- 12.7/89.2 +/- 7.4 mmHg; and placebo, from 162.5 +/- 14.4/99.9 +/- 3.9 to 161.3 +/- 17.9/97.6 +/- 6.6 mmHg. Both moxonidine and enalapril produced sustained reductions in blood pressure during 24-h recording (p < 0.01 for overall effect of either drug vs placebo). Average 24-h blood pressure was reduced from 149.8 +/- 14.3/92.2 +/- 7.0 to 134.0 +/- 13.1/82.3 +/- 8.9 mmHg with moxonidine and from 146.5 +/- 13.0/ 92.5 +/- 7.2 to 131.1 +/- 11.0/82.1 +/- 8.8 mmHg with enalapril; the change with placebo was small (from 147.3 +/- 13.3/90.0 +/- 6.2 to 144.8 +/- 12.9/89.5 +/- 8.0 mmHg). Both drugs were generally well tolerated. No patients withdrew from the study because of drug-attributed adverse events.\n Moxonidine 0.6 mg o.d. and enalapril 20 mg o.d. have similar antihypertensive efficacy.", "The Joint National Committee V suggested that combination therapy can provide effective blood pressure control in patients with stage I-IV hypertension. This 4 x 4 factorial trial design assessed the efficacy of monotherapy with trandolapril-an ACE inhibitor, and verapamil SR-a calcium antagonist, each in a range of 3 doses as monotherapy, and in combination therapy in patients with stage I-III diastolic hypertension. After a 4-week, single-blind placebo treatment period, 746 patients in 39 study centers were randomized to 1 of the 16 double-blind treatments for 6 weeks (placebo, verapamil SR monotherapy 120, 180, or 240 mg; trandolapril monotherapy 0.5, 2, or 8 mg; and trandolapril/verapamil SR combinations 0.5/120, 0.5/180, 0.5/240, 2/120, 2/180, 2/240, 8/120, 8/180, or 8/240 mg. Both mono and combination therapies achieved the primary efficacy parameters: lowered diastolic blood pressure (at trough) more than placebo, p < 01 (except the 120 mg verapamil SR, NS, 0.5 mg trandolapril, 0.5/180 and 2/120 combinations, p < 05), yielded a trough to peak ratio of > 0.52 and had higher percentages of responders compared to placebo. Combination therapy was more effective than monotherapy for sitting diastolic blood pressure 2/180, p < 01; 2/240 and 8/240, p < 05. There were no differences between active treatment groups and placebo as a percentage of patients having adverse reactions. Trandolapril, 2 and 8 mg, appeared to have a greater incremental effect on the systolic blood pressure reduction of the combination than verapamil SR 180 and 240 mg.", "To compare the effects of a calcium antagonist (nitrendipine) and an angiotensin converting enzyme inhibitor (enalapril) with those of placebo on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension.\n A double-blind randomized, placebo-controlled trial.\n General practitioners referred patients to the trial physician.\n The study population comprised 121 patients with non-insulin-dependent diabetes mellitus. Inclusion criteria for blood pressure were diastolic blood pressure 90-115 mmHg and systolic blood pressure < or = 200 mmHg, while subjects were not being administered blood-pressure-lowering drugs for 3 weeks.\n Patients were randomly allocated to receive nitrendipine (n = 40), enalapril (n = 40) or placebo (n = 41). The treatment period was 48 weeks.\n The effect of nitrendipine was defined as the difference in change in left ventricular mass index from baseline between nitrendipine treatment and placebo after 48 weeks of treatment. The effects of nitrendipine compared with that of enalapril and of enalapril compared with placebo were defined similarly. Left ventricular mass was measured by M-mode echocardiography.\n Use of nitrendipine and enalapril led to significant and almost identical reductions in systolic and diastolic blood pressures. During 48 weeks left ventricular mass index decreased by 5% for patients in the nitrendipine group (decrease by 12 g/m2, 95% confidence interval 1-23), remained about the same for patients in the enalapril group (decrease by 1 g/m2, 95% confidence interval decrease by 10 to increase by 9) and increased by 9% for patients in the placebo group (increase by 9 g/m2, 95% confidence interval 2-16).\n These results indicate that administration of nitrendipine to patients with non-insulin-dependent diabetes mellitus and hypertension reduces left ventricular mass index. Enalapril appears not to induce regression, but perhaps prevents progression with an effect that is intermediate between those of nitrendipine and placebo.", "In a double-blind, randomized, multicenter study the antihypertensive efficacy of cilazapril 5.0 and 2.5 mg once daily vs. placebo was examined on 180 ambulatory hypertensive subjects with supine diastolic office blood pressure (OBP) > or = 95 and < or = 115 mm Hg: a 4-week, single-blind, placebo period was followed by a 4-week double-blind treatment period. At the beginning and end of the latter, OBP measurements and ambulatory 24-h BP monitoring (ABPM) were both carried out on two different days (3 +/- 1), whereby each time two 24-h BP recordings were made using SpaceLabs 90202. Measurements were made every 30 min, and actual waking and sleeping phase evaluation was done using diary entries. White coat hypertensive patients were excluded by the ambulatory BP (ABP) inclusion criterion: mean diastolic 24-h BP > or = 85 mm Hg, or frequency of measurements > 90 mm Hg > or = 35%. One-hundred eighty patients were included in the study. Safety was evaluated in 170 of these patients, and efficacy on OBP in 162. Twenty-four-hour BP recordings that were amenable to analysis were available in the case of 146 patients (average age 56 +/- 10 years, 56 women, 90 men). The results of the main target variable for OBP, namely responder rates, were in the three treatment groups: placebo, 39.6%; cilazapril 2.5 mg, 55.6%; and cilazapril 5.0 mg, 65.5%.(ABSTRACT TRUNCATED AT 250 WORDS)", "The aims of this study were to examine the effects of trandolapril, a long acting angiotensin converting enzyme (ACE) inhibitor with high tissue uptake, on insulin sensitivity and lipid concentrations in hypertensive patients with Type 2 diabetes mellitus.\n Insulin sensitivity was assessed after an acute dose (day 3) and 19 days continuous treatment (days 3-21) using the isoglycaemic, hyperinsulinaemic glucose clamp with D[3-3H] labelled glucose, a variable D[3-3H] priming dose and a 'hot' glucose infusion. Rates of glucose appearance (Ra) and glucose disappearance (Rd) were isotopically determined during the basal and insulin stimulated periods of the clamp. Twenty-four (5 female) hypertensive (blood pressure >75th centile for age and sex) patients with Type 2 diabetes mellitus were studied. Patients were randomized, in a double-blind manner, to either trandolapril 4 mg daily (T) or placebo (P).\n Baseline (day 1) systolic (mean +/- SD; P 164+/-14 and T 168+/-13 mm Hg) and diastolic (P 93+/-6, and T 98+/-10 mm Hg) blood pressures were comparable. On days 3 and 21, significant reductions were observed in both groups (P<0.001). In the trandolapril-treated group, serum trandolapril concentrations were >200 pg/ml on days 3 and 21, in all patients apart from one subject at a single visit, while trandolapril was undetectable in the placebo group. Body mass index (BMI) was greater in T compared with P (32.2+/-5.4 v. 28.3+/-4.6, P = 0.07). After correcting for BMI, basal hepatic glucose output (HGO) P 2.6 (95% CI 2.23-3.13) and T 1.91 (1.33-2.51) mg x kg(-1) x min(-1) and clamped HGO P 0.32 (-0.44-1.09) and T 0.87 (0.40-1.34) mg x kg(-1) x min(-1) were similar in both groups. The insulin sensitivity index was comparable in both groups on all days. Total cholesterol concentrations were similar in both groups throughout the study. Triglyceride concentrations were significantly lower in group P 1.38 (1.07-1.68); T 2.14 (1.70-2.58) mmol/l, P<0.01), no significant treatment effect being observed.\n An acute dose and 19 days' continuous treatment with trandolapril resulted in no change in insulin sensitivity or plasma lipid profiles in patients with Type 2 diabetes mellitus and hypertension. These data support the metabolic neutrality of trandolapril in patients with Type 2 diabetes mellitus and hypertension.", "This study evaluated the blood pressure effects of administration of once daily oral benazepril hydrochloride, a new angiotensin-converting enzyme (ACE) inhibitor, for mild-to-moderate hypertension. After a 2 to 4 week placebo baseline period, patients with diastolic blood pressure between 95 and 114 mm Hg, were randomized to receive either placebo or benazepril hydrochloride, 5, 10, 20, or 40 mg, once daily in double-blind fashion for 28 days. Blood pressure was measured predose and at 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours after the dose during inpatient observation days at the end of the placebo baseline period, and on the first and last day of the double-blind treatment period; and 24 hours after the dose at weekly outpatient visits. All doses of benazepril hydrochloride resulted in clinically important reductions in diastolic and systolic blood pressures that lasted between 12 and 24 hours after both the first dose, and following the last dose after 4 weeks of treatment. The findings indicate that benazepril hydrochloride may be clinically useful as once-daily monotherapy in many patients with hypertension.", "The antihypertensive effect of the angiotensin-converting enzyme inhibitor trandolapril administered in doses of 1, 2, and 4 mg/d was compared in 207 white patients and 91 black patients with mild to moderate hypertension following a double-blind, randomized, placebo-controlled, parallel study design. Trandolapril is a prodrug that is rapidly hydrolyzed to its active diacid metabolite, trandolaprilat. After 6 weeks of double-blind treatment, trandolapril lowered baseline sitting diastolic pressure in both white and black patients. A comparison of the antihypertensive response of the two populations revealed that the black patients required between two and four times the dose of trandolapril to obtain a response similar to that observed in the white patients. A dose of 1 mg/d trandolapril resulted in a 6.1 mm Hg mean decrease in baseline sitting diastolic pressure for white patients; a similar response (-6.5 mm Hg) was observed in the black patients at 4 mg/d. In contrast to the population differences in blood pressure, the decreases in angiotensin-converting enzyme activity were similar for both populations. An evaluation of trandolaprilat levels revealed that there were no racial differences in the trandolaprilat concentrations required to achieve a given degree of angiotensin-converting enzyme inhibition. Therefore, it appears that the antihypertensive response of black patients is not completely explained by a reduction in angiotensin-converting enzyme activity. The lack of response at a lower dose but increasing response at a higher dose could reflect another vasodepressor activity of trandolapril or just be evidence of reduced sensitivity of high blood pressure in blacks to angiotensin-converting enzyme inhibition.", "This multicentre, double-blind, parallel-group, placebo-controlled study compared the antihypertensive effects of equal doses of two long-acting angiotensin converting enzyme (ACE) inhibitors. After a two-week, placebo run-in phase, 110 patients with mild to moderate hypertension were randomised to receive 10 mg lisinopril or enalapril, or placebo for 4 weeks. Office BPs were measured at regular intervals throughout the study. Twenty-four hour ambulatory blood pressure (ABP) was measured at baseline and after the first and final doses of study drug. Serum ACE activity and aldosterone were obtained concomitantly with each ABP monitoring. Office BP differences from placebo reached (P less than 0.05) or approached (P less than 0.10) statistical significance at all observations for the lisinopril group but were not significant for any observation in the enalapril group and approached significance on two occasions. After four weeks of treatment, ABP analysis revealed that the lisinopril and enalapril groups, when compared with placebo, had similar and significant systolic and diastolic AUC reductions (P less than 0.01) from baseline over the 24 h dosing interval. During the second half of the dosing interval, 13-24 h post drug administration, the lisinopril group was significantly different from placebo (systolic BP, P = 0.002; diastolic BP, P = 0.005) while the enalapril group was not. Both drugs were well tolerated. The results indicate that monotherapy with 10 mg of lisinopril is as effective as with 10 mg of enalapril, and that ABP monitoring is useful in more precisely depicting the clinical effect of the known pharmacokinetic properties of these two agents.", "This was a randomized double-blind parallel-group study of 283 patients who had mild-to-moderate [diastolic blood pressure (DBP) > 100 mmHg and < or = 115 mmHg] hypertension. After a 3 (or 4)-week placebo wash-out period followed by 6 weeks of active treatment with spirapril at either 3, 6, 12 or 24 mg once daily (or placebo), DBP decreased by approximately 10 mmHg in the (pooled) spirapril-treated patients compared with approximately 5 mmHg with placebo. There were statistically significant differences between all active-treatment groups (except the 24-mg dose group) and placebo, but not among the spirapril groups at the end of the +24-hour dosing interval. Reported adverse events were mostly not study drug-related and were similar to those with placebo except for headache, which was more frequent with spirapril than placebo (5.8% vs 1.7%, respectively). Similarly, the number and severity of the changes in laboratory variables did not differ between placebo vs spirapril, and none of these changes were dose-related. In conclusion, the studied dosages of spirapril were equally effective in reducing DBP, and the overall good decrease in blood pressure at the end of the dosing interval indicates that once-daily administration is effective in patients with mild-to-moderate hypertension.", "In a randomized, double-blind trial, 2 doses of ramipril (2.5 and 5 mg once daily) were compared with placebo in patients with mild to moderate essential hypertension. A 2-week placebo run-in phase was followed by 4 weeks of treatment. Eighty-six patients entered the study and 17 withdrew during the course of the study. Both doses of ramipril appeared to be more effective than placebo in reducing blood pressure, but significant differences between 2.5 mg of ramipril and placebo were not found in any statistical analyses. In the endpoint analyses (taking the last measurement from each patient), the patients receiving 5 mg of ramipril had significantly larger decreases in blood pressure than the patients receiving placebo (t tests: standing systolic, p less than 0.001; supine diastolic, p less than 0.05; standing diastolic, p less than 0.05) and also than the patients receiving 2.5 mg of ramipril (standing systolic, p less than 0.05). It appears from the results of this study that the minimum effective dosage of ramipril is 5 mg once daily. No clinically relevant side effects or clinically relevant changes in laboratory values were observed.", "The aim of the study was to identify the most appropriate dosage combination of ramipril and felodipine ER (an extended release tablet) for mild-to-moderate hypertension. Hypertensive patients (N = 507) with supinediastolic blood pressure (DBP) values between 100-115 mm Hg were included in a randomized, multicenter, double-blind study of 3x4 factorial design with a 2-4 week single-blind, placebo run-in and 6 week active treatment phase. The patients were randomized to 12 groups: placebo, ramipril (2.5, 5, 10 mg), felodipine ER (5, 10 mg), or ramipril-felodipine ER combinations (2.5/5 mg, 2.5/10 mg, 5/5 mg, 5/10 mg, 10/5 mg, 10/10 mg). Although the greatest reductions in blood pressure were observed with ramipril-felodipine ER (10/10 mg), consideration of the antihypertensive efficacy and safety factors suggest that the ramipril-felodipine ER (5/5 mg) combination has the best efficacy/tolerability ratio of the combinations tested. The incidence of adverse events with ramipril-felodipine ER combination therapy was similar to that with felodipine ER monotherapy, but peripheral edema, tachycardia and vasodilatation occurred less frequently with ramipril-felodipine ER (5/5 mg) combination than with felodipine ER monotherapy. The combination of ramipril-felodipine ER (5/5 mg) can be considered to be the most suitable option for hypertensive patients with an inadequate response to either of the monocomponents.", "Benazepril, a newer angiotensin-converting enzyme inhibitor, has been evaluated for the treatment of mild to moderate hypertension in patients 55 years of age and older. The results of the clinical trials conducted to date indicate that benazepril provides effective antihypertensive therapy in this population, with efficacy comparable to that demonstrated in younger patients. Benazepril does not produce precipitous decreases in diastolic blood pressure following the initial dose, and is well tolerated by the elderly. It has a safety profile similar to that of placebo and generally better than that of hydrochlorothiazide.", "Fourteen patients with mild to moderate essential hypertension were randomized, after a baseline placebo period of 4 weeks, to receive the angiotensin converting enzyme (ACE) inhibitor quinapril or a placebo. During a 12 week, double-blind phase, the dosage of quinapril was increased from 10 to 40 mg twice daily being doubled every 4 weeks. At the end of the baseline period and of each month of the double-blind phase, 12 h overnight urine collections were made and morning blood samples were taken about 12 h after the last dose of medication. During the double-blind phase, blood pressure in the quinapril group (n = 7) decreased from 159 +/- 3/105 +/- 1 to 141 +/- 6/94 +/- 2 mm Hg (mean +/- SEM). Serum ACE activity and plasma angiotensin II concentration were reduced to 4 +/- 1% and 14 +/- 1% of the pretreatment values, respectively. Neither the plasma concentrations nor the urinary excretions of prostaglandin E2, 6-keto-prostaglandin F1 alpha (a prostacyclin metabolite), or thromboxane B2 (a metabolite of thromboxane A2) were affected by quinapril. In the placebo group, blood pressure tended to decline but the biochemical variables remained essentially unchanged. These results indicate that prostanoids are not involved in the antihypertensive action of quinapril, the principal effect of which seems to be inhibition of the renin-angiotensin system.", "A double-blind, placebo-controlled multicenter study involving 34 centers from different Brazilian regions was performed to evaluate the antihypertensive efficacy and tolerability of trandolapril, an angiotensin I converting enzyme inhibitor, in the treatment of mild-to-moderate systemic arterial hypertension.\n Of 262 patients enrolled in this study, 127 were treated with trandolapril 2 mg/day for 8 consecutive weeks, and the remaining 135 patients received placebo for the same period of time. Reduction in blood pressure (BP) and the occurrence of adverse events during this period were evaluated in both groups.\n Significantly reductions in both systolic and diastolic pressures were observed in patients treated with trandolapril when compared with those on placebo. Antihypertensive efficacy was achieved in 57.5% of the patients on trandolapril and in 42% of these normal values of BP were obtained. The efficacy of trandolapril was similar in all centers, regardless of the area of the country. In a subset of 30 patients who underwent ABPM, responders showed a significant hypotensive effect to trandolapril throughout the 24 hour day. The adverse event profile was similar in both trandolapril and placebo groups.\n Our results demonstrate, for the first time in a large group of hypertensive patients from different regions in Brazil, good efficacy and tolerability of trando-lapril during treatment of mild-to-moderate essential systemic hypertension.", "We assessed blood pressure (BP) and heart rate (HR) responses in a double-blind, randomized study comparing cilazapril, a long-acting, nonsulfhydryl-group converting enzyme inhibitor, with placebo in 18 patients with mild to moderate (sitting diastolic BP, 95 to 114 mm Hg) essential hypertension. The BP and HR parameters were evaluated at rest (casual, 24 hours after administration), during treadmill exercise testing (Bruce protocol), and with 24-hour noninvasive ambulatory BP monitoring. These assessments were made after a 4-week drug washout period and after 8 to 12 weeks of therapy. After 8 weeks of therapy with cilazapril (mean dose 3.6 +/- 0.9 mg/day), casual BP decreased 19/11 mm Hg (p less than 0.01), whereas placebo lowered BP by 4/5 mm Hg (difference not significant) compared with the baseline period. The casual HR was modestly (7 beats/min) but significantly (p less than 0.05) lowered by cilazapril monotherapy. Exercise BP was reduced by cilazapril (reduction at peak HR, 23/11 +/- 10/5 mm Hg; p less than 0.05), and exercise HR was unchanged. Compared with baseline, the duration of exercise was improved with cilazapril but not with placebo (1.0 minute vs -0.2 minute; p less than 0.05). Twenty-four-hour mean, awake, and sleep BPs were reduced with cilazapril with the most impressive reduction occurring during the awake period (19/12 mm Hg; p less than 0.01). These data demonstrate that cilazapril lowers casual, exercise, and ambulatory BP with a modest but significant improvement in exercise time. Thus cilazapril may be particularly effective in the physically active hypertensive patient.", "To investigate the concept of initiating therapy with low doses of a calcium antagonist and an ACE inhibitor, a fixed combination of isradipine 2.5 mg plus the ACE inhibitor spirapril 3 mg was compared with its components, with the full-dose monotherapies (isradipine 5 mg or spirapril 6 mg), and with placebo. After a 2-week wash out phase in pretreated patients and a subsequent 2-week placebo period, 405 patients with a diastolic blood pressure (DBP) between 100 and 114 mmHg were randomly allocated to 12-week once-daily double-blind treatment in one of the six treatment arms. In patients whose blood pressure was not normalized (defined as DBP< or =90 mmHg) after 6 weeks of treatment, the dosage of either medication was doubled or, in the placebo group, was switched to the fixed combination. After week 6, the mean reductions from baseline in sitting systolic/diastolic blood pressure 24 hours after dosing (trough) for the fixed combination or the monotherapies isradipine 5 mg, isradipine 2.5 mg, spirapril 6 mg, spirapril 3 mg, and placebo were 10.4/8.7, 10.0/9.4, 6.5/6.7, 10.0/8.3, 7.0/5.8, and 2.2/4.7 mmHg, respectively. The blood pressure changes obtained with the low-dose fixed combination were essentially identical to those observed with the full-dose monotherapies, thus showing an additive effect of low-dose isradipine and spirapril. In terms of tolerability, the lowest rate of any adverse events was found in the combination group. In this group, typical adverse events of calcium antagonists, such as headache, flushing, ankle edema, or palpitations, were observed only in 5%, 2%, 1%, and 0%, respectively, dry cough, considered typical for ACE inhibitors, was observed in only 1% of the combination group. In conclusion, the low-dose components isradipine 2.5 mg and spirapril 3 mg were shown to have an additive effect when combined, exerting a blood pressure-lowering effect comparable with the full doses and a trend to a better tolerability profile in comparison with the standard doses. Thus, low-dose combination therapy with these drugs appears to be a rational alternative to conventional monotherapy in the first-line treatment of hypertension.", "Systolic time measurements, echocardiography, and bicycle exercise testing with cardiac output determinations (CO2 rebreathing) were used to evaluate cardiac performance in 16 male hypertensives at the end of a 4-wk placebo period and after 12 wk of treatment with increasing doses (maximum = 40 mg/day) of enalapril maleate (N = 11) and of placebo (N = 5). The effect of exercise on plasma renin activity (PRA) and plasma norepinephrine (NE) concentration was also measured. Mean arterial pressure was reduced by 10 mm Hg or more in all but one subject who received enalapril. In both the enalapril- and placebo-treated subjects, the preejection period/left ventricular ejection time ratio and fractional shortening of the left ventricle at rest and cardiac output and stroke volume during moderate exercise did not change during the study. Enalapril induced a compensatory rise in PRA (N = 10). Compared to plasma NE concentration, 1124 +/- 380 pg/ml (mean +/- SD), during exercise at the end of the initial placebo period, there was attenuation of the rise of plasma NE concentration, 851 +/- 290, at the same load of exercise during enalapril therapy. Unchanged cardiac performance despite effective long-term lowering of blood pressure with enalapril may relate to inhibition of angiotensin II-mediated facilitation of NE release from peripheral nerve endings.", "Microalbuminuria predicts early mortality and renal disease in non-insulin-dependent diabetic patients. In insulin-dependent diabetic patients, angiotensin converting enzyme inhibition decreases microalbuminuria and retards the progression of renal disease. The aim of this study was to evaluate the effect of low dose ramipril on albumin excretion rate (AER) and blood pressure in non-insulin-dependent diabetic patients with persistent microalbuminuria (AER > 20 < 200 micrograms/min) and normal blood pressure or mild hypertension. The study was a randomized, double-blind, placebo-controlled clinical trial of 6 months duration at 14 hospital-based diabetes centers in northeastern Italy. Blood pressure, plasma glucose, and body weight were determined every month; AER, serum creatinine, glycosylated hemoglobin, and plasma lipids at baseline, after 1 month, and at the end of the study. Of 122 non-insulin-dependent diabetic patients randomly allocated in blocks of four to receive either ramipril (1.25 mg/day) or placebo, 108 (54 in the ramipril group and 54 in the placebo group) completed the study. At baseline, age, duration of diabetes, body mass index, and glycosylated hemoglobin were similar in the two groups and remained unchanged throughout the study. In the placebo group, AER rose from a baseline median of 65 micrograms/min (range 53 to 76, 95% confidence Interval) to 72 micrograms/min (57 to 87) and to 83 micrograms/min (62 to 104) after 1 and 6 months, respectively, but fell from 62 micrograms/min (48 to 76) to 45 micrograms/min (33 to 57) and to 53 micrograms/min (38 to 69), respectively, in the ramipril group, a significant difference between the groups (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)", "Hypertension is an important cardiovascular risk factor and the goal of its pharmacologic treatment is to reduce morbidity and mortality. Treatment is usually initiated with a low dose of a single agent and titrated to a higher dose as required. As many as 50% of patients require the addition of a second agent to achieve satisfactory blood pressure control. The aim of this study was to assess the dose-response relationship of nitrendipine and enalapril alone or in fixed combination in the treatment of mild to moderate hypertension. A total of 496 patients were enrolled in a multicenter, randomized, double-blind, factorial-design, parallel-group clinical trial comparing placebo, nitrendipine (5, 10, and 20 mg) and enalapril (5, 10, and 20 mg) alone or in combination. After a single-blind, 2-week placebo run-in period, 414 patients whose diastolic blood pressure ranged between 90-109 mm Hg were randomly assigned to a treatment group. The combination of nitrendipine and enalapril, particularly regimens including nitrendipine 20 mg and enalapril 5 or 10 mg, were significantly superior to both monotherapies; mean diastolic blood pressure reductions from baseline to last visit were -12.5 and -14.3 mm Hg, respectively. Response surface analysis provided further evidence that these combinations were optimal in terms of anti-hypertensive efficacy. All treatments were well tolerated and the incidence of adverse events did not differ significantly between groups. In summary, the anti-hypertensive efficacy of the combination was found to be superior to both monotherapies at any doses. The dose combination achieving the greatest blood pressure reduction was nitrendipine 20 mg and enalapril 10 mg.", "After a 4- to 6-week placebo lead-in period, 382 mild-to-moderate hypertensive patients with diastolic blood pressures remaining between 92 and 109 mmHg were randomized to double-blind treatment with captopril (50 mg q.d.) (94), captopril (50 mg b.i.d.) (97), captopril (50 mg q.d.) plus hydrochlorothiazide (97), and placebo (94). After 4 weeks the captopril dosage was doubled, whereas the hydrochlorothiazide dose remained at 25 mg for an additional 4 weeks. Response to treatment was evaluated by means of blood pressure determinations at the end of 4 and 8 weeks. All three active treatment regimens reduced diastolic blood pressure more than placebo did (p less than or equal to 0.01). Patients receiving captopril with diuretic had a greater decrease in pressure than those receiving captopril alone. The once-daily captopril regimen was as effective as the twice-daily regimen, although the latter employed double the daily dose. Increasing the captopril dosage during the second 4-week period resulted in a minimal addition reduction in blood pressure. Full 24-hour monitoring confirmed that the blood pressure was controlled by once-daily captopril therapy. Captopril given once daily, alone or in combination with hydrochlorothiazide, is efficacious treatment for patients with mild-to-moderate hypertension. The once-daily regimen should further enhance patient compliance.", "To investigate the dose-response relationship and contribution of verapamil SR and trandolapril given in combination once a day for the treatment of essential hypertension.\n A randomized, double-blind, placebo controlled, factorial, 12 arm parallel group comparison with placebo, verapamil SR (120, 180 mg), trandolapril (0.5, 1.0, 2.0 mg) covering all combinations of both drugs. A 4 week placebo run-in period followed by 6 weeks of treatment. Four hundred and fifty-six patients from office practice (22 centres) with mild to moderate hypertension enrolled and 426 with diastolic pressure > or = 100 mm Hg at the end of run-in period were randomized. Main outcome measures were reduction in sitting systolic (SBP) and sitting diastolic (DBP) blood pressure.\n The combination of verapamil SR and trandolapril, particularly verapamil SR 180 mg and trandolapril 0.5 or 1.0 mg was significantly superior to both monocomponents at the same dose (P<0.05). For these combinations, the adjusted mean reductions in DBP from baseline to last visit were 14.1 and 16.0 mm Hg, respectively. Response surface analysis provided further evidence that these combinations were optimal for antihypertensive efficacy. All treatments were well tolerated. The incidence of adverse events did not differ significantly between treatment groups; the profile of adverse events on combination therapy was mild and consistent with that of each monocomponent.\n All dosage combinations of verapamil SR and trandolapril produced significantly greater reduction of blood pressure than the monotherapy at the same dosage. However, verapamil SR 180 mg in combination with trandolapril 1.0 mg was the dosage with the greatest blood pressure reduction and had the greatest effects compared with the monocomponents.", "Quinapril HCl is a novel, nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor. The Study Group evaluated its efficacy (20, 40, 80 mg daily with forced dose titration determination at trough blood pressure) once daily versus twice daily versus placebo, as well as its tolerability and safety, in 270 patients with mild to moderate essential hypertension (WHO Stages I and II, sitting diastolic blood pressure [DPB] greater than or equal to 95 mm Hg), for twelve weeks. Reductions in DBP of up to 13 mm Hg were obtained, and in full dosage more than 65% of patients achieved a reduction in DBP of 10 mm Hg or more from baseline or reduced their DBP to 90 mm Hg or less. Quinapril was well tolerated, and reported adverse effects were scarcely more frequent than in the placebo group. Once daily doses of quinapril were as safe and effective as twice-daily doses. Quinapril is likely to exhibit good therapeutic utility in the management of essential hypertension.", "The aim of the present study was to assess the efficacy and tolerability of a calcium antagonist/beta-blocker fixed combination tablet used as first-line antihypertesnive therapy in comparison with an angiotensin converting enzyme inhibitor and placebo. Patients with uncomplicated essential hypertension (diastolic blood pressure between 95 and 110 mm Hg at the end of a 4-week run-in period) were randomly allocated to a double-blind, 12-week treatment with either a combination tablet of felodipine and metoprolol (Logimax), 5/50 mg daily (n = 321), enalapril, 10 mg daily (n = 321), or placebo (n = 304), with the possibility of doubling the dose after 4 or 8 weeks of treatment if needed (diastolic blood pressure remaining >90 mm Hg). The combined felodipine-metoprolol treatment controlled blood pressure (diastolic < or =90 mm Hg 24 h after dose) in 72% of patients after 12 weeks, as compared with 49% for enalapril and 30% for placebo. A dose adjustment was required in 38% of patients receiving the combination, in 63% of patients allocated to placebo, and 61% of enalapril-treated patients. The overall incidence of adverse events was 54.5% during felodipine-metoprolol treatment; the corresponding values for enalapril and placebo were 51.7% and 47.4%, respectively. Withdrawal of treatment due to adverse events occurred in 18 patients treated with the combination, in 10 patients on enalapril, and 12 patients on placebo. No significant change in patients' well-being was observed in either of the three study groups. These results show that a fixed combination tablet of felodipine and metoprolol allows to normalize blood pressure in a substantially larger fraction of patients than enalapril given alone. This improved efficacy is obtained without impairing the tolerability. The fixed-dose combination of felodipine and metoprolol, therefore, may become a valuable option to initiate antihypertensive treatment.", "nan", "A factorial design was applied in this multicenter, double-blind, placebo-controlled trial of the calcium-channel blocker verapamil and the ACE inhibitor enalapril to assess the hypotensive effects of the combination compared with monotherapy, to evaluate safety, and to determine the effects on quality of life (QOL) of both drugs, alone and in combination. The study consisted of a 3 x 2 factorial design wherein 186 men and women with a sitting diastolic blood pressure (BP) of between 95 mm Hg and 114 mm Hg, after a 4-week placebo washout, were randomized to one of six treatment groups for 4 weeks of active treatment. Monotherapy with both 240 mg verapamil and 10 mg enalapril reduced systolic and diastolic BP to a similar extent and significantly more than placebo. The 240 mg verapamil + 10 mg enalapril combination was additive for both systolic and diastolic blood pressure; 120 mg verapamil + 10 mg enalapril was additive for systolic BP only. The total number of adverse events reported was similar for all six treatment groups. QOL scores were unchanged from baseline and not different between treatment groups. The combination of 240 mg verapamil and 10 mg enalapril was significantly more effective at reducing BP than either drug alone; this additivity of effect was not linked to a higher rate of adverse experiences or to a deterioration in QOL. Thus, combination therapy at lower doses may offer an alternative treatment option to higher dose monotherapy.", "The combination of an angiotensin converting enzyme inhibitor with a calcium antagonist has become a common way of treating patients with essential hypertension who respond insufficiently to monotherapy. This double-blind, randomized, parallel, placebo-controlled, multicenter, outpatient study evaluated the antihypertensive efficacy and safety of a calcium antagonist (verapamil SR) and an angiotensin converting enzyme inhibitor (trandolapril) in patients with mild-to-moderate (stages I and II) essential hypertension. Six hundred thirty-one patients were enrolled in this 10-week study. After a 4-week single-blind placebo phase, patients received one of the following daily dosage regimens in a double-blind fashion for 6 weeks: placebo, 4 mg of trandolapril, 240 mg of verapamil SR, or a combination of 4 mg of trandolapril and 240 mg of verapamil SR. Trough sitting diastolic blood pressure was lowered by 4.5 mm Hg, 4.3 mm Hg, and 8.1 mm Hg more than placebo in the trandolapril, verapamil SR, and combination groups, respectively. In the combination group, sitting diastolic blood pressure was significantly lowered (P < .01) by 3.6 mm Hg more than in the trandolapril group and by 3.8 mm Hg more than in the verapamil SR group. An analysis of the trough-to-peak ratio for sitting diastolic blood pressure revealed values of 0.75 and 0.67, for the 4-mg trandolapril and the combination groups, respectively, at end point. The overall incidence of adverse reactions was similar for all treatment groups. In this study the combination of an angiotensin converting enzyme inhibitor and calcium antagonist was well tolerated and more effective than either agent administered alone for the treatment of mild-to-moderate essential hypertension.", "To assess the efficacy and time-dependent effects of once-daily moexipril, a nonsulfhydryl ester prodrug of the angiotensin-converting enzyme (ACE) inhibitor, moexiprilat, we conducted a multicenter, double-blind, placebo-controlled trial in 51 hypertensive patients using both clinic and ambulatory blood pressure (BP) recordings. Patients were included in the trial based on a minimum of 40% of the daytime diastolic BPs of 90 mm Hg or more during a placebo baseline phase; and the primary endpoint was change in 24-hour ambulatory diastolic BP. Patients were randomized to receive placebo, 7.5 mg of moexipril, or 15 mg of moexipril once daily. Clinic and ambulatory BPs were taken on the first day and after eight weeks of double-blind therapy. After the 7.5-mg dose, there were no significant changes in the acute or prolonged clinic BPs compared with placebo. Compared with adjusted mean changes for placebo, the 15-mg moexipril dose lowered clinic systolic BP, but not diastolic BP. In contrast, acute (1 day) reductions in 24-hour diastolic BPs were -2/-3 mm Hg, -6/-4 mm Hg, and -14/-9 mm Hg on placebo, 7.5 mg of moexipril, and 15 mg of moexipril, respectively (P < .01 for the 15-mg dose). Similarly, after long-term dosing for 8 weeks, reductions in 24-hour diastolic BPs were 1/-2 mm Hg, -6/-4 mm Hg, and -12/-9 mm Hg for the respective treatment groups (P < .01 for the 15-mg dose).(ABSTRACT TRUNCATED AT 250 WORDS)", "The time to peak antihypertensive effect and the trough-to-peak ratio were determined in 64 Caucasian patients (19 men, 45 women) with mild to moderate hypertension [supine diastolic blood pressure (DBP) 95 to 115 mmHg]. They received placebo or fosinopril 10, 20, or 40 mg once daily for 4 weeks. The study consisted of a 4-week placebo lead-in, 4 weeks' double-blind treatment, and a 1-week placebo washout period. Vital signs were determined biweekly before dosing, and blood pressures were measured every 1 to 2 h during two 27-h periods at the beginning and end of treatment. After the first and last doses of all three regimens, the peak effect on blood pressure occurred 5 to 7 h after all three dosages. Neither peak nor trough blood pressure changes showed a clear dose-response relationship. Trough to peak ratios for the first dose, corrected for placebo effects, were 79% for fosinopril 10 mg, 48% for fosinopril 20 mg, and 74% for fosinopril 40 mg, and the trough-to-peak ratios for the last dose were 41% for fosinopril 10 mg, 32% for fosinopril 20 mg, and 44% for fosinopril 40 mg. In the 38 responders among the 48 patients receiving fosinopril (supine DBP decrease of at least 5 mmHg at 24 h postdose), trough-to-peak ratios ranged from 50 to 81%, and the range indicates that fosinopril is efficacious when administered once daily. Adverse effects were mild to moderate, and no patient discontinued treatment. Changes in the laboratory test results, electrocardiograms, or the results of physical examinations were unremarkable.(ABSTRACT TRUNCATED AT 250 WORDS)", "The aim of this study was to evaluate the effects of trandolapril on 24-hour blood pressure in patients with mild-to-moderate essential hypertension. After a washout period of 4 weeks, 42 patients were randomized to receive 2 mg of trandolapril once daily and 20 to receive placebo in a double-blind fashion for 6 weeks. This was followed by a second washout period of 4 weeks. At the end of each period, clinic blood pressure was assessed at 24 hours after the last dose and 24-hour ambulatory blood pressure was measured noninvasively, taking blood pressure readings every 15 minutes during the day and every 20 minutes during the night. Two patients were dropped out before any blood pressure evaluation under treatment. Analysis of ambulatory blood pressure was performed in 48 patients who met the criteria for the minimal number of ambulatory blood pressure data (2 values per hour during the day and 1 value per hour in the night). In the trandolapril-treated group (n = 41) clinic systolic/diastolic blood pressures were 159.8 +/- 2.0/102.4 +/- 0.8, 146.8 +/- 2.3/94.8 +/- 1.1, and 155.7 +/- 2.0/99.2 +/- 0.7 mm Hg in the pretreatment, treatment, and post-treatment periods, respectively. The corresponding values for 24-hour mean blood pressure (n = 31) were 139.5 +/- 1.9/91.2 +/- 1.5, 131.0 +/- 2.0/84.3 +/- 1.2, and 139.7 +/- 1.8/90.9 +/- 1.1 mmHg. The differences between the lower treatment, versus the higher pre- and post-treatment, values were all statistically significant (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)", "The efficacy of once-a-day cilazapril (a new long acting converting enzyme inhibitor) therapy for the 24 h control of hypertension and its effects on the renin-angiotensin axis were investigated. Twenty-four uncomplicated hypertensive patients whose sitting diastolic blood pressures remained within 94 to 114 mmHg after four weeks of placebo were randomly assigned on a double-blind basis to receive either continued placebo or cilazapril therapy at a single dose of 1.25, 2.5 or 5.0 mg/day for a further four weeks. At the end of weeks 4 and 8, systolic and diastolic blood pressures and heart rates were recorded, supine and standing, at 0, 2, 4, 6, 9, 12 and 24 h following a single dose of drug. At the same times, blood was withdrawn for determination of plasma renin activity and aldosterone. Supine and erect systolic and diastolic blood pressures were lowered to normotensive levels with an optimal response being achieved at a dose of 2.5 mg/day. Supine and erect heart rates were unchanged with respect to drug dosage, and the reflex increase in heart rate and diastolic blood pressure on changing from supine to erect posture was maintained in all groups. Maximum antihypertensive efficacy was from 2 to 6 h after drug ingestion. There were no changes in resting aldosterone, but plasma renin activity was increased at all drug dosages. A single 2.5 mg dose of cilazapril provides blood pressure control for a 24 h period. Cilazapril does not appear to interfere with the reflex autonomic responses to postural change.", "The antihypertensive effect and safety of fosinopril and hydrochlorothiazide combined were compared with each drug singly and placebo in a controlled manner. After a 4- to 5-week placebo lead-in period, 67 mild to moderate essential hypertensive patients (seated diastolic blood pressure > or = 95 and < or = 110 mm Hg) were randomized in a double-blind fashion into four parallel treatment groups: 20 mg fosinopril plus 12.5 mg hydrochlorothiazide, 20 mg fosinopril, 12.5 mg hydrochlorothiazide, and placebo during 8 weeks. Patients were seen biweekly. Sitting diastolic blood pressure was the outcome variable defining therapeutic response. The efficacy of fosinopril plus hydrochlorothiazide as a combined therapy was superior to any single drug (P < .05) and placebo (P < .01) in the treatment of mild to moderate essential hypertension. Mean adjusted systolic/diastolic blood pressure decrements at week 8 were -18.8/-13.7, -12.9/-11.8, -8.5/-9.3, and -2.7/-6.9 mm Hg for the fosinopril plus hydrochlorothiazide, fosinopril, hydrochlorothiazide, and placebo groups, respectively. Clinical adverse events and laboratory changes documented throughout the study were similar to placebo and were mild in severity in all groups.", "The combination of angiotensin converting enzyme (ACE) inhibitor and thiazide diuretic has advantages over monotherapy for the treatment of hypertension. Previous study designs have often been inadequate to demonstrate the details of interactions between these antihypertensive agents. This study used a modified 4 x 4 factorial randomized, double-blind, placebo-controlled, parallel group design to study the efficacy of 17 different doses of fosinopril (Fos), a phosphinic acid derived ACE inhibitor, and hydrochlorothiazide (HCTZ) in 550 patients with mild to moderate hypertension. Data from these variables were fit to quadratic response surface models (QRSM) using polynomial functions in the doses of the two components. Using QRSM, seated systolic (SeSBP) and diastolic blood pressure (SeDBP) responses at 8 weeks were predicted for actual doses and interpolated for intermediate doses not studied. Fos and HCTZ alone and in combination produced a dose-related reduction in SeSBP and SeDBP. Using 10 mg Fos + 12.5 mg HCTZ reduced the adjusted mean SeDBP 6.3 mm Hg and 20 mg Fos + 12.5 mg HCTZ lowered the same measure 9.1 mm Hg. Coadministration of Fos and HCTZ produced an additive antihypertensive effect. This study of combination agents for hypertension using a factorial design with QRSM accurately predicts dose responses and is a valuable clinical trial methodology.", "In a double-blind study, after a four- to six-week placebo period, 418 patients with mild to moderate hypertension were randomly assigned to receive 5, 10, 20, or 40 mg of fosinopril or matched placebo orally once daily for four weeks. Seated diastolic blood pressure was determined 24 hours after the most recent dose. For patients with an inadequate blood pressure response after four weeks, doses were doubled during the second four weeks, and hydrochlorothiazide was added during the final four weeks. The patients showed a significant, consistent antihypertensive response in seated and standing systolic and diastolic blood pressures after four weeks of 20 or 40 mg of fosinopril; both dosages produced similar responses. The results indicate that the dose level of fosinopril required to treat uncomplicated mild to moderate hypertension ranges from 5 to 40 mg taken once daily. Treatment was discontinued in 3% of the fosinopril patients and in 1% of the placebo patients because of side effects. No clinically significant abnormal laboratory test results were reported. Fosinoprilat, the active diacid of fosinopril, is eliminated by both the hepatobiliary and renal routes, which suggests that fosinopril may be particularly useful in the treatment of patients with impaired kidney or liver function and of elderly patients.", "Two hundred and eleven patients with mild or moderate hypertension, mean age 53.5 +/- 9.5 years (range 24-70) were randomised double-blind to treatment with either captopril 50 mg (C50), hydrochlorothiazide 25 mg (HCTZ 25), the fixed combination of captopril 50 mg and hydrochlorothiazide 25 mg (C50/HCTZ 25) or placebo. Blood pressure, heart rate, body weight and side effects were assessed at the end of the run-in period on placebo and after 4, 6, 8 weeks treatment at the same time, 20-24 h after the last dosing. Routine biochemical examinations were carried out on all patients after the placebo period as well as after 4 and 8 weeks. Blood pressure significantly decreased in all groups, but the mean percentage change from baseline was highly statistically significant at 8 weeks, for C50 and C50/HCTZ 25 groups. The incidence of clinical side effects was low and not statistically different for the four groups with few specific adverse effects (one transient alteration of taste in captopril group). No patient was withdrawn from the study due to side effects. A better anti-hypertensive efficacy was obtained with the fixed combination captopril 50 mg/hydrochlorothiazide 25 mg once daily compared to placebo or each component alone, and without any difference in side effects.", "OBJECTIVE: To compare the effects on office blood pressure and home blood pressure of placebo and active drug administration. DESIGN: After a 2-week wash-out period, patients with mild-to-moderate hypertension entered a 2-week single-blind placebo period and then a 4-week double-blind period. Patients were randomly assigned to be administered either 2 mg trandolapril once daily or its placebo in a 2:1 proportion. Office blood pressure was measured by a physician at the end of each period, using a mercury sphygmomanometer (mean of three consecutive measurements). Home blood pressure was measured during the last week of each period according to standard procedure carefully taught to each patient by the physician. Compliance was checked by using electronic pill boxes. RESULTS: Data for 34 of the 44 patients who entered the study were eligible for analysis. Baseline systolic blood pressure/diastolic blood pressure were significantly (P = 0.0001/P = 0.0001) higher for office blood pressure (161/101 mmHg) than they were for home blood pressure (145/93 mmHg). There was no statistically significant difference between the placebo and active-treatment groups at baseline. During the single-blind period, blood pressures measured at the office and at home did not change significantly. Office blood pressure decreased by 2.7 +/- 10 mmHg for systolic blood pressure and by 0.5 +/- 4 mmHg for diastolic blood pressure whereas home blood pressure increased by 0.8 +/- 6 mmHg for systolic blood pressure and by 0.7 +/- 4 mmHg for diastolic blood pressure. During the double-blind period, office blood pressure fell significantly with trandolapril treatment (systolic by 10.2 +/- 12 mmHg, diastolic by 8.3 +/- 6 mmHg; P = 0.0005/0.0001, versus single-blind placebo period) but this decrease was not significantly different (P = 0.45/0.92) from the fall in members of the placebo group (systolic by 6.9 +/- 9 mmHg, diastolic by 8.0 +/-6 mmHg; P = 0.04/0.002, versus single-blind placebo period). Thus, no antihypertensive effect of trandolapril was demonstrated. The fall lin home blood pressure with trandolapril treatment was significant (systolic by 10.7 +/- 8 mmHg, diastolic by 5.8 +/- 5 mmHg; both P = 0.0001, versus single-blind placebo period) and was significantly greater (P = 0.0004/0.004) than the minimal change observed with placebo (systolic fell by 0.2 +/- 5mmHg, diastolic fell by 0.6 +/- 4 mmHg; P = 0.90/0.62, respectively, versus single-blind placebo period). The evening decrease in home blood pressure was similar to the morning decrease in home blood pressure in members of the trandolapril-treated group. The resulting morning:evening decrease in blood pressure ratio was 0.83 for diastolic blood pressure and 0.95 for systolic blood pressure. For the subgroup of responders, mean of individual ratios was 0.77 +/- 0.43 for diastolic blood pressure and 0.70 +/- 0.39 for systolic blood pressure. CONCLUSION: The placebo effect observed with office blood pressure measurements does not occur with home blood pressure measurements. Expected treatment effect can alter a physician's blood pressure readings. The precision of measurements is greater with home blood pressure (there is a lower SD). Use of home blood pressure measurements increases the power of comparative trials, allowing one either to study fewer subjects or to detect a smaller difference in blood pressure.", "The efficacy of spirapril, 6 mg once daily, was compared with enalapril, 5-20 mg once daily, in the control of mild-to-moderate hypertension in a placebo-controlled, parallel-group study. A total of 251 patients participated in the study, all of whom underwent a 4-week washout period on placebo. Thereafter, 100 patients were randomized to spirapril, 6 mg once daily, 101 patients to enalapril, 5-20 mg once daily, and 50 patients remained on placebo. Sitting diastolic blood pressure (DBP) and systolic blood pressure (SBP) were measured at 2-weekly clinic visits. Blood pressure profiles during peak and trough plasma drug concentrations (2-4 hours and 24-26 hours postdose, respectively) were determined at baseline and 4 and 8 weeks after starting the double-blind phase. Compared with placebo, treatment with both spirapril and enalapril resulted in significant reductions (p < 0.001) in DBP and SBP. DBP was reduced to a greater extent with spirapril than with enalapril both at peak (-17.4 mmHg vs. -14.8 mmHg) and trough (-14.7 mmHg vs. -12.4 mmHg). Thus, although the trough/peak DBP ratios for spirapril and enalapril were very similar (84% vs. 82%), actual reductions in DBP were different. Spirapril and enalapril treatment resulted in similar reductions in SBP at both peak and trough levels. Both drugs were well tolerated, and there were very few adverse events or changes in hematological or biochemical parameters during the study. In conclusion, spirapril, 6 mg once daily, as the initial and maintenance dose, is at least as effective and well tolerated as enalapril individually titrated.", "This randomized, double-blind, double-dummy, placebo-controlled, parallel-group study evaluated the dose-response relationship of telmisartan in 207 patients with mild to moderate hypertension (diastolic blood pressure [DBP] 100 to 114 mmHg). After a 28-day placebo run-in period, patients were randomized to 28 days of once-daily, double-blind, double-dummy treatment with telmisartan 40, 80, or 120 mg; enalapril 20 mg; or placebo. Blood pressure (BP) was manually recorded for 12 hours after the first dose and after 24 hours at baseline (Day 0), Day 1, and Day 28 of double-blind treatment. Pharmacokinetic and pharmacodynamic parameters were assessed from telmisartan plasma concentrations. All doses of telmisartan and enalapril significantly reduced BP compared with placebo (p < or = 0.01). Mean +/- SE reductions in supine DBP after 28 days of treatment ranged between 7.9 +/- 1.3 mmHg and 9.8 +/- 1.3 mmHg in the telmisartan groups, 9.6 +/- 1.3 mmHg with enalapril, and 1.5 +/- 1.3 mmHg with placebo. Mean +/- SE reductions in supine systolic blood pressure (SBP) were between 10.0 +/- 2.2 mmHg and 15.5 +/- 2.2 mmHg with telmisartan versus 10.2 +/- 2.1 mmHg with enalapril; placebo increased supine SBP by 3.5 +/- 2.1 mmHg. The BP reductions after 4 weeks of treatment with telmisartan were no different from those achieved with enalapril. No significant linear trend in BP reduction was evident among telmisartan doses. Reductions in SBP and DBP were maintained over the 24-hour period at Day 28. Treatment did not affect supine heart rate. Trough/peak DBP ratios were > or = 85% for all telmisartan doses versus 65% for enalapril. High interpatient variability in telmisartan plasma concentrations was observed. For example, mean +/- SD values for Cmax were 159 +/- 104 ng/mL for telmisartan 40 mg, 693 +/- 606 ng/mL for telmisartan 80 mg, and 1635 +/- 1406 ng/mL for telmisartan 120 mg. Plasma concentration-effect analyses indicated that the antihypertensive effects of telmisartan 40, 80, and 120 mg are at the plateau region of the concentration-response curve. All active treatments were well tolerated, with tolerability profiles similar to placebo, and telmisartan did not produce any clinically relevant first-dose effects. These data confirm the antihypertensive efficacy and placebo-like tolerability of telmisartan.", "Angiotensin-converting enzyme inhibitors and calcium antagonists are 2 classes of antihypertensive agents frequently used either as monotherapy or in combination. A 6-week, multicenter, randomized, double-blind, placebo-controlled trial was conducted in essential hypertensive patients (diastolic blood pressures [BP] when seated, 95-115 mm Hg) to evaluate the efficacy, dose response, and safety profiles of enalapril combined with a new once-daily formulation of diltiazem. BP and heart rate were measured at 5 (peak) and 24 (trough) hours after dose to assess the efficacy and pharmacodynamic profile of the combination given once daily. There were 336 patients randomly assigned to either enalapril 5 mg plus 1 of 4 dose levels of diltiazem ER (60, 120, 180, or 240 mg), enalapril 5 mg alone, or placebo. Each combination dose level produced statistically significant reductions (p <0.05) in trough diastolic BP when seated, compared with placebo (-6.8, -8.3, -10.1, and -10.3 mm Hg for the diltiazem ER doses of 60, 120, 180, and 240 mg, respectively). The 3 highest combination dose levels resulted in statistically significant (p <0.05) decreases in trough diastolic BP when seated, compared with placebo. There was a significant (p <0.001) linear dose-response relation. A trough-to-peak ratio > or = 0.5 was shown for the 3 highest combination doses. Drug-related adverse events were seen in 8.9% to 19% of the combination patients, 14.3% of the enalapril patients, and 8.6% of the placebo patients. The frequency and type of adverse events were those currently noted with each drug studied when used as monotherapy.", "Compared with other angiotensin-converting enzyme (ACE) inhibitors, the elimination of temocapril is less dependent on renal function. To investigate the metabolic and antihypertensive effects of temocapril in diabetic hypertensives, 30 patients with diabetes mellitus type 2 and mild to moderate hypertension [diastolic blood pressure (BP) 90-115 mm Hg] and without azotemia (plasma creatinine < 180 microM) were evaluated in a prospective randomized double-blind placebo-controlled study. After a 4-week placebo run-in, they received temocapril, 20 mg daily (n = 19), or placebo (n = 11) for 6 weeks. Insulin sensitivity index (SI), determined by the Minimal Model method of Bergman, serum lipoproteins, plasma renin activity, fibrinogen, and microalbuminuria were assessed at the end of the placebo run-in phase and the double-blind treatment phases. Temocapril but not placebo administration produced a significant decrease in supine BP (152/92+/-5/3 vs. 162/98+/-5/2 mm Hg; p < 0.01) and increase in plasma renin (p < 0.05). Variation of SI during temocapril treatment did not reach statistical significance (0.95+/-0.2 before vs. 1.44+/-0.4 x 10(-4)/min/mU/L after treatment). During administration of temocapril or placebo, no significant changes in fasting plasma glucose, insulin, and serum levels of total triglycerides, cholesterol, lipoprotein cholesterol fractions, or fibrinogen were observed. Microalbuminuria decreased significantly on temocapril treatment (49+/-10 vs. 79+/-17 mg/24 h; p < 0.01) but not on placebo. These findings demonstrate that in hypertensive patients with diabetes mellitus type 2, short-term treatment with temocapril is neutral to insulin sensitivity, lipoprotein metabolism, and fibrinogen, and significantly reduces microalbuminuria.", "Co-administration of antihypertensive drug therapy and hormonal replacement therapy (HRT) is frequent in postmenopausal women but it is not known whether HRT interacts with concomitant antihypertensive therapy. The present study was designed to investigate efficacy and safety of the ACE inhibitor moexipril in comparison to placebo in hypertensive, postmenopausal women on HRT. After a 4-week placebo run-in phase, 95 postmenopausal women (35-74 years of age) who had a sitting diastolic blood pressure (BP) of 95-114 mm Hg and were treated with HRT were randomised to a 12-week treatment with moexipril 15 mg or placebo. Efficacy and safety were assessed by measuring changes in sitting BP and metabolic parameters associated with cardiovascular disease including triglycerides, total cholesterol, HDL, LDL, total cholesterol/HDL ratio and glucose. Adverse events were recorded continuously. After 12 weeks of treatment, moexipril 15 mg was significantly more effective in reducing sitting systolic and diastolic BP from baseline than placebo (-12.2/-9.9 mm Hg vs -1.6/-4.3 mm Hg, P < 0.001). Metabolic parameters were not affected by treatment with moexipril: mean levels of triglycerides, total cholesterol, HDL, LDL, total cholesterol/HDL ratio and glucose remained unchanged throughout the study. Fibrinogen, an independent cardiovascular risk factor, increased after placebo (+35.0 mg/dl) and decreased after treatment with moexipril (-33.6 mg/dl), the difference, however, was not statistically significant. Moexipril was well-tolerated by postmenopausal women using HRT. The most frequent adverse events included headache (21.3%), cough (12.8%) and rhinitis (10.6%) and there were no significant differences in the number and severity of adverse events between the moexipril and placebo groups. This study indicates that moexipril is effective and well tolerated in the treatment of hypertensive, postmenopausal women and can safely be co-administered to HRT.", "Therapeutic agents for the treatment of hypertension may differ in their efficacy during the early-morning period, a time when both morbid and mortal cardiovascular events are increased compared with other times of the day.\n We studied the effects of a chronotherapeutic delivery system of verapamil (controlled-onset extended release [COER]-24 system) dosed at bedtime versus conventional morning administration of both enalapril and losartan on the blood pressure (BP), heart rate, and the heart rate systolic BP product during the first 4 hours after awakening in a placebo-controlled, forced-titration trial. There were 357 men and women enrolled in the trial with an untreated sitting diastolic BP of 95 to 114 mm Hg and ambulatory daytime diastolic BP > or =85 mm Hg. Patients were randomized to either COER-verapamil hydrochloride each evening (240 mg titrated to 360 mg), enalapril each morning (10 mg titrated to 20 mg), losartan each morning (50 mg titrated to 100 mg), or placebo. Early morning assessments of BP, heart rate, and the heart rate systolic BP product were performed by use of 24-hour ambulatory recordings after 4 weeks (low dose) and 8 weeks (high dose) of therapy.\n Results were similar at weeks 4 and 8 for all treatment groups except that the magnitude of change was greater at week 8. After 8 weeks of treatment, reductions in early morning BP by COER-verapamil were significantly greater (-15/-10 mm Hg) than enalapril (-9/-7 mm Hg, P <.01) and losartan (-8/-5 mm Hg, P <.001). COER-verapamil also led to greater reductions in morning heart rate, the rate-pressure product, and the rate-of-rise of BP compared with the other 2 active treatment groups. Reductions in mean 24-hour BP were greater in patients treated with COER-verapamil compared with placebo and losartan, and similar to reductions in patients treated with enalapril.\n Bedtime administration of an agent designed to parallel the circadian rhythm of BP and heart rate led to significantly greater early morning hemodynamic effects compared with other conventional once-daily antihypertensive agents dosed in the morning.", "The new angiotensin converting enzyme inhibitor enalapril (MK-421), was given in a single daily dose of 20 mg to 53 patients with uncomplicated essential hypertension. Its effects were compared with those of a placebo given to 47 patients on a double-blind randomized basis. The blood pressure was measured in all patients by a physician, using a mercury sphygmomanometer, and by an automatic device in the absence of the physician. After 15 days of treatment, enalapril induced a significant reduction in systolic blood pressure (161.4 +/- 13 versus 145.1 +/- 15, p less than 0.001) and in diastolic blood pressure (103.3 +/- 6 versus 92.9 +/- 8, p less than 0.001) measured by the physician. The magnitude of the fall in blood pressure was identical after 30 days of active treatment. The reduction in blood pressure induced by enalapril was similarly detected by both methods of measurement, despite the fact that blood pressure values were higher when measured by the physician. A placebo effect was observed with the physician's values that was not present with the automatically recorded values. A very significant correlation between blood pressure values obtained by these two methods was observed. However, among nine of 53 patients treated with enalapril, a difference in the decrease of blood pressure of 10 mm Hg or more was noted between the two methods of measurement. The decrease in blood pressure occurred with no change noted in the pulse rate or orthostatic hypotension. Plasma renin activity increased after treatment. No changes were observed in creatinine clearance and plasma electrolyte levels.", "To compare the antihypertensive efficacy and tolerability of the imidazoline I1 receptor agonist moxonidine, a centrally acting antihypertensive, with the angiotensin converting enzyme inhibitor enalapril.\n An 8-week, double-blind, randomized, placebo-controlled study involving 140 outpatients with mild-to-moderate essential hypertension.\n Outpatients with WHO stage I or II hypertension were enrolled in the study. After a 4-week placebo-controlled stabilization phase patients were allocated randomly to placebo, 0.2 mg moxonidine once a day or 5 mg enalapril once a day for 2 weeks. Dosages were then doubled to 0.4 mg moxonidine once a day or 10 mg enalapril once a day for a further 6 weeks. Blood pressure responses to therapy were measured by conventional office techniques and by 24 h ambulatory blood pressure monitoring.\n The mean reduction in sitting blood pressure with moxonidine was similar to that with enalapril (19.5 +/- 16.0/12.3 +/- 8.7 versus 18.9 +/- 13.7/11.8 +/- 8.0 mmHg) and significantly superior to that with placebo (-4.6 +/- 12.3/-4.7 +/- 6.8 mmHg, P< 0.001). In addition to reducing blood pressure during conventional measurements, moxonidine administration reduced blood pressure throughout 24 h ambulatory measurements. The trough:peak ratio for moxonidine was 0.7. Both moxonidine and enalapril were tolerated well.\n Moxonidine is an effective and well-tolerated antihypertensive, at least as good as other established forms of antihypertensive medication. The trough:peak ratio of 0.7 indicates that the drug will be effective administered once a day.", "Cilazapril (CLZ) is a new, long-acting nonsulfhydril converting enzyme inhibitor (ACE-I). Its effect on peak and trough sitting diastolic blood pressure (SDBP) was studied in a total of 85 patients with uncomplicated, essential hypertension at three centers. After 4 weeks of a single-blind placebo (PLA) run-in period, patients whose SDBP was between 100 and 115 mm Hg, were randomized into active treatment with either PLA (n = 27), CLZ 2.5 mg (n = 29), or CLZ 5 mg (n = 29) once daily in a double-blind fashion for another 8 weeks. At the end of the PLA run-in and after 4 and 8 weeks active therapy, an hourly blood pressure (BP) profile during 1-10 and 21-24 h postdose was performed. The drop in SDBP at the end of the active treatment period at peak and trough was statistically and clinically significant for both CLZ doses in comparison with the PLA group. The peak/trough ratio after subtraction of the PLA effect was 62% for CLZ 2.5 mg and 59% for CLZ 5 mg. These results indicate that the dose regimen of CLZ 2.5-5 mg once daily is adequate and effective for 24 h.", "To compare the antihypertensive efficacy and systemic tolerability of valsartan, a new angiotensin II receptor antagonist, with placebo and with an angiotensin converting enzyme (ACE) inhibitor, enalapril.\n A total of 348 adult outpatients with mild-to-moderate uncomplicated essential hypertension participated in this double-blind, parallel, study. Patients were allocated randomly in a ratio of 2:2:1 to receive 80 mg valsartan once a day, 20 mg enalapril once a day, or placebo for 8 weeks in general practice. Patients were assessed at 4 and 8 weeks of therapy.\n The primary efficacy variable was the change from baseline in mean sitting diastolic blood pressure (SDBP) after 8 weeks of therapy. Secondary variables included the change in sitting systolic blood pressure (SSBP) and response rates at 8 weeks.\n Valsartan and enalapril produced statistically significant reductions in diastolic and systolic blood pressures compared with placebo. Similar falls were found in both of the active treatment groups with mean changes in SDBP at 8 weeks of -9.5 mmHg for valsartan and -9.4 mmHg for enalapril (-4.5 mmHg for placebo). No significant differences between valsartan and enalapril were found for reductions in SDBP or SSBP. Response rates at 8 weeks were significantly greater for valsartan (54%) and enalapril (58%) than for placebo (20%), with no significant difference between the two active treatments. Both valsartan and enalapril demonstrated a consistent antihypertensive effect over time, with 90% of patients with a response at 4 weeks responding at 8 weeks. Both of the treatments were tolerated well. Although the incidence of coughing was generally low in the study, more cases were reported with enalapril (three) than with valsartan (one) or placebo (none).\n The data show 80 mg valsartan once a day to be as effective as 20 mg enalapril once a day in the treatment of mild-to-moderate hypertension. Valsartan is tolerated well and does not appear to be associated with any increase in the incidence of coughing.", "Cilazapril, an angiotensin converting enzyme (ACE) inhibitor with a long half-life, effectively reduced sitting diastolic blood pressure in patients with uncomplicated essential hypertension at dosages of 2.5, 5.0, and 10.0 mg/day, evaluated in a double-blind, placebo-controlled study. After a four-week placebo run-in period, 235 patients received either cilazapril or placebo for four weeks. At the end of the treatment period, significant decreases from baseline in sitting diastolic blood pressure were seen in all four groups (mean decreases of 3.3 mm Hg with placebo and 6.4, 9.2 and 8.3 mm Hg with 2.5, 5.0 and 10.0 mg cilazapril, respectively). The cilazapril groups had significantly greater blood pressure reductions than did the placebo group (p less than or equal to 0.02). The 5.0 mg cilazapril dose was significantly more effective than the 2.5 mg dose (p less than 0.03). The response rate was notably greater in the cilazapril treatment groups than in the placebo group (placebo, 27.5%; 2.5 mg cilazapril, 42.9%; 5.0 mg cilazapril 62.5%; 10.0 mg cilazapril, 50.0%). Cilazapril was well tolerated at all three dosages.", "To test the antihypertensive and metabolic effects of lisinopril, 10 mg/d (L); hydrochlorothiazide, 12.5 and 25 mg/d (H12.5 and H25); and its combination with lisinopril (L/H12.5 and L/H25) against placebo in patients with mild to moderate (stage I and stage II) hypertension.\n Multicenter, double-blind, placebo-controlled outpatient study of 12 weeks' duration.\n After 4 weeks of single-blind placebo treatment, 505 patients whose sitting diastolic blood pressure was 100 to 114 mm Hg were randomized into the study--467 patients completed it (placebo, 71; L, 80; H12.5, 79; H25, 77; L/H12.5, 79; and L/H25, 81). The patients were seen in the clinic every 2 weeks, where measurements of their sitting and upright blood pressure and heart rate were taken 24 +/- 2 hours after drug administration. Complete blood cell counts with differential cell counts, blood chemistry studies, urinalyses, and electrocardiograms were done at baseline and during the study. Roentgenograms were done once at baseline.\n Compared with placebo, all drug regimens decreased sitting and upright blood pressure (P < .001) and had no effect on sitting and upright heart rate. The greatest effect was obtained with the combinations of L/H12.5 and L/H25. There was no difference between L/H12.5 and L/H25 or between H12.5 and H25. There were no serious clinical side effects except cough, which was slightly higher with L, L/H12.5, and L/H25. The only metabolic side effects were in serum potassium level, which was lower with H25 (P < .01), and serum glucose level, which was higher with H25 and L/H25 (P < .01).\n The data suggest that (1) monotherapy of hypertension with L, H12.5, H25, L/H12.5, and L/H25 was effective and well tolerated; (2) the best results were achieved with L/H12.5 and L/H25; (3) lower doses of hydrochlorothiazide either alone or in combination with lisinopril were equipotent with higher doses and were free of metabolic side effects.", "To assess the efficacy and safety of several combinations of benazepril, an angiotensin-converting enzyme inhibitor, and hydrochlorothiazide, as compared with placebo, in the treatment of patients with essential hypertension.\n A 6-week, randomized, double-blind, parallel study conducted at 24 centers. A placebo run-in period of 1 to 4 weeks preceded the double-blind phase.\n Male and female outpatients, aged 18 years and older, were eligible to participate if their sitting diastolic blood pressure was between 95 and 114 mm Hg at the last two consecutive visits during the placebo phase. Among the 334 patients who entered the double-blind phase, 17% were aged 65 years or older and 26% were black. Eleven patients withdrew because of adverse experiences, including two patients receiving placebo.\n Patients received placebo; benazepril, 20 mg; hydrochlorothiazide, 25 mg; or combination therapy with benazepril/hydrochlorothiazide, 5/6.25 mg, 10/12.5 mg, 20/25 mg, 20/6.25 mg, or 5/25 mg, once daily for 6 weeks.\n The mean change from baseline in sitting diastolic blood pressure at end point (last postrandomization measurement carried forward) in the double-blind phase. Combination therapy with benazepril/hydrochlorothiazide, 20/25 mg, was compared with benazepril, 20 mg alone, and hydrochlorothiazide, 25 mg alone. Sitting systolic blood pressure and the effect of race and age on treatment efficacy were also evaluated.\n Compared with placebo, all benazepril/hydrochlorothiazide combinations produced statistically significant reductions from baseline in sitting diastolic and systolic blood pressures at study end point. In the benazepril/hydrochlorothiazide, 20/25 mg, group, the adjusted mean changes in sitting diastolic blood pressure at end point were statistically significantly greater than those in the monotherapy treatment groups (benazepril, 20 mg, P < or = .05; hydrochlorothiazide, 25 mg, P < or = .001) alone. All therapies were generally well tolerated. Decreases in mean serum potassium level with hydrochlorothiazide monotherapy were reduced or eliminated with combination therapy.\n Benazepril in combination with hydrochlorothiazide, including a low-dose combination of 5/6.25 mg, is effective in reducing sitting diastolic and systolic blood pressure in patients with hypertension.", "The aim of this double-blind randomized placebo-controlled study was to evaluate the antihypertensive and safety of fosinopril in mild essential hypertension. After a 2-week placebo period, patients received either placebo or fosinopril 20 mg, once daily. Thirty-four patients finished the study (18 patients in the placebo group and 16 patients in the fosinopril group). Systolic blood pressure decreased from 160.1 +/- 22.1 mmHg to 156.0 +/- 24.2 in the placebo group (NS) and from 151.8 +/- 14.0 mmHg to 141.5 +/- 14.5 in the fosinopril group (p < 0.005); diastolic blood pressure decreased from 100.1 +/- 2.4 mmHg to 94.3 +/- 7.4 mmHg in the placebo group (p < 0.005) and from 100.8 +/- 4.8 mmHg to 88.1 +/- 9.0 mmHg in the fosinopril group (p < 0.001). Mean decrease in diastolic blood pressure was 5.7 mmHg in the placebo group and 12.6 mmHg in the fosinopril group (p < 0.05). A statistically significant difference was seen between the percentage of controlled patients in the two groups: 16.6% in the placebo group vs 56.2% in the fosinopril group (p < 0.05). No statistically significant difference in biochemical parameters was seen between the two groups. Tolerance was good and no patients were withdrawn from the study for adverse events.", "Perindopril erbumine, a new long-acting, non-sulfhydryl-containing angiotensin converting enzyme inhibitor, was evaluated in 289 patients with hypertension in a 16-week, double-blind, placebo-controlled dose-ranging study. After 4 weeks of single-blind placebo treatment, patients with supine diastolic arterial pressures from 95 to 114 mm Hg were randomized to receive placebo, 4 mg perindopril once daily, or 2 mg perindopril twice daily. The daily dose of perindopril was increased by 4 mg every 4 weeks to a maximum of 16 mg per day. Mean decreases in systolic and diastolic arterial pressure were greater with perindopril than with placebo (p < 0.05). The dose-response curve flattened after 8 mg per day, and there was no difference in arterial pressure reduction or in the percentage of responders between once- and twice-daily administration of perindopril. Adverse reactions with perindopril were generally mild and, with the exception of cough, were similar with placebo. The findings of this study indicate that perindopril is effective, well tolerated, and suitable for once-daily administration for the treatment of hypertension.", "A multicenter, double-blind, placebo-controlled trial with multifactorial design was conducted to evaluate the safety and efficacy of the calcium-channel blocker diltiazem, in a sustained release preparation, and the angiotensin converting enzyme inhibitor, lisinopril, in the treatment of elderly Chinese patients with mild-to-moderate hypertension. In addition to the hypotensive effects of combinations of both drugs compared with monotherapy, all given once daily, the effect on quality of life was also evaluated. This study consisted of a 3 x 2 multifactorial design in which 156 women and men with a sitting diastolic pressure of between 95 mm Hg and 114 mm Hg, after a 4-week placebo washout phase, were randomized to one of six treatment groups for 12 weeks of active treatment. Monotherapy with diltiazem 120 or 240 mg produced increasing reductions of systolic and diastolic blood pressure. Compared with placebo, lisinopril 10 mg had an effect intermediate between the diltiazem doses. The combinations of diltiazem 240 mg + lisinopril 10 mg and diltiazem 120 mg + lisinopril 10 mg showed increased efficacy in reducing systolic and diastolic blood pressure compared to these drug doses used in monotherapy, but the effect of the combinations was less than predicted by an additive model. Although the total number of other adverse events reported was similar for all active treatment groups compared to placebo, lisinopril-induced cough was common with an incidence of 31% after rechallenge. Premature drug withdrawal was necessary in four of 78 patients receiving lisinopril, due to intractable cough. The combination of diltiazem 240 mg and lisinopril 10 mg was significantly more effective at reducing blood pressure than either drug alone; this additive effect did not result in a higher rate of adverse effects or impairment of quality of life. Thus, combination therapy with these agents was well tolerated and resulted in increased efficacy in these elderly patients.", "Many hypertensive patients have other, usually long-term diseases. Antihypertensive therapy may interfere with these diseases and their therapies. In the present study, the possible interactions of the ACE-inhibitor perindopril with several of the most common long-term diseases was evaluated.\n In a multicenter, double-blind, randomized, placebo-controlled trial, the effect of perindopril was evaluated in 490 patients with mild essential hypertension and any one of the following concomitant diseases: hyperlipidemia, type II diabetes mellitus, ischemic heart disease, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, chronic obstructive pulmonary disease, or degenerative joint disease treated with nonsteroidal anti-inflammatory drugs (NSAIDs). After a 3-week single-blind placebo run-in, the patients received either perindopril (4 mg/d) or matching placebo for 6 weeks.\n Blood pressure was effectively reduced by perindopril irrespective of the associated disease. The rate of spontaneously reported side effects was low. Treatment with perindopril was free from adverse interactions with the concomitant diseases and therapies. Moreover, favorable actions could be observed in patients with ischemic heart disease (reduction of maximal ST-segment depression during peak exercise and decrease in the number of angina attacks), in patients with proteinuria (decrease in albuminuria in patients with normal serum creatinine levels), and in patients with NSAID-treatment (increase in prostaglandin E2 concentration in gastric mucosa suggesting gastric cytoprotection).\n This trial shows that ACE-inhibition with perindopril represents a simple, safe, and effective short-term therapeutic option for the large proportion of patients with mild essential hypertension and concomitant diseases and therapies.", "The antihypertensive effectiveness of twice-daily dosing with the converting enzyme inhibitor, captopril, was examined in a multicenter study of 294 patients (181 white, 111 black, two oriental) with essential hypertension whose supine diastolic blood pressure (SDBP) was 95 mm Hg or higher after 4 to 6 weeks of preliminary placebo administration. In this double-blind study, the patients were randomized into one placebo and three captopril-treated groups: twice-daily placebo (n = 77) or twice-daily captopril 25 mg (n = 77), 50 mg (n = 71), or 100 mg (n = 69). The average decreases in SDBP after 8 weeks of treatment were 5.2%, 7.7%, 11.7%, and 10.5%, respectively. Only the two higher dose groups differed significantly from the placebo group; they also differed from the lowest dose group. The proportions of patients classified as having normalized pressures (SDBP less than 90 mm Hg) in the four groups were 39%, 47%, 70%, and 50%. If the results were analyzed by race, all three captopril-treated groups differed significantly from the placebo-treated group in the white patients but not in the black patients. However, direct comparisons between the white and black groups showed a difference only at the low, 25 mg twice daily (b.i.d.), captopril dose. Thus, although conventionally given on a three-times daily basis, the twice-daily (12-hourly) administration of captopril provides effective antihypertensive treatment in doses of 50 or 100 mg b.i.d. Moreover, white patients also exhibit a significant response to captopril at doses as low as 25 mg b.i.d.(ABSTRACT TRUNCATED AT 250 WORDS)", "This multicenter, double-masked, randomized, parallel-group study compared the efficacy, tolerability, and safety of amlodipine 5 mg/benazepril 20 mg, amlodipine 5 mg, benazepril 20 mg, and placebo in patients with essential hypertension. After a placebo run-in period, 308 patients (all white) were randomized to treatment groups and took medication once daily for 8 weeks. Blood pressure was measured after 4 and 8 weeks of treatment in the 23- to 26-hour period after dosing. Patients wore a noninvasive blood pressure monitor for 24 hours before randomization and before the final visit. Investigators recorded adverse experiences at randomization and at study weeks 4 and 8, and obtained specimens for laboratory testing at randomization and at study week 8. Three hundred seven patients were evaluated for efficacy, and 308 for tolerability and safety. At end point (the last postrandomization measurement for each patient), the reduction in mean sitting diastolic blood pressure with the amlodipine 5 mg/benazepril 20 mg treatment was statistically significantly greater than with any comparative therapy. The results of 24-hour monitoring showed that the amlodipine/benazepril treatment, unlike monotherapy, maintained the hourly mean diastolic blood pressure at < or = 90 mm Hg. A responder rate of 87.0% was observed with amlodipine 5 mg/benazepril 20 mg versus 67.5%, 53.3%, and 15.8% with amlodipine, benazepril, and placebo, respectively. This difference between the amlodipine/benazepril treatment group and each comparative single-agent treatment group was statistically significant. Drug-related adverse events occurred in 15.6% of patients in the amlodipine/benazepril group and in 24.7%, 6.5%, and 11.7% of patients in the amlodipine, benazepril, and placebo groups, respectively. Edema occurred less often in the amlodipine/benazepril group than in the amlodipine group. Overall, once-daily therapy with amlodipine 5 mg/benazepril 20 mg provided an antihypertensive effect that was statistically and clinically superior to amlodipine 5 mg alone, benazepril 20 mg alone, and placebo, was well tolerated, and was associated with less edema than the amlodipine treatment.", "To evaluate the antihypertensive effects of cilazapril, a new angiotensin-converting enzyme inhibitor, on clinic and ambulatory blood pressure (ABP) after first and last dose administrations.\n Four weeks randomized, double-blind, controlled trial of three regimens.\n Six hypertensive research clinics in Canada.\n After a two-week placebo run-in period, 130 patients aged 22 to 77 years with mild to moderate essential hypertension were randomized and evaluated. Exclusion criteria were secondary hypertension, childbearing potential and other significant diseases.\n Patients were assigned to cilazapril 2.5 mg (44 patients), cilazapril 5 mg (42) or placebo (44). Fourteen patients in each group were further evaluated in a substudy by 24 h ABP monitoring.\n Cilazapril in either dosage induced significant and similar antihypertensive effects on clinic blood pressure shortly after dosing (2 to 4 h), persisting during chronic treatment; however, no relevant effect persisted at the end of dosing (24 h). After four weeks, at the end of dosing, 22, 24 and 38% of patients were clinical responders (decrease in sitting diastolic blood pressure 10 mmHg or greater) on placebo, 2.5 or 5 mg (differences not significant). Conversely, both cilazapril regimens induced similar and significant (P < 0.01) falls in mean 24 h ABP compared with placebo. Moreover, 7, 50 and 48% of patients exhibited a reduction in mean 24 h diastolic blood pressure 10 mmHg or greater on placebo, cilazapril 2.5 or 5 mg, respectively. Furthermore, both regimens induced adequate trough:peak ratios on ABP.", "The Veratran study investigated the antihypertensive efficacy of verapamil sustained release (SR) (180 mg), trandolapril (1 mg), and their fixed combination during a 24-h period. After a 4-week placebo run-in period, 272 patients (age 49 +/- 9 years, mean +/- SD) with essential hypertension and a clinic diastolic blood pressure > or =100 mm Hg were randomized to verapamil, trandolapril, their fixed combination, or placebo for 8 weeks, according to a multicenter double-blind parallel group study design. Clinic and semiautomatic blood pressure at trough and 24-h ambulatory blood pressure were measured at the end of run-in period and after 8 weeks of treatment. In the 234 patients included in the efficacy analysis, run-in clinic and semiautomatic blood pressures were reduced by verapamil, trandolapril, and combined verapamil and trandolapril significantly more than by placebo. The reductions obtained with the combination were significantly greater than those obtained by verapamil alone. Twenty-four-hour average blood pressures were not modified by placebo and were reduced by 8/6 mm Hg (systolic/diastolic) by verapamil, 11/7 mm Hg by trandolapril, and 14/11 mm Hg by the combination of the two drugs. The differences between the effect of the combination and the combination components were, in most instances, statistically significant. The verapamil-trandolapril combination was more effective also on day average blood pressure and superior to the monotherapies for the trough-to-peak ratio of the antihypertensive effect as well. Twenty-four-hour heart rate was slightly but significantly reduced by verapamil and the reduction was manifest in the group taking verapamil plus trandolapril. Thus, the antihypertensive treatment with the fixed verapamil SR-trandolapril combination is more effective and balanced over the 24 hours than the effect of the combination components administered alone." ]

[ "10819855", "8116700", "10819857" ]

[ "An oxytocin receptor antagonist (atosiban) in the treatment of preterm labor: a randomized, double-blind, placebo-controlled trial with tocolytic rescue.", "The effect of the oxytocin antagonist atosiban on preterm uterine activity in the human.", "Double-blind, randomized, controlled trial of atosiban and ritodrine in the treatment of preterm labor: a multicenter effectiveness and safety study." ]

[ "This study was designed to evaluate the efficacy and safety of the oxytocin receptor antagonist atosiban in the treatment of preterm labor.\n A multicenter, double-blind, placebo-controlled trial with tocolytic rescue was designed. Five hundred thirty-one patients were randomized to receive, and 501 received, either intravenous atosiban (n = 246) or placebo (n = 255), followed by subcutaneous maintenance with the assigned agent. Standard tocolytics as rescue tocolysis were permitted after 1 hour of either placebo or atosiban if preterm labor continued. The primary end point was the time from the start of study drug to delivery or therapeutic failure. Secondary end points were the proportion of patients who remained undelivered and did not receive an alternate tocolytic at 24 hours, 48 hours, and 7 days.\n No significant difference was found in the time from start of treatment to delivery or therapeutic failure between atosiban and placebo (median, 25.6 days vs 21.0 days, respectively; P =.6). The percentages of patients remaining undelivered and not requiring an alternate tocolytic at 24 hours, 48 hours, and 7 days were significantly higher in the atosiban group than in the control group (all P < or =.008). A significant treatment-by-gestational age interaction existed for the 48-hour and 7-day end points. Atosiban was consistently superior to placebo at a gestational age of > or =28 weeks. Fourteen atosiban-treated patients and 5 placebo-treated patients were randomized at <24 weeks; the incidence of fetal-infant deaths was higher for the atosiban group at <24 weeks. Maternal-fetal adverse events were similar except for injection-site reactions, which occurred more often with atosiban.\n In this trial the treatment of patients in preterm labor with atosiban resulted in prolongation of pregnancy for up to 7 days for those at a gestational age > or =28 weeks, and this occurred with a low rate of maternal-fetal adverse effects. In addition, at a gestational age > or =28 weeks, the infant morbidity and mortality of atosiban-initiated standard care were similar to those with placebo-initiated standard care. Given that all patients in this study were eligible for tocolysis and that, in practice, nearly all patients who are eligible for a tocolytic receive one, the benefit of using atosiban is the placebo-like maternal-fetal side effect profile. These observations support the use of this oxytocin receptor antagonist in the treatment of patients in preterm labor with intact membranes. Efficacy and infant outcome data at <28 weeks are inconclusive.", "The purpose of this study was to test the hypothesis that infusion of the oxytocin antagonist atosiban results in decreased preterm uterine activity in the human.\n A randomized, double-blind, placebo-controlled trial was performed. One hundred twenty women from 20 to 36 weeks' gestation with a complaint of labor who had more than four uterine contractions per hour after intravenous hydration but no evidence of cervical changes were randomized to receive a 2-hour intravenous infusion of atosiban at a rate of 300 micrograms/min or placebo. Ond hundred-twelve subjects (56 in each arm) were suitable for analysis of efficacy. Both groups remained at bed rest and received hydration.\n The mean percent decrease in contraction frequency was greater in atosiban subjects compared with controls (55.3% +/- 36.3% vs 26.7% +/- 40.4%, mean +/- SD, p < 0.001). A minimal (< 20%) decrease or an increase in contraction frequency was noted in 25 placebo subjects (45%) and seven atosiban subjects (13%). There was no clinically or statistically significant change in maternal blood pressure or heart rate during the infusion. The only adverse experiences possibly related to the drug were nausea and vomiting in one atosiban patient.\n A 2-hour infusion of the oxytocin antagonist atosiban resulted in a significantly greater decline in contraction frequency compared with controls. Oxytocin appears to play a role in the maintenance of preterm uterine activity in the human.", "This study was undertaken to compare the efficacy and safety of intravenous administration of atosiban versus ritodrine for the treatment of preterm labor. Study Design: Women with preterm labor and intact membranes diagnosed at 23 to 33 gestational weeks (n = 247) were randomly assigned to treatment arms and received atosiban (6.75 mg intravenous bolus, 300 microg/min for 3 hours, then 100 microg/min intravenously) or ritodrine (0.10-0.35 mg/min intravenously) for as long as 18 hours. Tocolytic effectiveness was assessed in terms of the numbers of women who had not been delivered after 48 hours and after 7 days. Safety was assessed in terms of maternal side effects and neonatal morbidity. Secondary outcomes included mean gestational age at delivery and mean birth weight. An intent-to-treat analysis was performed with the Cochran-Mantel-Haenszel test.\n The proportion of women who had not been delivered at 48 hours was 84.9% (n = 107) in the atosiban group and 86.8% (n = 105) in the ritodrine group. At 7 days 92 women had still not been delivered in both the atosiban (73.0%) and ritodrine (76.0%) groups. Neither of these differences was statistically significant. The incidence of maternal cardiovascular side effects was substantially lower in the atosiban group (4.0% vs 84.3%, P <.001). In addition, intravenous therapy was terminated more frequently as a result of maternal adverse events in the ritodrine group (29.8%) than in the atosiban group (0.8%). The overall occurrences of fetal adverse events in the two treatment groups were comparable. Neonatal morbidity was similar between the treatment groups after adjustment for unbalanced enrollment of women with multiple pregnancies and for gestational ages within treatment groups.\n Atosiban was comparable in clinical effectiveness to conventional ritodrine therapy but was better tolerated than ritodrine, with no evidence of significant maternal or fetal adverse events. Neonatal morbidity, which was similar between the two treatment arms, was apparently related to the gestational age of the infant rather than to the exposure to either tocolytic agent." ]

[ "20163990" ]

[ "Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta." ]

[ "Daclizumab, a humanised monoclonal antibody, reduced multiple sclerosis disease activity in previous non-randomised studies. We aimed to assess whether daclizumab reduces disease activity in patients with active relapsing multiple sclerosis who are receiving interferon beta treatment.\n We did a phase 2, randomised, double-blind, placebo-controlled study at 51 centres in the USA, Canada, Germany, Italy, and Spain. Patients with active relapsing multiple sclerosis who were taking interferon beta were randomly assigned to receive add-on subcutaneous daclizumab 2 mg/kg every 2 weeks (interferon beta and high-dose daclizumab group), daclizumab 1 mg/kg every 4 weeks (interferon beta and low-dose daclizumab group), or interferon beta and placebo for 24 weeks. The randomisation scheme was generated by Facet Biotech. All patients and assessors were masked to treatment with the exception of Facet Biotech bioanalysts who prepared data for the data safety monitoring board or generated pharmacokinetic or pharmacodynamic data, a drug accountability auditor, and the site pharmacist. The primary endpoint was total number of new or enlarged gadolinium contrast-enhancing lesions measured on brain MRI scans every 4 weeks between weeks 8 and 24. Effects of daclizumab on prespecified subsets of lymphocytes and quantitative T-cell proliferative response were assessed in an exploratory pharmacodynamic substudy. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00109161.\n From May, 2005, to March, 2006, 288 patients were assessed for eligibility, and 230 were randomly assigned to receive interferon beta and high-dose daclizumab (n=75), interferon beta and low-dose daclizumab (n=78), or interferon beta and placebo (n=77). The adjusted mean number of new or enlarged gadolinium contrast-enhancing lesions was 4.75 in the interferon beta and placebo group compared with 1.32 in the interferon beta and high-dose daclizumab group (difference 72%, 95% CI 34% to 88%; p=0.004) and 3.58 in the interferon beta and low-dose daclizumab group (25%, -76% to 68%; p=0.51). In the pharmacodynamic substudy, daclizumab was not associated with significant changes in absolute numbers of T cells, B cells, or natural killer cells, or T-cell proliferative response compared with interferon beta alone. The number of CD56(bright) natural killer cells was seven to eight times higher in both daclizumab groups than in the interferon beta and placebo group (interferon beta and low-dose daclizumab group p=0.002; interferon beta and high-dose daclizumab group p<0.0001). Common adverse events were equally distributed across groups.\n Add-on daclizumab treatment reduced the number of new or enlarged gadolinium contrast-enhancing lesions compared with interferon beta alone and might reduce multiple sclerosis disease activity to a greater extent than interferon beta alone.\n Facet Biotech and Biogen Idec.\n 2010 Elsevier Ltd. All rights reserved." ]

[ "18067630", "18569272", "17501955", "19336724", "1869646", "19370466", "17050927", "12117087", "17373172", "20133012", "12502122", "15262691", "8113458", "16485881", "11737438", "14616490", "12775317", "19470041", "19222455", "18643849", "12437457", "16924046", "20518784", "19537367", "18808378", "12271300", "17034536", "11423841", "3555597", "19180894", "17501954", "6120350", "8377777", "18937999", "17512087", "15837864", "18067628", "11142412", "17223873", "12833014", "18707799", "14732659", "16912977", "12582393", "20199551", "12353677", "2061443", "20426780", "19416257", "18042331", "16403097", "15097955", "20133013", "8771866", "12581080", "12140473", "12241628", "19545297", "16159735", "19309347", "18476957", "15389189", "14711141", "20865842", "18294318", "9431711", "20507841", "11841372", "18341663", "19467365" ]

[ "A randomised study of topical 5% imiquimod vs. topical 5-fluorouracil vs. cryosurgery in immunocompetent patients with actinic keratoses: a comparison of clinical and histological outcomes including 1-year follow-up.", "Comparison of the efficacy and tolerability of 3% diclofenac sodium gel and 5% imiquimod cream in the treatment of actinic keratosis.", "Vehicle-controlled, randomized, double-blind study to assess safety and efficacy of imiquimod 5% cream applied once daily 3 days per week in one or two courses of treatment of actinic keratoses on the head.", "Chemoprevention of human actinic keratoses by topical DL-alpha-tocopherol.", "A double-blind, vehicle-controlled study evaluating masoprocol cream in the treatment of actinic keratoses on the head and neck.", "Treatment of actinic keratoses on the dorsum of the hands: ALA-PDT versus diclofenac 3% gel followed by ALA-PDT. A placebo-controlled, double-blind, pilot study.", "Efficacy of 3% diclofenac gel for the treatment of actinic keratoses: a randomized, double-blind, placebo controlled study.", "Evaluation of the efficacy and tolerability of 0.5% fluorouracil cream and 5% fluorouracil cream applied to each side of the face in patients with actinic keratosis.", "Comparison of 5% 5-fluorouracil cream and 5% imiquimod cream in the management of actinic keratoses on the face and scalp.", "Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: results of two placebo-controlled studies of daily application to the face and balding scalp for two 3-week cycles.", "Randomized trial evaluating a new 0.5% fluorouracil formulation demonstrates efficacy after 1-, 2-, or 4-week treatment in patients with actinic keratosis.", "Effect of a 1-week treatment with 0.5% topical fluorouracil on occurrence of actinic keratosis after cryosurgery: a randomized, vehicle-controlled clinical trial.", "Clinical evaluation of topical isotretinoin in the treatment of actinic keratoses.", "One-week treatment with 0.5% fluorouracil cream prior to cryosurgery in patients with actinic keratoses: a double-blind, vehicle-controlled, long-term study.", "Topical 3.0% diclofenac in 2.5% hyaluronan gel in the treatment of actinic keratoses.", "Short-course therapy with imiquimod 5% cream for solar keratoses: a randomized controlled trial.", "A comparison of photodynamic therapy using topical methyl aminolevulinate (Metvix) with single cycle cryotherapy in patients with actinic keratosis: a prospective, randomized study.", "Intraindividual, right-left comparison of topical 5-aminolevulinic acid photodynamic therapy vs. 5% imiquimod cream for actinic keratoses on the upper extremities.", "Optimization of photodynamic therapy with a novel self-adhesive 5-aminolaevulinic acid patch: results of two randomized controlled phase III studies.", "Effective photodynamic therapy of actinic keratoses on the head and face with a novel, self-adhesive 5-aminolaevulinic acid patch.", "A randomized, double-blind, vehicle-controlled study to assess 5% imiquimod cream for the treatment of multiple actinic keratoses.", "Facial resurfacing for nonmelanoma skin cancer prophylaxis.", "Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a prospective, randomized, double-blind, placebo-controlled phase III study.", "Can topical calcipotriol be a treatment alternative in actinic keratoses? A preliminary report.", "Treatment of actinic keratoses with a novel betulin-based oleogel. A prospective, randomized, comparative pilot study.", "Clinical effect of imiquimod 5% cream in the treatment of actinic keratosis.", "Intraindividual, right-left comparison of topical methyl aminolaevulinate-photodynamic therapy and cryotherapy in subjects with actinic keratoses: a multicentre, randomized controlled study.", "Photodynamic therapy of actinic keratoses with topical aminolevulinic acid hydrochloride and fluorescent blue light.", "Topical chemotherapy of actinic keratoses of the upper extremity with tretinoin and 5-fluorouracil: a double-blind controlled study.", "Treatment of actinic keratoses with sequential use of photodynamic therapy; and imiquimod 5% cream.", "Randomized, double-blind, prospective study to compare topical 5-aminolaevulinic acid methylester with topical 5-aminolaevulinic acid photodynamic therapy for extensive scalp actinic keratosis.", "Etretinate in treatment of actinic keratosis. A double-blind crossover study.", "Reduction of solar keratoses by regular sunscreen use.", "Placebo-controlled, double-blind, randomized pilot study of imiquimod 5% cream applied once per week for 6 months for the treatment of actinic keratoses.", "Vehicle-controlled, double-blind, randomized study of imiquimod 5% cream applied 3 days per week in one or two courses of treatment for actinic keratoses on the head.", "Dosing with 5% imiquimod cream 3 times per week for the treatment of actinic keratosis: results of two phase 3, randomized, double-blind, parallel-group, vehicle-controlled trials.", "Topical immunomodulation under systemic immunosuppression: results of a multicentre, randomized, placebo-controlled safety and efficacy study of imiquimod 5% cream for the treatment of actinic keratoses in kidney, heart, and liver transplant patients.", "Chemoprevention of human actinic keratoses by topical 2-(difluoromethyl)-dl-ornithine.", "Treatment of post-transplant premalignant skin disease: a randomized intrapatient comparative study of 5-fluorouracil cream and topical photodynamic therapy.", "Assessment of adapalene gel for the treatment of actinic keratoses and lentigines: a randomized trial.", "Topical methyl-aminolevulinate photodynamic therapy using red light-emitting diode light for treatment of multiple actinic keratoses: A randomized, double-blind, placebo-controlled study.", "Photodynamic therapy with aminolevulinic acid topical solution and visible blue light in the treatment of multiple actinic keratoses of the face and scalp: investigator-blinded, phase 3, multicenter trials.", "A clinical comparison and long-term follow-up of topical 5-fluorouracil versus laser resurfacing in the treatment of widespread actinic keratoses.", "Photodynamic therapy with topical methyl aminolevulinate for actinic keratosis: results of a prospective randomized multicenter trial.", "Randomized, double-blinded, placebo controlled study to assess the effect of topical 1% nicotinamide on actinic keratoses.", "Effective treatment of actinic keratosis with 0.5% fluorouracil cream for 1, 2, or 4 weeks.", "Topical treatment of multiple actinic keratoses of the face with arotinoid methyl sulfone (Ro 14-9706) cream versus tretinoin cream: a double-blind, comparative study.", "Photodynamic therapy of multiple actinic keratoses: reduced pain through use of visible light plus water-filtered infrared A compared with light from light-emitting diodes.", "Photodynamic therapy of actinic keratoses with 8% and 16% methyl aminolaevulinate and home-based daylight exposure: a double-blinded randomized clinical trial.", "Efficacy of imiquimod as an adjunct to cryotherapy for actinic keratoses.", "Imiquimod-induced regression of actinic keratosis is associated with infiltration by T lymphocytes and dendritic cells: a randomized controlled trial.", "Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials.", "Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles.", "Beta-1,3-D-glucan gel in the treatment of solar keratoses.", "Topical diclofenac in hyaluronan gel for the treatment of solar keratoses.", "Photodynamic therapy using topical methyl 5-aminolevulinate compared with cryotherapy for actinic keratosis: A prospective, randomized study.", "Efficacy and safety assessment of 0.5% and 1% colchicine cream in the treatment of actinic keratoses.", "Effect of dosing frequency on the safety and efficacy of imiquimod 5% cream for treatment of actinic keratosis on the forearms and hands: a phase II, randomized placebo-controlled trial.", "A randomized multicenter study to compare two treatment regimens of topical methyl aminolevulinate (Metvix)-PDT in actinic keratosis of the face and scalp.", "Topical methyl aminolevulinate photodynamic therapy using red light-emitting diode light for multiple actinic keratoses: a randomized study.", "A phase II dose-ranging study of topical resiquimod to treat actinic keratosis.", "Imiquimod 5% cream for the treatment of actinic keratosis: results from a phase III, randomized, double-blind, vehicle-controlled, clinical trial with histology.", "Short incubation PDT versus 5-FU in treating actinic keratoses.", "A randomized, double-blinded, placebo-controlled, multicenter, efficacy and safety study of 3.75% imiquimod cream following cryosurgery for the treatment of actinic keratoses.", "Continuous activation of PpIX by daylight is as effective as and less painful than conventional photodynamic therapy for actinic keratoses; a randomized, controlled, single-blinded study.", "Topical diclofenac/hyaluronic acid gel in the treatment of solar keratoses.", "Results of a randomized, placebo-controlled safety and efficacy study of topical diclofenac 3% gel in organ transplant patients with multiple actinic keratoses.", "Topical treatment of actinic keratoses with 3.0% diclofenac in 2.5% hyaluronan gel.", "Multicentre intraindividual randomized trial of topical methyl aminolaevulinate-photodynamic therapy vs. cryotherapy for multiple actinic keratoses on the extremities.", "Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis." ]

[ "Actinic keratoses (AK) frequently occur on sun-exposed skin and are considered as in situ squamous cell carcinoma. To date, no treatment algorithm exists for first or second line therapies due to the lack of comparative studies.\n This study compared the initial and 12-month clinical clearance, histological clearance, and cosmetic outcomes of topically applied 5% imiquimod (IMIQ) cream, 5% 5-fluorouracil (5-FU) ointment and cryosurgery for the treatment of AK.\n Patients were randomised to one of the following three treatment groups: one or two courses of cryosurgery (20-40 s per lesion), topical 5-FU (twice daily for 4 weeks), or one or two courses of topical imquimod (three times per week for 4 weeks each).\n Sixty-eight per cent (17/25) of patients treated with cryosurgery, 96% (23/24) of patients treated with 5-FU, and 85% (22/26) of patients treated with IMIQ achieved initial clinical clearance, p = 0.03. The histological clearance rate for cryosurgery was 32% (8/25), 67% (16/24) for 5-FU, and 73% (19/26) in the IMIQ group, p = 0.03. The 12-month follow-up showed a high rate of recurrent and new lesions in the 5-FU and cryosurgery arms. The sustained clearance rate of initially cleared individual lesions was 28% (7/25) for cryosurgery, 54% (13/24) for 5-FU and 73% (19/26) for IMIQ (p < 0.01). Sustained clearance of the total treatment field was 4% (1/25), 33% (8/24), and 73% (19/26) of patients after cryosurgery, 5-FU, and IMIQ, respectively (p < 0.01). The patients in the IMIQ group were judged to have the best cosmetic outcomes (p = 0.0001).\n Imiquimod treatment of AK resulted in superior sustained clearance and cosmetic outcomes compared with cryosurgery and 5-FU. It should be considered as a first line therapy for sustained treatment of AK.", "Topical diclofenac and imiquimod have been reported to be effective in the treatment of actinic keratosis, but a study to compare these two drugs has not been reported yet.\n To compare the efficacy and safety of topical 3% diclofenac gel plus hyaluronic acid and 5% imiquimod cream in the treatment of actinic keratosis.\n Forty-nine patients with actinic keratosis were enrolled in this randomized comparative open-label study. Twenty-four patients applied 3% diclofenac gel once a daily to their lesions, while the other 25 patients were treated with a 5% imiquimod cream three times a week for 12 weeks. Patients were examined before treatment and every month of the treatment. Assessments were made by investigators according to the Investigator and the Patient Global Improvement Indices (IGII) and (PGII).\n According to the IGII results, a complete response was observed in 12% of the diclofenac group and 22% of the imiquimod group. For the PGII scores, a complete response was observed in 28% of the diclofenac group and 23% of the imiquimod group. There were no significant differences between the two groups (p > 0.05). Both treatments were well tolerated, with most adverse events related to skin.\n The two drugs were found to be equally effective and safe in the treatment of actinic keratosis but complete remission was very low. Therefore, topical treatments with these two drugs were not seen to be completely effective, and combined therapies and further studies are needed.", "Imiquimod has been investigated as a safe and effective therapeutic option for the treatment of actinic keratosis (AK).\n To evaluate imiquimod vs. vehicle applied three times a week for 4 weeks in one or two courses of treatment for AK on the face or balding scalp.\n Patients diagnosed with AK were enrolled in this multicentre, vehicle-controlled, double-blind study conducted in Europe. Twenty study centres enrolled a total of 259 patients in this study. Patients applied the study drug for 4 weeks, entered a 4-week rest period and if they did not have complete clearance, they then entered a second course of treatment.\n Patients in the imiquimod group had an overall complete clearance rate of 55.0% (71/129) vs. a rate of 2.3% (3/130) for the vehicle group. There was a high rate of agreement between the clinical assessment and histological findings with respect to AK lesion clearance. At both 8-week post-treatment visits, the negative predictive value of the investigator assessment was 92.2% for clinical assessments vs. histological results.\n A 4-week course of treatment with three times weekly dosing of imiquimod 5% cream, with a repeated course of treatment for those patients who fail to clear after the first course of treatment, is a safe and effective treatment for AK. The overall complete clearance rate (complete clearance after either course 1 or course 2) is comparable to the 16-week treatment regimen, while decreasing drug exposure to the patient and decreasing the overall treatment time.", "Prior research shows that topical application of free, nonfatty acid-conjugated vitamin E (DL-alpha-tocopherol) prevents skin cancer in mice, as well as immunosuppression induced by UVB radiation. This study investigated the chemopreventive potential of DL-alpha-tocopherol in humans through monitoring surrogate end point biomarkers in sun-damaged skin. Contralateral arms of healthy human volunteers with actinic keratoses (AK) were randomly assigned to receive either 12.5% DL-alpha-tocopherol or placebo in a crème base for 6 months. Changes in number of AKs, levels of p53 protein expression, proliferating cell nuclear antigen, and polyamines were assessed along with skin and systemic vitamin E levels. Following treatment, plasma concentration levels of DL-alpha-tocopherol were unchanged, but skin levels were highly elevated (P < 0.001). Levels of p53 and proliferating cell nuclear antigen did not change significantly, whereas number of AKs declined insignificantly in both placebo and treatment arms. Regression models showed significant decreases in putrescine, spermidine, spermine, and total polyamine concentrations following treatment. Topically applied DL-alpha-tocopherol was substantially absorbed in skin, but the 6-month application did not significantly reduce numbers of preexisting AKs on moderately to severely sun-damaged forearms. Increases in polyamine synthesis are expected during tumor initiation and promotion; conversely, the significant reductions in polyamine levels resulting from the topical DL-alpha-tocopherol application are consistent with reductions in tumorigenesis potential. Topical tocopherol did not normalize established sun-induced lesions, but DL-alpha-tocopherol-induced reductions in polyamine metabolism are consistent with the inhibition of skin squamous cell carcinogenesis as seen in previous human trials and animal models.", "This double-blind, vehicle-controlled, multicenter study evaluated the efficacy and safety of a new topical antineoplastic agent, masoprocol, in the treatment of actinic keratoses of the head and neck. Of the 113 patients who applied topical masoprocol twice a day for 14 to 28 days, there was a mean decrease in actinic keratoses from 15.0 to 5.4 and a median percent reduction from baseline actinic keratosis count of 71.4% at the 1-month follow-up visit. Comparable numbers for the vehicle-treated group were 13.4 to 11.1 actinic keratoses and 4.3% median percent reduction. Irritation, as manifested by erythema or flaking, occurred in 61.5% of topical masoprocol-treated patients versus 26.7% of those treated with vehicle and did not correlate with clinical response. Topical masoprocol appears to be useful in the treatment of actinic keratoses.", "Actinic keratoses (AK) are sun-induced epithelial skin lesions, which are at risk to progress to squamous cell carcinoma. One of the treatments of AK is photodynamic therapy (PDT), which often has to be repeated. Another treatment for these lesions is diclofenac 3% gel. Although both treatments have shown to be effective, they have never been studied together.\n To investigate whether a pre-treatment of AK on the dorsum of the hands with diclofenac 3% gel improves the efficacy of PDT.\n In this placebo-controlled, randomized, double-blind, pilot study with 10 patients, both hands were pre-treated--one with diclofenac gel and the other with placebo gel--and then the hands were treated with ALA-PDT. Total lesion number scores, total thickness scores and global improvement scores were used to assess efficacy. Pain scores were recorded during PDT.\n In both groups, the number of lesions significantly decreased. At 12 months' follow-up, significantly fewer AK were seen in the diclofenac group. Total lesion thickness scores decreased significantly in both groups. Pain during PDT was greater in the diclofenac group.\n Both treatments are effective in treating AK. A pre-treatment with diclofenac gel seems to result in fewer AK at 12 months' follow-up, compared to placebo. Side effects were worse when using the active drug.", "Actinic keratoses (AKs) are premalignant skin lesions caused by excessive sun exposure.\n To explore the therapeutic efficacy of 3% diclofenac in 2.5% hyaluronan gel in the topical treatment of AK.\n Sixty-four lesions in 20 patients were evaluated. They were randomized to receive either the active treatment, 3% diclofenac in 2.5% hyaluronan gel or placebo, which consisted of the inactive gel vehicle, hyaluronan for a period of three months. The collected data were analyzed by using Student t- tests.\n There was a reduction in the lesion size in 64.7% of diclofenac-treated lesions and 34.3% of control lesions during the three-month course of treatment. Only 9.3% of the lesions in the diclofenac group were completely cleared during three months of treatment. During the treatment, no significant side-effect was observed in both groups.\n Considering the malignant potential of actinic keratoses and the importance of clearing them to prevent their transformation to squamous cell carcinoma, the efficacy of diclofenac gel seen in our study seems to be low. This treatment may be useful for patients who do not tolerate other, more effective kinds of treatment for actinic keratoses.", "A new 0.5% fluorouracil cream has been developed that provides an alternative to the more highly concentrated topical formulations of fluorouracil that are currently available.\n This was a comparison of the tolerability and efficacy of the 0.5% and 5% fluorouracil creams in the treatment of actinic keratosis (AK).\n During this single-blind, randomized study, patients with > or =6 AK lesions were treated for 4 weeks with the 0.5% (once daily) and 5% (twice daily) fluorouracil creams applied to opposite sides of the face. After the end of treatment, patients were followed for an additional 4 weeks. Efficacy variables included absolute and percent reductions in AK lesions from baseline and total clearance of AK lesions. A questionnaire was used to evaluate patients' treatment preferences. Tolerability was evaluated through continuous monitoring of adverse events.\n Treatment with 0.5% fluorouracil cream reduced the number of AK lesions from 11.3 at baseline to 2.5 at the end of the 4-week follow-up phase, compared with a reduction from 10.3 to 4.2 lesions after treatment with 5% fluorouracil cream. The reduction was significantly greater with the 0.5% cream compared with the 5% cream (P = 0.044). The 0.5% cream was as effective as the 5% cream in terms of the percent reduction in AK lesions from baseline (67% and 47%, respectively) and in achieving total clearance of AK lesions (both treatments, approximately 43% of patients). Both treatments were associated with similar degrees of investigator-rated irritation; however, patients preferred the 0.5% cream because they felt it was more tolerable (P = 0.003), easier to apply, and had a once-daily application schedule. Although all patients experienced facial irritation in association with both creams, fewer patients treated with the 0.5% cream reported symptoms of facial irritation.\n In this study, 0.5% fluorouracil cream once daily was at least as effective as 5% fluorouracil cream twice daily in terms of the percent reduction in AK lesions and total clearance of AK lesions; it was more effective than the 5% cream in reducing the absolute number of AK lesions from baseline. Patients preferred the 0.5% cream to the 5% cream.", "It is timely to compare the efficacy and tolerability of 2 actinic keratosis (AK) therapies--5% 5-fluorouracil (5-FU) cream and imiquimod cream. Thirty-six patients with 4 or more AKs were randomly assigned to receive 5% 5-FU cream twice daily for 2 to 4 weeks or 5% imiquimod cream twice weekly for 16 weeks. Five percent 5-FU was more effective than imiquimod in exposing what were presumed to be subclinical AKs, reducing the final AK count (total AK count declined during the 24-week study by 94% vs. 66%, P < .05), achieving complete clearance (incidence of 84% vs. 24% by week 24, P < .01), and achieving clearance rapidly. Tolerability was similar except for erythema, which was initially significantly higher with 5-FU than imiquimod but resolved rapidly and was significantly lower than imiquimod by week 16. Five percent 5-FU remains the gold standard field therapy for AKs.", "Imiquimod 5% cream is approved as a 16-week regimen for the treatment of actinic keratoses involving a 25-cm(2) area of skin.\n We sought to evaluate imiquimod 2.5% and 3.75% creams for short-course treatment of the entire face and scalp.\n In two identical studies, adults with 5 to 20 lesions were randomized to placebo, or imiquimod 2.5% or 3.75% cream (1:1:1). Up to two packets (250 mg each) were applied per dose once daily for two 3-week treatment cycles, with a 3-week, no-treatment interval. Efficacy was assessed at 8 weeks posttreatment.\n In all, 490 subjects were randomized to placebo, or imiquimod 2.5% or 3.75% cream. Median baseline lesion counts for the treatment groups were 9 to 10. Complete and partial clearance rates were 5.5% and 12.8% for placebo, 25.0% and 42.7% for imiquimod 2.5%, and 34.0% and 53.7% for imiquimod 3.75% (P < .001, each imiquimod vs placebo; P = .034, 3.75% vs 2.5% for partial clearance). Median reductions from baseline in lesion count were 23.6%, 66.7%, and 80.0% for the placebo, imiquimod 2.5%, and imiquimod 3.75% groups, respectively (P < .001 each imiquimod vs placebo). There were few treatment-related discontinuations. Temporary treatment interruption (rest) rates were 0%, 17.1%, and 27.2% for the placebo, imiquimod 2.5%, and imiquimod 3.75%, respectively.\n Local effects of imiquimod, including erythema, may have led to investigator and subject bias.\n Both imiquimod 2.5% and 3.75% creams were more effective than placebo and had an acceptable safety profile when administered daily as a 3-week on/off/on regimen.\n Copyright 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.", "The efficacy and safety of a new 0.5% fluorouracil topical cream were compared with vehicle control for the treatment of actinic keratosis (AK). Active treatment applied once daily for 1, 2, or 4 weeks was more effective than vehicle control in achieving reduction from baseline in lesion counts and lesion clearance. Active treatment also resulted in significantly better global assessments of overall improvement. Treatment was effective regardless of the number of baseline lesions. Although longer treatment duration correlated with greater efficacy, treatment for 1, 2, or 4 weeks was effective. This new microsphere-based fluorouracil formulation was generally well tolerated; adverse events were primarily limited to facial irritation that resolved quickly after treatment. This new treatment provides a safe alternative to the topical fluorouracil formulations currently available for the 1-, 2-, or 4-week treatment of AK.", "No long-term randomized controlled clinical trial has compared the efficacy of cryosurgery alone vs cryosurgery following fluorouracil applications for the treatment of actinic keratosis.\n To determine the 6-month outcome of a 1-week course of 0.5% fluorouracil followed by cryosurgery.\n Prospective, multicenter, randomized, double-blind, vehicle-controlled clinical trial performed in community and academic outpatient clinics.\n A total of 144 patients with 5 or more visible or palpable actinic keratoses on the face.\n Topical 0.5% fluorouracil or vehicle once daily for 7 days. At the 4-week follow-up visit, residual lesions were treated with cryosurgery.\n Reduction in facial actinic keratoses from baseline to 4 weeks and 6 months.\n At 4 weeks, mean actinic keratosis lesion count was reduced by 62.4% in the 0.5% fluorouracil group vs 28.8% in the vehicle group (P<.001), and complete clearance was achieved in 16.7% of patients in the 0.5% fluorouracil group vs 0% of those in the vehicle group (P<.001). At 6 months, mean lesion count was reduced by 67.0% in the 0.5% fluorouracil plus cryosurgery group vs 45.6% in the vehicle plus cryosurgery group (P =.01), and significantly more patients in the 0.5% fluorouracil plus cryosurgery group than in the vehicle plus cryosurgery group had complete clearance (30% vs 7.7%; P<.001).\n A 1-week course of topical 0.5% fluorouracil before cryosurgery is significantly more effective in reducing patients' numbers of actinic keratosis lesions 6 months after treatment than cryosurgery alone. The high occurrence rate of actinic keratosis lesions at 6 months suggests a need for follow-up.", "Retinoids have been shown to improve the manifestations of skin photodamage, including actinic keratoses.\n The efficacy and tolerability of isotretinoin 0.1% cream in the treatment of actinic keratoses were evaluated in a randomized, double-blind, placebo-controlled, parallel-group study.\n One hundred patients were randomly assigned to treatment with 0.1% cream or vehicle twice daily for 24 weeks to the face, the scalp, and the upper extremities. Patients were assessed every 4 weeks by the investigators, who counted and recorded the number of lesions in each treatment area. The 93 patients who had at least one postbaseline assessment were included for efficacy analysis. Local tolerability was evaluated at each study visit.\n On the face, the reduction in number of actinic keratoses (mean +/- SEM) at the end of treatment was greater for patients treated with isotretinoin (3.9 +/- 0.6, i.e., 66% of patients with a reduction > 30%) than with placebo (1.7 +/- 0.5, i.e., 45% of patients with a reduction > 30%); this difference was statistically significant (p = 0.001). No significant drug effect was seen for lesions on the scalp or upper extremities. Mild to moderate local reactions with isotretinoin abated with reduced treatment frequency.\n Our results suggest that isotretinoin 0.1% cream cannot compete with more rapid treatments of actinic keratoses. However, its effect on facial lesions may be beneficial during long-term treatment of associated sun-damaged skin.", "Topical fluorouracil is currently approved for the treatment of actinic keratosis (AK) and is often used prior to or following cryosurgery as interval therapy in patients with severe AK lesions. No randomized, controlled studies are available to confirm anecdotal evidence suggesting pretreatment with fluorouracil is beneficial. This prospective, randomized, double-blind, vehicle-controlled study evaluated the effect of pretreatment with 0.5% fluorouracil cream (FC; Carac) or a vehicle cream (VC) once daily for 7 days to the face plus scalp, ears, neck, and/or lips in patients with > or = 5 visible or palpable AKs on the face prior to cryosurgery. Efficacy was determined by evaluating AK reduction and clearance (complete lack of AK lesions in the treatment area) at 4 weeks follow-up. Statistically significant decreases from baseline number of AKs were observed on all treatment areas in both groups. However, the mean number of facial AKs was significantly lower in the FC group at each treatment cycle (p = .011). No serious adverse events were considered related to treatment.", "Actinic keratoses (AKs) are epidermal skin lesions with the potential to develop into invasive squamous cell carcinoma (SCC). Treatment at an early stage may prevent development of SCC. Current treatment options are highly destructive and associated with significant side-effects. Early studies with topical diclofenac were encouraging and led to its evaluation for the treatment of actinic keratosis. Previous studies have demonstrated that 3% diclofenac in 2.5% hyaluronan gel is effective and well tolerated in the treatment of AK. The present study was designed to further explore the therapeutic potential of this gel.\n This randomized, double-blind, placebo-controlled trial involved outpatients with a diagnosis of five or more AK lesions contained in one to three 5 cm(2) blocks. Patients received either active treatment (3% diclofenac gel in 2.5% hyaluronan gel) or inactive gel vehicle (hyaluronan) as placebo (0.5 g b.i.d. in each 5 cm(2) treatment area for 90 days). Assessments included the Target Lesion Number Score (TLNS), Cumulative Lesion Number Score (CLNS), and Global Improvement Indices rated separately by both the investigator (IGII) and patient (PGII).\n Results obtained from 96 patients at follow up (30 days after end of treatment) indicated that a significantly higher proportion of patients who received active treatment had a TLNS = 0 compared to the placebo group (50% vs. 20%; P < 0.001). There was also a significant difference between the two groups in CLNS, with 47% of patients in the active treatment group having a CLNS = 0 compared with only 19% in the placebo group (P < 0.001). The proportion of patients with an IGII score of 4 (completely improved) at follow-up was 47% in the active treatment group compared with only 19% in the placebo group (P < 0.001); for PGII these values were 41% vs. 17%, P < 0.001. Both treatments were well tolerated, with most adverse events related to the skin.\n Topical 3% diclofenac in 2.5% hyaluronan gel was effective and well tolerated for the treatment of AK.", "A dual-centre, randomized, double-blind, vehicle-controlled study was conducted to evaluate the safety and efficacy of short courses of therapy with imiquimod 5% cream in clearing >/=75% of baseline solar keratoses (SK) within a field of treatment. Subjects with 5-15 baseline SK within one treatment area (scalp, forehead and temples, or both cheeks) were randomized to apply imiquimod or vehicle cream to the entire treatment area three times a week for 3 weeks. Subjects were assessed 4 weeks after completing the first course for clearance of lesions. Subjects with <75% clearance were commenced on a second 3-week course of study cream. Subjects with >/=75% clearance were followed up until study completion without further therapy. All subjects were evaluated at the study endpoint of 14 weeks after initiating therapy for assessment of the primary outcome (>/=75% clearance of baseline solar keratoses). Twenty-one out of 29 (72%) imiquimod-treated subjects cleared >/=75% of baseline lesions compared with 3/10 (30%) subjects using the vehicle cream (Fisher's exact test, P = 0.027). Imiquimod was well tolerated. The present study has a short follow-up endpoint, but suggests that imiquimod is a potential therapeutic alternative in patients with SK.", "Actinic keratosis (AK) is a very common condition, which has the potential of progressing to squamous cell carcinoma. The present study is a prospective, randomized study comparing the lesion response, cosmetic outcome, patient satisfaction and tolerability of a new treatment modality, photodynamic therapy (PDT), using topical methyl aminolevulinate (Metvix), with the most commonly used standard therapy for AK, cryotherapy.\n A total of 204 patients with clinically diagnosed AK were randomized to either cryotherapy or PDT. The PDT patients were further assigned to an active or placebo group in a random, double-blind manner. Cryotherapy was performed using liquid nitrogen spray in a single freeze-thaw cycle. PDT was performed using 160 mg/g methyl aminolevulinate cream or placebo, a 3-hour application time, red light (570-670 nm) and a total light dose of 75 J/cm(2). PDT was repeated after 7 days. Two sessions of PDT were undertaken, as a previous study had shown a single session had similar efficacy to cryotherapy. Lesion response was assessed clinically after 3 months (complete response or non-complete response).\n The lesion response rate was 91% in the methyl aminolevulinate PDT group, 68% in the cryotherapy group and 30% in the placebo PDT group. Methyl aminolevulinate PDT was statistically significantly better than both cryotherapy and placebo PDT in terms of response rates and cosmetic outcome. Most patients preferred PDT to other treatments.\n PDT with methyl aminolevulinate is an excellent treatment option, particularly for patients with widespread damage or AK lesions in cosmetically sensitive areas.", "Actinic keratoses (AKs) are considered as in situ squamous cell carcinoma. Early and effective treatment is important. Objective To compare the efficacy, cosmetic outcome and patient preference of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) with that of 5% imiquimod (IMIQ) cream in patients with AKs on the dorsa of hands and forearms.\n Subjects received two ALA-PDT treatment sessions and one or two courses of imiquimod (three times per week for 4 weeks each). Treatments were randomly allocated to alternate upper extremities. Assessments included lesion response one and six months after treatment, cosmetic outcome evaluated by the investigators and patients' preference 6 months after treatment. Efficacy end point included the individual AK lesion clearance rate.\n Thirty patients with 256 lesions were included in the study. At the first follow-up, treatment with ALA-PDT resulted in significantly larger rate of cured lesions relative to 5% IMIQ cream (70.16% vs. 18.26%). At the second follow-up both treatments showed a high rate of cured lesions (65.32% for PDT vs. 55.65% for IMIQ cream). Response rates obtained in grade I lesions were higher for both treatments (71.64% for PDT vs. 72.13% for IMIQ), while treatment with PDT resulted in a significant larger rate of cured grade II lesions (57.89% for PDT vs. 37.03 for IMIQ). Difference in cosmetic outcome was not statistically significant. Results for subject preference favoured ALA-PDT.\n Our study shows that ALA-PDT and 5% IMIQ cream are both attractive treatment options for upper extremities AKs with comparable efficacy and cosmetic outcomes.", "Photodynamic therapy (PDT) is increasingly used for treatment of actinic keratoses (AKs) but is a cumbersome procedure. A thin self-adhesive patch (PD P 506 A) containing 5-aminolaevulinic acid (5-ALA) was developed to facilitate PDT.\n To investigate efficacy and safety of the patch in comparison with placebo-PDT (superiority design, observer-blinded; study AK 03) and standard therapy, cryosurgery (noninferiority design, open; study AK 04).\n Two separate confirmatory randomized parallel-group phase III studies were set up. In total, 449 patients with up to eight mild to moderate AK study lesions located on the head were treated in 29 German study centres (study AK 03: 103 patients; study AK 04: 346 patients).\n Twelve weeks after treatment, 5-ALA patch-PDT proved to be superior to placebo-PDT (P < 0.001) and cryosurgery (P = 0.007). Efficacy rates on a lesion basis were 82% (AK 03) and 89% (AK 04) for PDT, 77% for cryosurgery and 19% (AK 03) and 29% (AK 04) for placebo-PDT. Local reactions at the treatment site occurred in almost all patients treated with 5-ALA patch-PDT or cryosurgery. Headache was the only side-effect not related to the treatment site which occurred in more than one patient.\n PD P 506 A is an innovative, easy-to-handle 5-ALA patch for PDT of mild to moderate AK lesions. Compared with current PDT procedures, pretreatment (e.g. curettage) is not needed and handling is considerably facilitated. A single PDT treatment results in efficacy rates being statistically significantly superior to placebo and cryosurgery.", "Photodynamic therapy (PDT) is increasingly used for the treatment of actinic keratosis (AK).\n To investigate both the efficacy of different application times and the safety of a novel patch (PD P 506 A) containing aminolaevulinic acid in the PDT of mild to moderate AK.\n Applications of PD P 506 A for 0.5, 1, 2 and 4 h were compared in a multicentre, randomized, blinded-observer, parallel-group study. After patch removal, study lesions were illuminated with red light (lambda(em) approximately 630 nm; 37 J/cm(2)). Study lesions were not pretreated (e.g. by curettage) prior to PDT. Efficacy was evaluated 4 and 8 weeks after treatment. Safety and tolerability were determined through laboratory analyses and documentation of both local reactions and adverse events.\n A total of 149 patients were initially enrolled. Of these, 140 patients (520 lesions) completed the study according to protocol. Eight weeks after treatment, 86% of the AK lesions (74% of the patients) treated with 4-h patch application showed complete clearance. The complete clearance rates of lesions (patients) for the 2-, 1- and 0.5-h treatment arms were 73% (47%), 72% (50%) and 51% (24%), respectively. Statistically, the 4-h application was identified as the 'best treatment'. Patients with clearance seemed to experience local reactions to a greater extent than patients without clearance. Local reactions to study treatments did not exceed the expected range.\n The results of this first clinical efficacy study suggest excellent therapeutic outcomes with a single PD P 506 A PDT with a 4-h application.", "Actinic keratoses (AKs) are precancerous epidermal lesions found most frequently on areas of the skin exposed to the sun. Several case studies published recently have indicated that 5% imiquimod cream, currently licensed for the treatment of genital warts, may be an effective treatment for AK.\n To assess the efficacy and safety of imiquimod for the treatment of AK.\n Patients in this randomized, double-blind, vehicle-controlled study applied 5% imiquimod cream or vehicle to AK lesions 3 times per week for a maximum of 12 weeks or until lesions had resolved. In the event of an adverse reaction, application of imiquimod was reduced to 1 or 2 times per week. Rest periods were also allowed if necessary.\n A specialized outpatient dermatology clinic within a state-funded hospital in Germany.\n The study population was aged 45 to 85 years. Of 52 patients screened, 36 men and women with AK confirmed by histological diagnosis were enrolled. Patients were excluded from the study if they did not have a histological diagnosis for AK, if they were older than 85 years, or if they did not comply with the protocol. All patients had responded to a notice asking for volunteers.\n The number and appearance of lesions were evaluated before, during, and after treatment. All adverse effects were recorded.\n Lesions treated with 5% imiquimod cream were clinically cleared in 21 (84%) of 25 patients and partially cleared in 2 (8%). Clearance was histologically confirmed 2 weeks after the last application of imiquimod in all patients clinically diagnosed as lesion free. Only 10% of patients treated with imiquimod were clinically diagnosed with recurrence 1 year after treatment. No reduction in the size or number of AK lesions was observed in vehicle-treated patients. Adverse effects reported by patients treated with imiquimod included erythema, edema, induration, vesicles, erosion, ulceration, excoriation, and scabbing. However, imiquimod was well tolerated since all patients completed the 12-week treatment. Only a few, mild adverse reactions to the vehicle cream were reported.\n Application of 5% imiquimod cream for 12 weeks is an effective and well-tolerated treatment for AK.", "To determine the effect of facial skin resurfacing for treatment of actinic keratoses (AKs) and prophylaxis against new primary basal and squamous cell carcinomas in individuals with previous nonmelanoma skin cancer (NMSC) or severe photodamage.\n Randomized, prospective 5-year trial.\n Dermatology and otolaryngology clinics of a Veterans Affairs hospital.\n Thirty-four patients with a history of facial or scalp AKs or basal or squamous cell carcinoma were enrolled. Five of 7 eligible patients who declined study-related treatment were used as controls. Twenty-seven patients were randomized to 3 treatment arms; 3 patients were discontinued from the study.\n Carbon dioxide laser resurfacing, 30% trichloroacetic acid peel, or 5% fluorouracil cream applied twice daily for 3 weeks.\n Reduction in the number of AKs was measured 3 months after treatment. The incidence of new NMSC in treated areas was assessed between January 1, 2001, and June 30, 2005. Times from baseline to diagnosis of first skin cancer were compared between the treatment and control groups.\n Treatment with fluorouracil, trichloroacetic acid, or carbon dioxide laser resulted in an 83% to 92% reduction in AKs (P< or =.03), a lower incidence of NMSC compared with the control group (P<.001), and a trend toward longer time to development of new skin cancer compared with the control group (P=.07). However, no significant differences were noted among the treatment groups.\n All 3 modalities demonstrated benefit for AK reduction and skin cancer prophylaxis compared with controls and warrant further study in a larger trial.", "Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) provides a therapeutic option for the treatment of actinic keratosis (AK). Different strategies are applied to overcome the chemical instability of ALA in solution and to improve skin penetration. A new stable nanoemulsion-based ALA formulation, BF-200 ALA, is currently in clinical development for PDT of AK.\n To evaluate the efficacy and safety of PDT of AK with BF-200 ALA.\n The study was performed as a randomized, multicentre, double-blind, placebo-controlled, interindividual, two-armed trial with BF-200 ALA and placebo. A total of 122 patients with four to eight mild to moderate AK lesions on the face and/or the bald scalp were included in eight German study centres. The efficacy of BF-200 ALA after one and two PDT treatments was evaluated. BF-200 ALA was used in combination with two different light sources under illumination conditions defined by European competent authorities.\n PDT with BF-200 ALA was superior to placebo PDT with respect to patient complete clearance rate (per-protocol group: 64% vs. 11%; P < 0.0001) and lesion complete clearance rate (per-protocol group: 81% vs. 22%) after the last PDT treatment. Statistically significant differences in the patient and lesion complete clearance rates and adverse effect profiles were observed for the two light sources, Aktilite CL128 and PhotoDyn 750, at both time points of assessment. The patient and lesion complete clearance rates after illumination with the Aktilite CL128 were 96% and 99%, respectively.\n BF-200 ALA is a very effective new formulation for the treatment of AK with PDT. Marked differences between the efficacies and adverse effects were observed for the different light sources used. Thus, PDT efficacy is dependent both on the drug and on the characteristics of the light source and the illumination conditions used.", "Recent research demonstrated that vitamin D, apart from calcium-related actions, has antiproliferative, prodifferentia-tive and immunomodulatory activities.\n To determine whether actinic keratoses may benefit from the antiproliferative and prodifferentiative effects of topical vitamin D.\n The study was an investigator-blinded, half-side comparison trial. Patients applied calcipotriol cream to one side and Ultrabase cream as placebo to the other side of the scalp and/or face for 12 weeks. The total number of actinic keratoses (AKs), diameters and total scores of the target lesions were determined at each visit.\n Nine patients were included, eight of whom completed the treatment. There was a statistically significant difference between the total number of AKs at baseline and at week 12 on calcipotriol applied side whereas no difference was detected on placebo applied side (p = 0.028 vs p = 1.00). The mean total score of the target lesions reduced significantly at week 12 on calcipotriol side; however, no significant reduction was found on placebo side (p = 0.017 vs p = 0.056). Although side effects were more common on calcipotriol side, the difference was not statistically significant.\n Topical calcipotriol may show promise in the treatment of actinic keratoses. More studies are needed to confirm its efficacy.", "Actinic keratoses (AK) are squamous cell carcinomas in situ and require treatment. Betulin-based oleogel prepared from a standardized triterpene dry extract from birch bark represents a new topical agent with anti-inflammatory and anti-tumor potential.\n In the prospective, randomized, monocentric phase 2a study 45 patients with < 10 AK were included and randomly assigned to one of the three treatment groups. Intervention consisted of topical betulin-based oleogel twice daily versus cryotherapy with liquid nitrogen versus the combination of cryotherapy with topical betulin-based oleogel. Treatment response was assessed clinically after three months. The clinical response was graded into complete clearing (100 %), therapy responders (> 75 % clearing of the lesions) and non-responders (< 75 % clearing). Additionally, punch biopsies were obtained from some patients before and at the end of treatment.\n Therapy with betulin-based oleogel was well tolerated.Three patients discontinued therapy because of personal reasons. After three months, the 100% (and > 75%) clearing rates of the lesions were as follows: 64% (86%) with betulin-based oleogel (n = 14),79% (93%) with cryotherapy (n = 14),and 71% (71%) with the combined therapy (n = 14). Histological analysis of biopsies taken before and after treatment (n = 8) showed a reduced degree of dysplasia in the epidermis in all study arms.\n Betulin-based oleogel seems to be an effective novel approach in the topical treatment of actinic keratoses. However,the clinical and histological findings of the present pilot study have to be verified against placebo with larger case numbers.", "Actinic keratosis (AK) is the earliest clinical manifestation of squamous cell carcinoma. Metastatic SCC causes the majority of the 1300 to 2300 deaths attributed to nonmelanoma skin cancer in the United States each year. Recent studies have shown that intralesional administration of interferon can be used successfully in the treatment of AK.\n Imiquimod is an immune response modifier, currently approved for the treatment of genital warts. The topically applied immune response modifier acts by up-regulating interferon and other cytokines involved in the cell-mediated immune response at the site of application. The aim of this was to determine the efficacy and safety of imiquimod 5% cream for the treatment of AK.\n Twenty-two patients with AK lesions were treated with imiquimod 5% cream, initially at 3 times per week for 8 weeks, or until total clearance of lesions. Patients applied imiquimod to lesions on one side of the body and vehicle cream to the other side. A total of 17 patients who completed treatment were evaluated for number of lesions and adverse reactions before treatment and at weeks 2, 4, 6, and 8 after initiation of treatment. AK lesions were also assessed 4 and 8 weeks after treatment.\n A significant reduction in the average number of lesions per patient was observed for patients treated with imiquimod. The most frequent reactions to treatment were erythema, itching, and scabbing; however, all adverse events were mild to moderate.\n Imiquimod 5% cream may be a promising treatment for AK.", "Actinic keratosis (AK), the most common premalignant skin condition, can represent a management challenge. Treatment should not only be effective, but also well tolerated and allow for good cosmesis on typical sun-exposed highly visible body sites.\n The primary objective was to compare the lesion response and subject preference for topical methyl aminolaevulinate (MAL)-photodynamic therapy (PDT) vs. cryotherapy for the treatment of AK.\n In this 24-week, multicentre, randomized, intraindividual (right-left) study, subjects received both one treatment session of MAL-PDT and a double freeze-thaw cryotherapy; the treatments were randomly allocated to either side of the face/scalp. Lesions with a noncomplete response were retreated after 12 weeks. The primary assessments were the subject's overall preference and lesion response at week 24. Secondary assessments included lesion response at week 12, cosmetic outcome, subject and investigator cosmetic outcome preference at week 24, and investigator overall preference at week 24. Skin discomfort and adverse events were also evaluated.\n In total, 119 subjects with 1,501 lesions were included in the study. At week 12, treatment with MAL-PDT resulted in a significantly larger rate of cured lesions relative to cryotherapy (percentage lesion reduction from baseline: 86.9% vs. 76.2%; P < 0.001). At week 24, both treatment groups showed a high rate of cured lesions (89.1% for MAL-PDT vs. 86.1% for cryotherapy; P = 0.20; 95% confidence interval: -1.62 to 7.67). Results for subject and investigator preferences as well as cosmetic outcome favoured MAL-PDT. Both treatment regimens were safe and well tolerated.\n The present study shows that, when treated with both MAL-PDT and cryotherapy, subjects significantly prefer MAL-PDT treatment for AK. MAL-PDT is an attractive treatment option for AK, with comparable efficacy and superior cosmetic outcomes compared with double freeze-thaw cryotherapy.", "Aminolevulinic acid hydrochloride (ALA, Levulan) applied topically to actinic keratoses (AKs) leads to accumulation of the photosensitizer protoporphyrin IX, which, when activated by exposure to light, eradicates AKs.\n We examined the safety and efficacy of photodynamic therapy using topical 20% ALA in a solution formulation and varying blue light doses to treat multiple AKs on the face and scalp.\n This is a multicenter, investigator-blinded, randomized, vehicle-controlled study.\n Thirty-six patients with clinically typical AKs were treated with 20% ALA; 14 to 18 hours later, they were irradiated with a nonlaser fluorescent blue light source. With the optimal light dose of 10 J/cm(2), 88% of the AKs completely cleared 8 weeks after a single photodynamic treatment, compared with 6% after treatment with vehicle and light.\n Topical ALA PDT using a nonlaser, blue light source is an effective treatment for multiple AKs.", "In a randomized double-blind controlled study, 19 patients applied 5% 5-fluorouracil (5-FU) cream to actinic keratoses (AK) on each arm twice daily, followed by nightly application of 0.05% tretinoin cream to one arm, and a control cream to the other arm until discomfort precluded further applications. After 3 months, the number of residual AK was compared to pre-treatment values. The tretinoin-treated arms had 15.7 +/- 6.1 AK before treatment and 3.4 +/- 2.6 AK following therapy. The control arms had 15.3 +/- 6.9 AK before therapy and 4.2 +/- 2.5 lesions afterwards. Using a one-tailed paired t-test, the difference in response was statistically significant (0.03 less than P less than 0.04). It was concluded that daily application of 0.05% tretinoin cream appeared to enhance the efficacy of topical 5-FU in destruction of AK of the arms and may represent a useful treatment modality.", "Field-directed therapies for actinic keratosis include photodynamic therapy and imiquimod.\n The author designed a randomized, vehicle-controlled, split-face study to explore the safety and efficacy of photodynamic therapy followed by imiquimod.\n The entire face of adults with > or =10 facial actinic keratoses were treated with photodynamic therapy with aminolevulinic acid 20% at baseline and at month 1. At month 2, imiquimod 5% cream was applied to one-half of the face and vehicle to the other half, 2-times-per-week for 16 weeks. Lesion counts were performed at baseline and months 1, 2, 3, 4, 6, and 12; and local skin reactions assessments at months 2, 3, 4, and 6.\n Of 25 participants enrolled, 24 completed the study. Baseline median lesions were 23.5 and 21.5 for the imiquimod- and vehicle-treated sides, respectively. At month 12, median lesion reductions was 89.9% versus 74.5% (P=.0023), respectively. No subject discontinued for an adverse event. Severe local skin reactions occurring in the most participants were erythema (17%) and flaking/scaling/dryness (13%).\n Photodynamic therapy followed by imiquimod was well tolerated and improved reduction of actinic keratoses.", "5-aminolaevlinic acid methylester (MAL) and 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) are both effective treatment options for actinic keratosis (AK). While MAL is significantly more expensive than ALA, no studies have directly compared their efficacy in the treatment of extensive scalp AK.\n To compare the efficacy and adverse effects of MAL-PDT with ALA-PDT in the treatment of scalp AK.\n Sixteen male patients aged 59-87 years with extensive scalp AK were randomized into a double-blind, split-scalp prospective study. Two treatment fields were defined (right and left frontoparietal scalp) and treated 2 weeks apart. These fields were randomized to receive either MAL or ALA as first or second treatment. MAL cream was applied for 3 h; 20% ALA cream was applied for 5 h. A blinded observer assessed efficacy comparing AK counts before and 1 month after treatment. Pain was assessed using a visual analogue scale at 3, 6, 12 and 16 min.\n Fifteen patients completed treatment to both fields. There was a mean reduction from baseline in AK counts with the use of ALA-PDT of 6.2 +/- 1.9 compared with 5.6 +/- 3.2 with MAL-PDT (P = 0.588). All patients experienced pain which was of greater intensity in the ALA-treated side at all time points: 3 min (P = 0.151), 6 min (P = 0.085), 12 min (P = 0.012) and 16 min (P = 0.029). Similarly, duration of discomfort post-procedure persisted for longer following treatment with ALA when compared with MAL-PDT (P = 0.044).\n This study demonstrates that both ALA-PDT and MAL-PDT result in a significant reduction in scalp AK. There is no significant difference in efficacy. However, ALA-PDT is more painful than MAL-PDT in the treatment of extensive scalp AK.", "50 patients with actinic keratosis were studied over four months of treatment with either etretinate ('Tigason') or placebo. Each treatment was given for two months and the order of administration was randomised. The clinical response to treatment was assessed by direct measurement and photographs of the lesions at monthly intervals. Of the 44 patients who completed treatment with etretinate 37 had a complete or partial response. Of the 42 patients who completed treatment on placebo only 2 showed a complete or partial response. The response to treatment occurred within the first month of therapy and was maintained even when the dose was reduced because of toxicity.", "The incidence of and mortality from skin cancer are increasing in many countries. In view of the added concern about ozone depletion, many organizations are promoting the regular use of sunscreens to prevent skin cancer, despite the absence of evidence that these products have this effect. Solar (actinic) keratosis is a precursor of squamous-cell carcinoma of the skin.\n We conducted a randomized, controlled trial of the effect on solar keratoses of daily use of a broad-spectrum sunscreen cream with a sun-protection factor of 17 in 588 people 40 years of age or older in Australia during one summer (September 1991 to March 1992). The subjects applied either a sunscreen cream or the base cream minus the active ingredients of the sunscreen to the head, neck, forearms, and hands.\n The mean number of solar keratoses increased by 1.0 per subject in the base-cream group and decreased by 0.6 in the sunscreen group (difference, 1.53; 95 percent confidence interval, 0.81 to 2.25). The sunscreen group had fewer new lesions (rate ratio, 0.62; 95 percent confidence interval, 0.54 to 0.71) and more remissions (odds ratio, 1.53; 95 percent confidence interval, 1.29 to 1.80) than the base-cream group. There was a dose-response relation: the amount of sunscreen cream used was related to both the development of new lesions and the remission of existing ones.\n Regular use of sunscreens prevents the development of solar keratoses and, by implication, possibly reduces the risk of skin cancer in the long-term.", "Imiquimod 5% cream applied twice weekly for 16 weeks is effective for treating actinic keratoses but may be limited by local side effects.\n We sought to explore the efficacy and safety of a once weekly for 24 weeks dosing regimen using a left versus right side of head design.\n Twenty patients were enrolled; 15 completed and 5 discontinued for reasons unrelated to adverse events. At the posttreatment visit (week 28), 7 (46.7%) of 15 patients had marked improvement or better on the imiquimod side versus one (6.7%) of 15 on the placebo side. The average investigator assessment scale score change was +2.20 for imiquimod compared with -0.27 for placebo (P = .0002, Wilcoxon signed rank test). Skin reactions were minimal or nonexistent in most patients.\n Limitations of the study include a small sample size and a lack of objective measure of local side effects.\n Imiquimod 5% cream applied once weekly for 24 weeks was convenient for patients and resulted in improvement of actinic keratoses with minimal side effects.", "A shorter dosing regimen of imiquimod for the treatment of actinic keratosis may be effective, with long-term clinical benefits.\n Imiquimod in one or two shorter courses of treatment was evaluated.\n Patients with actinic keratosis lesions on the head applied imiquimod or vehicle cream 3x/wk for 4 weeks (course 1). Patients with remaining lesions received another course of treatment. Complete and partial clearance rates were evaluated after course 1, after course 2 (overall), and 1 year later.\n Complete clearance rates were 26.8% (course 1) and 53.7% (overall). Partial clearance rates were 36.6% (course 1) and 61.0% (overall). One-year follow-up recurrence rates were 39% (imiquimod) and 57% (vehicle).\n Blinded investigators may have been biased toward patients treated with imiquimod identified by treatment site reactions.\n Imiquimod 3x/wk in one or two courses of treatment appears to be effective for the treatment of actinic keratoses on the head, providing long-term clinical benefits. Some recurrences do occur, so long-term follow-up is recommended.", "To evaluate the efficacy and safety of 5% imiquimod cream compared with vehicle in the treatment of actinic keratosis (AK).\n Two phase 3 randomized, double-blind, parallel-group, vehicle-controlled studies.\n Twenty-six ambulatory care offices, including dermatologists in private practice or research centers.\n Four hundred ninety-two patients, 18 years and older, with 4 to 8 AK lesions in a 25-cm(2) treatment area on the face or the balding scalp were randomized; an additional 162 patients underwent screening but were ineligible.\n Patients applied 5% imiquimod (Aldara) or vehicle cream to the treatment area once daily, 3 times per week, for 16 weeks, followed by an 8-week posttreatment period.\n Complete clearance rate (proportion of patients at the 8-week posttreatment visit with no clinically visible AK lesions in the treatment area), partial clearance rate (proportion of patients at the 8-week posttreatment visit with a >/=75% reduction in the number of baseline AK lesions in the treatment area), and frequency and severity of adverse events and local skin reactions were measured.\n Complete and partial clearance rates for imiquimod-treated patients (48.3% and 64.0%, respectively) were clinically and statistically significantly higher than for vehicle-treated patients (7.2% and 13.6%, respectively). The median percentage reduction of baseline lesions was 86.6% for the imiquimod-treated group and 14.3% for the vehicle-treated group.\n The 5% imiquimod cream dosed 3 times weekly for 16 weeks is safe and effective for the treatment of AK.", "In this study the safety and efficacy of imiquimod 5% cream for the treatments of actinic keratoses in kidney, heart and liver transplant recipients is evaluated.\n Growing populations of organ transplant recipients face increased risk of developing actinic keratosis (AK) and skin cancer secondary to continuous systemic immunosuppressive therapy. Imiquimod 5% cream is an effective option for the treatment of AK, but the safety of topical immune stimulation in immunocompromised patients has not been widely evaluated.\n A total of 43 patients in six European transplant centres applied two sachets of topical imiquimod or vehicle cream three times per week to a 100 cm(2) field. Dosing continued for 16 weeks regardless of lesion clearance. Patients were assessed for safety variables that included adverse events, local skin reactions, laboratory results, vital signs, dosage of immunosuppressive medication and indication of graft rejection. A blinded independent expert committee was responsible for safety monitoring and final safety assessment.\n No graft rejections or trends for a deterioration of graft function were detected. No meaningful trends were observed in laboratory results. Among patients randomized to imiquimod, the complete clearance rate was 62.1% (18/29); for vehicle patients, the complete clearance rate was 0% (0/14). Clinical clearance was confirmed histologically in all cases.\n Imiquimod appears to be a safe alternative for the treatment of multiple actinic keratoses in patients with solid organ transplants. Efficacy was within the range previously observed in nontransplanted populations.", "Alpha-2-(Difluoromethyl)-dl-ornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, has been shown to suppress skin carcinogenesis in murine models after oral or topical administration. We designed a randomized, placebo-controlled study using a topical hydrophilic ointment formulation with or without 10% (w/w) DFMO. Forty-eight participants with moderate-severe actinic keratoses (AKs) on their forearms (i.e., at least 10 well-circumscribed lesions on the lateral surface) completed a 1-month run-in on placebo ointment. Before randomization, all lateral forearm AKs were circled, counted, photographed, and skin biopsies were obtained for DFMO and polyamine levels. Then participants were randomized to receive DFMO ointment on the right versus the left forearm and placebo hydrophilic ointment on the contralateral forearm twice daily for 6 months. DFMO was not detected in the blood of any subject, and there were no systemic toxicities. None of a subsample of 17 placebo forearms had measurable concentrations of DFMO, whereas 13 of the corresponding DFMO-treated forearms had high DFMO skin levels. As compared with placebo, the 6-month DFMO treatment caused a 23.5% reduction in the number of AKs (P = 0.001) as well as significant suppression of AK biopsy spermidine levels (26%; P = 0.04). Seven of the 48 (14.6%) participants experienced severe (2; 4.2%) or moderate (5; 10.4%) inflammatory reactions on their DFMO-treated arms which required dosing modification. Topical DFMO for 6 months can reduce the number of AK lesions and skin spermidine concentrations in high-risk participants and deserves additional study as a skin cancer chemopreventive agent.", "Organ transplant recipients (OTR) are at high risk of developing nonmelanoma skin cancer and premalignant epidermal dysplasia (carcinoma in situ/ Bowen's disease and actinic keratoses). Epidermal dysplasia is often widespread and there are few comparative studies of available treatments.\n To compare topical methylaminolaevulinate (MAL) photodynamic therapy (PDT) with topical 5% fluorouracil (5-FU) cream in the treatment of post-transplant epidermal dysplasia.\n Eight OTRs with epidermal dysplasia were recruited to an open-label, single-centre, randomized, intrapatient comparative study. Treatment with two cycles of topical MAL PDT 1 week apart was randomly assigned to one area of epidermal dysplasia, and 5-FU cream was applied twice daily for 3 weeks to a clinically and histologically comparable area. Patients were reviewed at 1, 3 and 6 months after treatment. The main outcome measures were complete resolution rate (CRR), overall reduction in lesional area, treatment-associated pain and erythema, cosmetic outcome and global patient preference.\n At all time points evaluated after completion of treatment, PDT was more effective than 5-FU in achieving complete resolution: eight of nine lesional areas cleared with PDT (CRR 89%, 95% CI: 0.52-0.99), compared with one of nine lesional areas treated with 5-FU (CRR 11%, 95% CI: 0.003-0.48) (P = 0.02). The mean lesional area reduction was also proportionately greater with PDT than with 5-FU (100% vs. 79% respectively). Cosmetic outcome and patient preference were also superior in the PDT-treated group.\n Compared with topical 5-FU, MAL PDT was a more effective and cosmetically acceptable treatment for epidermal dysplasia in OTRs and was preferred by patients. Further studies are now required to confirm these results and to examine the effect of treating epidermal dysplasia with PDT on subsequent development of squamous cell carcinoma in this high risk population.", "Adapalene is a synthetic retinoid with an established clinical efficacy against acne and good local tolerability. Its effectiveness in the treatment of photodamaged skin has not been studied.\n We sought to determine the safety and efficacy of adapalene gel in the treatment of actinic keratoses and solar lentigines.\n In a prospective, 2-center, randomized, controlled, investigator-masked, parallel-group study, 90 patients with actinic keratoses and solar lentigines were treated daily with either adapalene gel (0.1% or 0.3%) or its vehicle gel for 4 weeks, followed by twice-daily applications, if tolerated, for up to 9 months.\n Of the 90 Caucasian patients (69 male, 21 female; mean age 63.1 years) who were enrolled into the study, 83 patients completed 9 months of treatment. With adapalene gel 0.1% and 0.3%, the mean number of actinic keratoses was reduced by 0.5 +/- 0.9 (mean +/- SE) and 2.5 +/- 0.9, respectively. Whereas, with the vehicle gel, there was an increase of 1.5 +/- 1.3 (P <.05). After 1 month of treatment, the patients who received adapalene had significant lightening of solar lentigines as compared with the patients who were treated with vehicle gel (P <.05). After 9 months, 57% and 59% of the patients had lighter lesions in the adapalene 0.1% and 0.3% groups, respectively, in comparison with only 36% in the vehicle group (P <.05). Histologic evaluations revealed improved cellular atypia and reduced epidermal melanin in adapalene-, as compared with vehicle-treated group. The differences, however, were not statistically significant. A retrospective evaluation of paired clinical photographs (before and after 9-month treatment) by 2 dermatologists who were treatment-blinded revealed significant improvement in wrinkles and other clinical features of photoaged skin with adapalene as compared with its vehicle.\n Adapalene gel 0.1% and 0.3% were well tolerated and improved actinic keratoses, solar lentigines, and other features of photodamaged skin.", "The use of light-emitting diode light offers practical advantages in photodynamic therapy (PDT) with topical methyl-aminolevulinate (MAL) for management of actinic keratoses (AK).\n We sought to evaluate the efficacy of MAL PDT using red light-emitting diode light.\n We conducted a multicenter, double-blind, randomized study. A total of 49 patients with 363 AK lesions had 16.8% MAL cream applied under occlusion for 3 hours, and 47 patients with 360 AK lesions had vehicle cream similarly applied. The lesions were then illuminated (630 nm, light dose 37 J/cm2) with repeated treatment 1 week later. Complete lesion and patient (all lesions showing complete response) response rates were evaluated 3 months after last treatment.\n MAL PDT was superior (P<.0001) to vehicle PDT with respect to lesion complete response (86.2% vs 52.2%, odds ratio 6.9 [95% confidence interval 4.7-10.3]) and patient complete response (59.2% vs 14.9%, odds ratio 13.2 [95% confidence interval 4.1-43.1]).\n The study population may not be representative of all patients with AK.\n MAL PDT using red light-emitting diode light is an appropriate treatment alternative for multiple AK lesions.", "To determine the safety and efficacy of photodynamic therapy (PDT) using 20% wt/vol aminolevulinic acid hydrochloride (hereinafter \"ALA\") and visible blue light for the treatment of multiple actinic keratoses of the face and scalp.\n Randomized, placebo-controlled, uneven parallel-group study.\n Patients (N = 243) were randomized to receive vehicle or ALA followed within 14 to 18 hours by PDT. Follow-up visits occurred 24 hours and 1, 4, 8, and 12 weeks following PDT. Target lesions remaining at week 8 were re-treated.\n Clinical response based on lesion clearing by week 8.\n Most patients in both groups had 4 to 7 lesions. Complete response rates for patients with 75% or more of the treated lesions clearing at weeks 8 and 12 were 77% (128/166) and 89% (133/149), respectively, for the drug group and 18% (10/55) and 13% (7/52), respectively, for the vehicle group (P<.001, Cochran-Mantel-Haenszel general association test). The 95% confidence interval for the difference in response rates at week 8 was 46.9% to 71.0% and at week 12, 65.3% to 86.3%. The week 12 response rate includes 30% of patients who received a second treatment. Most patients experienced erythema and edema at the treated sites, which resolved or improved within 1 to 4 weeks after therapy, and stinging or burning during light treatment, which decreased or resolved by 24 hours after light treatment.\n Findings indicate that topical ALA PDT is an effective and safe treatment for multiple actinic keratoses of the face and scalp.", "Many treatment modalities exist for actinic keratoses (AK). Topical 5-fluorouracil (5-FU) has been one of the standard treatments. Laser resurfacing is a more recent treatment option. In the literature prospective randomized studies comparing these treatments are lacking.\n Prospective randomized study to compare topical 5-FU with Er:YAG laser resurfacing. Fifty-five patients with multiple AK on the scalp and or the face were included. Clinical and histopathological evaluation took place at 3, 6, and 12 months after treatment.\n At 3, 6, and 12 months after treatment, there were significantly less recurrences in the laser group compared to the group of patients treated with 5-FU. Side effects did occur more frequently in the laser group, especially erythema and hypopigmentation.\n Compared to treatment with topical 5-FU, Er:YAG laser resurfacing is more effective regarding recurrence rates. Although significantly more side effects occur, laser resurfacing is a useful therapeutic option especially in patients with widespread AK.\n (c) 2006 Wiley-Liss, Inc.", "Photodynamic therapy (PDT) is a promising new treatment modality for actinic keratoses. Methyl aminolevulinate (MAL) (Metvix, PhotoCure, Oslo, Norway) leads to selective accumulation of photoactive porphyrins in premalignant skin lesions and makes the lesions susceptible to phototoxic effects on illumination with red light.\n This multicenter, randomized, double-blind study compared complete response rates, cosmetic outcome, and patient satisfaction for PDT with cream containing 160 mg/g MAL or placebo cream in the treatment of actinic keratoses.\n After application of the cream under occlusion for 3 hours, the lesions were illuminated by noncoherent red light (570-670 nm, light dose 75 J/cm(2)). Treatment was repeated after 1 week and response was assessed 3 months later. A total of 80 patients were randomized into the study, 42 in the active and 38 in the placebo group.\n Complete lesion response rate was higher after MAL PDT than placebo, 89% versus 38% per protocol analysis (P =.001). An excellent or good cosmetic outcome was reported in more than 90% of patients treated with MAL.\n In this small study, PDT using topical MAL was a safe and effective treatment for actinic keratoses with excellent cosmetic outcome. It is a promising treatment that could benefit from further study.", "nan", "New therapeutic options would benefit patients with actinic keratosis (AK), a precancerous condition that is a significant health concern. The efficacy and safety of a microsphere-based formulation of 0.5% fluorouracil cream were evaluated in a randomized, double-blind, multicenter, parallel-group study. Patients (N= 177) were randomized to receive 0.5% fluorouracil or vehicle once daily for 1, 2, or 4 weeks. Efficacy was assessed by lesion counts and clearance. Safety was evaluated by monitoring adverse events, including facial irritation. Significant improvements were seen from baseline to posttreatment follow-up in all efficacy variables for all fluorouracil regimens compared with vehicle. Patients treated for one week experienced significant improvements compared with vehicle, although efficacy increased with increasing treatment duration. Most patients experienced mild to moderate facial irritation of predictable onset and duration. Once-daily administration of 0.5% fluorouracil cream for 1, 2, or 4 weeks is safe and effective for the treatment of AKs.", "In a double-blind, randomized, within-patient comparative study, the efficacy and tolerability of Ro 14-9706 (an arotinoid methyl sulfone) in the treatment of actinic keratoses was compared with that of tretinoin (all-trans-retinoic acid). A total of 25 patients with more than three lesions on each side of the face completed the study. All patients applied each agent twice daily for 16 weeks as a 0.05% cream to opposite sides of the face. The number of actinic keratoses in each treatment area was counted before treatment and at weekly intervals. The mean percent decrease in the number of actinic keratoses was 37.8% for areas treated with Ro 14-9706 and 30.3% for areas treated with tretinoin. Each of these decreases was significantly different from baseline (p less than 0.01), but not from each other. Ro 14-9706 was better tolerated; local inflammation was slight or absent in most patients, whereas tretinoin caused severe erythema in 50% and severe scaling in 23% of patients.", "Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is an effective treatment for multiple actinic keratoses (AKs). Pain, however, is a major side-effect.\n To compare pain intensity, efficacy, safety and cosmetic outcome of MAL PDT with two different light sources in an investigator-initiated, randomized, double-blind study.\n Eighty patients with multiple AKs grade I-II were assigned to two groups: group 1, MAL PDT with visible light and water-filtered infrared A (VIS+wIRA); group 2, MAL PDT with light from light-emitting diodes (LEDs), with a further division into two subgroups: A, no spray cooling; B, spray cooling on demand. MAL was applied 3 h before light treatment. Pain was assessed before, during and after PDT. Efficacy, side-effects, cosmetic outcome and patient satisfaction were documented after 2 weeks and 3, 6 and 12 months. Where necessary, treatment was repeated after 3 months.\n Seventy-six of the 80 patients receiving MAL PDT completed the study. Patient assessment showed high efficacy, very good cosmetic outcome and high patient satisfaction. The efficacy of treatment was better in the group of patients without spray cooling (P=0·00022 at 3 months, P=0·0068 at 6 months) and showed no significant differences between VIS+wIRA and LED. VIS+wIRA was significantly less painful than LED: the median of maximum pain was lower in the VIS+wIRA group than in the LED group for PDT without spray cooling. Pain duration and severity assessed retrospectively were less with VIS+wIRA than with LED, irrespective of cooling.\n All treatments showed high efficacy with good cosmetic outcome and high patient satisfaction. Efficacy of treatment was better without spray cooling. VIS+wIRA PDT was less painful than LED PDT for PDT without spray cooling.\n © 2010 The Authors. Journal Compilation © 2010 British Association of Dermatologists.", "Photodynamic therapy (PDT) is an effective but time-consuming and often painful treatment for actinic keratosis (AK). Home-based daylight-PDT has the potential to facilitate treatment procedure and to reduce associated pain due to continuous activation of small amounts of porphyrins. Moreover, a reduced methyl aminolaevulinate (MAL) concentration may reduce associated inflammation, making the treatment more tolerable for the patients.\n To compare response rates and adverse effects after PDT using conventional 16% and 8% MAL with home-based daylight exposure in treatment of AK.\n Thirty patients with mostly thin-grade AK of the face or scalp were treated with 16% and 8% MAL-PDT in two symmetrical areas after application of sunscreen. Immediately after, patients left the hospital with instructions to spend the remaining day outside at home in daylight. Patients scored pain during treatment and light exposure was monitored with an electronic wristwatch dosimeter.\n The complete response rate after 3 months was 76.9% for 16% MAL and 79.5% for 8% MAL (P = 0.37). Patients spent a mean of 244 min outdoors and received a mean effective light dose of 30 J cm(-2). Light doses of 8-70 J cm(-2) induced similar response rates (P = 0.25). Patients experienced mild to moderate pain during daylight exposure (mean maximal pain score of 3.7). No differences in pain scores and erythema were seen between the areas treated with 16% MAL and with 8% MAL.\n Home-based daylight-mediated MAL-PDT was an effective and well-tolerated treatment for AK. No differences in response rates or adverse events were found between the areas treated with 16% MAL and with 8% MAL.", "Cryotherapy is the standard of care for clinically apparent (target) actinic keratoses (AKs). Topical imiquimod may reduce initially inapparent or subclinical AKs.\n We evaluated the potential of topical imiquimod to decrease subclinical AKs after cryotherapy of target AKs.\n A randomized trial of imiquimod or vehicle twice weekly for 8 weeks following 3- to 5-second cryotherapy of target AKs within a 50 cm(2) field at the face or scalp was conducted. Efficacy outcomes included clearance of target, subclinical, and total AKs and proportions clear of AKs. Subjects with residual AKs were offered cryotherapy and open-label imiquimod twice weekly for 8 weeks.\n Sixty-three subjects completed the randomized phase. At 12 weeks, target AK clearance was similar for imiquimod and vehicle (79% vs 76%), but fewer total AKs were noted for imiquimod (78 vs 116). This was due to a progressive reduction in subclinical AKs with imiquimod compared with a progressive increase with vehicle. More subjects treated with imiquimod achieved clearance of subclinical (58% vs 34%; p = .06) and total (23% vs 9%; p = .21) AKs.\n Imiquimod postcryotherapy may increase clearance of subclinical and total AKs and proportions of subjects clear at 3 months. These findings require confirmation in larger controlled trials powered for statistical significance.", "Imiquimod 5% cream is a topically applied immune response modifier that has been shown to give effective treatment of actinic keratosis (AK). The therapeutic effects of imiquimod are likely to involve the provocation of a cutaneous immune response against abnormal cells, an assumption based on a strong correlation between complete clearance rates and the severity of the local skin reactions (erythema, oedema, erosion/ulceration, weeping/exudation and scabbing/crusting); however, no clinical studies have conclusively proved this mechanism.\n To determine the nature of cellular infiltrates induced by the application of imiquimod to AK lesions and to study cells involved in the cutaneous immune response.\n Eighteen patients participated in this phase I, randomized, double-blind, parallel group, vehicle-controlled study. Enrolled patients were randomized in a 2 : 1 ratio to receive imiquimod cream or vehicle cream and applied study cream to five lesions on the scalp, forearm or upper trunk once daily, three days per week for up to 16 weeks. Each patient had punch biopsies of two distinct AK lesions: a lesion was biopsied before treatment to obtain baseline biomarker levels, and a different lesion was biopsied after 2 weeks of treatment. Biopsy specimens were examined using routine and immunohistochemical staining.\n The imiquimod group showed statistically significant increases from baseline to week 2 in tissue biomarker levels for CD3, CD4, CD8, CD11c, CD86/CD11c, CD68, HLA-DR and TUNEL. No significant differences were seen for the vehicle group. Complete clearance of all treated AK lesions was achieved in five of 11 (45%) imiquimod patients and in none of six vehicle patients.\n Imiquimod stimulates a cutaneous immune response characterized by increases in activated dendritic cells and CD4+ and CD8+ T cells.", "The immune system plays a critical role in the development and pathogenesis of actinic keratosis (AK). Imiquimod has been shown to stimulate the cutaneous immune response and be effective for the treatment of nonmelanoma skin cancers.\n Two phase III, randomized, double-blind, vehicle-controlled studies evaluated the efficacy of imiquimod 5% cream compared with vehicle in the treatment of AK lesions on the face and balding scalp.\n A total of 436 participants at 24 centers in the United States and Canada were randomized to either imiquimod 5% or vehicle cream. Study cream was applied one time per day, 2 days per week for 16 weeks. Clearance of AK lesions was clinically assessed at an 8-week posttreatment visit.\n The complete clearance rate was 45.1% for the imiquimod group and 3.2% for the vehicle group. The difference in complete clearance rates (imiquimod minus vehicle) was 41.9% with a 95% confidence interval of 34.9% to 49%. The partial (> or =75%) clearance rate was 59.1% for the imiquimod group and 11.8% for the vehicle group. The difference in partial clearance rates (imiquimod minus vehicle) was 47.3% with a 95% confidence interval of 39.5% to 55.1%. The median percent reduction in AK lesions was 83.3% for the imiquimod group and 0% for the vehicle group. Local skin reactions were common. Severe erythema was reported by 17.7% of participants who received imiquimod and 2.3% of participants who received vehicle. Overall, imiquimod was very well tolerated.\n Imiquimod 5% cream used 2 times per week for 16 weeks is an effective and well-tolerated treatment for AK.", "The approved imiquimod 5% cream regimen for treating actinic keratoses requires a long treatment time and is limited to a small area of skin.\n We sought to evaluate imiquimod 2.5% and 3.75% for short-course treatment of the full face or balding scalp.\n In two identical studies, adults with 5 to 20 lesions were randomized to placebo, imiquimod 2.5%, or imiquimod 3.75% (1:1:1). Up to two packets (250 mg each) were applied per dose once daily for two 2-week treatment cycles, with a 2-week, no-treatment interval between cycles. Efficacy was assessed at 8 weeks posttreatment.\n A total of 479 patients were randomized to placebo, or imiquimod 2.5% or 3.75%. Complete and partial clearance (> or =75% lesion reduction) rates were 6.3% and 22.6% for placebo, 30.6% and 48.1% for imiquimod 2.5%, and 35.6% and 59.4% for imiquimod 3.75%, respectively (P < .001 vs placebo, each; P = .047, 3.75% vs 2.5% for partial clearance). Median reductions from baseline in lesion counts were 25.0% for placebo, 71.8% for imiquimod 2.5%, and 81.8% for imiquimod 3.75% (P < .001, each active vs placebo; P = .048 3.75% vs 2.5%). There were few treatment-related discontinuations. Patient rest period rates were 0% for placebo, 6.9% for imiquimod 2.5%, and 10.6% for imiquimod 3.75%.\n Local pharmacologic effects of imiquimod, including erythema, may have limited concealment of treatment assignment in some patients.\n Both imiquimod 2.5% and 3.75% creams were more effective than placebo and were well tolerated when administered daily as a 2-week on/off/on regimen to treat actinic keratoses.\n Copyright 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.", "beta-1,3-D-glucans are yeast-derived carbohydrate polymers which have been shown to be potent immunoresponse modulators which promote the regression of certain tumours. To date there is no published data concerning the efficacy of topical beta-1,3-D-glucan in the treatment of solar keratoses. This randomized double-blind prospective pilot study of 20 patients was performed to investigate the efficacy and skin tolerance of beta-1,3-D-glucan gel versus placebo in the treatment of solar keratoses. The results of this study showed no significant benefit in using beta-1,3-D-glucan gel over placebo in reducing counts of solar keratoses. No adverse effects were reported by any patient at any stage of the trial.", "This randomized, double-blind, placebo-controlled study assessed the efficacy and safety of a topical gel containing 3% diclofenac in 2.5% hyaluronan in 150 patients with solar keratoses (SK). The active treatment was compared with the vehicle only, hyaluronan gel, as placebo over a 12-week period. Patients in both groups applied the active treatment or placebo to a targeted area of skin (0.25 g b.d.). At 12 weeks the mean lesion-count reduction in the targeted area was not significantly different between treatments. However, at post-termination follow up (16 weeks), there was a highly significant decrease in the number of lesions, 6.2 +/- 7.5 standard deviations (SD) (56.1% reduction) in the active treatment group compared with 2.4 +/- 4.3 SD (23.6% reduction) in the placebo group (P < 0.001). Other efficacy measures (complete lesion resolution, >50% lesion reduction) were also significantly different (P < 0.01) between treatments at 16 weeks. In conclusion, topical 3% diclofenac in 2.5% hyaluronan gel was effective and well tolerated in this study, suggesting a role for this therapy in the treatment of SK.", "Actinic keratoses (AKs) are the most common premalignant tumors. Without treatment, a significant number of patients with AK will experience squamous cell carcinoma. Photodynamic therapy (PDT) using the new highly selective photosensitizer methyl 5-aminolevulinate is a promising new treatment modality for AK.\n We investigated the complete response rates, cosmetic outcome, and patient satisfaction after photodynamic therapy (PDT) using methyl 5-aminolevulinate (Metvix) versus cryotherapy in the treatment of AKs.\n Patients were randomized to receive either cryotherapy with liquid nitrogen spray or PDT using methyl 5-aminolevulinate cream 160 mg/g, 3 hours application time, and red light (75 J/cm(2)).\n Efficacy results from 193 patients with 699 lesions (92% face/scalp and 93% thin/moderately thick) were analyzed. Overall complete response rates after 3 months were 69% for PDT and 75% for cryotherapy. Both treatments gave higher response rates in thin lesions (PDT 75%, cryotherapy 80%). PDT gave better cosmetic results and higher patient satisfaction than cryotherapy.\n PDT using methyl 5-aminolevulinate is an attractive treatment option for patients with AK, with a response rate similar to that of cryotherapy, but with superior cosmetic results and high patient satisfaction.", "Topical colchicine has been reported to be an effective treatment for actinic keratoses, but the optimal concentration has not been fully defined.\n The aim of this study was to further support the beneficial effect of topical colchicine therapy for actinic keratoses, and to compare the efficacy and safety of two different concentrations of colchicine cream, 0.5% and 1%.\n Sixteen patients with actinic keratoses were enrolled in this comparative randomized study. Eight patients applied 1% colchicine cream, twice daily on their lesions while the other eight were treated with a 0.5% colchicine cream for 10 days. Some patients were applied a second course of 10 days' therapy. Patients were examined before treatment and at 10 days, and followed up at 1, 2 and 6 months of treatment. Visible and palpable actinic keratoses lesions in each group were counted. Safety and efficacy were also assessed by clinical examination at each study visit. Routine laboratory tests were performed before and after treatment.\n Actinic keratoses lesions showed significant clinical improvement following treatment with 0.5% and 1% colchicine cream. Complete healing of actinic keratoses were observed in six of the eight patients in the 1% colchicine group, and in seven of the eight patients in the 0.5% colchicine group. The reduction rate in number of actinic keratoses at the end of treatment in the 1% colchicine group was 73.9% (48/65) (p < 0.001), and the reduction rate in the 0.5% colchicine group was 77.7% (52/67) in total (p < 0.001). The reduction in number of actinic keratoses (mean +/- SD) at the end of treatment was similar in the 1% colchicine group (0.7 +/- 1.3), and the 0.5% colchicine group (mean 0.6 +/- 1.7) (p > 0.05). Systemic side effects were not seen in either concentration.\n Topical colchicine is an effective and safe alternative agent. Cream containing 0.5% of colchicine is equally effective as 1% colchicine cream in the treatment of actinic keratoses.", "Clinical studies in cutaneous conditions other than actinic keratosis (AK) have revealed that the safety and efficacy profile of imiquimod is influenced by dosing frequency.\n To evaluate dosing frequency response of imiquimod 5% for treatment of AK.\n This was a phase II, multicentre, randomized, double-blind, placebo-controlled study. Adults with > or = 10 but < or = 50 clinical AKs, one of which was histologically confirmed, were randomized (4:1) to 2-6 packets of imiquimod or placebo cream applied to the dorsum of the forearms and hands once daily 2, 3, 5 or 7 times per week for 8 weeks. The primary endpoint was complete clearance of AKs in the treatment area at 8 weeks post-treatment.\n One hundred and forty-nine (94 men and 54 women) white subjects, with a mean +/- SD age of 71 +/- 10.2 years, were enrolled. Twenty-eight subjects (18.8%) discontinued from study: 0%, 3.1%, 6.9%, 30.0% and 33.3% withdrew for local skin reactions or adverse events in the combined placebo, and in the imiquimod 2, 3, 5 or 7 times per week groups, respectively. Seven serious adverse events occurred; none was related to the study drug. Median baseline lesions ranged from 38 to 40 for the treatment groups. Complete clearance was achieved in 0%, 3.2%, 6.9%, 3.3% and 6.7% of subjects, and partial clearance (> or = 75% lesion reduction) in 0%, 22.6%, 24.1%, 20.0% and 36.7% of subjects for the placebo and imiquimod 2, 3, 5 or 7 times per week regimens, respectively.\n Imiquimod 5% applied more frequently than 3 times per week to AKs was not well tolerated. Complete clearance rates were low; however, partial clearance rates increased with increased dosing frequency (P = 0.002).", "Photodynamic therapy (PDT) with topical methyl aminolevulinate (MAL) administered in two treatment sessions separated by 1 week is an effective treatment for actinic keratoses. This open prospective study compared the efficacy and safety of MAL-PDT given as a single treatment with two treatments of MAL-PDT 1 week apart. Two hundred and eleven patients with 413 thin to moderately thick actinic keratoses were randomized to either a single treatment with PDT using topical MAL (regimen I; n=105) or two treatments 1 week apart (regimen II; n=106). Each treatment involved surface debridement, application of Metvix cream (160 mg/g) for 3 h, followed by illumination with red light using a light-emitting diode system (peak wavelength 634+/-3 nm, light dose 37 J/cm2). Thirty-seven lesions (19%) with a non-complete response 3 months after a single treatment were re-treated. All patients were followed up 3 months after the last treatment. A total of 400 lesions, 198 initially treated once and 202 treated twice, were evaluable. Complete response rate for thin lesions after a single treatment was 93% (95% CI=87-97%), which was similar to 89% (82-96%) after repeated treatment. Response rates were lower after single treatment of thicker lesions (70% (60-78%) vs 84% (77-91%)), but improved after repeated treatment (88% (82-94%)). The conclusion of this study is that single treatment with topical MAL-PDT is effective for thin actinic keratosis lesions; however, repeated treatment is recommended for thicker or non-responding lesions.", "Photodynamic therapy (PDT) is an effective treatment for actinic keratoses (AKs). Light-emitting diodes (LEDs) offer practical advantages when treating multiple lesions.\n To evaluate the efficacy and tolerability of PDT using a LED and topical methyl aminolevulinate (MAL) for treatment of multiple AKs.\n One hundred thirty-one patients with four to 10 non-pigmented, previously untreated thin or moderately thick AKs on the face or scalp were enrolled in this multicenter, double-blind, randomized, placebo-controlled study. MAL or matching placebo cream was applied to the débrided lesion surface for 3 hours before illumination with noncoherent red light (630 nm, light dose 37 J/cm(2)). Treatment was repeated 1 week later.\n Efficacy was evaluated in 57 patients with 418 lesions treated with MAL PDT and 58 with 414 lesions treated with placebo PDT. Sixteen patients were excluded as protocol violators (not randomized). MAL PDT was superior (p< .001) to placebo PDT in lesion complete response rates (83.3%, 95% confidence interval (CI)=79.3-86.7%, vs 28.7%, 95% CI=24.4-33.4%) and patient complete response rates (all lesions showing complete response; 68.4%, 95% CI=54.8-80.1% vs 6.9%, 95% CI=1.9-16.7%).\n Topical MAL PDT using a LED is an effective treatment for multiple AKs.", "Resiquimod, a toll-like receptor 7 and 8 agonist, may be effective as a topical treatment of actinic keratosis (AK).\n To evaluate the effect of resiquimod gel concentration on lesion clearance.\n Patients with AK lesions on the face or balding scalp were randomly assigned to resiquimod 0.01%, 0.03%, 0.06% or 0.1% gel applied once daily three times a week for 4 weeks to a contiguous 25-cm(2) area with four to eight lesions. Patients with persistent lesions received a second course after an 8-week treatment-free interval. Complete and partial lesion clearance was assessed 8 weeks after treatment for each course.\n For the 132 patients randomized, overall complete clearance rates were 77.1% (27/35), 90.3% (28/31), 78.1% (25/32) and 85.3% (29/34) and complete clearance rates after course 1 only were 40.0%, 74.2%, 56.3% and 70.6%, respectively, for the resiquimod 0.01%, 0.03%, 0.06% and 0.1% groups. During course 1, respectively 0%, 13%, 31% and 38% of patients discontinued treatment for adverse events or local skin reactions, for the resiquimod 0.01%, 0.03%, 0.06% and 0.1% groups. Possibly or probably related nonapplication site adverse events of severe intensity, including influenza-like symptoms, were reported by 0%, 3%, 13% and 12% of patients, respectively, for the resiquimod 0.01%, 0.03%, 0.06% and 0.1% groups.\n Efficacy in clearing AK lesions was similar between the resiquimod concentrations evaluated, but resiquimod 0.01% and 0.03% were better tolerated than the higher concentrations.", "Increasing evidence suggests imiquimod may be a safe therapeutic option for the treatment of actinic keratosis (AK). The diagnosis and assessment of most AK lesions is made clinically, without histologic confirmation.\n A phase III, randomized, double-blind, parallel group, vehicle-controlled study evaluated the efficacy of imiquimod 5% cream compared with vehicle in the treatment of AK lesions on the face and balding scalp including pretreatment and posttreatment biopsy specimens.\n A total of 286 patients at 18 centers in 6 European countries with histologically confirmed AK were randomized to either imiquimod 5% cream or vehicle cream. Study cream was applied once per day, 3 days per week, for 16 weeks. Clearance of AK lesions was clinically and histologically assessed at an 8-week posttreatment visit.\n The complete clearance rate for the imiquimod group was 57.1% versus 2.2% for the vehicle group (P <.001). The partial clearance rate (> or =75% reduction in baseline lesions) for the imiquimod group was 72.1% versus 4.3% for the vehicle group (P <.001). The most common side effects were erythema, scabbing/crusting, and erosions/ulceration. For the imiquimod group the incidence of severe erythema, scabbing/crusting, or erosions/ulceration was 30.6%, 29.9%, and 10.2%, respectively.\n Imiquimod 5% cream used 3 times per week for 16 weeks is an effective treatment for AK. Clinical clearance was established by both clinical observation and histologic analysis.", "The efficacy of photodynamic therapy (PDT) using broad area treatment with 5-aminolevulinic acid (ALA) has not been compared to topical 5-fluorouracil (5-FU) in the treatment of actinic keratoses (AK). The purpose of this study was to compare the efficacy and tolerability of PDT using short incubation time, broad area treatment with ALA plus activation with either blue light or laser light to topical 5-FU in the treatment of AK of the face and scalp. Thirty-six subjects with AK of either the face or scalp were randomized to receive either application of ALA for 1 hour followed by activation with blue light or pulsed dye laser or topical 5-FU. Efficacy was evaluated by grading AK lesions and photoaging signs. Tolerability was assessed by scoring crusting/erosions, erythema and stinging/burning. Treatment with PDT using ALA plus blue light was as effective as topical 5-FU in clearing AK. PDT using ALA plus laser light was the least effective treatment. All treatments made improvements in the signs of photoaging. Both PDT treatments were better tolerated than 5-FU. In conclusion, broad area PDT treatment with ALA plus activation with blue light appears to be as effective as 5-FU in the treatment of AK. ALA plus laser light is somewhat less effective than the above therapies. Efficacy could likely be improved with further study of laser parameters and incubation times.", "Evaluate cryosurgery followed by 3.75% imiquimod cream to treat actinic keratoses (AK).\n Adults with > or =10 AKs on the face underwent cryosurgery of five to 14 lesions. Subjects with > or =5 lesions remaining were randomized to 3.75% imiquimod or placebo cream applied to the entire face daily for two two-week cycles. Efficacy was assessed through week 26.\n For the cryosurgery/3.75% imiquimod (n=126) and cryosurgery/placebo (n=121) groups, respectively, median total AK reductions were 86.5 and 50 percent, and proportions of subjects with complete clearance were 30.2 and 3.3 percent (P < 0.0001, both). Analyzing cryosurgery-treated lesions only, median reductions were 100 and 80 percent (P = 0.0008), and subject complete clearance rates were 59.5% and 29.8% (P < 0.001), respectively. Only one subject discontinued for a treatment-related adverse event (cryosurgery/3.75% imiquimod group).\n Cryosurgery was performed per usual study center practice and not standardized.\n A short, cyclical treatment course of field-directed daily 3.75% imiquimod cream following lesion-directed cryosurgery was well tolerated and provided additional therapeutic benefits to cryosurgery alone.", "Photodynamic therapy (PDT) is a highly effective treatment for actinic keratoses (AK); however, it is time consuming and often painful for the patient. Daylight-PDT would make the treatment independent of the clinic and less painful due to the continuous activation of small amounts of porphyrins during its formation.\n The objective of this randomized controlled study was to compare response rates and adverse effects after methyl aminolevulinate (MAL)-PDT using conventional red light-emitting diode (LED) light vs. daylight.\n Twenty-nine patients with AK of the face and scalp were treated with MAL-PDT in two symmetrical areas. One area was illuminated by red LED light (37 J cm(-2)) after 3-h incubation with MAL under occlusive dressing. The other area was treated with daylight for 2.5 h after the MAL cream had been under occlusion for half an hour.\n We found no significant difference in the treatment effect between the two treatments (P = 0.13), with a reduction of AK lesions of 79% in the daylight area compared with 71% in the LED area. Treatment response in the daylight area did not depend on the intensity of the daylight. Illumination with LED was more painful than daylight (P < 0.0001). Erythema and crusting occurred after both treatments and were similar in the two areas.\n PDT of AK by continuous activation of porphyrins by daylight proved to be as effective as conventional PDT. PDT using daylight activation will make the treatment of these extremely common premalignant tumours more time and cost effective, and more convenient for the patient.", "A randomized double-blind controlled trial of 130 patients was performed to study the efficacy and tolerability of topical 3% diclofenac in 2.5% hyaluronic acid (HA) gel (active) versus gel containing 2.5% HA alone (control) in the treatment of solar keratoses. Patients were asked to apply trial gel to the target lesion twice a day and also sunscreen once a day for 24 weeks. The complete response rates were 29% for the active gel and 17% for the control gel. The difference was not statistically significant (P = 0.14). A high percentage of patients in both groups experienced a partial response to treatment (38% active, 45% control) but there was no significant difference in the spectrum of response between the two treatments (P = 0.18). Local adverse reactions occurred significantly more frequently in patients using the active gel (29% compared to 5% using control gel, P = 0.0002).", "Increasing incidence rates of cutaneous malignancies, paralleling rising survival times of grafts and patients in organ transplant recipients, represents an escalating challenge for dermatologists worldwide. Especially, invasive squamous cell carcinomas (SCC) in immuno-compromised patients are characterized by significantly increased morbidity and mortality and characteristically outnumber basal cell carcinoma in this population. Effective management of actinic keratoses (AK) could help to prevent the further development of invasive SCC. Diclofenac in hyaluronic acid has previously shown to be an effective and well tolerated option for the treatment of AK in immuno-competent patients. However, its safety and efficacy in organ-transplant patients has not been evaluated in a controlled study so far. 32 organ transplant patients (kidney (+/- pancreas), liver, heart) screened at our specialized transplant dermatology outpatient clinic were found eligible and were randomized to either active treatment (24) or vehicle (8). Patients who had stable status of the transplanted graft in the 12 months prior to entering the study and >/= 3 AK lesions in a contiguous 50 cm2 area on the face, forehead, hands or balding scalp were eligible for inclusion in the study. Treatment of AK with 3% diclofenac in 2.5% hyaluronic acid or placebo twice daily was conducted over a total of 16 weeks, followed by a final evaluation 4 weeks after last application of the study drug. Biopsies were taken from the treated areas at the final visit to verify clinical clearance. Patients were assessed for safety variables that included adverse events, local skin reactions, laboratory results, dosage of immunosuppressive medication and indication of graft rejection. A 24 months follow up was conducted after the end of treatment. 87% (n = 28/32) of the patients completed the 16 week treatment phase and presented for final evaluation 4 weeks after end of treatment. In the diclofenac 3% gel treatment group, a complete clearance of AK lesions was achieved in 41% (9/22) compared to 0% (0/6) in the vehicle group. Side effects in most of the patients included a mild erythema and a mild to moderate swelling of the areas treated. No graft rejections or trends for a deterioration of graft function were detected. No meaningful trends were observed in laboratory results. In 55% of the previously cleared patients, new AK developed in the study area after an average of 9.3 months. None of these patients developed invasive SCC in the study area within 24 months of follow-up. This study demonstrated a greater lesion clearance rate of AKs in OTRs treated with diclofenac 3% gel than with vehicle. Despite recurrent AK in 55% of the previously cleared patients, the 24 month results showed no invasive SCC in this group. This study suggests that diclofenac 3% gel is not only an efficient and well tolerated treatment for multiple AKs in OTRs but also may prevent invasive SCC in these high-risk patients.", "Actinic keratoses (AKs) are premalignant skin lesions, which, if left untreated, can develop into squamous cell carcinoma. Current treatments for AKs are destructive and are often associated with significant adverse events. The development of an effective and well-tolerated topical treatment for AK is desirable.\n To evaluate the efficacy and safety of 3.0% diclofenac in 2.5% hyaluronan gel as a treatment for AK.\n This was a multicentre, double-blind, placebo-controlled study in which 195 patients with at least five AKs in up to three designated treatment blocks were randomized to four treatment groups. Patients randomized into the active treatment groups A30 (n = 49) and A60 (n = 48) received topical treatment with 3.0% diclofenac in 2.5% hyaluronan gel 0.5 g twice daily for 30 or 60 days, respectively. Patients in the placebo (vehicle gel) groups V30 (n = 49) and V60 (n = 49) received topical treatment with 2.5% hyaluronan gel 0.5 g twice daily for 30 or 60 days, respectively. Treatment efficacy was assessed by target and cumulative lesion number scores (TLNS and CLNS, respectively) and lesion total thickness score (TTS). Investigator and patient global improvement indices (IGII and PGII) were also used to rate overall improvement.\n Compared with placebo, significantly more patients given active treatment for 60 days had TLNS = 0 (33% vs. 10%, P < 0.05; an improvement of 64% compared with 34% with placebo), CLNS = 0 (31% vs. 8%, P < 0.05; an improvement of 54% compared with 23% with placebo) and TTS = 0 (25% vs. 6%, P < 0.05; an improvement of 59% compared with 31% with placebo). The IGII and PGII scores were also significantly better when active treatment was compared with placebo (P < 0.05). Both treatments were generally well tolerated and the incidence of the most common adverse events was similar between groups.\n Treatment with 3.0% diclofenac in 2.5% hyaluronan gel was effective when used for 60 days and was well tolerated in patients with AK.", "Methyl aminolaevulinate-photodynamic therapy (MAL-PDT) is an effective treatment in facial/scalp actinic keratosis (AK).\n The aims of this study were to compare efficacy, safety, cosmetic outcome and patient preference of MAL-PDT vs. cryotherapy in patients with AK at other locations.\n A multicentre, controlled, randomized, open, intraindividual, right-left comparison was performed. Patients with nonhyperkeratotic AK were treated once with MAL-PDT and cryotherapy on either side of the body. At week 12, lesions showing noncomplete response were retreated. The primary efficacy variable was the lesion response at week 24. Investigator's assessment of cosmetic outcome, patient's preference in terms of cosmetic outcome and a patient preference questionnaire were also analysed at week 24.\n In total, of 121 patients with 1343 lesions (98% located on the extremities and the remainder on the trunk and neck) were included. Both treatments provided a high mean percentage reduction in lesion count at week 24 with significantly higher efficacy for cryotherapy: 78% for MAL-PDT and 88% for cryotherapy (P=0.002, per protocol population). Investigator's assessment of cosmetic outcome was significantly better for MAL-PDT than cryotherapy (P<0.001), 79% of lesions having an excellent cosmetic outcome with MAL-PDT vs. 56% with cryotherapy at week 24. The cosmetic outcome achieved by MAL-PDT compared with cryotherapy was also preferred by patients (50% vs. 22%, respectively, P<0.001), and 59% of patients would prefer to have any new lesions treated with MAL-PDT compared with 25% with cryotherapy (P<0.001). Both treatment regimens were safe and well tolerated.\n MAL-PDT showed inferior efficacy for treatment of non-face/scalp AK compared with cryotherapy. However, both treatments showed high efficacy, and MAL-PDT conveyed the advantages of better cosmesis and higher patient preference.", "There is a need for improved medical approaches to the treatment of actinic keratosis. Ingenol mebutate, a diterpene ester extracted and purified from the plant Euphorbia peplus, is being evaluated as a topical therapy for actinic keratosis.\n Assess the efficacy and safety of ingenol mebutate (formerly PEP005) gel at 3 dosing regimens for the treatment of actinic keratosis.\n Patients with non-facial actinic keratoses applied vehicle gel for 3 days, ingenol mebutate gel, 0.025% for 3 days, or ingenol mebutate gel, 0.05% for 2 or 3 days, with an 8-week follow-up period.\n All 3 active treatments were significantly more effective than vehicle at clearing actinic keratosis lesions, with a dose response observed. The partial clearance rate (primary efficacy end point) for patients treated with ingenol mebutate gel ranged from 56.0% to 75.4% compared with 21.7% for vehicle gel (P = .0002 to P < .0001 vs vehicle). The complete clearance rate was also significantly higher (P < or = .0006) for patients in the ingenol mebutate gel treatment groups (range: 40.0% to 54.4%) compared with vehicle (11.7%), as was the baseline clearance rate (range: 42.0% to 57.9% for ingenol mebutate gel compared with 13.3% for vehicle, P < .0001 to .0007 vs vehicle). The median percentage reduction in baseline actinic keratosis lesions for patients treated with ingenol mebutate gel ranged from 75% to 100% compared with 0% for vehicle gel (P < .0001 vs vehicle). Active treatment was well tolerated at all dosages. The mechanism of action of this agent is the localized induction of necrosis followed by a transient inflammatory response, and this was manifested in most patients as transient local skin responses consisting primarily of erythema, flaking/scaling, and crusting. There was no evidence of treatment-related scarring.\n Local skin responses may have suggested active treatment to investigators.\n Short-course, field-directed therapy with ingenol mebutate gel for actinic keratoses on non-facial sites seems to be effective with a favorable safety profile and potential benefits over topical agents that require a more prolonged course of treatment." ]

[ "10668412", "9921605", "11990913", "10541229" ]

[ "A double-blind, placebo-controlled study of the safety, tolerability and pharmacokinetics of CP-101,606 in patients with a mild or moderate traumatic brain injury.", "Sample size review in a head injury trial with ordered categorical responses.", "Dexanabinol (HU-211) in the treatment of severe closed head injury: a randomized, placebo-controlled, phase II clinical trial.", "Failure of the competitive N-methyl-D-aspartate antagonist Selfotel (CGS 19755) in the treatment of severe head injury: results of two phase III clinical trials. The Selfotel Investigators." ]

[ "CP-101,606 is a postsynaptic antagonist of the glutamate-mediated NR2B subunit of the N-methyl-D-aspartate (NMDA) receptor. When administered intravenously (i.v.) at the time of injury, CP-101,606 is neuroprotective in animal models of traumatic brain injury (TBI) and ischemia. Minimal adverse effects have been observed in normal human volunteers given i.v. doses of up to 3 mg/kg/hr for 72 hours. The objective of the present clinical trial was to assess the safety, pharmacokinetics, and tolerability of CP-101,606 infused for various times in patients who had suffered either an acute moderate or mild TBI (Glasgow Coma Score 9-14) or hemorrhagic stroke. Patients began receiving treatment within 12 hours of brain injury. A total of 53 subjects (45 with TBI and 8 with stroke) were randomized in a double-blind fashion to receive CP-101,606 or placebo (4 drug: 1 placebo). Drug/placebo was administered by i.v. infusion (0.75 mg/kg/hr) for 2 hours and then stopped (n = 25) or continued for 22 hours (n = 4) or 70 hours (n = 24) at a rate of 0.37 mg/kg/hr. Mean plasma drug concentrations were well above the predicted therapeutic concentration of 200 ng/ml within two hours of initiating treatment and were sustained as long as drug was infused. All the patients tolerated their drug/placebo treatment, and there were no clinically significant cardiovascular or hematological abnormalities in either group. A Neurobehavioral Rating Scale, used to detect personality changes and behavioral disturbances, indicated that all subjects showed an improvement from their postinjury, predosing baseline but did not significantly differ from each other with respect to type of head injury and/or treatment with drug or placebo. Modified Kurtzke Scoring also showed a similar pattern of improvement irrespective of type of head injury or drug/placebo treatment. This study suggests that CP-101,606, infused for up to 72 hours has no psychotropic effects and is well-tolerated in patients who have sustained a mild or moderate TBI or hemorrhagic stroke.", "Between 1993 and 1996, a total of 452 patients were entered into a randomized trial evaluating eliprodil (a non-competitive NMDA receptor antagonist) in patients suffering from severe head injury. The primary efficacy analysis concerned the Glasgow Outcome Score (GOS), six months after randomization. This outcome was classified into three ordered categories: good recovery; moderate disability, and the worst category made up by combining severe disability, vegetative state and dead. A sample size calculation was performed prior to the commencement of the study, using a formula which depends on the anticipated proportions of patients in the three different outcome categories, the proportional odds assumption and on the relationship between outcome and prognostic factors such as Glasgow Coma Score at entry. Owing to uncertainty about the influence of prognostic factors, and about the proportion of patients in the three GOS categories, a blinded sample size review was planned. This review was performed on the basis of the first 93 patients to respond, and this led to an increase in the sample size from 400 to 450. In this paper the pre-trial simulations showing that the type I error rate would be influenced and the power would be preserved will be presented, and the implementation of the procedure will be described.", "To establish the safety of intravenous dexanabinol in severe head injury.\n Prospective, randomized, double-blind, placebo- (vehicle) controlled, multicenter, escalating dose study of a single administration of drug (48 or 150 mg) or vehicle (1 or 3 mL).\n All Israeli neurosurgical intensive care units (a total of six units).\n Sixty-seven patients, aged 16-65 yrs, Glasgow Coma Scale score of 4-8, injured within 6 hrs of treatment.\n Intracranial pressure, cerebral perfusion pressure, blood pressure, and heart rate were measured continuously in the intensive care unit. Adverse medical events were recorded and clinical outcome was assessed by the Glasgow outcome scale throughout a 6-month follow-up period. A highly significant reduction in the percentage of time with intracranial pressure >25, cerebral perfusion pressure <50, and systolic blood pressure <90 mm Hg was observed in the drug-treated group. The nature and incidence of adverse medical events were similar in the two groups. The percentage of patients achieving good neurologic outcome on the Glasgow outcome scale was 21% and 14% higher in the drug-treated group at 3 and 6 months, respectively. Statistical analysis of these differences by a logistic model using dose, entry Glasgow coma scale score, and computed tomograph as covariates yielded p values for the effect of treatment of .03 and .14 at 3 and 6 months, respectively.\n Dexanabinol was safe and well tolerated in severe head injury. The treated patients achieved significantly better intracranial pressure/cerebral perfusion pressure control without jeopardizing blood pressure. A trend toward faster and better neurologic outcome was also observed.", "Excessive activity of excitatory amino acids released after head trauma has been demonstrated to contribute to progressive injury in animal models and human studies. Several pharmacological agents that act as antagonists to the glutamate receptor have shown promise in limiting this progression. The efficacy of the N-methyl-D-aspartate receptor antagonist Selfotel (CGS 19755) was evaluated in two parallel studies of severely head injured patients, defined as patients with post resuscitation Glasgow Coma Scale scores of 4 to 8.\n A total of 693 patients were prospectively enrolled in two multicenter double-blind studies. Comparison between the treatment groups showed no significant difference with regard to demographic data, previous incidence of hypotension, and severity of injury. As the study progressed, the Safety and Monitoring Committee became concerned about possible increased deaths and serious brain-related adverse events in the treatment arm of the two head injury trials, as well as deaths in the two stroke trials being monitored concurrently. The Selfotel trials were stopped prematurely because of this concern and because an interim efficacy analysis indicated that the likelihood of demonstrating success with the agent if the studies had been completed was almost nil.\n Subsequently, more complete data analysis revealed no statistically significant difference in mortality rates in all cases between the two treatment groups in the head injury trials. In this report the authors examine the studies in detail and discuss the potential application of the data to future trial designs." ]

[ "10361400", "12038883", "8275737", "15148348", "10790249", "9489788", "16509174", "10095691", "8708877", "16322169" ]

[ "Children with cystic fibrosis benefit from massage therapy.", "A randomized, controlled trial of a community-based support program for families of children with chronic illness: pediatric outcomes.", "The effects of biofeedback assisted breathing retraining on lung functions in patients with cystic fibrosis.", "Controlled evaluation of the STARBRIGHT CD-ROM program for children and adolescents with Cystic Fibrosis.", "Benefits of music therapy as an adjunct to chest physiotherapy in infants and toddlers with cystic fibrosis.", "Psychosocial and educational outcomes associated with home- and clinic-based pretest education and cystic fibrosis carrier testing among a population of at-risk relatives.", "Benefits of an education programme on the self-management of aerosol and airway clearance treatments for children with cystic fibrosis.", "Self-administration of drugs for cystic fibrosis.", "Behavioral intervention to improve calorie intake of children with cystic fibrosis: treatment versus wait list control.", "Randomized clinical trial of behavioral and nutrition treatment to improve energy intake and growth in toddlers and preschoolers with cystic fibrosis." ]

[ "To measure the effects of parents giving massage therapy to their children with cystic fibrosis to reduce anxiety in parents and their children and to improve the children's mood and peak air flow readings.\n Twenty children (5-12 years old) with cystic fibrosis and their parents were randomly assigned to a massage therapy or a reading control group. Parents in the treatment group were instructed and asked to conduct a 20-minute child massage every night at bedtime for one month. Parents in the reading control group were instructed to read for 20 minutes a night with their child for one month. On days 1 and 30, parents and children answered questions relating to present anxiety levels and children answered questions relating to mood, and their peak air flow was measured.\n Following the first and last massage session, children and parents reported reduced anxiety. Mood and peak air flow readings also improved for children in the massage therapy group.\n These findings suggest that parents may reduce anxiety levels by massaging their children with cystic fibrosis and their children may benefit from receiving massage by having less anxiety and improved mood, which in turn may facilitate breathing.", "Children with chronic illnesses have a heightened risk for mental health problems.\n To develop, implement, and evaluate child outcomes of a 15-month, community-based, family-support intervention designed to reduce risk for poor adjustment and mental health problems in children with 1 of 4 chronic illnesses (diabetes mellitus, sickle cell anemia, cystic fibrosis, or moderate to severe asthma) and their mothers.\n Randomized, controlled clinical trial design with multiple measures of mental health based on both child and parent reports taken 1 year apart.\n Community-based intervention linked to subspecialty and general pediatric clinics and practices in Baltimore, Md.\n One hundred thirty-six mothers and children aged 7 to 11 years with diabetes mellitus, sickle cell anemia, cystic fibrosis, or moderate to severe asthma.\n The program, provided by \"experienced mothers\" and child life specialists, included telephone contacts, face-to-face visits, and special family events.\n Outcomes were measured using the following instruments: the Personal Adjustment and Role Skills Scale III, the Children's Depression Inventory, the Revised Children's Manifest Anxiety Scale, and the Self-Perception Profile for Children.\n The experimental group's mean adjustment score increased over the intervention period while the control group's mean adjustment score decreased. Analysis of variance demonstrated that the intervention had a significant main effect on postintervention adjustment controlling for baseline scores (P =.01). Using a cutoff score indicating maladjustment, the percentage of experimental group children in the maladjustment range fell from 19% at baseline to 10% after the intervention; the percentage of control group children in the maladjustment range rose from 15% at baseline to 21% after the intervention. The effect of the intervention was more pronounced for children who had low physical self-esteem than for those who had moderate to high physical self-esteem at the beginning of the program.\n Our results demonstrate modest positive effects of a family support intervention in promoting the adjustment of children with selective chronic health conditions. Including child life specialists in a community-based intervention may be especially salient for children with chronic illnesses who have low physical self-esteem. The intervention had a similar outcome for all diagnostic groups, suggesting that it could be effective for children with any chronic illness and implemented in a variety of pediatric settings.", "This study examines the effects of respiratory muscle feedback and breathing retraining (BRT) on lung function in patients with cystic fibrosis (CF). Twenty-six patients with CF were matched for age and severity of disease. Standard respiratory spirometry was performed on all subjects before and after biofeedback training. Thirteen experimental subjects underwent eight sessions of pneumographic or strain-gauge feedback from the abdominal muscles and electromyogram feedback from accessory respiratory muscles to assist in learning diaphragmatic and pursed-lips breathing maneuvers. Control subjects received biofeedback-assisted (hand warming) relaxation training. Results revealed a significant improvement in FEV1 and mean forced expiratory flow during the middle half of forced vital capacity (FVC) for the biofeedback group, while the control group showed no change. A similar trend was noted for FVC. These data suggest that respiratory muscle feedback and BRT may improve lung function in patients with CF.", "To evaluate the effectiveness of the STARBRIGHT Fitting Cystic Fibrosis Into Your Life Everyday CD-ROM. Data were analyzed to evaluate the effectiveness of the program as an educational tool for children and adolescents with cystic fibrosis (CF).\n Forty-seven children and adolescents with CF between the ages of 7 and 17 years were enrolled in the study. Participants completed an initial evaluation of CF-related knowledge and coping skills and were then randomly assigned to one of two groups: the treatment group or the wait-list control group. Participants then viewed the CD-ROM, and researchers completed posttest measures.\n Analyses indicated that both disease-related knowledge and coping strategies generated by children and adolescents with CF improved as a result of the intervention and that this effect was replicated in the wait-list group.\n In sum, the results of the current study indicate that the STARBRIGHT CD-ROM program is a promising intervention for increasing CF-related knowledge and the competence of children's and adolescents' coping strategies. These positive results are enhanced by the brief, inexpensive, and portable nature of this educational program.", "Routine chest physiotherapy (CPT) is an important component of prophylactic therapy in children with cystic fibrosis (CF) and requires a significant commitment of time and energy. It is important, therefore, to establish CPT as a positive experience. In this study, we evaluated the effect of recorded music as an adjunct to CPT. Specifically, we compared the use of newly composed music, familiar music, and the family's usual routine on children's and parents' enjoyment of CPT and the parents' perception of time taken to complete CPT. Enjoyment and perception of time were evaluated via questionnaires designed specifically for this study. Participants were caregivers of one or more children with CF who were aged between 4(1/2) months and 24 months at the commencement of the clinical trial and required CPT on a daily basis. Participants were randomly allocated into control and treatment groups. Control group participants experienced two conditions consecutively: no audiotape (NT; control) and familiar music tape (FT; placebo control). Treatment group participants were given the treatment music tape (TT), which was composed and compiled by a music therapist. After baseline assessment, evaluation occurred at two 6-weekly intervals. Children's enjoyment increased significantly after use of the TT (+1. 25 units) compared to NT (-0.5 units; P = 0.03), as did parents' enjoyment (+1.0 vs. 0.0 units, P = 0.02). Children's enjoyment did not change significantly after use of the FT (+0.75 units) compared to NT (n.s.). Likewise, parents' enjoyment did not change significantly after use of the FT (+1.0 units, n.s.). There was no change in perception of time after use of the TT (-4.5 vs. +0.2 min, n.s.) or the FT (+3.3 min, n.s.). These results indicate that children's and parents' enjoyment of CPT significantly increased after the use of specifically composed and recorded music as an adjunct. We therefore recommend that recorded music, such as that provided in this study, be given to parents to use as an adjunct to CPT when their young children are diagnosed with CF, in order to assist the establishment of a positive routine.\n Copyright 2000 Wiley-Liss, Inc.", "We report on the psychosocial and knowledge outcomes of two different approaches to cystic fibrosis (CF) gene pretest education and carrier testing offered to 288 proactively recruited first-, second-, and third-degree relatives of people with CF. One group received pretest education and gene testing in a clinical setting from a certified genetic counselor. The other group received pretest education in their homes from a specially prepared pamphlet and were asked to send in a buccal cell sample for genotyping. No statistically significant differences between groups were noted on measures of CF knowledge, anxiety, and positive or negative affect, either while waiting for their test results or within a few weeks after they had learned their results. At both measurement points, participants who had received home education and testing reported that the testing was more convenient, but that they had received less information than they would have liked, and they were more likely to report being confused by the testing, although their level of CF knowledge was comparable to that of people who had been seen by a genetic counselor. In light of the increasing interest in home-based medical testing of all kinds, this study suggests that CF carrier testing in the home warrants further consideration as one possible approach to facilitating access to testing.", "Adherence to recommended aerosol medicines and airway clearance techniques (ACT) for children with cystic fibrosis (CF) requires self-management skills. A multi-centre, randomized, controlled trial was conducted to investigate the effectiveness of a self-management education programme called 'Airways' for six- to 11-year old children with CF and their caregivers. Assessments were conducted immediately before and after the intervention period, and six and 12 months after the post-intervention assessment. The pen and paper education programme was completed by the child and caregiver together at home. Participants in the intervention and control groups had similar baseline characteristics. A per-protocol analysis was conducted and for variables that changed significantly, an additional intention-to-treat analysis was performed that included data from participants in the intervention group who withdrew from the study during the intervention period. The intervention group increased the percentage of prescribed aerosols taken (P < 0.001) and this was maintained at 12-month follow-up (P < 0.001). There was no change in the percentage of prescribed ACT performed, although when the child was unwell, caregivers in the intervention group increased the frequency and/or duration of ACT (P = 0.028) in the per-protocol analysis but not in the intention-to-treat analysis. Children in the intervention group increased their knowledge of ACT (P < 0.001) which was maintained at 12-month follow-up (P < 0.001) and felt more positively about their chest treatment regimens immediately following the intervention (P = 0.017) but not at 12-month follow-up. There were no significant changes in the control group for these variables over time. No significant changes occurred in the caregivers' reports of self-management behaviours and self-efficacy in either group. The positive results suggest that 'Airways' is a valuable educational tool for primary school-aged children with CF and their caregiver.", "Self-administration of medication encourages individuals to participate in their own health care and provides structure for regular assessment and teaching about their drugs. Patient-friendly drug leaflets can provide consistent information to patients cared for by a number of staff. Self-administration studies found in the nursing literature must be interpreted cautiously because of the lack of true experimental trials.", "Changes in calorie intake and weight gain were evaluated in five children with cystic fibrosis (CF) who received behavioral intervention and four children with CF who served as wait list controls. The behavioral intervention was a 6-week group treatment that provided nutritional education plus management strategies aimed at mealtime behaviors that parents find most problematic. The control group was identified prospectively and was evaluated on all dependent measures at the same points in time pre- and posttreatment as the intervention group. Difference scores on calorie intake and weight gain from pre- to posttreatment were compared between groups using t tests for independent samples. The behavioral intervention group increased their calorie intake by 1,032 calories per day, while the control group's intake increased only 244 calories per day from pre- to posttreatment [t(6) = 2.826, p = 0.03]. The intervention group also gained significantly more weight (1.7 kg) than the control group (0 kg) over the 6 weeks of treatment [t(7) = 2.588, p = 0.03] and demonstrated catchup growth for weight, as indicated by improved weight Z scores (-1.18 to -0.738). The control group showed a decline in weight Z scores over this same time period (-1.715 to -1.76). One month posttreatment, the intervention was replicated with two of the four children from the control group. Improved calorie intake and weight gain pre- to posttreatment were again found in these children. At 3- and 6-month follow-up study of children receiving intervention, maintenance of calorie intake and weight gain was confirmed. No changes were found on pulmonary functioning, resting energy expenditure, or activity level pre- to posttreatment. This form of early intervention appears to be promising in improving nutritional status and needs to be investigated over a longer period of time to evaluate the effects of treatment gains on the disease process.", "To conduct a randomized clinical trial comparing a behavioral and nutrition intervention (BEH) with a usual care control condition (CTL) for children (ages 18 months to 4 years) with cystic fibrosis (CF) and pancreatic insufficiency. This trial was designed to (1) evaluate a randomized comparison of BEH with CTL over 8 weeks, (2) provide a replication of the impact of BEH by inviting the CTL group to receive BEH after 8 weeks, and (3) examine the maintenance of BEH at 3- and 12-month follow-up.\n Of 14 eligible children, 10 were randomly assigned and initiated treatment (71% recruitment rate). Four participants were randomly assigned to BEH, and 6 were assigned to CTL (5 of whom chose to crossover to BEH). BEH included nutrition counseling to increase energy intake (via types of foods and addables/spreadables) and child behavioral management training to teach parents differential attention and contingency management skills. CTL was consistent with the 2002 CF Foundation Consensus Conference Guidelines for nutritional care.\n BEH led to greater increases in energy intake pre- to posttreatment than CTL as measured by calories per day (842 kcal/day vs -131 kcal/day change). On receiving BEH, the change in energy intake was replicated with the CTL group (892 kcal/day change). At 3- and 12-month follow-up, energy intake was maintained (672 kcal/day increase from baseline and 750 kcal/day increase from baseline, respectively). Children in this study met or exceeded normal weight and height velocities from pretreatment to the 3-month follow-up (mean weight: 1.4 kg/6 months; mean height: 5.1 cm/6 months) and from posttreatment to the 12-month follow-up (mean weight: 2.5 kg/12 months; mean height: 8.3 cm/12 months).\n Toddlers and preschoolers who have CF and received BEH were able to meet the energy intake recommendations for this disease and maintain these gains up to 12 months after treatment. In addition, these children demonstrated weight and height velocities from pretreatment to 12-month follow-up, consistent with the goal of normal growth. BEH is a promising, evidence-based, early nutritional intervention for children with CF. An upcoming multisite clinical trial will test BEH versus an attention control condition using a larger sample (N = 100), providing additional evidence about the efficacy of this treatment for energy intake and growth in young children with CF." ]

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[ "Efficacy and safety of fluticasone propionate/salmeterol 250/50 mcg Diskus administered once daily.", "Asthma therapy modulates priming-associated blood eosinophil responsiveness in allergic asthmatics.", "Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial.", "Initiation of maintenance treatment of persistent asthma: salmeterol/fluticasone propionate combination treatment is more effective than inhaled steroid alone.", "Inhaled salmeterol and fluticasone: a study comparing monotherapy and combination therapy in asthma.", "Formoterol, montelukast, and budesonide in asthmatic children: effect on lung function and exhaled nitric oxide.", "Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial.", "Fluticasone propionate, salmeterol xinafoate, and their combination in the treatment of nocturnal asthma.", "Formoterol added to low-dose budesonide has no additional antiinflammatory effect in asthmatic patients.", "Comparison of an inhaled corticosteroid (triamcinolone acetonide) to a long-acting bronchodilator (salmeterol), the combination, and placebo in mild-moderate adult asthmatic patients.", "The effectiveness of asthma therapy alternatives and evaluating the effectivity of asthma therapy by interleukin-13 and interferon gamma levels in children.", "Combined salmeterol/fluticasone propionate versus fluticasone propionate alone in mild asthma : a placebo-controlled comparison.", "The safety and efficacy of formoterol (Oxis) turbuhaler plus budesonide (Pulmicort) turbuhaler in mild to moderate asthma: a comparison with budesonide Turbuhaler alone and current non-corticosteroid therapy in Russia.", "Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study.", "Initiation of maintenance therapy with salmeterol/fluticasone propionate combination therapy in moderate asthma: a comparison with fluticasone propionate.", "Fluticasone propionate and salmeterol administered via Diskus compared with salmeterol or fluticasone propionate alone in patients suboptimally controlled with short-acting beta2-agonists.", "Effect of fluticasone propionate-salmeterol therapy on seasonal changes in airway responsiveness and exhaled nitric oxide levels in patients with pollen-induced asthma.", "Comparison of different long-term asthma treatments in subjects with mild-to-moderate asthma.", "Salmeterol/fluticasone propionate via Diskus once daily versus fluticasone propionate twice daily in patients with mild asthma not previously receiving maintenance corticosteroids." ]

[ "The twice daily administration of an inhaled corticosteroid (ICS) and long-acting beta(2)-agonist (LABA) has been shown to be effective in achieving asthma control. The once daily administration of an ICS/LABA may be a treatment option for some patients.\n To assess the effectiveness of fluticasone propionate (FP)/salmeterol via a single inhaler (FSC) administered once daily compared with FP once daily, FSC twice daily, or placebo.\n A 12-week, randomized, double-blind multicenter study conducted in 844 patients > or = 12 years of age who were symptomatic while using a short-acting beta(2)-agonist alone. Blinded treatments included: FSC 250/50 mcg once daily in the evening (FSC 250/50 QD), FP 250 mcg once daily in the evening (FP 250 QD), FSC 100/50 mcg twice daily (FSC 100/50 mcg BID), or placebo. All treatments were delivered via the Diskus device.\n All treatments demonstrated greater improvements in efficacy measures compared with placebo. Overall, the greatest improvements were observed in the patients receiving FSC, either once or twice daily, compared with the FP 250 QD group. The two FSC treatments were similar except that QD dosing did not maintain improvements in lung function for 24h compared with twice daily dosing. All treatments were well tolerated. No suppression of HPA axis, as assessed by 24-h urinary cortisol excretion, was observed in any of the active treatment groups.\n In patients symptomatic on a short-acting beta(2)-agonist alone, FSC 100/50 mcg BID was shown to provide better efficacy than a higher strength (FSC 250/50 mcg) administered once daily. However, a once daily regimen was effective and may be a valuable treatment option for some patients. Registered at (http://ctr.gsk.co.uk/welcome.asp) (SAS30022).", "Eosinophils play an important role in the pathogenesis of asthma. Several pro-inflammatory responses of eosinophils are primed in vivo in this disease. The aim of the present study was to investigate whether regular antiasthma treatment could modulate priming-sensitive cytotoxic mechanisms of human eosinophils. In a randomized, two-centre, double-blind parallel group study, the effect of 8 weeks of treatment with salmeterol xinafoate 50 microg b.i.d., beclomethasone dipropionate 400 microg b.i.d. or both on pulmonary function and the activation of priming-sensitive cytotoxic mechanisms of eosinophils, i.e. degranulation of eosinophil cationic protein (ECP) in serum, and activation of isolated eosinophils in the context of induction of the respiratory burst and release of platelet-activating factor (PAF) were tested. These effects were evaluated in 40 allergic asthmatics before and 24 h after allergen inhalation challenge. Whereas baseline forced expiratory volume in one second (FEV1) improved in all treatment groups, only treatment with a combination of salmeterol and beclomethasone significantly inhibited the allergen-induced increase in serum ECP, and (primed/unprimed) PAF-release, suggesting inhibition of eosinophil priming after allergen challenge. In contrast to the combination therapy, monotherapy with beclomethasone had no influence on allergen-induced PAF-release, suggesting an additional anti-inflammatory effect of salmeterol during combination therapy. Monotherapy with beclomethasone inhibited the prechallenge serum-treated zymosan (STZ) (0.1 mg mL(-1))-induced respiratory burst and the allergen-induced increase in serum ECP levels, reflecting pre- and postchallenge anti-inflammatory effects. During monotherapy with salmeterol, an allergen-induced increase in serum ECP concentration and STZ (0.1 mg x mL(-1))-induced respiratory burst was observed, suggesting that treatment with salmeterol alone had no effect on priming-sensitive eosinophil cytotoxic mechanisms. In conclusion, this study shows that standard asthma therapy leads to inhibition of eosinophil priming of cytotoxic mechanisms in vivo.", "More evidence is needed on which to base recommendations for treatment of mild-moderate persistent asthma in school-aged children.\n The Pediatric Asthma Controller Trial (PACT) compared the effectiveness of 3 regimens in achieving asthma control.\n A total of 285 children (ages 6-14 years) with mild-moderate persistent asthma on the basis of symptoms, and with FEV(1) >or= 80% predicted and methacholine FEV(1) PC(20) <or= 12.5 mg/mL, were randomized to 1 of 3 double-blind 48-week treatments: fluticasone 100 microg twice daily (fluticasone monotherapy), fluticasone 100 microg/salmeterol 50 microg in the morning and salmeterol 50 mug in the evening (PACT combination), and montelukast 5 mg in the evening. Outcomes included asthma control days (primary outcome), exacerbations, humanistic measurements, and pulmonary function measurements.\n Fluticasone monotherapy and PACT combination were comparable in many patient-measured outcomes, including percent of asthma control days, but fluticasone monotherapy was superior for clinic-measured FEV(1)/forced vital capacity (P = .015), maximum bronchodilator response (P = .009), exhaled nitric oxide (P < .001), and PC(20) (P < .001). Fluticasone monotherapy was superior to montelukast for asthma control days (64.2% vs 52.5%; P = .004) and for all other control outcomes. Growth over 48 weeks was not statistically different (fluticasone, 5.3 cm; PACT combination, 5.3 cm; montelukast, 5.7 cm).\n Both fluticasone monotherapy and PACT combination achieved greater improvements in asthma control days than montelukast. However, fluticasone monotherapy was superior to PACT combination in achieving other dimensions of asthma control. Growth was similar in all groups.\n Therefore, of the regimens tested, the PACT study findings favor fluticasone monotherapy in treating children with mild-moderate persistent asthma with FEV(1) >or= 80% predicted, confirming current guideline recommendations.", "To determine whether initiation of maintenance treatment with the salmeterol (S)/fluticasone propionate (FP) combination (Seretide/Viani/Advair) is more effective than inhaled steroid alone in patients with asthma symptomatic on short-acting bronchodilator alone.\n 150 asthma patients with symptoms and prn use of short-acting bronchodilator at least once a week were randomised to 24 weeks' treatment with either S/FP 50/100 microg bd (n = 78) or FP 100 microg bd (n = 72). The primary endpoint was the percentage of symptom-free 'day + night's.\n The percentage of symptom-free 'day + night's increased significantly more for S/FP (20 to 64%) compared to FP (24 to 51%). The treatment difference was 15.3%, P = 0.008. In the sub-group of patients with mild asthma the treatment difference was also statistically significant in favour of S/FP (P = 0.0245, n = 74). S/FP was also significantly superior to FP alone for: lung function, salbutamol use prn, day symptom score, symptom-free days, and episode-free 'day + night's. Treatments were equally well tolerated.\n Initial maintenance treatment with S/FP is significantly more effective than with inhaled steroid alone for patients symptomatic when treated with short-acting bronchodilator alone. This also apply to patients with mild persistent asthma.", "The current stepwise approach to pharmacotherapy in the treatment of asthma includes the initiation of an inhaled corticosteroid with the addition of a long-acting inhaled bronchodilator if low dose inhaled corticosteroid fails to control asthma symptoms.\n To determine whether initiation of salmeterol and fluticasone propionate treatment together improves asthma control greater than initiation of monotherapy with the individual agents alone with no additional safety risk in patients with asthma who had not previously been treated with inhaled corticosteroids.\n A total of 136 male and female patients at least 12 years of age with asthma [forced expiratory volume in 1 second (FEV) between 50% and 80% of predicted] were randomized to twice daily salmeterol 42 microg, fluticasone propionate 88 microg, fluticasone propionate 220 microg, salmeterol 42 microg plus fluticasone propionate 88 microg, salmeterol 42 microg plus fluticasone propionate 220 microg, or placebo for 4 weeks.\n Patients treated with salmeterol combined with fluticasone propionate had improvements over baseline in FEV at endpoint that were at least twice as great (0.6 to 0.7 L) as improvements in patients treated with salmeterol (0.3 L) or fluticasone propionate alone (0.3 L) (P < .05). Patient-rated data (peak expiratory flow, asthma symptom scores, percent of days with no asthma symptoms) confirmed greater (P < .05) mean change from baseline improvements after combined treatment compared with fluticasone propionate alone. No clinically significant differences were noted between treatment groups in any safety measurement.\n Initiation of maintenance therapy with salmeterol and fluticasone propionate in patients with asthma treated with short-acting beta2-agonists alone provides greater improvements in pulmonary function and symptom control than initiation of maintenance therapy with fluticasone propionate alone.", "It has been proposed that asthma control may be achieved in part by minimizing airway inflammation. The simultaneous effects of inhaled steroids associated with long-acting beta-agonists and leukotriene antagonists on pulmonary function and airway inflammation are still largely unexplored in children with moderate persistent asthma.\n The aim of this study was to investigate the effects of add-on therapy with long-acting beta-agonists and leukotriene antagonists on FEV1 and exhaled nitric oxide levels (FENO) in children.\n Forty-eight steroid-naïve atopic asthmatic children, 7-11 years of age, were randomly treated in four groups for two consecutive one-month periods, as follows: (1) first month: budesonide 200 microg twice daily; second month: budesonide 400 microg twice daily; (2) first month: budesonide 200 microg twice daily+formoterol 9 microg twice daily; second month: budesonide 200 microg twice daily+montelukast 5mg once daily; (3) first month: budesonide 200 microg twice daily+montelukast 5mg once daily; second month budesonide 200 microg+formoterol 9 microg twice daily; (4) first and second month: budesonide 400 microg twice daily.\n All treatments resulted in a significant increase in lung function and a decrease in FENO compared with values at baseline. Budesonide+montelukast in combination was the most effective treatment for reducing FENO levels.\n This study demonstrates that add-on therapy with montelukast plus low-dose budesonide is more effective than the addition of long-acting beta-agonists or doubling the dose of budesonide for controlling FENO in asthmatic children.", "The optimal treatment for mild asthma is uncertain. We assessed the effects of adding a long-acting inhaled beta-agonist, formoterol, to low doses of an inhaled corticosteroid, budesonide, for 1 yr in subjects with mild asthma, receiving no or only a small dose of inhaled corticosteroid. The 698 corticosteroid free patients (Group A) were assigned to twice daily treatment with 100 microg budesonide, 100 microg budesonide plus 4.5 microg formoterol, or placebo. The 1,272 corticosteroid-treated patients (Group B) were assigned to twice daily treatment with 100 microg budesonide, 100 microg budesonide plus 4.5 microg formoterol, 200 microg budesonide, or 200 microg budesonide plus 4.5 microg formoterol. The main outcome variables were time to the first severe asthma exacerbation and poorly controlled asthma days. In Group A, budesonide alone reduced the risk for severe exacerbations by 60% and poorly controlled days by 48%; adding formoterol increased lung function with no change in other end points. By contrast, in Group B, adding formoterol reduced the risk for the first severe exacerbation and for poorly controlled days by 43 and 30%, respectively. Thus, in corticosteroid-free patients, low dose inhaled budesonide alone reduced severe exacerbations and improved asthma control, and in patients already receiving inhaled corticosteroid, adding formoterol was more effective than doubling the corticosteroid dose.", "Inhaled corticosteroids have been shown to effectively reduce large circadian fluctuations in peak expiratory flow (PEF). Salmeterol xinafoate (SLM), a new long-acting beta2-agonist being used in the treatment of nocturnal airway obstruction, has proved to be very effective in this respect as well. However, it is yet unknown whether using SLM alone or in combination with fluticasone propionate (FP) constitutes the best treatment. We studied, in a randomized, double-blind, parallel manner, 46 asthmatics with increased circadian variation in PEF (> or = 15%) for 6 wk to compare FP 250 microg, SLM 50 microg, and a combination of them, all given twice a day. These three treatment protocols were equally effective in improving the generally used clinical outcome parameters, i.e., the circadian variation in PEF and FEV1 and bronchial hyperresponsiveness (BHR) to methacholine (MCh) during the day and at night. FEV1 increased more at 4:00 A.M. than at 4:00 P.M. (FEV1 at both time points > 90% predicted). BHR to MCh improved with at least 1.5 doubling concentrations, thereby reducing the significant nocturnal decline in the SLM and FP group, but not in combination. The improvement in BHR to adenosine 5'monophosphate was greater (p = 0.05) when FP was combined with SLM but not when FP or SLM were used alone. Our data support the clinical view that FP, with its anti-inflammatory capacity, has greater beneficial effects as monotherapy than does SLM. However, this was detectable only by using the \"indirect\" stimulus adenosine 5'monophosphate, which is more specific in assessing changes in different components of airway wall inflammation than is MCh.", "Adding inhaled long-acting beta2-agonists to a low dose of inhaled corticosteroids (ICSs) results in better asthma control than increasing the dose of ICSs. An important, but as yet unresolved, question is whether this is due to an additional reduction of airway inflammation.\n Double-blind, parallel-group trial.\n Forty asthma patients (FEV1, 50 to 90% predicted; provocative concentration of a substance [methacholine] causing a 20% fall in FEV1 of < 8 mg/mL; no ICSs in the last 4 weeks).\n Randomization to 8 weeks of treatment with 100 microg of budesonide bid plus placebo (BUD200) or 100 microg of budesonide bid plus 12 microg of formoterol (BUD200 + F). Then the dose of budesonide (BUD) was increased to 400 microg bid in both groups for another 8 weeks. Bronchial biopsy specimens were collected before, and after 8 and 16 weeks of treatment. Eosinophils (major basic protein [MBP]) and mast cells (tryptase) were analyzed by immunohistochemistry.\n BUD200 reduced the MBP staining (p = 0.008) and tryptase staining (p = 0.048) in the epithelium compared to baseline levels. There were no significant differences between the BUD200 and BUD200 + F groups. In both groups, increasing the dosage of BUD to 800 microg had no significant additional antiinflammatory effect.\n Our results demonstrate that BUD administered at a low dose has significant antiinflammatory effects in patients with mild asthma. No significant additional antiinflammatory effects could be demonstrated either by adding formoterol or by increasing the dose of BUD.", "nan", "This study evaluated the superiority of combination therapy over steroid therapy alone by using clinical and laboratory data including interleukin (IL)-13 and interferon (IFN) gamma, which participate in the characteristic inflammation and have not been studied to evaluate the efficiency of asthma treatment sufficiently. Moderate persistent asthma patients, aged 7-17 years were included in the study. Patients were randomized to three groups. Group 1 used inhaled budesonide, group 2 used inhaled budesonide plus inhaled formoterol fumarate, and group 3 used inhaled budesonide and oral montelukast sodium therapy. At the beginning and at the end of the 2nd month a detailed physical examination and clinical evaluation; total IgE levels and total eosinophil count in peripheral venous blood, serum IL-13, and IFN-gamma levels; pulmonary function tests; and an assessment questionnaire (Pediatric Asthma Quality-of-Life Questionnaire with Standardized Activities [PAQLQ{S}] were performed. Sixty-seven patients completed the study. Serum IL-13 levels and PAQLQ(S) scores before the therapy and serum IL-13 levels after the therapy were significantly different between the groups and other parameters did not show any significant differences. Serum IgE level was decreased after the therapy in group I and increased in groups 2 and 3, but the difference was insignificant. In all groups total eosinophil levels were decreased insignificantly. After the therapy, IL-13 levels were decreased in groups 1 and 2 and increased in group 3, but the difference was not statistically significant. When compared with the levels before the therapy IFN-gamma levels were decreased after the therapy but the difference was not statistically significant. When the improvement rates for IgE, total eosinophil, IL-13, and IFN-gamma levels and each parameter of respiratory function tests were compared, there were no significant differences between the therapy groups. In all groups PAQLQ(S) scores were significantly improved after the therapy. Our results showed that steroid and other agent combinations do not have any superiority to steroids only; but according to pulmonary function tests and clinical indicators, all three therapy models are effective. These results suggested that the inhalation steroids, as the oldest agents, are still preserving their place and importance in asthma therapy.", "Combined therapy with inhaled corticosteroids (ICSs) and long-acting beta(2)-adrenoceptor agonists (LABAs) is the recommended approach for the treatment of patients with asthma that is uncontrolled on ICSs alone. Additional studies are needed to assess the safety and efficacy of combination treatment with ICSs and LABAs in patients with mild asthma. The aim of this study was to compare the efficacy and tolerability of once-daily salmeterol/fluticasone propionate combination (SFC) with once-daily fluticasone propionate (FP) over a 12-week treatment period in patients with mild persistent asthma.\n This was a randomized, double-blind, placebo-controlled, parallel-group, multicentre study carried out in primary care or at a hospital outpatient department and included patients 12-79 years of age with mild persistent asthma (n = 458). After a 2-week run-in period, patients were randomized to receive SFC 50 microg/100 microg (n = 149), FP 100 microg (n = 154) or placebo (n = 155) once daily in the morning for 12 weeks. The primary efficacy endpoint was patient-recorded pre-dose mean morning peak expiratory flow (PEF). Other assessments included asthma symptom scores, use of rescue medication and investigator-recorded exacerbations. Lung function was measured and assessed during clinic visits.\n For the primary efficacy endpoint of mean change in morning PEF, SFC achieved significantly greater increases from baseline than both placebo (difference in adjusted means 23 L/min; 95% CI 15.0, 30.3; p < 0.001) and FP (difference in adjusted means 14 L/min; 95% CI 6.3, 21.7; p < 0.001). Compared with those who received FP, patients in the SFC group demonstrated significantly greater improvements in mean evening PEF (95% CI 11.7, 28.1; p < 0.001), forced expiratory volume in 1 second (95% CI 0.093, 0.257; p < 0.001), forced expiratory flow between 25% and 75% of forced vital capacity (95% CI 0.242, 0.617; p < 0.001), the percentage of symptom-free days (95% CI 0.34, 0.87; p = 0.011), and the percentage of rescue medication-free days (95% CI 0.34, 0.90; p = 0.018). During weeks 5-12, 52% of patients in the SFC group achieved 'well controlled' asthma, compared with 42% and 26% of patients in the FP and placebo groups, respectively. Only one patient (receiving placebo) had a severe asthma exacerbation during the study; the frequency of adverse events was similar across the three treatment groups.\n Once-daily SFC 50 microg/100 microg provided significantly greater improvements in lung function and in asthma symptoms than once-daily FP 100 microg alone in patients with mild persistent asthma. However, twice-daily treatment with either SFC or ICSs plus short acting beta(2)-adrenoceptor agonists could be required to achieve guideline-defined asthma control in some patients.", "Current therapy in Russia for long-term management of asthma is mainly non-steroidal. This provided the opportunity to compare the efficacy and safety of formoterol (Oxis) Turbuhaler plus budesonide (Pulmicort) Turbuhaler with budesonide Turbuhaler alone in adults (n=338) with mild to moderate asthma who had little previous exposure to inhaled corticosteroids. The 12-week study followed a randomised, double-blind, parallel group design and included an open control group of patients who were treated with conventional non-corticosteroid therapy. Patients treated with formoterol plus budesonide benefited from a significantly greater improvement in their pulmonary function and asthma symptoms compared with budesonide alone (95% Cl of difference in mean morning peak expiratory flow [PEF] 8.7-36.3 l/min, p=0.0015). Non-corticosteroid treatment was significantly less effective than formoterol plus budesonide and budesonide alone (95% CIs of differences in mean morning PEF were 36.4-63.6 l/min and 14.1-41.1 l/min, respectively, both p=0.0001). Although the incidence and frequency of adverse events was not significantly different between the groups, formoterol plus budesonide and budesonide alone were better tolerated than non-corticosteroid treatment, and there were fewer incidences of asthma deterioration. Overall, formoterol Turbuhaler plus budesonide Turbuhaler was the safest and most effective treatment.", "For most patients, asthma is not controlled as defined by guidelines; whether this is achievable has not been prospectively studied. A 1-year, randomized, stratified, double-blind, parallel-group study of 3,421 patients with uncontrolled asthma compared fluticasone propionate and salmeterol/fluticasone in achieving two rigorous, composite, guideline-based measures of control: totally and well-controlled asthma. Treatment was stepped-up until total control was achieved (or maximum 500 microg corticosteroid twice a day). Significantly more patients in each stratum (previously corticosteroid-free, low- and moderate-dose corticosteroid users) achieved control with salmeterol/fluticasone than fluticasone. Total control was achieved across all strata: 520 (31%) versus 326 (19%) patients after dose escalation (p < 0.001) and 690 (41%) versus 468 (28%) at 1 year for salmeterol/fluticasone and fluticasone, respectively. Asthma became well controlled in 1,071 (63%) versus 846 (50%) after dose escalation (p < 0.001) and 1,204 (71%) versus 988 (59%) at 1 year. Control was achieved more rapidly and at a lower corticosteroid dose with salmeterol/fluticasone versus fluticasone. Across all strata, 68% and 76% of the patients receiving salmeterol/fluticasone and fluticasone, respectively, were on the highest dose at the end of treatment. Exacerbation rates (0.07-0.27 per patient per year) and improvement in health status were significantly better with salmeterol/fluticasone. This study confirms that the goal of guideline-derived asthma control was achieved in a majority of the patients.", "The objective of this study was to investigate initial maintenance treatment with salmeterol/fluticasone propionate (Seretide) 50/250 microg twice daily (SFC) compared with fluticasone propionate (Flixotide) 250 microg twice daily (FP) (both via Diskus inhaler, GlaxoSmithKline, Greenford, UK) in patients with moderate persistent asthma currently only treated with inhaled short-acting beta2-agonists. A total of 362 adults and adolescents (12 to 80 years of age) were randomized to this 12-week double-blind parallel-group study. The primary endpoint was mean morning peak expiratory flow (PEF). Secondary efficacy endpoints included median percentages of symptom-free and rescue-free days and nights; the percentage of patients who achieved the pre-defined criteria for well-controlled asthma over weeks 5 to 12; and the incidence of asthma exacerbations. Safety was assessed by the incidence of adverse events. Superiority of SFC over FP alone was demonstrated for the primary and each secondary endpoint. The difference in adjusted mean change from baseline in morning PEF between SFC and FP was 21 L/min (95% CI: 11, 31; p<0.001). Significantly more patients achieved well-controlled asthma during treatment with SFC (46%) compared with FP (32%) (odds ratio 1.84; 95% CI: 1.17, 2.89; p=0.008). Both treatments were safe and well-tolerated. This study demonstrates that initial maintenance treatment with SFC 50/250 mug twice daily provides superior efficacy to FP 250 microg twice daily alone in patients with moderate persistent asthma.", "Optimal therapy for many patients with persistent asthma requires control of both main components of this disease: inflammation and bronchoconstriction.\n To compare the efficacy and safety of initiating maintenance therapy with an inhaled, long-acting beta2-agonist and an inhaled corticosteroid administered from a single device with that of the individual agents alone.\n A 12-week, randomized, double-blind study was conducted in patients 12 years and older with persistent asthma who were symptomatic while taking as-needed, short-acting beta2-agonists alone. Treatments were administered twice daily via the Diskus device: salmeterol, 50 microg; fluticasone propionate, 100 microg; or fluticasone propionate, 100 microg, with salmeterol, 50 microg.\n Of 555 patients screened, 267 were randomly assigned to treatment. At end point, fluticasone propionate and salmeterol significantly increased predose forced expiratory volume in 1 second (FEV1) compared with salmeterol alone (0.51 +/- 0.05 L vs 0.38 +/- 0.04 L, P = .04). Fluticasone propionate and salmeterol significantly increased area under the serial FEV1 curve at treatment week 12 relative to predose FEV1 (baseline) on treatment day 1 (AUCb1, 8.4 +/- 0.6 L/h; P < or = .02) compared with salmeterol (6.2 +/- 0.5 L/h) and fluticasone propionate (7.0 +/- 0.6 L/h). Fluticasone propionate and salmeterol were significantly (P < or = .02) more effective than the individual agents used alone in improving morning and evening peak expiratory flow rate and asthma symptoms. In addition, fluticasone propionate and salmeterol effectively reduced rescue albuterol use (P < or = .04). All treatments were well tolerated.\n In patients symptomatic while taking short-acting beta2-agonists alone, initial maintenance treatment of the 2 main components of asthma, inflammation and smooth muscle dysfunction, with fluticasone propionate and salmeterol, 100 and 50 microg, administered via the Diskus results in greater improvements in overall asthma control compared with treatment of either component alone.", "There has been concern that in allergic asthmatic patients there might be an interactive effect on inflammation between regular salmeterol use and exposure to allergens, resulting in increased airway responsiveness.\n To determine the effects of salmeterol on allergen-induced changes in airway responsiveness and exhaled nitric oxide (ENO) levels in allergic asthmatic patients concomitantly taking inhaled corticosteroids.\n Forty-two asthmatic patients sensitized to pollen allergens were randomly allocated to treatment with fluticasone propionate-salmeterol (n=21) or fluticasone propionate alone (n=21). Spirometry, the methacholine provocation concentration causing a 20% decline in forced expiratory volume in 1 second (PC20), the adenosine 5'-monophosphate (AMP) PC20, and ENO levels were measured before and at the height of the pollen season after 6 weeks of treatment.\n Changes in the methacholine PC20, the AMP PC20, and ENO levels were not significantly different between treatment groups. No significant changes in the AMP PC20 were observed among the fluticasone propionate-salmeterol and fluticasone propionate groups during natural pollen exposure. However, a significant increase in the methacholine PC20 was observed in the fluticasone propionate-salmeterol group (P = .03) and in the fluticasone propionate group (P = .04); ENO concentrations decreased significantly in both groups during natural allergen exposure (P = .009 and .005).\n In patients with pollen-induced asthma, treatment with either fluticasone propionate or fluticasone propionate-salmeterol is associated with significant reductions in methacholine responsiveness and ENO concentrations, even during natural pollen exposure. Furthermore, at least in patients with mild asthma, natural allergen exposure and the regular use of fluticasone propionate-salmeterol are not associated with a greater increase in ENO levels and airway responsiveness than natural allergen exposure and fluticasone propionate use alone.", "In order to compare the efficacy of different asthma treatment in subjects with mild-to-moderate asthma, three groups of 11 patients were treated with nedocromil sodium (NS), beclomethasone dipropionate (BDP) and beclomethasone dipropionate plus salmeterol (BDP + S) in an open, randomized study. Symptom score, peak expiratory flow (PEF) maximal amplitude, forced expiratory volume in one second (FEV1), and methacholine reactivity were measured at the baseline and at intervals of 3 months up to 12 months. After 3 months, symptoms reduced significantly in all treatment groups, while PEF variability improved in BDP and BDP + S groups; FEV1 and bronchial responsiveness to methacholine were significantly improved in comparison with baseline value in the BDP + S group only. No significant difference was observed after 6 and 12 months of treatment in PEF variability, FEV1 or bronchial hyperreactivity in the NS group compared with baseline values, while a significant difference was observed in symptom score. BDP group showed a significant improvement in FEV1 and bronchial reactivity to methacholine after 6 and 12 months of treatment. In the BDP + S group, the improvement in symptoms and pulmonary function persisted until the end of the study. In conclusion, the combination of beclomethasone dipropionate and salmeterol improved pulmonary function and bronchial reactivity earlier than beclomethasone dipropionate alone, while nedocromil sodium improved symptoms but not pulmonary function. Assuming that bronchial reactivity could be an indirect measurement of airway inflammation, overtreatment of asthma in relationship with the classification of asthma severity of the International Guidelines could improve both airway inflammation and the prognosis of airway obstruction.", "BACKGROUND and objective: The efficacy and safety of twice-daily inhaled salmeterol/fluticasone propionate combination (SFC) therapy have been well established in the treatment of adults and adolescents with asthma. Once-daily administration of SFC could also be appropriate in patients with mild persistent asthma. This study aimed to investigate whether once-daily SFC 50 microg/100 microg was at least as effective as fluticasone propionate (FP) 100 microg twice daily, and more effective than twice-daily placebo, over 52 weeks as initial maintenance therapy in patients with mild persistent asthma.\n This was a randomized, double-blind, double-dummy, placebo-controlled, multicentre, parallel-group study carried out in primary and secondary care. Patients aged between 12 and 79 years with a documented clinical history of asthma for > or =6 months who were currently receiving inhaled short-acting beta(2)-adrenoceptor agonists only were enrolled. Patients were randomized to receive either once-daily inhaled SFC 50 microg/100 microg, twice-daily inhaled FP 100 microg (i.e. twice the dose of FP compared with SFC) or placebo for 52 weeks. The primary efficacy endpoints were mean morning peak expiratory flow (PEF), as recorded by patients prior to the use of bronchodilator or study medication, and the rate of investigator-recorded asthma exacerbations.\n Patients receiving twice-daily FP and once-daily SFC showed greater improvements in mean morning PEF compared with those receiving placebo (FP, difference in means 20.1 L/min; 95% CI 14.7, 25.5; p < 0.001; SFC, difference in means 14.8 L/min; 95% CI 9.4, 20.2; p < 0.001). The difference in adjusted mean PEF between once-daily SFC and twice-daily FP was -5.3 L/min (95% CI -9.1, -1.6). PEF results showed that once-daily SFC was non-inferior to twice-daily FP. Over 52 weeks, there was a 35% reduction in exacerbation rates with once-daily SFC, which in this respect demonstrated superiority over placebo (p < 0.001). Non-inferiority between once-daily SFC and twice-daily FP with respect to exacerbation rates was not shown. Once-daily SFC significantly improved clinic forced expiratory flow between 25% and 75% of forced vital capacity (difference in means 0.129 L/s; p < 0.001) and clinic PEF (difference in means 10.8 L/min; p < 0.001) compared with twice-daily FP. Both treatments were well tolerated and the safety profile of each was similar to that seen with placebo.\n In patients with mild persistent asthma not previously receiving maintenance therapy, once-daily SFC 50 microg/100 microg is an effective treatment compared with placebo, and was non-inferior to twice-daily FP 100 microg with respect to mean morning PEF. However, in this study, once-daily SFC was not as efficacious as twice-daily FP in reducing asthma exacerbation rates. This study confirms the benefits of regular maintenance treatment in patients with mild persistent asthma." ]

[ "11933303", "10776222", "8427642", "11933280", "12671572", "2056290", "8338511", "2777121", "12964222", "3310792", "16740528" ]

[ "A clinical evaluation of the Nimbus 3 alternating pressure mattress replacement system.", "Comparative study of a foam mattress and a water mattress.", "Seeking quality care for patients with pressure ulcers.", "Randomised controlled trial of two pressure-relieving systems.", "Randomized comparison trial of the RIK and the Nimbus 3 mattresses.", "The cost of home air-fluidized therapy for pressure sores. A randomized controlled trial.", "A randomized trial of low-air-loss beds for treatment of pressure ulcers.", "Pressure ulcers: one bed or another?", "Profiling beds versus standard hospital beds: effects on pressure ulcer incidence outcomes.", "Air-fluidized beds or conventional therapy for pressure sores. A randomized trial.", "Pressure relieving support surfaces (PRESSURE) trial: cost effectiveness analysis." ]

[ "This study assessed the clinical effectiveness of the Nimbus 3 alternating pressure mattress replacement system (APMRS) on pressure ulcer healing and comfort in subjects > or = 65 years, with at least a Grade 2 ulcer and some mobility problems. Twelve patients in a hospital setting were randomly allocated to the Nimbus 3 or another APMRS, and 20 residents in a nursing home setting to the Nimbus 3 or an alternating pressure mattress overlay. Wound surface area (WSA) (cm2) was recorded twice weekly and comfort once weekly. In the hospital setting, there were no significant differences between groups in the reduction in WSA per day. In the nursing home setting, though subjects on Nimbus 3 had significantly more pressure ulcers at baseline, there were no significant differences between groups in the reduction in WSA per day. Nimbus 3 was statistically more comfortable than control surfaces. The study's sample size has not shown the products were different with regard to clinical effectiveness. However, it might serve as a pilot for a larger, multi-centre RCT aimed at establishing the efficacy of a pressure-relieving (PR) device on pressure ulcer healing.", "In order to determine the effectiveness of high-quality foam replacement mattresses in the treatment of pressure ulcers, one such mattress (TheraRest) was compared with a water mattress (Secutex). One hundred and twenty nursing home patients with pressure ulcers were randomised into two groups and nursed on one of the mattresses for four weeks. After four weeks, 45% of the patients using the foam mattress were completely healed, compared with 48.3% of those using the water mattress. This difference is not significant. Since high-quality foam mattresses are cheaper in the long term than water mattresses, and are easier for nursing staff to manage, it is suggested that these mattresses are preferable.", "Improving quality care for patients with pressure ulcers resulted in a two-year intensive effort to educate staff, keep morale high, standardize care plans by stage of ulcer, and participate in a comparison study of two support surfaces (Thera-Pulse, Kinetic Concepts and Geo-Matt, SpanAmerica). When all pressure ulcers were considered, the analysis of covariance revealed no statistically significant difference in the healing of pressure ulcers with respect to type of support surface used (F[1, 78] = 0.35, p > .05). For patients with stage III and IV pressure ulcers, the proportion of patients improving more than 10cm2 was higher in the air-suspension group. There was relatively little difference in the Stage II ulcer patients.", "The primary objective of this randomised controlled trial was to determine whether there were significant differences between two pressure-relieving systems. A secondary aim was to investigate whether the availability of extra pressure-relieving equipment would reduce the incidence of ulcers in an acute hospital setting. A total of 141 patients in a care-of-the-elderly unit, who were assessed to have a high risk of developing pressure ulcers using the Waterlow score, were recruited; 70 were nursed using Huntleigh Nimbus 3 in conjunction with the Aura cushion (Group A), and 71 using the Pegasus Cairwave Therapy System in conjunction with the Proactive 2 Seating cushion (Group B). The main outcome measure was visual assessment, supported by a photographic record. There were three main findings: for non-heel ulcers and overall improvement, there was no statistically significant difference between the two products tested; for heel ulcers there was a significant difference (P = 0.019) with more patients healing in Group A than in Group B. The average length of stay of patients who completed the trial was 21.6 days (Group A) and 21.7 days (Group B) for patients completing a live (range 1-121 days) and for patients who died 29.7 days (Group A) and 24.3 days (Group B). Routine monitoring showed that, before the trial, the incidence of hospital-acquired pressure ulcers (Torrance grade 2+) was 0.2%; during the trial, this dropped to 0.13%. The study showed differences in the efficacy of different mattress products; with a sufficiently large study, it is possible to demonstrate statistically significant results. Provision of extra pressure-relieving equipment can reduce the incidence of pressure ulcers but may not influence length of stay.", "A randomized comparison trial was carried out at Queen's Hospital, Burton-on-Trent, to compare patient outcomes on the RIK mattress (KCI) and the Nimbus 3 mattress (Huntleigh Healthcare). One hundred and fifty-eight patients, who were assessed to be at particular risk of development of pressure ulcers using the Waterlow score (85 on RIK mattress, 83 on Nimbus), completed the trial. There were no statistically significant differences in baseline parameters at recruitment or pressure ulcer progress. Lack of difference can be as useful as evidence of superiority. Other factors such as nursing interventions required accessible equipment, and costs are important when making equipment choices. For a significant proportion of patients, a static (RIK) mattress can be as effective as an active (Nimbus 3) mattress for management of pressure ulcers.", "Recurrent pressures sores are a serious problem that often cause chronically ill patients to be hospitalized. We hypothesized that home air-fluidized bed therapy may be a safe and effective way to treat these patients, thus avoiding the costs of hospitalization.\n One hundred twelve patients with 3rd or 4th stage pressure sores were randomly assigned to 36 weeks of either (1) home air-fluidized bed therapy that included the services of a visiting nurse specialist as long as the patient had 3rd or 4th stage sores, or (2) conventional therapy.\n Compared with patients in the control group, patients receiving air-fluidized bed therapy spent fewer days in the hospital (11.4 days vs 25.5 days, P less than .01) and used fewer total inpatient resources, as reflected both in charges ($13,263 vs $25,736, P less than .05) and in Medicare DRG and physician payments ($6,646 vs $12,131, P less than .05). Total resources used (inpatient and outpatient) were lower for patients treated with air-fluidized bed therapy, but the difference was not statistically significant. Clinical outcomes were similar.\n Home air-fluidized bed therapy is safe, reduces hospitalizations, is no more costly than alternative therapy, and allows the patients to receive their needed care in a more desirable, nonhospital setting.", "To assess the effectiveness of low-air-loss beds for the treatment of pressure ulcers in nursing homes.\n Prospective, randomized, clinical trial.\n Three teaching nursing homes in Los Angeles, Calif.\n Eighty-four nursing home residents with trunk or trochanter pressure ulcers (Shea stage > or = 2).\n Subjects were randomly assigned to use either a low-air-loss bed (n = 43) or a 10-cm corrugated foam mattress (n = 41) throughout the healing of their ulcers.\n Ulcers were assessed twice weekly using surface area and two observational scales (median follow-up, 37.5 days; range, 4 to 571 days).\n Groups were similar with respect to demographics, medical variables, wound care, and early dropouts. Results indicate more than a threefold improvement in median rate of healing for low-air-loss beds compared with foam mattresses (9.0 vs 2.5 mm2/d; P = .0002). This finding was true for deep as well as superficial ulcers (deep ulcers, 9.9 vs 0.7 mm2/d; P = .02; superficial ulcers, 9.0 vs 3.2 mm2/d; P = .004). Cox regression models revealed that the bed, ulcer depth, and fecal continence had independent effects on healing. After controlling for fecal continence, the deep and superficial subgroups using low-air-loss beds remained 2.5 times more likely to heal in a given length of time compared with those using foam mattresses (combined cure probability ratio, 2.66; 95% confidence interval, 1.34 to 5.17; P < .004).\n Low-air-loss beds provide substantial improvement compared with foam mattresses despite other factors in pressure ulcer healing.", "nan", "Most standard hospital beds are flat based with a pull-out backrest, resulting in a tendency for the patient to slide down the bed. This study aimed to compare the outcome for patients at high risk of developing pressure ulcers nursed on either this type of bed or an electrically operated, multi-sectioned profiling bed. A total of 100 patients were randomly assigned either to the profiling bed with a pressure-reducing foam mattress (experimental group) or a flat-based bed with an appropriate pressure-redistributing mattress (control group) for a maximum of 10 days. Risk status and pressure damage were assessed daily. Both a patient and a nurse questionnaire were completed. Data from 70 patients who participated in the study for five days or more were included in the analysis. Pressure ulcer incidence was 0% in both groups. All patients (35) in the experimental group were able to maintain a sitting position compared with only 12/35 in the control group (p = 0.0001). While the questionnaire results suggest there were significant differences in postural control and ease of transfer between patients in the two groups, it was not possible to map this to pressure ulcer formation. Poor recruitment into the study was due to the 'blocking' of electric beds by heavily dependent patients who did not meet the inclusion criteria, precluding a significant result in terms of pressure ulcer outcomes. This nurse-led use of the profiling beds was examined alongside the main study to investigate why they were allocated in this way.", "To compare the effectiveness and adverse effects of air-fluidized beds and conventional therapy for patients with pressure sores.\n Randomized trial with both masked and unmasked comparisons of outcome after a median follow-up of 13 days (range, 4 to 77 days).\n Urban, academic referral, and primary care medical center.\n Of 140 potentially eligible hospitalized patients with pressure sores, 72 consented to randomization; 65 (90%) completed the study.\n Thirty-one patients on air-fluidized beds (Clinitron Therapy, Support Systems International, Inc., Charleston, South Carolina) repositioned every 4 hours from 0700h to 2300h without use of other antipressure devices. Thirty-four patients on conventional therapy used an alternating air-mattress covered by a foam pad (Lapidus Air Float System, American Pharmaceal Company, Cincinnati, Ohio) on a regular hospital bed; were repositioned every 2 hours; and had elbow or heel pads as needed. Topical therapy was standardized for both groups.\n Pressure sores showed a median decrease in total surface area (-1.2 cm2) on air-fluidized beds, but showed a median increase (+ 0.5 cm2) on conventional therapy; 95% confidence interval (CI) for the difference between medians, -9.2 to -0.6 cm2 (p = 0.01). Improvement, as assessed from serial color photographs by investigators masked to treatment group, occurred in 71% and 47%, respectively; 95% CI for the difference, 1% to 47% (p = 0.05). For pressure sores 7.8 cm2 or greater, outcome differences between air-fluidized beds and conventional therapy were greater: median total surface area change was -5.3 and +4.0 cm2, respectively; 95% CI for the difference, -42.2 to -3.2 cm2 (p = 0.01). Improvement rates were 62% and 29% respectively; 95% CI for difference, 1% to 65% (p = 0.05). After adjusting for other factors associated with sore outcome, the estimated relative odds of showing improvement with air-fluidized beds were 5.6-fold (95% CI, 1.4 to 21.7) greater than with conventional therapy (p = 0.01). No significant increase in adverse effects was seen with air-fluidized beds.\n Our findings suggest that air-fluidized beds are more effective than conventional therapy, particularly for large pressure sores. Studies are needed to determine the effectiveness of air-fluidized beds in long-term care settings.", "To assess the cost effectiveness of alternating pressure mattresses compared with alternating pressure overlays for the prevention of pressure ulcers in patients admitted to hospital.\n Cost effectiveness analysis carried out alongside the pressure relieving support surfaces (PRESSURE) trial; a multicentre UK based pragmatic randomised controlled trial.\n 11 hospitals in six UK NHS trusts.\n Intention to treat population comprising 1971 participants.\n Kaplan Meier estimates of restricted mean time to development of pressure ulcers and total costs for treatment in hospital.\n Alternating pressure mattresses were associated with lower overall costs (283.6 pounds sterling per patient on average, 95% confidence interval--377.59 pounds sterling to 976.79 pounds sterling) mainly due to reduced length of stay in hospital, and greater benefits (a delay in time to ulceration of 10.64 days on average,--24.40 to 3.09). The differences in health benefits and total costs for hospital stay between alternating pressure mattresses and alternating pressure overlays were not statistically significant; however, a cost effectiveness acceptability curve indicated that on average alternating pressure mattresses compared with alternating pressure overlays were associated with an 80% probability of being cost saving.\n Alternating pressure mattresses for the prevention of pressure ulcers are more likely to be cost effective and are more acceptable to patients than alternating pressure overlays." ]

[ "16342302", "8564589", "10772372", "18093505", "15151791", "9717348", "2012087", "9230143", "8123955", "11440296" ]

[ "Effect of intervention through a pharmaceutical care program on patient adherence with prescribed once-daily atorvastatin.", "Failure of educational videotapes to improve medication compliance in a health maintenance organization.", "Impact of pharmacy counseling on compliance and effectiveness of combination lipid-lowering therapy in patients undergoing coronary artery revascularization: a randomized, controlled trial.", "[Therapy compliance in cases of hyperlipaemia, as measured through electronic monitors. Is a reminder calendar to avoid forgetfulness effective?].", "[Efficacy of an intervention to improve treatment compliance in hyperlipidemias].", "[Therapeutic compliance in dyslipidemias. A trial of the efficacy of health education].", "Efficacy and compliance with cholestyramine bar versus powder in the treatment of hyperlipidemia.", "Moderate dose, three-drug therapy with niacin, lovastatin, and colestipol to reduce low-density lipoprotein cholesterol <100 mg/dl in patients with hyperlipidemia and coronary artery disease.", "Telephone contacts do not improve adherence to niacin or bile acid sequestrant therapy.", "The effects of postal and telephone reminders on compliance with pravastatin therapy in a national registry: results of the first myocardial infarction risk reduction program." ]

[ "Correct execution of prescribed dosing regimen(s) is essential for patients to benefit from lipid lowering treatments. The objective of this study was to estimate the effect of a pharmaceutical care program on the adherence of once-daily atorvastatin treatment in patients with elevated cholesterol levels.\n In both linguistic regions of Belgium, two districts were randomized between usual care and a supportive intervention program. Eligible patients included hyperlipemic subjects taking atorvastatin for at least 3 months. 'Adherence' was defined as the proportion of days during which the electronic device record showed that the patient had taken the daily dose. 'Persistence' quantifies how long the treatment is executed.\n A total of 392 patients from 35 pharmacies were included in the intent-to-treat (ITT) analysis of the data (194 patients received intervention and 198 in the control group). The intervention resulted in a 6.5% increase in post-baseline adherence (p < 0.001) mainly driven by a 13% increase in persistence at 1 year (p = 0.002).\n A supportive pharmaceutical care program consisting of review by patient and pharmacist of each patient's electronically compiled dosing history, plus educational reminders, improves patient adherence to the once-daily atorvastatin dosing regimen, mainly by extending persistence.\n Copyright 2005 John Wiley & Sons, Ltd.", "The value of mailed educational videotapes as a means of enhancing compliance with drug therapy was studied. Members of a health maintenance organization with a pharmacy claim for benazepril, metoprolol, simvastatin, or transdermal estrogen were randomly assigned to a study group or a control group. Subjects in the study group were mailed one of four videotape programs giving information on the drug prescribed and the inferred disease state. Control subjects received no educational materials. Subjects were enrolled from July 1, 1993, through January 2, 1994. Refill data were collected from July 1, 1993, through April 1, 1994. The medication possession ratio (MPR) was calculated as the total number of days' supply of a drug obtained by a member divided by the number of days between the time of enrollment and April 1, 1994, or the date the member was terminated from the plan. A subject was deemed compliant if his or her MPR was > or = 0.80. There were no significant differences in mean MPRs between the study group (n = 1993) and the control group (n = 2253). None of the mean MPRs was > or = 0.80, although 44% of control subjects and 46% of study-group subjects were compliant. Of 97 respondents to a survey mailed to a randomly selected subset of the study group, almost 87% reported that they had viewed the videotapes, and of these subjects, about 88% said they found them very useful or somewhat useful. A one-time mailing of videotapes to patients, with no individual follow-up, did not increase compliance with the medications monitored.", "This randomized, controlled trial evaluated the impact of personalized follow-up on compliance rates in high-risk patients receiving combination lipid-lowering therapy over 2 years. A random sample of 30 patients 7-30 days after cardiac surgery had baseline fasting low-density lipoprotein levels higher than 130 mg/dl. All patients received lovastatin 20 mg/day and colestipol 5 g twice/day. Weekly telephone contact was made with each patient for 12 weeks. Short- and long-term compliance was assessed by pill and packet counts and refill records. Compliance and lipid profile results were significantly better in the intervention group (p<0.05) up to 2 years after the start of therapy than in the control group for all parameters except high-density lipoprotein. However, this effect was not apparent during the first 12 weeks of therapy. Short-term telephone follow-up favorably affected compliance and lipid profile results up to 2 years after start of therapy.", "To analyse the efficacy of the intervention with a calendar reminder of the medication taking in the treatment of the hyperlipidemias.\n Controlled, randomised clinical trial.\n Twelve clinics at 5 primary care centres, Spain.\n Two hundred and twenty people diagnosed with hypercholesterolaemia according to Spanish Consensus criteria were chosen.\n Two groups were formed. The control group (CG) of 110 patients, who received the doctor's normal treatment; and the Intervention group (IG) of 110 patients, who received in addition a calendar remider of medication taking.\n Meausured of compliance was performed by moniotrs electronic (MEMS) and cholesterol, triglycerides, HDL-C, and LDL-C determined at the start, and at the third and sixth months. Percentages of patients complying (80%-110%), the mean compliance percentage and the degree of control were compared. The reduction of absolute and relative risk (RAR and RRR) and the mean number of people that required an intervention in order to avoid non-compliance (NI) were calculated.\n One hundred and eighty eight people (85.45%) completed the survey, 96 in the IG and 92 in the CG; 26.55% were non compliers with the therapy (CI, +/-6.3%) (IG, 10.5%, CI, +/-4.6%; CG, 42.6%, CI, +/-10.1% [P<.0001]). Mean compliance ran at 88,1% (IC, +/-4.6%) overall, at 92% (CI, +/-5.4%) in the IG and at 84% (CI, +/-7.4%) in the IG (P<.05). The RAR was 32.1%, the RRR 75.35%, and the NI was 3.1 patients. The patients with cholesterol controlled ran at 66.7% (CI, +/-9.4%) in the IG and 41.2% in the CG (P<.001).\n The calendar reminder intervention is an efficacious way of improving the percentage of patients complying with lipaemia treatment.", "To analyse the efficacy of the intervention through a telephone call about patients' compliance with lipaemia therapy.\n Controlled, randomised clinical trial.\n Ten clinics at 6 primary care centres.\n 126 people diagnosed with hypercholesterolaemia according to Spanish Consensus criteria were chosen.\n Two groups were formed. The control group (CG) of 63 patients, who received the doctor's normal treatment; and the Intervention group (IG) of 63 patients, who received in addition a telephone call at 2 weeks, 2 months and 4 months.\n Pills were counted and cholesterol, triglycerides, HDL-C and LDL-C determined at the start, and at the third and sixth months. Percentages of patients complying (80%-110%), the mean compliance percentage and the degree of control were compared. The reduction of absolute and relative risk (RAR and RRR) and the mean number of people that required an intervention in order to avoid non-compliance (NI) were calculated.\n 115 people (91.26%) completed the survey, 56 in the IG and 59 in the CG. 77.1% complied with the therapy (CI, 68.4-85.8), (CG=64.4%, CI, 55.3-73.5; IG=93.5%, CI, 88.8-98 [P<.001]). Mean compliance ran at 88.7 +/- 10.2 overall, at 84.4 +/- 12.8 in the CG and at 93 +/- 8.2 in the IG (P<.001). The RAR was 29.1%, the RRR 81%, and the NI was 3.43 patients. The patients controlled ran at 43.9% in the IG (CI, 34.9-52.9) and 23.1% in the CG (CI, 15.4-30.8) (P<.005).\n The telephone intervention is an efficacious way of improving the percentage of patients complying with lipaemia treatment.", "To analyse the efficacy of health education (HE) through group session with postal back-up in furthering compliance with therapy for Lipaemia.\n Controlled clinical trial, with random distribution.\n Primary care.\n 110 patients with Hypercholesterolaemia, with new diagnoses or not in treatment, in which medical treatment with statins was indicated as a start or change in medication.\n They were distributed in two groups at random, with observation four months after being included in the study and appointments after one, two and four months. 1. Control group (CG): 55 patients who received HE from their family doctor. 2. Intervention group (IG): 55 patients whose HE was monitored: a) a group HE session and b) back-up by letter sent to their homes.\n Patients whose consumption was between 80 and 110% of the amount prescribed were defined as compliant. The pill count was recorded. The percentages of compliant patients and mean compliance (chi squared, Student's t) were analysed. 108 individuals, 41 men and 67 women, completed the trial. There was no difference between the two groups as to age, sex, evolution time, number of diseases and dosage of medicines consumed. 71.3% were compliant (CI, 62.8-79.8%), CG = 61.8% and IG 81.1% (p < 0.05). The mean percentage of compliance was 86.1 +/- 14.3 overall, with CG = 83.8 +/- 14 and IG 88.5 +/- 14 (p = NS).\n The HE intervention with a group session and postal back-up is an effective way of improving therapeutic compliance in cases of hypercholesterolaemia.", "The purpose of the study was to compare the powder and the bar forms of cholestyramine to determine efficacy and patient compliance.\n A prospective, randomized trial was conducted that included 83 healthy men and women with hyperlipidemia greater than the 90th percentile for low-density lipoprotein (LDL) or total cholesterol. Patients were randomly assigned to receive either cholestyramine powder, two packets (8 g), twice daily, or cholestyramine confectionery bar, in maple or mint flavors, two bars (8 g), twice daily. Fasting serum total cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides were measured at baseline, after 6 to 8 weeks of following the American Heart Association Step I diet alone, and after 8 weeks of taking either the cholestyramine bar or powder.\n Total cholesterol decreased significantly (p less than 0.01) by 16% in the bar group and 17% in the powder group. LDL cholesterol decreased by 28% and 29% in the bar and powder groups, respectively (p less than 0.01). There was no significant change in HDL cholesterol. Triglycerides increased in both groups, by 29% in the bar group and by 25% in the powder group. There was no difference between bar and powder in the effect on blood lipids. The majority of the lipid-lowering effect was seen within 14 days. Mean patient endpoint compliance with the therapy was 91.8 +/- 3.6% in the bar group and 94.8 +/- 2.1% in the powder group. There was no difference between groups.\n The cholestyramine confectionery bar is as effective as cholestyramine powder in the treatment of hyperlipidemia. The majority of the lipid-lowering effect is seen within 14 days of therapy. Although patient compliance is comparable between the two forms, gastrointestinal side effects were slightly greater with the bar form. Therefore, although the bar offers an alternative form of therapy, there appears to be no advantage with regard to patient compliance or palatability.", "The efficacy, safety, and tolerability of a moderate dose, 3-drug lipid-lowering regimen were evaluated among 29 male patients with hyperlipidemia and coronary artery disease. In an initial 12-month phase, regular niacin, 500 mg qid, lovastatin, 20 mg bid, and colestipol, 10 g/bid, were given with dose adjustment for lipid targets and side effects. This was followed by 2 random sequence crossover phases (8 months each) alternating regular niacin with a polygel controlled-release formulation of niacin for use in this regimen. Lipid, lipoprotein, apoprotein, and clinical chemistry determinations were obtained at baseline, during the initial phase, at the 2 crossover phases, and at 6 weeks after therapy. A final questionnaire queried specific side effects and overall preferences. Low-/high-density lipoprotein (LDL/HDL) changed from means of 215/46 mg/dl at baseline, to 94/59 mg/dl after run-in, to 85/52 mg/dl after 8 months of controlled-release niacin, and to 98/56 mg/dl after 8 months of regular niacin (regular niacin vs controlled-release niacin, p <0.005/<0.05). The target of LDL < or = 100 mg/dl was achieved at 8 months by 83% of these patients with controlled-release niacin and by 52% with regular niacin (p <0.01). Compliance was 95% with controlled-release niacin versus 85% with regular niacin (p <0.001). The controlled-release niacin and regular niacin regimens did not differ in terms of uric acid, glucose, insulin, or asparate aminotransferase levels. Overall, 21% of patients called the 3 drugs \"very easy\" and 72% \"fairly easy\" to take. The controlled-release niacin-containing regimen was preferred by 21 patients and the regular niacin by 4. In conclusion, these regimens achieve striking lipid changes among hyperlipidemic patients. Controlled release is the preferred niacin preparation in terms of LDL reduction, compliance, patient preference, and achieving the National Cholesterol Education Program guideline of LDL < or = 100 mg/dl. The 2 niacin preparations did not differ in evidence of toxicity.", "Noxious adverse effects frequently limit patient acceptance of niacin and bile acid sequestrants (BAS), first-line agents in the management of hypercholesterolemia. The purpose of this study was to determine whether telephone contacts from a healthcare professional could improve drug adherence and tolerance in patients prescribed these medications.\n This was a randomized, single-blind trial of telephone contacts vs. no intervention in patients with hyperlipidemia who were prescribed either niacin or BAS in a large, Veterans Affairs, lipid clinic. Patients randomized to telephone contact (n = 81) received weekly calls from a trained healthcare professional during the first month of drug therapy. Counseling regarding adverse effects, and prescriptions to overcome minor adverse effects, were provided as needed to patients during the telephone contact.\n Significant differences were not observed between groups in the drug discontinuance rate, adherence assessed by two independent methods, or in the final dosage of medication ingested.\n Telephone contacts do not improve either adherence or tolerance to niacin or BAS. Alternative approaches to enhance acceptance of these medications requires further evaluation.", "Noncompliance with cardiovascular therapy and prevention initiatives is well documented.\n The purpose of the First Myocardial Infarction (MI) Risk Reduction Program, an open-label drug registry involving mainly primary-care patients at increased risk of a first MI, was to examine the effects of postal and telephone reminders, as well as demographic and other baseline characteristics, on patient self-reported compliance with pravastatin treatment. A second objective was to determine whether regimen adherence was associated with the adoption of other lifestyle modifications recommended to decrease the risk of coronary artery disease.\n Patients with risk scores of > or = 4 on a scale of -1 to +16 for men and -1 to +17 for women on the First Heart Attack Risk Test were considered to be at increased risk of a first MI and eligible for enrollment in the registry program. An elevated total cholesterol level despite dietary interventions was an additional inclusion criterion. Patients were prospectively randomized (4:1) to either an intervention involving postal and telephone reminders (about coronary risk reduction and medication compliance), which were sent during the first 2 months of pravastatin treatment, or usual care. Both groups received reminder postcards at 4 and 5 months, in addition to counseling by physicians about coronary risk reduction. At 3 and 6 months (or study discontinuation), patients completed and mailed to the program-coordinating center questionnaires concerning compliance with care, including current use of prescribed pravastatin, as well as self-reported adoption of other lifestyle modifications, such as changing eating habits, losing weight, increasing physical activity, and/or quitting smoking. Compliance with pravastatin therapy and with these coronary risk-reducing behaviors was also assessed by physicians at the 3-month follow-up visit.\n A total of 10,335 patients were in the intervention group, and 2765 received usual care. The 2 groups were well balanced at baseline with respect to age, race, and total cholesterol values. Neither early reminders nor baseline patient characteristics were significantly associated with reported pravastatin compliance rates, which were approximately 79% overall. However, according to self-reports at 6 months, regimen compliance was associated with the adoption of other coronary risk-reducing behaviors.\n The results of this study suggest that early telephone and postal reminders do not improve compliance with drug treatment or with recommended coronary risk-reducing behaviors." ]

[ "17310820", "18580610" ]

[ "A randomized trial to evaluate continuation versus discontinuation of lamivudine in individuals failing a lamivudine-containing regimen: the COLATE trial.", "Second-line antiretroviral therapy in resource-limited settings: the experience of Médecins Sans Frontières." ]

[ "Lamivudine (3TC) therapy can cause the emergence of M1841/V. Previous studies suggest a higher fidelity of the mutant reverse transcriptase and lower replication capacity of the mutant virus. No data exist from clinical comparative studies evaluating the benefit of M1841/V in patients receiving combination antiretroviral therapy (cART).\n HIV-1-infected adults failing a 3TC-containing regimen were randomized to continue (On-3TC) or discontinue 3TC (Off-3TC) whilst receiving cART. The primary efficacy measure was the log10 average-area-under-the-curve-minus-baseline reduction in HIV RNA over 48 weeks. Cryopreserved plasma samples from patients with baseline and > or =1 follow-up sample with HIV RNA >500 copies/ml were sequenced for a nucleotide distances substudy. Evolutionary distances were compared between treatment arms and between viruses with and without M1841/V.\n The overall 48-week log10 HIV RNA change was -1.4 (95% CI: -1.6, -1.1) for On-3TC (n=65) and -1.5 (95% CI: -1.7, -1.2) for Off-3TC (n=66; P=0.51). No difference was seen in the magnitude of the CD4+ T-cell count increases (median increase: 87 vs 76 cells/ml for 3TC vs Off-3TC, respectively). Thirty-seven patients had baseline and follow-up sequencing. Overall, there were 1.2 (95% CI: -2.2, 4.6) more nucleotide substitutions from baseline for Off-3TC patients (P=0.50), and 10.7 (95% CI: 7.5, 14.0) fewer nucleotide changes in viruses containing M18411V (P<0.0001).\n This study found no added virological or immunological benefit of continuing 3TC in patients on cART harbouring M1841/V. Evolutionary distances from baseline were larger in viruses that did not contain M1841/V. More discernable benefits may be seen in patients with fewer drug options as potent cART may eclipse a benefit of M1841/V in COLATE.", "To describe the use of second-line protease-inhibitor regimens in Médecins Sans Frontières HIV programmes, and determine switch rates, clinical outcomes, and factors associated with survival.\n We used patient data from 62 Médecins Sans Frontières programmes and included all antiretroviral therapy-naive adults (> 15 years) at the start of antiretroviral therapy and switched to a protease inhibitor-containing regimen with at least one nucleoside reverse transcriptase inhibitor change after more than 6 months of nonnucleoside reverse transcriptase inhibitor first-line use. Cumulative switch rates and survival curves were estimated using Kaplan-Meier methods, and mortality predictors were investigated using Poisson regression.\n Of 48,338 adults followed on antiretroviral therapy, 370 switched to a second-line regimen after a median of 20 months (switch rate 4.8/1000 person-years). Median CD4 cell count at switch was 99 cells/microl (interquartile ratio 39-200; n = 244). A lopinavir/ritonavir-based regimen was given to 51% of patients and nelfinavir-based regimen to 43%; 29% changed one nucleoside reverse transcriptase inhibitor and 71% changed two nucleoside reverse transcriptase inhibitors. Median follow-up on second-line antiretroviral therapy was 8 months, and probability of remaining in care at 12 months was 0.86. Median CD4 gains were 90 at 6 months and 135 at 12 months. Death rates were higher in patients in World Health Organization stage 4 at antiretroviral therapy initiation and in those with CD4 nadir count less than 50 cells/microl.\n The rate of switch to second-line treatment in antiretroviral therapy-naive adults on non-nucleoside reverse transcriptase inhibitor-based first-line antiretroviral therapy was relatively low, with good early outcomes observed in protease inhibitor-based second-line regimens. Severe immunosuppression was associated with increased mortality on second-line treatment." ]

[ "12678188", "11437026", "12463616", "12593490", "11377600" ]

[ "The LONFLIT4--Concorde Deep Venous Thrombosis and Edema Study: prevention with travel stockings.", "Venous thromboembolism from air travel: the LONFLIT study.", "Prevention of edema, flight microangiopathy and venous thrombosis in long flights with elastic stockings. A randomized trial: The LONFLIT 4 Concorde Edema-SSL Study.", "The LONFLIT4-Concorde--Sigvaris Traveno Stockings in Long Flights (EcoTraS) Study: a randomized trial.", "Frequency and prevention of symptomless deep-vein thrombosis in long-haul flights: a randomised trial." ]

[ "The LONFLIT1+2 studies have established that in high risk subjects after long flights (> 10 hours) the incidence of deep venous thrombosis (DVT) is between 4% and 6%. The LONFLIT4 study was designed to evaluate the control of edema and DVT in low-medium risk subjects. The aim of this study was to evaluate edema and its control with specific stockings (ankle pressure between 20 and 30 mm Hg) in long-haul flights. The first part of the study included flights lasting 7-8 hours and the second part included flights lasting 11-12 hours. Ultrasound scans were used to assess thrombosis before and after the flights and a composite edema score was used to evaluate edema and swelling. A group of patients with microangiopathy associated to edema (diabetes, venous hypertension, anti-hypertensive treatment) were also included to evaluate the preventive effects of stockings during flight. Part I: DVT evaluation: Of the 74 subjects in the stocking group and 76 in the control group (150), 144 completed the study. Dropouts were due to low compliance or traveling and connection problems. Age and gender distribution were comparable in the 3 groups as was risk factor distribution. In this part of the study there were no DVTs. Edema Evaluation: The level of edema at inclusion was comparable in the two groups of subjects. After the flight there was an average score of 6.9 (1) in the control group. In the stocking group, the score was on average 2.3 (1), three times lower than in the control group (p < 0.05). Part II: DVT evaluation: Of the 66 included subjects in the stocking group and 68 in the control group (134), 132 completed the study. Dropouts were due to low compliance or connection problems. Age and gender distribution were comparable in the two groups. In the stocking group no DVT was observed. In the control group, 2 subjects had a popliteal DVT and 2 subjects had superficial venous thrombosis (SVT); in total 4 subjects (6%) in the control group had a thrombotic event; the incidence of DVT was 3%. The difference (p < 0.02) is significant.\n The composite edema score at inclusion was comparable in the two groups. After the flight there was a score of 7.94 (2) in the control group, while in the treatment group the score was 3.3 (1.2).\n In all these subjects, the level of edema was very high in the control group and significantly lower in the compression stocking group. Stockings are effective in controlling edema during flights even in subjects with microangiopathy and edema. Compression was well tolerated in normal subjects and in patients.\n The Kendall Travel Socks (Tyco Healthcare, Mansfield, MA, USA) which provide 20-30 mm Hg pressure at the ankle, are effective in controlling edema and reducing the incidence of DVT in both low-medium-risk subjects and in patients with microangiopathy and edema in long-haul flights (7-11 hours).", "The LONFLIT study was planned to evaluate the incidence of deep venous thrombosis (DVT) occurring as a consequence of long flights. In the Lonflit study 355 subjects at low-risk for DVT and 389 at high-risk were studied. Low-risk subjects had no cardiovascular disease and used no drugs. All flights were in economy class. The average flight duration was 12.4 hours (range, 10-15 hr). The mean age of the studied subjects was 46 years (range 20-80 yr, SD 11; 56% males). DVT diagnosis was made by ultrasound scans after the flights (within 24 hours). In low-risk subjects no events were recorded while in high-risk subjects 11 had DVT (2.8%) with 13 thromboses in 11 subjects and 6 superficial thromboses (total of 19 thrombotic events in 389 patients [4.9%]). In the Lonflit2 study the authors studied 833 subjects (randomized into 422 control subjects and 411 using below-knee stockings). Mean age was 44.8 years (range, 20-80 yr, SD 12; 57% males). The average flight duration was 12.4 hours. Scans were made before and after the flights. In the control group there were 4.5% of subjects with DVT while only 0.24% of subjects had DVT in the stockings group. The difference was significant. The incidence of DVT observed when subjects were wearing stockings was 18.75 times lower than in controls. Long-haul flights are associated to DVT in some 4-5% of high-risk subjects. Below-knee stockings are beneficial in reducing the incidence of DVT.", "The LONFLIT1/2 studies have established that in high-risk subjects after long (> 10 hours) flights the incidence of deep venous thrombosis (DVT) is between 4% and 6%. The LONFLIT4 study has been planned to evaluate the control of edema and DVT in low-medium-risk subjects. The aim of this study was to evaluate edema and its control with specific flight stockings, in long-haul flights. In the first part of the study 400 subjects at low-medium risk for DVT were contacted; 28 were excluded for several nonmedical problems; 372 were randomized into 2 groups to evaluate prophylaxis with stockings in 7-8-hour flights; the control group had no prophylaxis. Below-knee, Scholl, Flight Socks, producing 14-17 mm Hg of pressure at the ankle, were used in the treatment group. The occurrence of DVT was evaluated with high-resolution ultrasound scanning (femoral, popliteal, and tibial veins). Edema was assessed with a composite score based on parametric and nonparametric measurements. Part II: In this part of the study 285 subjects at low-medium risk for DVT were included and randomized into 2 groups to evaluate edema prophylaxis in 11-12-hour flights; the controls had no prophylaxis while the prevention group had below-knee, Scholl, Flight Socks (comparable to part I).\n Part 1: DVT evaluation. Of the 184 included subjects in the stockings group and 188 in the control group, 358 (96.2%) completed the study. Dropouts were due to compliance or connection problems. Age/sex distributions were comparable in the groups. Stockings Group: of 179 subjects (mean age 49; SD 7; M:F = 101:78), none had DVT or superficial thromboses. Control Group: of 179 subjects (mean age 48.4; SD 7.3; M:F = 98:81), 4 (2.2%) had a DVT. There were also 2 superficial thromboses. In total, 3.35% (6) subjects had a thrombotic event. The difference (p<0.002) is significant. Intention-to-treat analysis detects 15 failures in the control group (9 lost + 6 thromboses) out of 188 subjects (7.9%) versus 5 subjects (2.7%) in the stockings group (p <0.05). All thrombotic events were observed in passengers sitting in nonaisle seats. The tolerability of the stockings was very good and there were no complaints or side effects. Thrombotic events were asymptomatic. No difference was observed in the distribution of events between men and women. The 3 women who had a thrombotic event were taking low-dose, oral contraceptives. Edema evaluation: The level of edema at inclusion was comparable in the 2 groups. After the flight there was a score of 6.7 (3.1) in controls; in the stockings group the score was 2.9 times lower (p<0.05). The control of edema with stockings was clear considering both parametric (circumference, volume) and nonparametric (analogue scale lines) data. Part II: DVT evaluation. Of the 285 included subjects, 271 (95%) completed the study. Dropouts were due to low compliance or connection problems. Age/sex distributions were comparable in the groups. Stockings Group: of 142 subjects (mean age 48; SD 8; M:F = 89:53), none had DVT or superficial thromboses. Control Group: of 143 subjects (mean age 47; SD 8; M:F = 87:56), 3 had a popliteal DVT and 3 a superficial thrombosis. In total, 4.2% (6) subjects had a thrombotic event. The difference (p<0.02) between groups is significant. Intention-to-treat analysis detects 14 failures in the control group (8 lost + 6 thromboses = 9.7%) versus 6 (all lost = 4.2% in the stockings group) (p<0.05). Four of 6 events (3 DVT + 1 SVT) were observed in non-aisle seats. The tolerability of the stockings was very good. No difference was observed in the distribution of events between men and women. Edema evaluation: The level of edema at inclusion was comparable in the 2 groups. After the flight there was a score of 8.08 (2.9) in controls while in the stockings group the score was 2.56 (1.5) (p < 0.005). In conclusion. Scholl Flight Socks are very effective in controlling edema. Also this type of compression is effective in significantly reducing the incidence of DVT and thrombotic events in low-medium-risk subjects, in long-haul flights.\n Considering these observations, Flight Socks are effective in controlling edema and in reducing the incidence of DVT in low-medium-risk subjects, in long-haul flights (7-11 hours).", "The LONFLIT1/2 studies have established that in high-risk subjects after long ( > 10 hours) flights the incidence of deep venous thrombosis (DVT) may be between 4% and 6%. The LONFLIT4 study was aimed at evaluating the control of edema and DVT prevention in low-medium-risk subjects. In this study prophylaxis of edema with specific travel stockings was evaluated in 2 separate studies involving flights lasting 7 hours and 10-12 hours. Part I. Subjects at low-medium risk for DVT were contacted; 55 subjects were excluded for several nonmedical, travel-related problems or inconvenient evaluation time; the remaining 211 were randomized into 2 groups to evaluate prophylaxis with elastic stockings in 7-8-hour, long-haul flights. The control group had no prophylaxis; the treatment group used below-knee, Sigvaris Traveno elastic stockings (Ganzoni, Switzerland, producing 12-18 mm Hg of pressure at the ankle). Color duplex scanning was used to evaluate the possible presence of DVT; edema/swelling were evaluated with a composite score including the presence of edema (with an edema tester), variations in ankle circumference and leg volumetry, subjective swelling, and discomfort (scale ranging from 0 to 10). Results: Of the 103 included subjects in the stockings group and 108 in the control group (total 211), 195 subjects completed the study. Dropouts (16) were due to low compliance or traveling and connection problems. Age, sex distribution, and risk factors distributions were comparable in the 2 groups. Stockings Group: Of 97 subjects none had DVT or superficial thromboses. Control Group: Of 98 subjects none had thrombosis. The level of edema at inclusion was comparable in the 2 groups of subjects. After flights there was an average score of 6.4 (1.3) in the control group, while in the stockings group the score was on average 2.4 (SD 1), 2.6 times lower than in the control group (p < 0.05). In the control group 83% of the subjects had an evident increase in ankle circumference and volume that was visible at inspection and associated with discomfort. The control of edema with stockings was clear, considering both parametric data (circumference and volume) and nonparametric (analogue scale lines) measurements. Part II. In this part of the study 200 subjects at low-medium risk for DVT were contacted; 35 subjects were excluded for several nonmedical, travel-related problems or inconvenient evaluation time; the remaining 165 were randomized into 2 groups to evaluate prevention in flights lasting between 11 and 12 hours. The control group had no prophylaxis; the treatment group used Traveno stockings. Of the 83 included subjects in the stockings group and 82 in the control group (total 165), 146 subjects completed the study. Dropouts were due to low compliance or connection problems. Age/sex distribution were comparable. Of 75 subjects completing the study in the stockings group and 71 in the control group, none had thrombosis. The average level of edema at inclusion was comparable in the 2 groups (1.1). After the flight there was a score of 8.9 (2) in controls; in the stockings group the score was 2.56 (1.3) (p < 0.05). The control of edema and swelling with stockings even after 11 hours of flight was clear, considering both parametric (circumference, volume) and nonparametric (analogue scale lines) measurements. The tolerability of the stockings was very good and there were no complaints or side effects. In conclusion Sigvaris Traveno stockings are very effective in controlling edema in long-haul flights.", "The true frequency of deep-vein thrombosis (DVT) during long-haul air travel is unknown. We sought to determine the frequency of DVT in the lower limb during long-haul economy-class air travel and the efficacy of graduated elastic compression stockings in its prevention.\n We recruited 89 male and 142 female passengers over 50 years of age with no history of thromboembolic problems. Passengers were randomly allocated to one of two groups: one group wore class-I below-knee graduated elastic compression stockings, the other group did not. All the passengers made journeys lasting more than 8 h per flight (median total duration 24 h), returning to the UK within 6 weeks. Duplex ultrasonography was used to assess the deep veins before and after travel. Blood samples were analysed for two specific common gene mutations, factor V Leiden (FVL) and prothrombin G20210A (PGM), which predispose to venous thromboembolism. Asensitive D-dimer assay was used to screen for the development of recent thrombosis.\n 12/116 passengers (10%; 95% CI 4.8-16.0%) developed symptomless DVT in the calf (five men, seven women). None of these passengers wore elastic compression stockings, and two were heterozygous for FVL. Four further patients who wore elastic compression stockings, had varicose veins and developed superficial thrombophlebitis. One of these passengers was heterozygous for both FVL and PGM. None of the passengers who wore class-I compression stockings developed DVT (95% CI 0-3.2%).\n We conclude that symptomless DVT might occur in up to 10% of long-haul airline travellers. Wearing of elastic compression stockings during long-haul air travel is associated with a reduction in symptomless DVT." ]

[ "19488999", "19123322", "15307692", "15729570", "15386806", "14679093", "19404608", "19008007", "18397986", "21088056", "12685875", "15993359", "8621013" ]

[ "Protective effects of 1-alpha-hydroxyvitamin D3 on residual beta-cell function in patients with adult-onset latent autoimmune diabetes (LADA).", "[Effect of Tangyikang in improving the function of pancreatic islet beta cells in patients with latent autoimmune diabetes mellitus in adults].", "[Study on improvement of islet beta cell function in patients with latent autoimmune diabetes mellitus in adults by integrative Chinese and Western medicine].", "Islet autoantibodies in clinically diagnosed type 2 diabetes: prevalence and relationship with metabolic control (UKPDS 70).", "Rosiglitazone combined with insulin preserves islet beta cell function in adult-onset latent autoimmune diabetes (LADA).", "Multicenter prevention trial of slowly progressive type 1 diabetes with small dose of insulin (the Tokyo study): preliminary report.", "GAD65 vaccination: 5 years of follow-up in a randomised dose-escalating study in adult-onset autoimmune diabetes.", "Rosiglitazone preserves islet beta-cell function of adult-onset latent autoimmune diabetes in 3 years follow-up study.", "Insulin intervention in slowly progressive insulin-dependent (type 1) diabetes mellitus.", "β-cell function and metabolic control in latent autoimmune diabetes in adults with early insulin versus conventional treatment: a 3-year follow-up.", "Slowly progressing type 1 diabetes: persistence of islet cell autoantibodies is related to glibenclamide treatment.", "Clinical evidence for the safety of GAD65 immunomodulation in adult-onset autoimmune diabetes.", "Small doses of subcutaneous insulin as a strategy for preventing slowly progressive beta-cell failure in islet cell antibody-positive patients with clinical features of NIDDM." ]

[ "Previous in vitro and in vivo studies have demonstrated that vitamin D could prevent pancreatic beta-cell destruction and reduce the incidence of autoimmune diabetes. In children with type 1 diabetes, vitamin D treatment produces moderate protective effects on residual beta-cell function and has proven to be safe. Therefore, we hypothesized that vitamin D might have protective effects on beta-cell function in patients with latent autoimmune diabetes in adults (LADA), a form of slowly progressive autoimmune type 1 diabetes.\n Thirty-five patients with LADA were randomly assigned to receive subcutaneous insulin alone (n = 18) or insulin plus 1-alpha-hydroxyvitamin D3 (1-alpha(OH)D3; 0.5 microg per day) (n = 17) for 1 year. Plasma C-peptide levels in fasting state (FCP) and 2 h after 75-g glucose load (PCP) were measured every 6 months with radioimmunoassay.\n Both FCP and PCP levels stayed steady in the insulin plus 1-alpha(OH)D3 group, while FCP decreased in insulin-alone group (P = 0.006) during the 12-month intervention. Seventy percent of patients treated with 1-alpha(OH)D3 maintained or increased their FCP concentrations after 1 year of treatment, while only 22% of patients treated with insulin alone maintained stable FCP levels (P < 0.01). Further analysis on LADA subgroups with different durations of diabetes demonstrated that islet beta-cell function was better preserved (as reflected by significantly higher FCP and PCP levels) in the 1-alpha(OH)D3 plus insulin group only in patients with diabetes duration no longer than 1 year. No severe side effects were observed in any group.\n Our data suggest that 1-alpha(OH)D3 plus insulin therapy can preserve pancreatic beta-cell function in patients with LADA.", "To investigate the effect and mechanism of Tangyikang (TYK) for improving pancreatic islet beta cell function in patients with latent autoimmune diabetes mellitus in adults (LADA).\n Seventy-four LADA patients were randomly assigned to two groups. The 37 patients in the treatment group were treated with TYK decoction (one dose consisted of red ginseng 10 g, milkvetch root 30 g, lilyturf root 15 g, wild weed 10 g, coptis root 15 g, cape-jasmine fruit 10 g, giant knotweed rhizome 10 g, safflower 10 g and moutan bark 10 g) combined with insulin therapy, and the 37 in the control group treated with insulin therapy alone, and the course for all was 3 months. Changes of glycosylated hemoglobin, index of pancreatic islet beta-cell function (delta CP(2h)/delta BS(2h)), serum interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were observed before and after treatment.\n All the above-mentioned indexes were improved after treatment in both groups, the post-treatment data showed significant difference between groups in delta CP(2h)/delta BS(2h), (0.258 +/- 0.106 vs 0.168 +/- 0.054, higher in the treatment group, t = 4.626, P < 0.01), but with insignificant difference in glycosylated hemoglobin (t = 0.441, P = 0.660). Besides, the dosage of insulin used in the treatment group was less than that in the control group (t = -4.169, P < 0.01); covariance analysis showed, through excluding impact of different dosages insulin used, IL- 4 level was higher (F = 24.217, P < 0.01) and IFN-gamma level was lower (F = 14.198, P < 0.01) in the treatment group than those in the control group.\n TYK could improve the function of islet beta-cell, its possible mechanism is related with the regulation on cell immunity and the correction of T-lymphocyte subsets (Th1/Th2 ratio) imbalance.", "To study the effect of integrative Chinese and Western medicine (ICWM) on improvement of the islet beta cell function in treating patients with latent autoimmune diabetes mellitus in adults (LADA).\n Eighty-four patients of LADA were randomly divided into 3 groups (20 in A, 33 in B and 31 in C), they were treated respectively with sulfonylurea, insulin and combination of insulin and Chinese medicine. The changes before and after treatment in blood glucose, glycohemoglobin and islet beta cell function were observed.\n After treatment, the damaged islet beta cell function in Group A was not improved, the secrete peak value of C-peptide was still low and delayed in Group A, but in Group B and C, it shifted earlier, suggesting that a certain degree of improvement and recovery of islet beta cell function. The improving effect in Group C was better.\n Chinese herbal medicine had effect in lowering blood glucose and improving islet beta cell function in patients with diabetes mellitus, and showed a synergistic and enhancing action when combined use with insulin. Early treatment of insulin or combination of insulin and Chinese medicine should be applied to patients with LADA.", "We examined the prevalence of islet autoantibodies and their relationship to glycaemic control over 10 years in patients diagnosed clinically with new-onset type 2 diabetes.\n Patient clinical characteristics and autoantibody status were determined at entry to the UK Prospective Diabetes Study (UKPDS) before randomisation to different glucose control policies. Patients were followed for 10 years.\n Data available on 4,545 of the 5,102 UKPDS patients showed that 11.6% had antibodies to at least one of three antigens: islet cell cytoplasm, glutamic acid decarboxylase and islet autoantibody 2A (IA-2A). Autoantibody-positive patients were younger, more often Caucasian and leaner, with lower beta cell function and higher insulin sensitivity than autoantibody-negative patients. They also had higher HbA1c, and HDL-cholesterol levels, and lower blood pressure, total cholesterol and plasma triglyceride levels. Despite relative hyperglycaemia, autoantibody-positive patients were less likely to have the metabolic syndrome (as defined by the National Cholesterol Education Program Adult Treatment Program III), reflecting a more beneficial overall risk factor profile. Of 3,867 patients with post-dietary run-in fasting plasma glucose (FPG) values between 6.0 and 14.9 mmol/l and no hyperglycaemic symptoms, 9.4% were autoantibody-positive, compared with 25.1% of 678 patients with FPG values of 15.0 mmol/l or higher, or hyperglycaemic symptoms. In both groups, no differences were seen between those with and without autoantibodies in changes to HbA1c over time, but autoantibody-positive patients required insulin treatment earlier, irrespective of the allocated therapy (p<0.0001).\n Autoantibody-positive patients can be treated initially with sulphonylurea, but are likely to require insulin earlier than autoantibody-negative patients.", "LADA is thought to result from the chronic autoimmune destruction of the insulin-producing pancreatic beta cells. In addition to antidiabetic effects, the newly developed insulin sensitizer-thiazolidinediones have the potential to increase the insulin content of islet cells by downregulating local inflammation and autoimmune response. Therefore, we hypothesized that LADA patients might benefit from thiazolidinediones treatment.\n LADA patients, with a fasting C-peptide (FCP) of 0.3 nmol/L or more, were enrolled and randomly assigned to receive subcutaneous insulin alone (insulin group, n = 12) or rosiglitazone plus insulin (insulin + RSG group, n = 11) to compare the impacts on islet beta cell function. Plasma glucose, HbA 1c, fasting C-peptide (FCP) and C-peptide after 2 h 75-g glucose load (PCP) were determined every 6 months. GAD-Ab and C-peptide were measured with radioimmune assays. Islet beta cell function was evaluated by PCP and DeltaCP(DeltaCP = PCP-FCP).\n All of the 23 patients have been followed up for 6 months, 17 cases for 12 months and 14 for 18 months. (1) During 6 months' follow-up, there were no significant changes for DeltaCP and PCP levels in both groups. (2) PCP and DeltaCP levels in insulin + RSG group patients stayed steady during the 12 months' observation (P = 0.161 for both PCP and DeltaCP), while in the insulin alone group, both FCP (P = 0.021) and PCP (P = 0.028) levels decreased significantly. Furthermore, PCP (P = 0.004) and DeltaCP(P = 0.015) differences between 12th month and baseline were higher in insulin + RSG group than those in the insulin group. (3) When observed up to 18 months, PCP and DeltaCP levels in insulin + RSG group patients still stayed steady, while PCP and DeltaCP levels decreased more in the insulin alone group.\n This pilot study suggests that rosiglitazone combined with insulin may preserve islet beta cell function in LADA patients.", "In 1996, we designed a randomized multicenter study to assess the effects of small doses of insulin on beta cell failure in slowly progressive type 1 diabetes (the Tokyo Study). We report here the preliminary results of this study. Glutamic acid decarboxylase 65 antibody (GADA)-positive patients were randomly divided into 2 groups: one group received insulin (Ins group), the other a sulfonylurea (SU group). Fifty-four patients (24 Ins group, 30 SU group) were analyzed at the end of a 4-year period. All patients underwent a 75 g oral-glucose test (O-GTT) every 6-12 months. The insulin-dependent stage was defined based on an integrated value of serum C-peptide levels on O-GTT ( summation operator CPR; sum of CPR at 0, 30, 60, 90, and 120 min) below 4.0 ng/mL. The summation operator CPR in the SU group decreased progressively from 22.0 +/- 10.6 to 11.3 +/- 7.5 ng/mL over the 48-month period (p < 0.001 vs. baseline). The summation operator CPR in the Ins group was unchanged. Among the SU group, 30% of subjects (9/30) progressed to IDDM, while 8.3% of Ins group subjects (2/24) progressed to IDDM (p = 0.087). With regard to the subjects who had a preserved C-peptide response ( summation operator CPR >/= 10 ng/mL), the proportion of SU group subjects who progressed to IDDM was significantly higher than that of the Ins group (7/28, 25% vs. 0/21, 0%, p = 0.015). Among subjects with a high GADA titer (>/=0 U/mL), 9/14 (64.3%) of the SU group, but only 2/16 (12.5%) of the Ins group, developed IDDM (p = 0.0068). As to those with a high GADA titer and a preserved C-peptide response, SU group subjects progressed to IDDM (7/12, 58.3%) more frequently than Ins group subjects (0/14, 0%) (p = 0.0012). In summary, our results suggest that small doses of insulin effectively prevent beta cell failure in slowly progressive type 1 diabetes. We recommend avoiding SU treatment and instead administering insulin to NIDDM patients with high GADA titer.", "The aim of this study was to ascertain whether treatment of GAD65 autoantibody (GADA)-positive diabetic patients with alum-formulated recombinant GAD65 (GAD-alum) is safe and does not compromise beta cell function.\n This Phase 2, placebo-controlled, dose-escalation clinical trial, which was randomized through a central office, was performed in 47 GADA-positive type 2 diabetic patients, who received subcutaneous injections of GAD-alum (4 [n = 9], 20 [n = 8], 100 [n = 9] or 500 [n = 8] microg) or placebo (n = 13) at weeks 1 and 4 of the trial. Participants and caregivers were blinded to group assignments. The primary outcome was safety as assessed by neurological tests, medications and beta cell function evaluated over 5 years, representing the end of the trial.\n No severe study-related adverse events occurred during the 5 year follow-up. None of the dose groups was associated with an increased risk of starting insulin treatment compared with the placebo group. The use of oral hypoglycaemic agents did not differ between the dose groups. After 5 years, fasting C-peptide levels declined in the placebo group (-0.24; 95% CI -0.41 to -0.07 log(10) nmol/l; p = 0.01) and the 500 microg dose group (-0.37; 95% CI -0.57 to -0.17 log(10) nmol/l; p = 0.003), but not in the 4 microg (-0.10; 95% CI -0.28 to 0.07 log(10) nmol/l; p = 0.20), 20 microg (0.04; 95% CI -0.12 to 0.19 log(10) nmol/l; p = 0.58) and 100 microg (0.00; 95% CI -0.20 to -0.20 log(10) nmol/l; p = 0.98) dose groups.\n The primary outcome of safety was achieved, since no severe study-related adverse events occurred.\n Because the study was initiated before 1 July 2005, the protocol was not registered in a registry.", "The newly developed insulin sensitizer-thiazolidinediones have the potential to downregulate inflammation and autoimmune response. The objective of this study was to observe the beneficial effects on beta-cell function in the LADA patients treated with rosiglitazone. 54 LADA patients were assigned to oral hypoglycemic agents group (GAD-Ab<175 U/mL and FCP>0.3 nmol/L) or early insulin administration group (GAD-Ab>or=175 U/mL or GAD-Ab<175 U/mL and FCP<or=0.3 nmol/L). Then, those patients were randomly assigned to receive sulfonylureas (SUs group) or rosiglitazone (RSG group) therapy, or to receive insulin alone (INS group) or rosiglitazone plus insulin (INS+RSG group). Plasma glucose, HbA1c, fasting C-peptide (FCP) and C-peptide after 2h 75-g glucose load (PCP) were determined every 6 months. The levels of PCP and delta CP were higher in RSG group compared with those in SUs group after the 18th month. The PCP level (after the 12th month) and delta CP level (after the 18th month) in INS+/-RSG group were higher than those in INS group. Rosiglitazone combined with insulin wherever or not preserved beta-cell function in LADA patients after 3 years.", "We tested the hypothesis that insulin therapy rather than sulfonylurea (SU) treatment is preferable to reverse or preserve beta-cell function among patients with slowly progressive insulin-dependent (type 1) diabetes (SPIDDM) or latent autoimmune diabetes in adults.\n This multicenter, randomized, nonblinded clinical study screened 4089 non-insulin-dependent diabetic patients for glutamic acid decarboxylase autoantibodies (GADAb). Sixty GADAb-positive non-insulin-requiring diabetic patients with a 5-yr duration or shorter of diabetes were assigned to either the SU group (n = 30) or the insulin group (n = 30). Serum C-peptide responses to annual oral glucose tolerance tests were followed up for a mean of 57 months. The primary endpoint was an insulin-dependent state defined by the sum of serum C-peptide values during the oral glucose tolerance test (SigmaC-peptide) less than 4 ng/ml (1.32 nmol/liter).\n The progression rate to an insulin-dependent state in the insulin group (three of 30, 10%) was lower than that in the SU group (13 of 30, 43%; P = 0.003, log-rank). Longitudinal analysis demonstrated that SigmaC-peptide values were better preserved in the insulin group than in the SU group. Multiple regression analysis demonstrated that insulin treatment, a preserved C-peptide response, and a low GADAb titer at entry were independent factors in preventing progression to an insulin-dependent state. Subgroup analysis suggested that insulin intervention was highly effective for SPIDDM patients with high GADAb titers [> or =10 U/ml (180 World Health Organization U/ml)] and preserved beta-cell function [SigmaC-peptide > or = 10 ng/ml (3.31 nmol/liter)] at entry. No severe hypoglycemic episodes occurred during the study.\n Insulin intervention to preserve beta-cell function is effective and safe for patients with SPIDDM or latent autoimmune diabetes in adults.", "The optimal treatment of latent autoimmune diabetes in adults (LADA) is not established. We explored whether early insulin treatment, which has shown beneficial effects in rodents and in human pilot studies, would result in better preservation of β-cell function or metabolic control, compared with conventional treatment.\n Glucagon-stimulated C-peptide and HbAlc were evaluated at baseline and after 12, 24 and 36 months in 37 patients recently diagnosed with diabetes, aged ≥ 30 years, non-insulin-requiring and GADAb and/or ICA positive. Twenty patients received early insulin and 17 received conventional treatment (diet ± oral hypoglycaemic agents (OHA), metformin, some and/or sulfonylurea) and insulin when necessary. RESUlts: Level of metabolic control, HbAlc, was preserved in the early insulin treated, while it significantly deteriorated in the conventionally treated. There was no significant difference between the groups in C-peptide after 12, 24 or 36 months, or in the decline of C-peptide. Only baseline C-peptide predicted a C-peptide of ≥ 0.5 nmol/l at 36 months. Gender, body mass index, antibody titres or HbAlc did not influence the levels of C-peptide or HbAlc at baseline or end-of-study, or the decline in C-peptide. Among the diet ± OHA-treated, 5/17 (30%) developed insulin dependency during the follow-up. No major hypoglycaemic events occurred.\n Early insulin treatment in LADA leads to better preservation of metabolic control and was safe. Superior preservation of C-peptide could not be significantly demonstrated. Only baseline level of C-peptide significantly influenced C-peptide level after 3 years. Further studies exploring the best treatment in LADA are warranted.", "Several experimental studies in rats have demonstrated that sulfonylurea treatment increases autoantigen expression in B-cells. This phenomenon may be deleterious for the preservation of residual beta cell function in patients with slowly progressing type 1 diabetes or latent autoimmune diabetes of adult (LADA).\n The aim of the present study was to evaluate whether the exclusion of glibenclamide in the treatment of ICA positive type 2 diabetic patients may diminish or halt the humoral autoimmune response against B-cells as well as improve metabolic control and insulin secretion.\n Fourteen type 2 diabetic patients with pancreatic autoimmunity (ICA+ and GABA+) and treated with insulin and glibenclamide (duration of disease 2.0 +/- 2.2, range 0.1-7 years and age 53 +/- 12.5, range 36-75 years) were studied. Patients were randomly assigned to two treatment groups, Group 1: insulin monotherapy (n = 8, age 53 +/- 6.4 years) (Exclusion of glibenclamide) and, Group 2: insulin plus glibenclamide (n = 6, age 53.5 +/- 16.9) (Unmodified treatment). Both groups were investigated at the beginning of the study and after one year for the following parameters: ICA and anti-GAD65 antibodies, fasting glucose and fasting C-peptide.\n In group 1, six out of eight patients became ICA negative while all patients in group 2 remained ICA positive (p = 0.0097). Fasting glucose concentrations improved in group 1 (4.6 +/- 2.8) in relation to group 2 (11.5 +/- 5.5, p = 0.0023) after one year of treatment. No differences were found for anti-GAD antibodies and fasting C-Peptide between the groups.\n These data show that exclusion of glibenclamide in the treatment of ICA+ type 2 diabetic patients partially decreases specific autoimmunity against endocrine pancreatic cells and improves metabolic control. This may reflect decreased expression of B-cell autoantigens suggesting that insulin monotherapy is a better choice for the treatment of LADA.", "The purpose of this Phase II study was to evaluate if alum-formulated human recombinant GAD65 is safe and does not compromise beta cell function. The study was conducted as a randomized, double blind, placebo-controlled, dose-escalation clinical trial in a total of 47 Latent Autoimmune Diabetes in Adults (LADA) patients who received either placebo or 4, 20, 100, or 500 microg Diamyd subcutaneously at Weeks 1 and 4. Safety evaluations, including neurology, beta cell function tests, diabetes status assessment, hematology, biochemistry, and cellular and humoral immunological markers, were repeatedly assessed over 24 weeks. None of the patients had significant study-related adverse events (AE). Fasting c-peptide levels at 24 weeks were increased compared with placebo (P=.0015) in the 20 microg but not in the other dose groups. In addition, both fasting (P=.0081) and stimulated (P=.0236) c-peptide levels increased from baseline to 24 weeks in the 20 microg dose group. GADA log levels clearly increased (P=.0002) in response to 500 microg Diamyd. The (CD4+)(CD25+)/(CD4+)(CD25-) cell ratio increased (P=.0128) at 24 weeks in the 20 microg group. No sudden increase in HbA1c or plasma glucose or decrease in beta cell function was observed in any of the dose groups. These positive findings for clinical safety further support the clinical development of Diamyd as a therapeutic to prevent autoimmune diabetes.", "We report a pilot study to determine the preventive effect of small doses of insulin injected subcutaneously on slowly progressive beta-cell damage in islet cell antibody (ICA)-positive patients with apparent NIDDM. Ten NIDDM patients who were ICA' were divided into two groups of five. In the insulin group (age: 51 +/- 8 years [mean +/- SD], sex: 3 men and 2 women), intermediate-type insulin (3-16 U/day) was given once or twice daily as a subcutaneous injection. The sulfonylurea (SU) group (age: 48 +/- 11 years, sex: 3 men and 2 women) was initially treated with a SU agent. Changes in beta-cell function, as indicated by serum C-peptide responses and blood glucose values during a 100-g oral glucose tolerance test, as well as ICA and GAD antibody status, were evaluated for up to 30 months in both groups. ICA status became negative in four of five patients in the insulin group. ICA status did not become negative in any of the patients in the SU group (P = 0.047 vs. insulin group). ICA status was persistently positive in two patients whose beta-cell function eventually progressed to an insulin-dependent state and fluctuated in the remaining three patients. In the insulin group, GAD antibody status became negative in one of four initially GAD antibody-positive NIDDM patients. In the SU group, GAD antibody status was persistently positive in three NIDDM patients (NS vs. insulin group). The serum C-peptide response improved significantly within 6 and 12 months in the insulin group, whereas it decreased progressively in the SU group. The changes in C-peptide response were significantly different between the two groups at 6, 12, 24, and 30 months. Two-hour blood glucose and HbA1 values were unchanged in the insulin group, but they increased in the SU group. Subcutaneous small doses of insulin, resulting in a high rate of negative conversion of ICA and an improved serum C-peptide response, may be effective in treating ICA+ NIDDM patients who are at high risk for slowly progressive beta-cell failure." ]

[ "11889661" ]

[ "The effectiveness of adding pharmacologic treatment with clonazepam or cyclobenzaprine to patient education and self-care for the treatment of jaw pain upon awakening: a randomized clinical trial." ]

[ "To compare the relative effectiveness of a benzodiazepine (clonazepam), a muscle relaxant (cyclobenzaprine), and a placebo for the treatment of jaw pain upon awakening, when each is combined with the recommended nonpharmacological components of initial medical management.\n Forty-one subjects were recruited with a diagnosis of myofascial pain based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). All subjects were given education about TMD and a self-care program. Subjects were randomized into 1 of 3 groups: clonazepam (0.5 mg/night), cyclobenzaprine (10 mg/night), or placebo. The primary outcome measure was the subjects' average intensity of jaw pain upon awakening over the prior week. This was recorded with a visual analog scale at pretreatment and at the completion of the 3-week trial. A secondary outcome measure was sleep quality based on the Pittsburg Sleep Quality Index.\n Within-group changes showed a statistically significant (P < .001) decrease in jaw pain upon awakening for all 3 groups. Between-group differences demonstrated a statistically significant difference (P < .016) between cyclobenzaprine and placebo, and between cyclobenzaprine and clonazepam. There was no significant effect on sleep quality in any group.\n This study suggests that cyclobenzaprine is statistically superior to either placebo or clonazepam when added to self-care and education for the management of jaw pain upon awakening. Based on the subjects' report of sleep quality, these medications failed to significantly improve sleep in the short term." ]

[ "18187561", "11994246" ]

[ "Influenza vaccination in secondary prevention from coronary ischaemic events in coronary artery disease: FLUCAD study.", "Influenza vaccine pilot study in acute coronary syndromes and planned percutaneous coronary interventions: the FLU Vaccination Acute Coronary Syndromes (FLUVACS) Study." ]

[ "To evaluate the effect of influenza vaccination on the coronary events in patients with confirmed coronary artery disease (CAD).\n Randomized, double-blind, placebo controlled study. We included 658 optimally treated CAD patients; 477 men, mean age 59.9+/-10.3 years. Three hundred and twenty-five patients received the influenza vaccine, and 333 patients placebo. Median follow-up was 298 (interquartile range 263-317) days. Primary endpoint was the cardiovascular death. Its estimated 12-month cumulative event rate was 0.63% in the vaccine vs. 0.76% in controls (HR 1.06 95% CI: 0.15-7.56, P = 0.95). There were two secondary composite endpoints: (i) the MACE (cardiovascular death, myocardial infarction, coronary revascularization) tended to occur less frequently in the vaccine group vs. placebo with the event rate 3.00 and 5.87%, respectively (HR 0.54;95% CI: 0.24-1.21, P = 0.13). (ii) Coronary ischaemic event (MACE or hospitalization for myocardial ischaemia) estimated 12-month event rate was significantly lower in the vaccine group 6.02 vs. 9.97% in controls (HR 0.54; 95% CI: 0.29-0.99, P = 0.047).\n In optimally treated CAD patients influenza vaccination improves the clinical course of CAD and reduces the frequency of coronary ischaemic events. Large-scale studies are warranted to evaluate the effect of influenza vaccination on cardiovascular mortality. (ClinicalTrials.gov: NCT 00371098).", "Recent reports have detected an increase in the number of patients with acute coronary syndromes during the flu season. In addition, the World Health Organization recommended vaccination against influenza infection for the Southern hemisphere in the winter of 2001. We evaluated the preventive impact of vaccination on subsequent ischemic events in myocardial infarction patients and in subjects undergoing planned percutaneous coronary angioplasty.\n We included 200 myocardial infarction patients admitted in the first 72 hours and 101 planned angioplasty/stent (PCI) patients without unstable coronary artery disease, prior bypass surgery, angioplasty, or tissue necrosis, in a prospective, multicenter log during the winter season. Infarct patients received a standard therapy and were then randomly allocated in a single-blind manner to either a unique intramuscular influenza vaccination or a control group. Similarly, PCI patients were allocated to either vaccination or control groups. Combined end points (death, reinfarction, and rehospitalization for ischemia) were assessed at 6 months' follow-up. The first primary outcome, cardiovascular death, occurred in 2% of the patients in the vaccine group compared with 8% in the control group (relative risk with vaccine as compared with controls, 0.25; 95% CI 0.07 to 0.86; P=0.01). The triple composite end point occurred in 11% of the patients in the vaccine group compared with 23% in controls (P=0.009).\n Influenza vaccination may reduce the risk of death and ischemic events in patients suffering from infarction and those recovering from angioplasty during flu season. This response could be related to a humoral immune response with positive consequences during flu seasons." ]

[ "56650", "360495", "4118203", "2436359", "2880214", "2310658", "495045", "451497", "1189985" ]

[ "Double-blind trial of glycerol therapy in early stroke.", "Intravenous glycerol in cerebral infarction: a controlled 4-month trial.", "Double-blind evaluation of glycerol therapy in acute cerebral infarction.", "Glycerol and dextran combined in the therapy of acute stroke. A placebo-controlled, double-blind trial with a planned interim analysis.", "Double-blind randomised trial of intravenous glycerol in acute stroke.", "Investigation of intravascular haemolysis during treatment of acute stroke with intravenous glycerol.", "Association of glycerol to dexamethasone in treatment of stroke patients.", "[Treatment with 10% glycerin in acute ischemic cerebral infarct. Doubleblind study].", "The effect of glycerol infusion in acute cerebral infarction." ]

[ "The effects of intravenous glycerol and intravenous dextrose were compared using a double-blind trial in twenty-seven patients with acute stroke. Administration continued for up to 6 days. A standard scoring system was used for neurological evaluation. There was no difference in mortality or in improvement in neurological score between the two groups.", "A double-blind, randomized trial was performed with 51 patients suffering from focal ischemic lesions in the territory of the middle cerebral artery. Intravenous infusions of 10% glycerol in 0.9% NaCl--5% glucose solutions were administered twice daily for 6 days to 26 patients, and the same amount of NaCl--glucose solutions to 25 controls. Glycerol did not reduce mortality (9 deaths in each group). The functional recovery was assessed by repeated neurological examinations during the 4 month trial. Glycerol significantly improved global performances and motor and sensory functions in patients with moderate disability, but its effect on global performances was transient. The patients with severe disability were not improved at all.", "nan", "The results of clinical trials investigating various therapies in acute ischemic stroke have been inconsistent. The effect of glycerol therapy and a combination therapy of glycerol and dextran was evaluated in a double-blind, placebo-controlled study. Repeated neurologic examinations (Day 0, Weeks 1, 6, 12, and 24) according to a modified Mathew score were performed on 62 patients. Statistical analysis showed no superiority of either treatment compared with placebo in acute ischemic stroke. A retrospective estimation of the Type II error of the study yielded approximately p = 0.25. A major side effect was hemolysis in 98% of patients treated with glycerol.", "The effects of intravenous glycerol in elderly patients with recent onset of acute ischaemic stroke were evaluated in a double-blind randomised controlled trial. 173 patients received either 500 ml of a 10% solution of glycerol in physiological saline or 500 ml of physiological saline administered intravenously over 4 h daily for 6 consecutive days. The number of deaths within the first week was 10 (12%) in the glycerol group versus 26 (30%) in the controls. Subsequent mortality up to 12 months was similar in the two groups and a survival analysis confirmed a beneficial effect of treatment (p less than 0.02). The neurological and functional recovery of survivors, their length of hospital stay, and the proportion able to return to live in their own home were similar in the two groups. The improvement in survival time with glycerol was achieved without serious adverse effects and without an increase in the proportion of survivors with severe residual disability.", "1. In patients with acute strokes entering a large ongoing randomised double-blind controlled trial of intravenous glycerol therapy, the extent and pathogenesis of any ensuing haemolysis were evaluated using standard clinical investigations and in vitro techniques. 2. Twenty patients received 10% glycerol in saline (500 ml over 4 h on 6 consecutive days) and 15 received corresponding control treatment with saline. 3. Intravascular haemolysis was evident after the first infusion; compared with the controls the glycerol group had i) a greater mean reduction in serum haptoglobin concentration (P less than .05), and ii) a greater proportion exhibiting haemoglobinaemia (P = 0.03). 4. After 6 days of glycerol treatment, the mean reduction in haemoglobin concentration was only 0.8 g more than in controls; this difference being neither clinically nor statistically significant. 5. Glycerol therapy was not associated with haemoglobinuria, renal insufficiency or disseminated intravascular coagulation. 6. Exposure of red blood cells to 1-10% glycerol in vitro did not induce haemolysis per se; on re-exposure to lower concentrations lysis ensued provided a minimum osmotic gradient was present. 7. Whilst taking standard dosage regimes of glycerol, the stroke patients we studied manifested a degree of intravascular haemolysis but its consequences were not clinically significant; lysis probably ensued after venous blood acquiring high glycerol concentrations mixed with blood containing little or no glycerol.", "A prospective study of 93 acute stroke patients randomly selected by type of antiedema treatment given (hypertonic glicerol infusion plus dexamethasone versus dexamethasone alone) failed to elicit any statistically significant difference between the two treatments on survival rates and quality of survival 7 and 30 days after the stroke.", "56 patients with acute ischemic cerebral infarction were randomly allocated to intravenous treatment for 6 days with either 500 ml of a 10% glycerol solution or 500 ml of a 5% dextrose solution (placebo). The neurological status of the patients was evaluated by a blinded investigator before the beginning of the treatment, after 2 weeks and again after 6 months. According to the initial degree of neurological deficit, patients were stratified into a mild, intermediate and severe group (using a scoring system). After 2 weeks there was significantly less neurological deficit in the total glycerol-treated group than in the placebo group (2p less than 0.02). This favourable effect of glycerol was even greater in the patients with an initially intermediate degree of neurological deficity (2p less than 0.01). After 6 months there was no difference between the total glycerol-treated and the placebo group. A beneficial effect of glycerol treatment, however, was still demonstrable in the intermediate group (2p less than 0.05). Mortality was not influenced by glycerol treatment. No side effects of the glycerol treatment could be detected. Intravenous administration of 10% glycerol can thus be recommended in patients with acute cerebral infarction.", "Intravenous administration of glycerol has been used in an effort to improve the prognosis for patients with acute cerebral infarction. Fifty patients were treated actively and 56 served as a control group. The neurological status before, during and after treatment for six days was assessed by a score system. The patients were grouped according to the initial score. Those with the highest and lowest scores did not improve from glycerol infusion. However, the treated patients with intermediate scores, where the prognosis is known to be dubious, showed a significant improvement compared to the controls. The mortality was not influenced. No undesirable side-effects from glycerol were registered." ]

[ "17690310", "19269254", "17690311" ]

[ "Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): a randomized, controlled trial.", "Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial.", "Sequential-design, multicenter, randomized, controlled trial of early decompressive craniectomy in malignant middle cerebral artery infarction (DECIMAL Trial)." ]

[ "Decompressive surgery (hemicraniectomy) for life-threatening massive cerebral infarction represents a controversial issue in neurocritical care medicine. We report here the 30-day mortality and 6- and 12-month functional outcomes from the DESTINY trial.\n DESTINY (ISRCTN01258591) is a prospective, multicenter, randomized, controlled, clinical trial based on a sequential design that used mortality after 30 days as the first end point. When this end point was reached, patient enrollment was interrupted as per protocol until recalculation of the projected sample size was performed on the basis of the 6-month outcome (primary end point=modified Rankin Scale score, dichotomized to 0 to 3 versus 4 to 6). All analyses were based on intention to treat.\n A statistically significant reduction in mortality was reached after 32 patients had been included: 15 of 17 (88%) patients randomized to hemicraniectomy versus 7 of 15 (47%) patients randomized to conservative therapy survived after 30 days (P=0.02). After 6 and 12 months, 47% of patients in the surgical arm versus 27% of patients in the conservative treatment arm had a modified Rankin Scale score of 0 to 3 (P=0.23).\n DESTINY showed that hemicraniectomy reduces mortality in large hemispheric stroke. With 32 patients included, the primary end point failed to demonstrate statistical superiority of hemicraniectomy, and the projected sample size was calculated to 188 patients. Despite this failure to meet the primary end point, the steering committee decided to terminate the trial in light of the results of the joint analysis of the 3 European hemicraniectomy trials.", "Patients with space-occupying hemispheric infarctions have a poor prognosis, with case fatality rates of up to 80%. In a pooled analysis of randomised trials, surgical decompression within 48 h of stroke onset reduced case fatality and improved functional outcome; however, the effect of surgery after longer intervals is unknown. The aim of HAMLET was to assess the effect of decompressive surgery within 4 days of the onset of symptoms in patients with space-occupying hemispheric infarction.\n Patients with space-occupying hemispheric infarction were randomly assigned within 4 days of stroke onset to surgical decompression or best medical treatment. The primary outcome measure was the modified Rankin scale (mRS) score at 1 year, which was dichotomised between good (0-3) and poor (4-6) outcome. Other outcome measures were the dichotomy of mRS score between 4 and 5, case fatality, quality of life, and symptoms of depression. Analysis was by intention to treat. This trial is registered, ISRCTN94237756.\n Between November, 2002, and October, 2007, 64 patients were included; 32 were randomly assigned to surgical decompression and 32 to best medical treatment. Surgical decompression had no effect on the primary outcome measure (absolute risk reduction [ARR] 0%, 95% CI -21 to 21) but did reduce case fatality (ARR 38%, 15 to 60). In a meta-analysis of patients in DECIMAL (DEcompressive Craniectomy In MALignant middle cerebral artery infarction), DESTINY (DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY), and HAMLET who were randomised within 48 h of stroke onset, surgical decompression reduced poor outcome (ARR 16%, -0.1 to 33) and case fatality (ARR 50%, 34 to 66).\n Surgical decompression reduces case fatality and poor outcome in patients with space-occupying infarctions who are treated within 48 h of stroke onset. There is no evidence that this operation improves functional outcome when it is delayed for up to 96 h after stroke onset. The decision to perform the operation should depend on the emphasis patients and relatives attribute to survival and dependency.", "There is no effective medical treatment of malignant middle cerebral artery (MCA) infarction. The purpose of this clinical trial was to assess the efficacy of early decompressive craniectomy in patients with malignant MCA infarction.\n We conducted in France a multicenter, randomized trial involving patients between 18 and 55 years of age with malignant MCA infarction to compare functional outcomes with or without decompressive craniectomy. A sequential, single-blind, triangular design was used to compare the rate of development of moderate disability (modified Rankin scale score < or =3) at 6 months' follow-up (primary outcome) between the 2 treatment groups.\n After randomization of 38 patients, the data safety monitoring committee recommended stopping the trial because of slow recruitment and organizing a pooled analysis of individual data from this trial and the 2 other ongoing European trials of decompressive craniectomy in malignant MCA infarction. Among the 38 patients randomized, the proportion of patients with a modified Rankin scale score < or =3 at the 6-month and 1-year follow-up was 25% and 50%, respectively, in the surgery group compared with 5.6% and 22.2%, respectively, in the no-surgery group (P=0.18 and P=0.10, respectively). There was a 52.8% absolute reduction of death after craniectomy compared with medical therapy only (P<0.0001).\n In this trial, early decompressive craniectomy increased by more than half the number of patients with moderate disability and very significantly reduced (by more than half) the mortality rate compared with that after medical therapy." ]

[ "15737962", "16971716", "17584571", "16154019", "18498953", "16160130", "12900339", "17562666", "14724301", "16286586", "15585732", "17932898", "17950142", "14769686", "18489933", "19755236", "17540198", "15028375", "17442201", "14744971", "16670444", "17616297", "15054589", "15619406", "15723977", "19081412", "17589978", "17498576", "14550694", "15464315", "19112781", "17680858", "17290437", "18261680", "19758877" ]

[ "Drug-eluting stents compared with thin-strut bare stents for the reduction of restenosis: a prospective, randomized trial.", "Sirolimus-eluting versus uncoated stents in acute myocardial infarction.", "Sirolimus-eluting stents compared with standard stents in the treatment of patients with primary angioplasty.", "Incremental cost-effectiveness of drug-eluting stents compared with a third-generation bare-metal stent in a real-world setting: randomised Basel Stent Kosten Effektivitäts Trial (BASKET).", "Long-term outcome in patients treated with sirolimus-eluting stents in complex coronary artery lesions: 3-year results of the SCANDSTENT (Stenting Coronary Arteries in Non-Stress/Benestent Disease) trial.", "Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial.", "Randomized study to assess the effectiveness of slow- and moderate-release polymer-based paclitaxel-eluting stents for coronary artery lesions.", "Long-term clinical benefit of sirolimus-eluting stent implantation in diabetic patients with de novo coronary stenoses: long-term results of the DIABETES trial.", "A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease.", "Clinical efficacy of polymer-based paclitaxel-eluting stents in the treatment of complex, long coronary artery lesions from a multicenter, randomized trial: support for the use of drug-eluting stents in contemporary clinical practice.", "Sirolimus-eluting vs uncoated stents for prevention of restenosis in small coronary arteries: a randomized trial.", "Randomized, double-blind, multicenter study of the polymer-based 17-beta estradiol-eluting stent for treatment of native coronary artery lesions: six-month results of the ETHOS I trial.", "One-year results of the SCORPIUS study: a German multicenter investigation on the effectiveness of sirolimus-eluting stents in diabetic patients.", "Analysis of 1-year clinical outcomes in the SIRIUS trial: a randomized trial of a sirolimus-eluting stent versus a standard stent in patients at high risk for coronary restenosis.", "Comparison of effectiveness and safety of sirolimus-eluting stents versus bare-metal stents in patients with diabetes mellitus (from the Italian Multicenter Randomized DESSERT Study).", "Direct stenting of de novo coronary stenoses with tacrolimus-eluting versus carbon-coated carbostents. The randomized JUPITER II trial.", "Randomized comparison of dexamethasone-eluting stents with bare metal stent implantation in patients with acute coronary syndrome: serial angiographic and sonographic analysis.", "The Canadian study of the sirolimus-eluting stent in the treatment of patients with long de novo lesions in small native coronary arteries (C-SIRIUS).", "Midterm outcomes of prospective, randomized, single-center study of the Janus tacrolimus-eluting stent for treatment of native coronary artery lesions.", "Inhibition of restenosis with a paclitaxel-eluting, polymer-free coronary stent: the European evaLUation of pacliTaxel Eluting Stent (ELUTES) trial.", "Evaluation of a new polymer-coated paclitaxel-eluting stent for treatment of de novo lesions: six-month clinical and angiographic follow-up results of the APPLAUSE trial.", "Two-year clinical follow-up after sirolimus-eluting versus bare-metal stent implantation assisted by systematic glycoprotein IIb/IIIa Inhibitor Infusion in patients with myocardial infarction: results from the STRATEGY study.", "ABT-578-eluting stents. The promising successor of sirolimus- and paclitaxel-eluting stent concepts?", "Angiographic results of the first human experience with everolimus-eluting stents for the treatment of coronary lesions (the FUTURE I trial).", "Maintenance of long-term clinical benefit with sirolimus-eluting coronary stents: three-year results of the RAVEL trial.", "Three-year clinical outcome after primary stenting of totally occluded native coronary arteries: a randomized comparison of bare-metal stent implantation with sirolimus-eluting stent implantation for the treatment of total coronary occlusions (Primary Stenting of Totally Occluded Native Coronary Arteries [PRISON] II study).", "Comparison of stent graft, sirolimus stent, and bare metal stent implanted in patients with acute coronary syndrome: clinical and angiographic follow-up.", "Randomized trial of Sirolimus-Eluting Stent Versus Bare-Metal Stent in Acute Myocardial Infarction (SESAMI).", "Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: double-blind, randomised controlled trial (E-SIRIUS).", "High-dose 7-hexanoyltaxol-eluting stent with polymer sleeves for coronary revascularization: one-year results from the SCORE randomized trial.", "Two year follow-up after primary PCI with a paclitaxel-eluting stent versus a bare-metal stent for acute ST-elevation myocardial infarction (the PASSION trial): a follow-up study.", "Single-center randomized evaluation of paclitaxel-eluting versus conventional stent in acute myocardial infarction (SELECTION).", "Randomized comparative trial of a thin-strut bare metal cobalt-chromium stent versus a sirolimus-eluting stent for coronary revascularization.", "Sirolimus-eluting stents versus bare-metal stents in patients with ST-segment elevation myocardial infarction: 9-month angiographic and intravascular ultrasound results and 12-month clinical outcome results from the MISSION! Intervention Study.", "Six-month results of a randomized study to evaluate safety and efficacy of a Biolimus A9 eluting stent with a biodegradable polymer coating." ]

[ "Drug-eluting stents have considerably reduced restenosis. Their relative merits have been assessed on the basis of comparisons made with control bare stents with thick struts. However, increased strut thickness negatively affects restenosis. No direct comparisons between drug-eluting stents and bare stents with thin struts have been performed. The aim of this study was to evaluate the relative efficacy of sirolimus-eluting stents (Cypher) as compared with that of bare stents with thin struts (BeStent 2).\n A total of 500 patients with coronary artery disease were randomly assigned to receive a Cypher stent or BeStent. The primary endpoint was angiographic restenosis defined as a stenosis diameter > or = 50% at 6-month angiographic follow-up. The secondary endpoint was the need for target vessel revascularization (TVR) during the year following the procedure. Follow-up angiography was performed in 81.8% of the patients. Patients treated with Cypher stents had a lower angiographic restenosis rate [8.3 vs. 25.5%, relative risk, 0.33 (95% confidence interval, 0.19-0.56), P<0.001] and a lower incidence of TVR [7.2 vs. 18.8%, relative risk, 0.38 (0.22-0.66), P<0.001]. For smaller vessels (< 2.8 mm), the angiographic restenosis rates were 7.0% with the Cypher stent and 34.2% with the BeStent (P<0.001). For larger vessels (> or = 2.8 mm), angiographic restenosis rates were 10.0% with the Cypher stent and 13.1% with the BeStent (P=0.52).\n The drug-eluting stent, Cypher, is associated with a significantly lower risk of restenosis compared with the bare thin-strut BeStent. The advantage of the Cypher stent is vastly reduced in large vessels.", "Sirolimus-eluting stents reduce rates of restenosis and reintervention, as compared with uncoated stents. Data are limited regarding the safety and efficacy of such stents in primary percutaneous coronary intervention (PCI) for acute myocardial infarction with ST-segment elevation.\n We performed a single-blind, multicenter, prospectively randomized trial to compare sirolimus-eluting stents with uncoated stents in primary PCI for acute myocardial infarction with ST-segment elevation. The trial included 712 patients at 48 medical centers. The primary end point was target-vessel failure at 1 year after the procedure, defined as target-vessel-related death, recurrent myocardial infarction, or target-vessel revascularization. A follow-up angiographic substudy was performed at 8 months among 174 patients from selected centers.\n The rate of the primary end point was significantly lower in the sirolimus-stent group than in the uncoated-stent group (7.3% vs. 14.3%, P=0.004). This reduction was driven by a decrease in the rate of target-vessel revascularization (5.6% and 13.4%, respectively; P<0.001). There was no significant difference between the two groups in the rate of death (2.3% and 2.2%, respectively; P=1.00), reinfarction (1.1% and 1.4%, respectively; P=1.00), or stent thrombosis (3.4% and 3.6%, respectively; P=1.00). The degree of neointimal proliferation, as assessed by the mean (+/-SD) in-stent late luminal loss, was significantly lower in the sirolimus-stent group (0.14+/-0.49 mm, vs. 0.83+/-0.52 mm in the uncoated stent group; P<0.001).\n Among selected patients with acute myocardial infarction, the use of sirolimus-eluting stents significantly reduced the rate of target-vessel revascularization at 1 year. (ClinicalTrials.gov number, NCT00232830 [ClinicalTrials.gov].).\n Copyright 2006 Massachusetts Medical Society.", "Sirolimus-eluting stents have been shown to decrease restenosis and reintervention as compared with standard stents. We evaluated the use of sirolimus-eluting stents in primary percutaneous coronary intervention for acute myocardial infarction with ST-segment elevation.\n We randomly assigned 120 patients to compare sirolimus-eluting stents with uncoated stents in primary percutaneous coronary intervention for acute myocardial infarction with ST-segment elevation. The primary end point was composite: death from cardiac causes, recurrent myocardial infarction, or target-lesion revascularization after 360 days.\n The rate of the primary end point was 6.7% in the sirolimus-eluting stent and 11% in the bare-metal stent group (relative risk 1.75, 95% CI 0.47-6.57, P = .402). The survival free from target-vessel failure showed a higher trend in the sirolimus-eluting stent group than in the bare-metal stent group (0.0% vs 5.7%, P = .064). There was no significant difference between the 2 groups in the rate of death (5% and 3.6%, respectively; P = .736), reinfarction (1.7% and 1.8%, respectively; P = .940), or stent thrombosis (3.4% and 1.8%, respectively; P = .621).\n Among selected patients with acute myocardial infarction and ST-segment elevation, the use of sirolimus-eluting stents shows a trend to reduce the rate of target-vessel revascularization in comparison with bare-metal stent.", "No prospective trial-based data are available for incremental cost-effectiveness of drug-eluting stents (DES) compared with bare-metal stents (BMS) in unselected patients, as treated in everyday practice.\n The Basel stent cost-effectiveness trial (BASKET) included 826 consecutive patients treated with angioplasty and stenting for 1281 de-novo lesions, irrespective of indication for angioplasty. Patients were randomised to one of two DES (Cypher, n=264; Taxus, n=281) or to a cobalt-chromium-based BMS (Vision, n=281) and followed up for 6 months for occurrence of major adverse cardiac events and costs. Analysis was by intention-to-treat. The primary endpoint was cost-effectiveness after 6 months, with effectiveness defined as reduction of major adverse cardiac events.\n Cardiac death, myocardial infarction, or target vessel revascularisation occurred in 39 of 544 (7.2%) patients with DES and 34 of 280 (12.1%) with BMS (odds ratio 0.56, 95% CI 0.35-0.91; p=0.02), without significant differences between the two DES. Total costs at 6 months were higher with DES (mean 10,544, SD 6849) than with BMS (9639, 9067; p<0.0001); higher stent costs of DES were not compensated for by lower follow-up costs. Incremental cost-effectiveness ratio of DES compared with BMS to avoid one major event was 18,311, and costs per quality-adjusted life-year gained were more than 50 000. Subgroup analyses showed that DES were more cost-effective for elderly patients in specific high-risk groups.\n In a real-world setting, use of DES in all patients is less cost effective than in studies with selected patients. Use of these stents could be restricted to patients in high-risk groups.", "Our purpose was to evaluate the long-term use of sirolimus-eluting stents (SES) and bare-metal stents (BMS) in patients with complex coronary artery lesions.\n Although the use of SES has proved to be effective in patients with simple coronary artery lesions, there are limited data of the long-term outcome of patients with complex coronary artery lesions.\n We randomly assigned 322 patients with total coronary occlusions or lesions located in bifurcations, ostial, or angulated segments of the coronary arteries to have SES or BMS implanted.\n At 3 years, major adverse cardiac events had occurred in 20 patients (12%) in the SES group and in 59 patients (38%) in the BMS group (p < 0.001). Four versus 2 patients suffered a cardiac death (p = NS), and 5 versus 1 died of a noncardiac disease (p = NS) in the SES versus the BMS group. Six patients in the SES group versus 15 patients in the BMS group suffered a myocardial infarction (p < 0.05) during the 3-year observation period, and target lesion revascularization was performed in 8 patients (4.9%) versus 53 patients (33.8%), respectively (p < 0.001); of these, 4 in the SES versus 7 in the BMS group were performed between 1 and 3 years after the index treatment (p = NS). According to revised definitions, stent thrombosis occurred in 5 patients (3.1%) in the SES group and in 7 patients (4.4%) in the BMS group (p = NS); very late stent thrombosis was observed in 4 versus 1 patient.\n A continued benefit was observed up to 3 years after implantation of SES in patients with complex coronary artery lesions. The rate of late adverse events was similar in the 2 groups, and stent thromboses occurred rarely after 1 year. (Sirolimus Eluting Stents in Complex Coronary Lesions [SCANDSTENT]; NCT00151658)", "Compared with bare metal stents, drug-eluting stents reduce restenosis in noncomplex lesions. The utility of drug-eluting stents has not been evaluated in more difficult stenoses.\n To investigate the safety and efficacy of the polymer-based, slow-release paclitaxel-eluting stent in a patient population with more complex lesions than previously studied.\n Prospective, placebo-controlled, double-blind, multicenter randomized trial conducted from February 2003 to March 2004 at 66 academic and community-based institutions with 1156 patients who underwent stent implantation in a single coronary artery stenosis (vessel diameter, 2.25-4.0 mm; lesion length, 10-46 mm), including 664 patients (57.4%) with complex or previously unstudied lesions (requiring 2.25-mm, 4.0-mm, and/or multiple stents) and 9-month clinical and angiographic follow-up.\n Patients were randomly assigned to receive 1 or more bare metal stents (n = 579) or identical-appearing paclitaxel-eluting stents (n = 577).\n Ischemia-driven target vessel revascularization at 9 months.\n Baseline characteristics were well matched. Diabetes was present in 31% of patients. The mean (SD) reference vessel diameter was 2.69 (0.57) mm, the reference lesion length was 17.2 (9.2) mm, and 78% of lesions were type B2/C. A mean (SD) of 1.38 (0.58) stents (total mean [SD] length, 28.4 [13.1] mm) were implanted per lesion; 33% of lesions required multiple stents. Stents that were 2.25 mm and 4.0 mm in diameter were used in 18% and 17% of lesions, respectively. Compared with bare metal stents, paclitaxel-eluting stents reduced the 9-month rate of target lesion revascularization from 15.7% to 8.6% (P<.001) and target vessel revascularization from 17.3% to 12.1% (P = .02). Similar rates were observed for cardiac death or myocardial infarction (5.5% for bare metal stent group vs 5.7% for paclitaxel-eluting stent group) and stent thrombosis (0.7% in both groups). Angiographic restenosis was reduced from 33.9% to 18.9% in the entire study cohort (P<.001), including among patients receiving 2.25-mm stents (49.4% vs 31.2%; P = .01), 4.0-mm stents (14.4% vs 3.5%; P = .02), and multiple stents (57.8% vs 27.2%; P<.001).\n Compared with a bare metal stent, implantation of the paclitaxel-eluting stent in a patient population with complex lesions effectively reduces clinical and angiographic restenosis.", "Early clinical studies demonstrated the feasibility of local paclitaxel delivery in reducing restenosis after treatment of de novo coronary lesions in small patient populations.\n We conducted a randomized, double-blind trial of 536 patients at 38 medical centers evaluating slow-release (SR) and moderate-release (MR) formulations of a polymer-based paclitaxel-eluting stent (TAXUS) for revascularization of single, primary lesions in native coronary arteries. Cohort I compared TAXUS-SR with control stents, and Cohort II compared TAXUS-MR with a second control group. The primary end point was 6-month percent in-stent net volume obstruction measured by intravascular ultrasound. Secondary end points were 6-month angiographic restenosis and 6- and 12-month incidence of major adverse cardiac events, a composite of cardiac death, myocardial infarction, and repeat revascularization. At 6 months, percent net volume obstruction within the stent was significantly lower for TAXUS stents (7.9% SR and 7.8% MR) than for respective controls (23.2% and 20.5%; P<0.0001 for both). This corresponded with a reduction in angiographic restenosis from 17.9% to 2.3% in the SR cohort (P<0.0001) and from 20.2% to 4.7% in the MR cohort (P=0.0002). The incidence of major adverse cardiac events at 12 months was significantly lower (P=0.0192) in the TAXUS-SR (10.9%) and TAXUS-MR (9.9%) groups than in controls (22.0% and 21.4%, respectively), predominantly because of a significant reduction in repeat revascularization of the target lesion in TAXUS-treated patients.\n Compared with a bare metal stent, paclitaxel-eluting stents reduced in-stent neointimal formation and restenosis and improved 12-month clinical outcome of patients with single de novo coronary lesions.", "Sirolimus stent implantation has been demonstrated to be safe and effective in diabetics; however, the long-term outcomes in this high-risk population remain unknown. The aim of this study was to determine the long-term safety and efficacy of the sirolimus-eluting stent (SES) when compared with the bare metal stent (BMS) in patients included in the DIABETES (DIABETes and sirolimus Eluting Stent) trial.\n The prospective multicentre DIABETES trial randomized 160 diabetic patients with one or more significant coronary stenoses in one, two, or three vessels to either SES or BMS implantation. One-year dual antiplatelet therapy (aspirin plus clopidogrel) was routinely prescribed. Clinical follow-up was scheduled at 1, 9, 12, and 13 months and 2 years. Baseline clinical and angiographic characteristics were comparable between groups. At 2 years, the rate of target lesion revascularization was significantly lower in the SES group compared with the BMS group (7.7 vs. 35.0%, P < 0.001). However, the total revascularization rate at 2 years increased in both groups due to progression of atherosclerosis in coronary segments remote from the target lesion (rate of atherosclerosis progression: 7.7% in SES group vs. 10% in BMS group; P = 0.7). During dual antiplatelet treatment (1 year), there was no stent thrombosis in the SES group, whereas two patients presented it in the BMS group. However, after clopidogrel withdrawal, three patients allocated to the SES group presented stent thromboses vs. none in the BMS group.\n SES implantation in diabetic patients remains effective at 2-year follow-up. However, clinical efficacy appeared to be reduced by the occurrence of stent thrombosis between 1 and 2 years.", "Restenosis after coronary stenting necessitates repeated percutaneous or surgical revascularization procedures. The delivery of paclitaxel to the site of vascular injury may reduce the incidence of neointimal hyperplasia and restenosis.\n At 73 U.S. centers, we enrolled 1314 patients who were receiving a stent in a single, previously untreated coronary-artery stenosis (vessel diameter, 2.5 to 3.75 mm; lesion length, 10 to 28 mm) in a prospective, randomized, double-blind study. A total of 652 patients were randomly assigned to receive a bare-metal stent, and 662 to receive an identical-appearing, slow-release, polymer-based, paclitaxel-eluting stent. Angiographic follow-up was prespecified at nine months in 732 patients.\n In terms of base-line characteristics, the two groups were well matched. Diabetes mellitus was present in 24.2 percent of patients; the mean reference-vessel diameter was 2.75 mm, and the mean lesion length was 13.4 mm. A mean of 1.08 stents (length, 21.8 mm) were implanted per patient. The rate of ischemia-driven target-vessel revascularization at nine months was reduced from 12.0 percent with the implantation of a bare-metal stent to 4.7 percent with the implantation of a paclitaxel-eluting stent (relative risk, 0.39; 95 percent confidence interval, 0.26 to 0.59; P<0.001). Target-lesion revascularization was required in 3.0 percent of the group that received a paclitaxel-eluting stent, as compared with 11.3 percent of the group that received a bare-metal stent (relative risk, 0.27; 95 percent confidence interval, 0.16 to 0.43; P<0.001). The rate of angiographic restenosis was reduced from 26.6 percent to 7.9 percent with the paclitaxel-eluting stent (relative risk, 0.30; 95 percent confidence interval, 0.19 to 0.46; P<0.001). The nine-month composite rates of death from cardiac causes or myocardial infarction (4.7 percent and 4.3 percent, respectively) and stent thrombosis (0.6 percent and 0.8 percent, respectively) were similar in the group that received a paclitaxel-eluting stent and the group that received a bare-metal stent.\n As compared with bare-metal stents, the slow-release, polymer-based, paclitaxel-eluting stent is safe and markedly reduces the rates of clinical and angiographic restenosis at nine months.\n Copyright 2004 Massachusetts Medical Society", "Intracoronary polymer-based stent delivery of paclitaxel has been shown to be effective in reducing restenosis in simple coronary lesions, but the evidence base for contemporary use in longer, more complex coronary stenoses is lacking.\n TAXUS VI is a prospective, multicenter, double-blind, randomized trial assessing clinical and angiographic outcomes of the TAXUS Moderate Release paclitaxel-eluting stent in the treatment of long, complex coronary artery lesions. Four hundred forty-eight patients at 44 sites were randomized (1:1) between a drug-eluting TAXUS Express2 and an uncoated Express2 control stent. Per protocol, the 9-month follow-up included an angiographic reevaluation in all patients. The primary end point was the rate of target-vessel revascularization 9 months after the study procedure; secondary end points included the rate of target-lesion revascularization and binary restenosis at follow-up. Mean lesion length in the study was 20.6 mm, with a mean stent-covered length of 33.4 mm. Of all lesions, 55.6% were classified as complex lesions (type C of the AHA/ACC classification). At 9 months, target-vessel revascularization was 9.1% in the TAXUS group and 19.4% in the control group (P=0.0027; relative reduction, 53%). Target-lesion revascularization was reduced from 18.9% to 6.8%, respectively (P=0.0001). The incidence of major adverse cardiac events was similar in the 2 groups, 16.4% and 22.5% in TAXUS and control, respectively (P=0.12), including comparable rates for acute myocardial infarction. Binary restenosis in the stented area was reduced from 32.9% in the control group to 9.1% in the TAXUS patients (P<0.0001).\n The finding that the TAXUS Moderate Release stent system is safe and effective in the treatment of long, complex coronary artery lesions provides the evidence base for the more widespread use of drug-eluting stents in contemporary clinical practice.", "Percutaneous coronary revascularization of small vessels is associated with a high restenosis rate. Sirolimus-eluting stents reduce restenosis in simple and previously untreated lesions of large coronary arteries, but their outcomes in small vessels have not been adequately investigated.\n To determine whether sirolimus-eluting stents are associated with a reduced 8-month rate of angiographic restenosis in comparison with an uncoated stent.\n This was a randomized, multicenter, single-blind, prospective trial performed with 257 patients undergoing percutaneous coronary revascularization for ischemic heart disease, and who had a previously untreated atherosclerotic lesion located in a small segment with a diameter of 2.75 mm or less, in 20 Italian centers between August 2002 and December 2003.\n Patients were randomly assigned to receive a sirolimus-eluting stent (129 patients) or an uncoated stent having an identical architecture and radiographic appearance (128 patients).\n The primary end point was the 8-month binary in-segment restenosis rate; secondary end points included procedural success and the 8-month rate of major adverse cardiac and cerebrovascular events.\n The mean (SD) reference diameter of the treated segment was 2.2 (0.28) mm; the lesion length, 11.84 (6.15) mm. After 8 months, the binary in-segment restenosis rate was 53.1% (60/113) in the patients receiving an uncoated stent and 9.8% (12/123) in those receiving a sirolimus-eluting stent (relative risk [RR], 0.18; 95% confidence interval [CI], 0.10-0.32; P<.001). Fewer patients randomized to sirolimus-eluting stents experienced major adverse cardiac events (12/129 [9.3%] vs 40/128 [31.3%]; RR, 0.30; 95% CI, 0.15-0.55; P<.001) mainly because of a reduction in target lesion revascularization (9/129 [7%] vs 27/128 [21.1%]; RR, 0.33; 95% CI, 0.14-0.70; P = .002) and myocardial infarction (2/129 [1.6%] vs 10/129 [7.8%]; RR, 0.20; 95% CI, 0.01-0.93; P = .04).\n The use of sirolimus-eluting stents to treat atherosclerotic lesions in small coronary arteries reduces restenosis and may also reduce major adverse cardiac events.", "The ETHOS I trial was the first in-human experience evaluating the safety and efficacy of two different release formulations of the 17-beta estradiol-eluting R-Stent versus uncoated control stents for the treatment of patients with single de novo native coronary lesions.\n Estrogens were reported to inhibit neointimal proliferation and to accelerate endothelial regeneration after coronary angioplasty and thus could be an ideal compound to deliver on a stent for the purpose of reducing in-stent restenosis.\n Ninety-five patients were randomized to receive a slow-release (n = 32) or the moderate release (n = 31) formulations or the bare metal stent (n = 32). The primary end point was the 6-month percent in-stent volume obstruction by intravascular ultrasound (IVUS).\n Diabetes was present in 29.5% of patients; the mean reference vessel diameter was 2.90 mm; and the mean lesion length was 13.5 mm. Primary endpoint, 6-month percent in-stent volume obstruction by IVUS, did not differ significantly between the 3 groups (31% +/- 14%, 33% +/- 11%, and 31% +/- 14%, P = 0.83). Secondary endpoints also did not differ significantly between the groups including 6-month rates of in-lesion binary angiographic restenosis (13.3%, 14.3%, and 12.5%, P = 0.98), in-stent late loss (0.82 +/- 0.49 mm, 0.86 +/- 0.53 mm, and 0.84 +/- 0.46 mm, P = 0.97), target lesion revascularization (12.5%, 6.9%, and 6.5%, P = 0.64), and major adverse cardiac events (18.8%, 10.3%, and 6.5%, P = 0.31).\n In this first-in-man randomized trial, the 17-beta estradiol-eluting R-Stent, in either slow- or moderate-release formulations, was well-tolerated, but showed no benefit for treatment of coronary lesions when compared to controls.\n (c) 2007 Wiley-Liss, Inc.", "This study sought to analyze the effectiveness of drug-eluting stents in a high-risk group of diabetic patients. Previously, this had been analyzed only in substudies of larger trials or in clinical investigations enrolling a small number of patients.\n Drug-eluting stents are highly effective in reducing the rate of in-stent restenosis.\n Two hundred patients with diabetes and de novo coronary artery lesions were enrolled in 16 centers: 98 were randomly assigned to sirolimus-eluting stents (SES) and 102 received bare-metal stents (BMS). The primary end point was in-segment late luminal loss. Major adverse cardiac events (MACE) rate was analyzed at 30 days and 8 and 12 months.\n The extent of in-segment late luminal loss in the SES group was 0.18 mm compared with 0.74 mm in the BMS group. In-segment restenosis was identified on follow-up angiography in 8.8% of the patients in SES and in 42.1% in BMS (p < 0.0001). Target lesion revascularization was performed in 5.3% of the patients in SES and in 21.1% of the patients in BMS (p = 0.002). The SES was effective in the treatment group with oral diabetic medication as well as in the insulin-dependent treatment group (3.6% SES vs. 38.8% BMS). There was no subacute stent thrombosis in the SES group up to 1 year. The MACE rate was not significantly different at 30 days. At 12 months, MACE rate was 14.7% in SES versus 35.8% in BMS.\n The SES is safe and highly effective in patients with diabetes mellitus and coronary artery disease and associated with a significant decrease in the extent of late luminal loss.", "This study evaluated a large group of patients enrolled in a double-blind randomized trial of the sirolimus-eluting stent to document whether the initial clinical improvement seen in previous smaller series is maintained out to 12 months and to study the potential treatment effect in patient subsets known to be at increased risk of restenosis.\n A total of 1058 patients with de novo native coronary stenosis undergoing clinically indicated percutaneous coronary intervention were randomly assigned to sirolimus-eluting stent (533) or control bare stent (525). Procedural success and in-hospital outcomes were excellent and did not differ between the 2 groups. At 9 months, clinical restenosis, defined as target-lesion revascularization, was 4.1% in the sirolimus limb versus 16.6% in the control limb (P<0.001). At 12 months, the absolute difference in target-lesion revascularization continued to increase and was 4.9% versus 20% (P<0.001). There were no differences in death or myocardial infarction rates. In high-risk patient subsets, defined by vessel size, lesion length, and presence of diabetes mellitus, there was a 70% to 80% reduction in clinical restenosis at 1 year.\n Placement of the sirolimus-eluting stent results in continued clinical improvement at 1 year after initial implantation, with significant reduction in clinical restenosis as defined by target-lesion revascularization. Between 9 and 12 months, the absolute reduction of clinical restenosis continues to increase. Even in high-risk subsets of patients, there is a 70% to 80% relative reduction in clinical restenosis at 12 months with this drug-eluting stent.", "Few studies directly compared drug-eluting stents and bare-metal stents (BMSs) in diabetic patients. DESSERT was an Italian multicenter randomized trial to show the efficacy of sirolimus-eluting stents (SESs) compared with BMSs in de novo lesions of diabetic patients treated with insulin and/or oral antidiabetics for > or =3 months on top of glycoprotein IIb/IIIa inhibitors. The primary end point was in-stent late lumen loss, assessed using centralized quantitative coronary angiography at 8-month follow-up. Centrally adjudicated composite major adverse cardiac events (MACEs) and target-vessel failure (TVF; death, treated vessel-related acute myocardial infarction, and target-vessel revascularization) at 30 days and 9 and 12 months were secondary end points. Seventy-five patients were randomly assigned to an SES (109 lesions), and 75 (109 lesions), to a BMS. The 2 groups were well balanced for clinical, anatomic, and procedural characteristics. In-stent late lumen loss decreased from 0.96 +/- 0.61 mm for BMSs to 0.14 +/- 0.33 for SESs (p <0.001), and in-segment binary restenosis was 38.8% versus 3.6%, respectively (p <0.001). Twelve-month clinical events were significantly lower in the sirolimus group: MACEs 22.1% versus 40% (p = 0.023), target-lesion revascularization 5.9% versus 30% (p <0.001), and TVF 14.7% versus 34.3% (p = 0.008). At multivariate analysis, stent type was confirmed as an independent predictor of in-segment late loss (p <0.001), binary restenosis (p <0.001), 12-month TVF (p = 0.010), and 12-month MACEs (p = 0.037). In conclusion, the randomized DESSERT showed SESs to be safe and effective in decreasing both angiographic parameters of restenosis and incidence of MACEs compared with BMSs in diabetic patients with de novo 1- or 2-vessel coronary stenoses.", "Aims: Drug-eluting stents are being increasingly used for the treatment of de novo coronary lesions. This trial compared the performance of tacrolimus-eluting stents (TES) with that of equivalent carbon-coated stents (CCS).Methods and results: The JUPITER II trial enrolled 332 patients (mean age = 64 years, 75% men) with de novo coronary stenoses. Patients were randomly assigned to TES versus CCS and underwent repeat coronary angiography at 6 months. The primary study endpoint was in-stent and in-segment late lumen loss (LLL). The main secondary endpoints included binary restenosis, and rates of major adverse clinical events (MACE), including death, myocardial infarction, target lesion revascularisation and stent thrombosis at 1, 6, and 12 months of follow-up. The procedure was successful in 99.4% of patients in both groups. There was no procedural death, 1 cardiac death at 2 months, and 1 acute and 2 subacute CCS thromboses. Angiographic follow-ups were available in 94.4% and 95.1% of patients assigned to TES and CCS, respectively. The mean in-segment and in-stent LLL was 0.42+/-0.46 mm and 0.65+/-0.47 mm, respectively, in the TES, versus 0.48+/-0.52 mm and 0.66+/-0.53 mm, respectively, in the CCS group (ns). The 12-month cumulative MACE rate was 19.5% in the CCS versus 16.1% in the TES group (ns).Conclusions: Both stents showed high safety, with no stent thrombosis in the TES group. No difference was observed in 6-month angiographic results and 12-month MACE rates between TES and CCS.", "The aim of this study is to compare the anti-inflammatory effect of the dexamethasone preloaded stent (Dexamet, Abbott, Galway, Ireland) with the bare metal stent (BMS; BiodivYsio, Biocompatibles Cardiovascular LTD, Galway, Ireland) in patients with acute coronary syndrome (ACS) assessed by angiographic (QCA) and intracoronary ultrasound (ICUS).\n One hundred twenty patients with ACS were randomly assigned to revascularization using the Dexamet stent (n = 60) or BMS (n = 60). Serial QCA analysis and ICUS analysis were performed during long-term follow-up (2.9 F; 20 MHz transducer; Volcano Corp, Brussels, Belgium). Power calculations were performed for QCA-derived differences of lumen loss. In addition, statistical analysis was performed (SPSS for Windows 12.0.1). The target lesion revascularization rate was lower in the Dexamet group (10 [16.67%] vs 20 [33.33%] patients; P = .031). The QCA revealed improved lumen restoration in the Dexamet stent group (lumen loss, 0.55 +/- 0.65 vs 1.07 +/- 0.92 mm [P = .001]; loss index, 0.20 +/- 0.23 vs 0.46 +/- 0.42 [P < .001]). The ICUS revealed greater neointimal proliferation in the BMS versus the Dexamet stent group (3.36 +/- 1.03 vs 3.05 +/- 1.38 mm2; P < .001). Death (n = 1) and the number of total occlusions of the stent segment (n = 1) were identical in both groups.\n Dexamet stents, in comparison with the BMS stents, reduced the target lesion revascularization rate in patients with ACS and lead to better lumen restoration during long-term follow-up.", "We assessed the safety and effectiveness of the sirolimus-eluting stent (SES) in treating single de novo long lesions in small native coronary arteries compared to an identical bare metal stent (BMS).\n The SES was previously demonstrated to reduce restenosis significantly. However, patients with long lesions in small vessels have not been well studied and may define a group at very high risk.\n The Canadian Study of the Sirolimus-Eluting Stent in the Treatment of Patients With Long De Novo Lesions in Small Native Coronary Arteries (C-SIRIUS) was a multicenter, randomized, double-blind trial comparing SES versus identical BMS. The primary end point was in-stent minimal lumen diameter (MLD) at eight months. Secondary end points included angiographic restenosis at 8 months, target lesion revascularization (TLR), and major adverse cardiac events (MACE) at 270 days.\n A total of 100 patients were enrolled at eight Canadian sites. The in-stent MLD at eight months was 2.46 +/- 0.37 mm in the SES compared with 1.49 +/- 0.75 mm in the BMS (a 65% increase, p < 0.001). Angiographic restenosis occurred in 1 of 44 SES patients (2.3%, with no in-stent restenosis) and in 23 of 44 BMS patients (52.3%, p < 0.001). At 270 days, there were two clinically driven TLRs in the SES (4%) and nine in the BMS (18%, p = 0.05). The Kaplan-Meier estimate of freedom from MACE at 270 days was 96.0% for SES patients and 81.7% for BMS patients (p = 0.029).\n Patients with long lesions in small vessels are at very high risk of restenosis. In these patients, the SES dramatically reduces the risk of restenosis at eight months, translating into an excellent clinical outcome at nine months.", "Long-term efficacy and safety of tacrolimus-eluting stent (Janus) for treatment of coronary artery disease in percutaneous coronary interventions (PCI) \"real world\" is uncertain. The aim of this study was to evaluate the efficacy and safety of Janus stent for treating coronary heart disease in PCI daily practice, the safety of 4-month clopidogrel therapy after Janus stent implantation and the feasibility for treating patients with acute myocardial infarction (AMI) for first time.\n From February 20, 2006 to August 26, 2006, a total of 200 patients were enrolled and randomly assigned to receive either Janus stent (n = 100) or bare metal stent (Tecnic Carbostent, n = 100). All patients were administered with clopidogrel for 4 months and aspirin for life long after stenting.\n Baseline clinical and angiographic characteristics were comparable between the two groups. AMI was present in 37% of patients with Janus and 36% with Tecnic Carbostent. At an average of 246-day follow-up, major adverse cardiac events (MACE) was 6% with the Janus stent and 15% with the Tecnic Carbostent (P = 0.038). Primary events included 1 cardiac death, 1 myocardial infarction (MI) due to subacute stent thrombosis and 13 target lesion revascularizations (TLR) due to restenosis in patients with Tecnic Carbostent and 6 TLR due to restenosis in patients with Janus stent. Although all patients had discontinued clopidogrel for an average of 126 days, there was no additional thrombotic event in the two groups.\n Janus stent is efficient in reducing MACE compared with Tecnic Carbostent at an average of 8-month follow-up. Discontinuation of clopidogrel at 4 months after PCI is safe for patients with Janus stent, including AMI patients. Long-term efficacy of Janus stent in reducing restenosis requires further study.", "The use of a stent to deliver a drug may reduce in-stent restenosis. Paclitaxel interrupts the smooth muscle cell cycle by stabilizing microtubules, thereby arresting mitosis.\n On the basis of prior animal studies, the European evaLUation of the pacliTaxel Eluting Stent (ELUTES) pilot clinical trial (n=190) investigated the safety and efficacy of V-Flex Plus coronary stents (Cook Inc) coated with escalating doses of paclitaxel (0.2, 0.7, 1.4, and 2.7 microg/mm2 stent surface area) applied directly to the abluminal surface of the stent in de novo lesions compared with bare stent alone. The primary efficacy end point was angiographic percent diameter stenosis at 6 months. At angiographic follow-up, percent diameter stenosis was 33.9+/-26.7% in controls (n=34) and 14.2+/-16.6% in the 2.7-microg/mm2 group (n=31; P=0.006). Late loss decreased from 0.73+/-0.73 to 0.11+/-0.50 mm (P=0.002). Binary restenosis (> or =50% at follow-up) decreased from 20.6% to 3.2% (P=0.056), with no significant benefit from intermediate paclitaxel doses. Freedom from major adverse cardiac events in the highest (effective) dose group was 92%, 89%, and 86% at 1, 6, and 12 months, respectively (P=NS versus control). No late stent thromboses were seen in any treated group despite clopidogrel treatment for 3 months only.\n Paclitaxel applied directly to the abluminal surface of a bare metal coronary stent, at a dose density of 2.7 microg/mm2, reduced angiographic indicators of in-stent restenosis without short- or medium-term side effects.", "This trial assesses the safety and efficacy of the PicoElite stent (amg International GmbH, Raesfeld-Erle, Germany), a new paclitaxel-eluting polymer-based stent.\n This is a first-in-man, single-center pilot trial that randomized 30 patients with 35 de novo coronary lesions in a 2:1 proportion to either the paclitaxel-eluting PicoElite stent (PES group: 20 patients with 24 lesions) or the bare metal ArthosPico stent (BMS group: 10 patients with 11 lesions).\n Baseline characteristics were similar in both groups, apart from younger patients in the PES group (mean age 63.5 years vs. 71.7 years in the BMS group; p = 0.032) and shorter lesion length in the PES group (9.56 mm vs. 14.25 mm in the BMS group; p = 0.02). In both groups, there was no difference in the primary endpoint of major adverse cardiac events (MACE) at 30-day follow up. There was a nonsignificant trend towards lower 6-month MACE and target lesion revascularization (TLR) rates in the PES group (10.5% PES vs. 40.0% in the BMS group for both; p = 0.143), and no stent thrombosis in the PES group. At 6-month angiographic follow up, the PES group demonstrated a significantly reduced in-stent binary restenosis rate (5.0% vs. 40.0%; p = 0.031), in-stent late loss (0.47 mm vs. 1.10 mm; p = 0.004), and in-segment late loss (0.72 mm vs. 1.16 mm; p = 0.016) as compared to the BMS group.\n The 6-month results of the APPLAUSE study demonstrate the safety and efficacy of the paclitaxel-eluting PicoElite stent for de novo lesions, with a significant reduction in late loss and a trend towards less TLR compared to a bare metal control.", "We sought to investigate whether the previously reported midterm clinical benefit of planned sirolimus-eluting stent (SES) implantation in patients with ST-segment elevation myocardial infarction (STEMI) was maintained over a 24-month time period. Moreover, the distribution of clinical events in relation to thienopyridine discontinuation was thoroughly investigated.\n No randomized data are currently available on the safety/benefit profile of SES in this subset of patients beyond 12 months.\n Between March 2003 and April 2004, 175 patients with STEMI were randomly allocated to tirofiban infusion followed by SES or abciximab plus bare-metal stent (BMS). Complete follow-up information up to 720 days was available for all patients.\n The cumulative incidence of death, myocardial infarction (MI), or target vessel revascularization (TVR) remained lower in the tirofiban-SES compared with the abciximab-BMS group at 2 years (24.2% vs. 38.6%, respectively; hazard ratio [HR] 0.56 [95% confidence interval (CI) 0.33 to 0.98]; p = 0.038). The composite of death/MI was similar in the tirofiban-SES (16.1%) and the abciximab-BMS groups (20.5%, HR 0.77 [95% CI 0.38 to 1.55]; p = 0.43) while the need for TVR was markedly reduced (9.8% vs. 25.5%, respectively; HR 0.34 [95% CI 0.16 to 0.77]; p = 0.01) in the tirofiban-SES arm. The rate of confirmed, probable, or possible stent thrombosis did not differ in the 2 groups, nor the incidence of death/MI after thienopyridine discontinuation.\n The midterm clinical benefit of planned SES implantation assisted by tirofiban infusion in STEMI patients was mainly carried over after 2 years with no overall excess of late adverse events after thienopyridine discontinuation.", "ABT-578 is a new synthetic analog of rapamycin, designed to inhibit smooth muscle cell proliferation-a key contributor to restenosis-by blocking the function of the mTOR cell cycle regulatory protein. Given these pharmacodynamics, ABT-578 was considered beneficial for intracoronary delivery to arrest the process responsible for neointimal hyperplasia after angioplasty and stenting. Consequently, the ABT-578-eluting ENDEAVOR stent system has been created, representing a potential new alternative for treating patients with coronary heart disease. In order to evaluate safety, feasibility and efficacy of this stent design, the ENDEAVOR clinical program has been started, including three randomized clinical trials. ENDEAVOR I is the first-in-man trial including 100 patients with native de novo coronary lesions. The 4-month follow-up data, recently presented, demonstrated safety and feasibility of this new drug-eluting stent (DES) concept with a 4-month MACE (major adverse cardiac events) rate of 2.0%. In order to evaluate this stent system in a larger patient population as well as more complex lesion subsets, the multicenter study ENDEAVOR II has been started including a total of 1,200 patients. The enrollment of this study was completed in January 2004. The aim of the US multicenter study ENDEAVOR III is a head-to-head comparison of the ENDEAVOR ABT-578-eluting stent system with the already approved sirolimus-eluting Cypher stent in 369 patients. If the results of both pivotal studies ENDEAVOR II and III confirm the efficacy of the ENDEAVOR stent design observed so far, the ENDEAVOR stent will be established as a new and promising contender in the field of DES.", "The purpose of this study was to report the angiographic findings of the first human evaluation of the everolimus-eluting stent (EES) for the treatment of noncomplex coronary lesions. Forty-two patients with de novo coronary lesions (2.75 to 4.00 mm vessels; lesion length, <18 mm) were prospectively randomized in a 2:1 ratio to receive either the EES (n = 27) or a metallic stent (n = 15). Baseline clinical and angiographic characteristics were similar among both groups. At 6-month follow-up, EES had a lower in-stent late lumen loss (0.10 +/- 0.22 vs 0.85 +/- 0.32 mm, p <0.0001) and in-segment diameter stenoses (20.7 +/- 12.3% vs 37.0 +/- 15.8%, p = 0.002). There was no in-stent restenosis with EES; however, 1 focal distal edge restenosis was present. There was 1 in-stent and 1 in-segment (proximal edge) restenosis in the metallic stent group. There was no stent thrombosis or aneurysm formation at follow-up in either group.", "The use of sirolimus-eluting coronary stents has been associated with a nearly complete elimination of restenosis at 6 months and with a very low 1-year incidence of major adverse cardiac events (MACE). This analysis examined whether these beneficial effects persist over the longer term.\n This multicenter trial randomly assigned 238 patients to revascularization of single, de novo, native coronary artery lesions with sirolimus-eluting versus conventional bare-metal stents. Survival free from target lesion revascularization (TLR), target vessel failure (TVF), and MACE up to 3 years of follow-up was compared between the 2 treatment groups. Complete data sets were available in 94.2% of patients treated with sirolimus-eluting stents and in 94.1% of patients randomized to the control group. The cumulative 1-, 2-, and 3-year event-free survival rates were 99.2%, 96.5%, and 93.7% for TLR and 95.8%, 92.3%, and 87.9% for TVF, respectively, in the sirolimus-eluting stent group, versus 75.9%, 75.9%, and 75.0% for TLR and 71.2%, 69.4%, and 67.3% for TVF in the control group (P<0.001 for both comparisons at 3 years). Rates of MACE at 3 years were 15.8% in patients randomly assigned to sirolimus-eluting stents versus 33.1% in patients assigned to bare-metal stents (P=0.002). One patient treated with a sirolimus-eluting stent died of a cardiac cause between 12 and 36 months.\n Treatment of de novo coronary stenosis with sirolimus-eluting stents was associated with a sustained clinical benefit and very low rates of TLR and of other MACE up to 3 years after device implantation.", "The purpose of this study was to examine the 3-year clinical outcome in patients enrolled in the Primary Stenting of Totally Occluded Native Coronary Arteries II study.\n Patients with totally occluded coronary arteries randomized to either sirolimus-eluting Cypher stents (SESs) (Cordis, a Johnson & Joshson Company, Miami Lakes, FL) (100 patients) or bare-metal BxVelocity stents (BMSs) (Cordis) (100 patients) were followed clinically for 3 years.\n Between 1 and 3 years, there were infrequent additional clinical events that were equally distributed between the SES and the BMS group. After 3 years, target lesion revascularization was 7% in the SES group versus 27% in the BMS group (P < .001); and target vessel revascularization was seen in 11% in the SES group versus 30% in the BMS group (P = .002). Major adverse cardiac events were noted in 10% of the SES group versus 34% in the BMS group (P < .001). There were no statistically significant differences in death, myocardial infarction, and stent thrombosis according to the Academic Research Consortium criteria between the 2 groups.\n Clinical outcome up to 3 years after implantation of SESs for total coronary occlusions continues to demonstrate a significant reduction in adverse clinical events compared with BMSs without the evidence for either disproportionate late restenosis or late stent thrombosis.", "To compare polytetrafluoroethylene stent graft (PTFE) with sirolimus and bare metal stents in reducing in-stent restenosis in native coronary vessels in patients with acute coronary syndrome.\n The study included patients who underwent stent implantation in acute coronary syndrome from January 2003 to May 2004. The patients (n=119) were randomized either to stent graft group (n=40), sirolimus eluting stent group (n=39), or bare metal stent group (n=40). The main outcome measure of the study was the incidence restenosis at 6-month. The secondary outcome was 6-month major adverse coronary event rate.\n The incidence of 6-month major adverse coronary events was similar in all three groups (8 events in stent graft, 9 in sirolimus eluting stent, and 16 in bare metal stent group events). The target lesion revascularization was higher in the bare metal stent group (P=0.044). Restenosis rate, at six-month follow-up was higher in the bare metal stent group compared with the stent graft and sirolimus eluting stent groups. The percent diameter stenosis in the follow-up was significantly higher in the bare metal stent group (P=0.005). The late loss was significantly lower in the sirolimus eluting stent group (mean+/-standard deviation, 0.2+/-0.5 mm), compared with the bare metal stent group (0.7+/-0.7 mm, P=0.034). There was a trend of lower late loss in the stent graft group than in the bare metal stent group.\n Three groups of stents implanted in patients with acute coronary syndrome did not differ in the incidence of major adverse cardiac events. Sirolimus-eluting stents had a lower incidence of in-stent restenosis than bare metal stent group. Stent graft implanted in native coronary arteries appears to be safe and efficient in patients with acute coronary syndrome, but a significant reduction in in-stent restenosis was not achieved.", "To confirm whether sirolimus-eluting stents (SES) safely reduce the incidence of restenosis in patients with ST-segment elevation acute myocardial infarction compared with bare-metal stents (BMS).\n In the setting of primary angioplasty, stent restenosis occurs in up to 27% of patients. The introduction of drug-eluting stents has drastically reduced the incidence of restenosis in clinically stable patients.\n We conducted a randomized trial of 320 patients with acute ST-segment elevation myocardial infarction assigned to receive SES or BMS. The primary end point was binary restenosis at 1-year angiographic follow-up.\n At 1 year, the incidence of binary restenosis was lower in the SES group than in the BMS group (9.3% vs. 21.3%, respectively; p = 0.032), as were the rates of target lesion revascularization (4.3% vs. 11.2%; p = 0.02), target vessel revascularization (5% vs. 13.1; p = 0.015), major adverse cardiac events (6.8% vs. 16.8%; p = 0.005), and target vessel failure (8.7% vs. 18.7%; p = 0.007). The incidence of angiographically documented stent thrombosis was 1.2% (n = 2) in the SES group and 0.6% (n = 1) in the BMS group.\n In patients with acute myocardial infarction, SES are superior to BMS, reducing the incidence of binary restenosis by 56%, target lesion revascularization by 61%, target vessel revascularization by 62%, adverse cardiac events by 59%, and target vessel failure by 53% at 1 year. (Sirolimus Eluting Stenting in Acute Myocardial Infarction; http://www.clinicaltrials.gov/ct/show/NCT00288210; NCT00288210).", "Sirolimus-eluting stents have been developed to prevent restenosis in the treatment of coronary artery disease. We investigated the risk of restenosis with use of sirolimus-eluting stents compared with bare-metal stents to assess possible differences.\n We enrolled 352 patients in whom one coronary artery required treatment, with diameter 2.5-3.0 mm and lesion length 15-32 mm. We randomly assigned patients sirolimus-eluting stents (n=175) or bare-metal stents (control, n=177). At 8 months we assessed differences in minimum lumen diameter and binary restenosis within the lesion (restenosis of > or =50% diameter, including 5 mm vessel segments proximal and distal to stented segment). Patients were also followed up for 9 months for major adverse cardiac events. Analysis was by intention to treat.\n Stent implantation was successful in 100% of sirolimus-stent patients and 99.4% of controls. The mean diameter of treated coronary arteries was 2.55 mm (SD 0.37) and mean lesion length was 15.0 mm (6.0). Multiple stents were implanted in 170 (48%) patients. At 8 months, minimum lumen diameter was significantly higher with sirolimus-eluting stents than with control stents (2.22 vs 1.33 mm, p<0.0001). The rate of binary restenosis was significantly reduced with sirolimus-eluting stents compared with control stents (5.9 vs 42.3%, p=0.0001). Significantly fewer patients with sirolimus-eluting stents had major adverse cardiac events at 9 months than did controls (8.0 vs 22.6%, p=0.0002), due mainly to a lower need for target-lesion revascularisations (4.0 vs 20.9%, p<0.0001).\n Sirolimus-eluting stents are better than bare-metal stents for treatment of single long atherosclerotic lesions in a coronary vessel smaller than 3 mm in diameter.", "The Study to COmpare REstenosis Rate between QueST and QuaDDS-QP2 (SCORE) trial was a multicenter, randomized, open-label trial comparing the safety and performance of 13- and 17-mm QuaDDS stents (n = 126) (Quanam Medical Corp., Santa Clara, California/Boston Scientific Corp., Natick, Massachusetts) versus uncoated control stents (n = 140) in focal, de novo coronary lesions.\n The pioneering drug-delivery QuaDDS stent used four to six acrylate polymer sleeves, each loaded with 800 microg of the paclitaxel derivative 7-hexanoyltaxol.\n Clinical end points were assessed at 1, 6, and 12 months post procedure. Quantitative coronary angiography and intravascular ultrasound were performed post procedure and at six-month follow-up.\n In the QuaDDS group, early stent thrombosis and myocardial infarction (MI) rates were significantly higher, leading to premature cessation of enrollment. For the QuaDDS group, the stent thrombosis rate increased from 3.2% to 10.3% between 1 and 12 months, associated with increased non-Q-wave MI and death rates. The angiographic restenosis rate at six months was reduced from 32.7% (control) to 7.4% (p < 0.0001). However, the primary end point was not met with six-month target vessel revascularization (TVR) rate as well as the composite major adverse cardiac event rates (cardiac death, MI, and TVR) comparable between groups.\n Despite angiographic indications of potential anti-restenotic benefit, increased rates of stent thrombosis, MI, and cardiac death associated with the QuaDDS stent show an unacceptable safety profile.", "This follow-up study was performed to assess the long-term effects of paclitaxel-eluting stents (PES) compared with bare-metal stents (BMS) in patients who had undergone a percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI).\n The PASSION trial randomly assigned 619 patients with STEMI to receive either a PES or BMS. The composite endpoint for the follow-up study was the occurrence of the combination of cardiac death, recurrent myocardial infarction, target lesion revascularisation (TLR) or stent thrombosis at two years. A trend towards a lower rate of the composite endpoint was observed in the PES compared to the BMS group (hazard ratio [HR] 0.70; 95% C.I. 0.45-1.09). This was driven by a reduced TLR in favour of PES (HR 0.60; 95% C.I. 0.34-1.09). Angiographically proven stent thrombosis at two years did not differ significantly between groups (2.1% in the PES group versus 1.4%; HR 1.48; 95% C.I. 0.42-5.23).\n PES implantation for STEMI did not significantly improve clinical outcome at two years after the index event, although there was a trend towards a lower rate of target-lesion revascularisation. The rate of stent thrombosis did not differ significantly between groups.", "To evaluate the superiority of the paclitaxel-eluting stent (PES) in reducing neointimal hyperplasia (NIH) over its corresponding bare metal stent (BMS) during primary percutaneous coronary intervention (PCI).\n Primary PCI with stent implantation is the repercussion strategy of choice for ST-elevation myocardial infarction (STEMI); nonetheless restenosis rate is still high. Drug-eluting stents have been proven to reduce restenosis rate in many settings, but their use during primary PCI is still controversial.\n Consecutive patients with STEMI <12 hours were randomized to receive PES or BMS. The primary end-point was the percentage of the stent volume obstructed by neointimal proliferation (NIH) measured by intravascular ultrasound (IVUS) at a 7-month angiographic follow-up. Secondary end-points were binary restenosis rate and major adverse cardiac events (MACE, i.e., death, nonfatal myocardial infarction, and target lesion revascularization).\n Eighty patients with STEMI were randomized into the PES or BMS group. Patients were well matched for baseline characteristics and the index procedure was always successful. In-hospital and 1-month MACE were 2.5% per group. NIH at 7 months was 4.6% versus 20% (P< 0.01), late lumen loss 0.1 versus 1.01 mm (P = 0.01). MACE were 7.5% versus 42.5% (P = 0.001) with no difference in death and recurrent myocardial infarction rates. Late-acquired incomplete stent apposition (ISA) rate was 5.1% versus 2.7% (P = 0.65). One subacute stent thrombosis was reported in each group.\n PES was superior to its corresponding BMS in reducing NIH in the STEMI setting without any increase in early and long-term clinical adverse events.", "To see whether use of a sirolimus-eluting stent (SES) is superior to a third-generation thin-strut, cobalt-chromium stent (CCS) in terms of in-segment late loss at 9 months in patients with symptomatic coronary artery disease.\n Stent-strut thickness has been shown to be strictly related with risk of in-stent restenosis, but available demonstrations of the angiographic efficacy of SES have been based on comparisons with thick-strut bare metal control stents.\n The primary outcome measure of this single-center, single-blind randomized comparative trial was 9-month in-segment late loss. Eligibility criteria were symptomatic coronary artery disease and target vessel diameter appropriate for implantation a 3-mm stent. Based on a power calculation, 104 patients were randomly assigned to receive a SES (Cypher) or a CCS (Vision).\n In-segment late loss was significantly lower in the SES group (0.18 +/- 0.40 mm vs 0.58 +/- 0.51 mm, P < 0.001). Regarding subsidiary outcome measures, in-segment restenosis (at 9 months) was recorded in 10% (5/50) patients treated with SES and 23% (11/48) receiving CCS (P = 0.14). No clinical difference between the two groups was apparent at 12 months. Freedom from target vessel failure at 12 months was 72% for SES patients and 68% for CCS patients (P = 0.65).\n In patients with de-novo coronary lesions at medium risk of restenosis the anti-proliferative effect of SES is greater than that of a thin-strut CCS. Nevertheless, the angiographic results of the CCS were rather good. It remains to be seen whether the angiographic superiority of SES can translate into clinical superiority.\n (c) 2007 Wiley-Liss, Inc.", "Our purpose was to evaluate the efficacy and safety of drug-eluting stents in the setting of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI).\n There is inconsistent and limited evidence about the efficacy and safety of drug-eluting stents in STEMI patients.\n A single-blind, single-center, randomized study was performed to compare bare-metal stents (BMS) with sirolimus-eluting stents (SES) in 310 STEMI patients. The primary end point was in-segment late luminal loss (LLL) at 9 months. Secondary end points included late stent malapposition (LSM) at 9 months as determined by intravascular ultrasound imaging and clinical events at 12 months.\n In-segment LLL was 0.68 +/- 0.57 mm in the BMS group and 0.12 +/- 0.43 mm in the SES group with a mean difference of 0.56 mm, 95% confidence interval 0.43 to 0.68 mm (p < 0.001). Late stent malapposition at 9 months was present in 12.5% BMS patients and in 37.5% SES patients (p < 0.001). Event-free survival at 12 months was 73.6% in BMS patients and 86.0% in SES patients (p = 0.01). The target-vessel-failure-free survival was 84.7% in the BMS group and 93.0% in the SES group (p = 0.02), mainly because of a higher target lesion revascularization rate in BMS patients (11.3% vs. 3.2%; p = 0.006). Rates of death, myocardial infarction, and stent thrombosis were not different.\n Sirolimus-eluting stent implantation in STEMI patients is associated with a favorable midterm clinical and angiographic outcome compared with treatment with BMS. However, LSM raises concern about the long-term safety of SES in STEMI patients.", "Objectives: The STEALTH (STent Eluting A9 BioLimus Trial in Humans) trial was the first-in-man study to assess the safety and efficacy of the bioabsorbable-polymer-coated Biolimus A9-eluting BioMATRIX-Stent, as compared to a bare metal stent control (S-Stent). Methods: One hundred twenty patients were enrolled in a prospective, 2:1 randomised, double-blind, multi-center clinical study. Patients with single de novo coronary lesions received either a Biolimus-eluting stent (n=80 patients with 82 lesions) or bare metal control stent (n=40 patients with 40 lesions). The primary study endpoint was in-lesion late lumen loss at 6 month follow-up. Results: The six month in-lesion late loss was significantly reduced in the Biolimus-eluting stent group (0.14 +/- 0.45mm) as compared to the control (0.40 +/- 0.41mm) (p=0.004). The in-stent late loss was 0.26 +/- 0.43mm in the Biolimus-eluting stent group vs. 0.74 +/- 0.45mm in the control (p<0.001). The secondary study endpoint of event-free survival at 6-months was similar in both groups (96.3% Biolimus group vs. 97.5% control; p=0.72). There was no significant difference in target lesion revascularizations due to the low binary restenosis rates in both groups (3.9% in Biolimus group vs. 7.7% in control; p=ns). Conclusions: In this first-in-man feasibility trial, the bioabsorbable-polymer-coated Biolimus A9-eluting stent demonstrated superior efficacy in reducing 6-month in-stent and in-lesion late loss and percent diameter stenosis, with clinical safety similar to bare metal control stents." ]

[ "8846172", "9357454" ]

[ "Exercise training versus angioplasty for stable claudication. Long and medium term results of a prospective, randomised trial.", "Is intermittent claudication improved by percutaneous transluminal angioplasty? A randomized controlled trial." ]

[ "To compare percutaneous transluminal angioplasty (PTA) against exercise training in the treatment of stable claudication.\n Prospective, randomised trial.\n Fifty-six patients with unilateral, stable, lower limb claudication assessed prior to randomisation, at 3 monthly intervals for 15 months, and at approximately 6 years follow-up. Thirty-seven patients were available for long term review.\n Ankle/brachial pressure index (ABPI), treadmill claudication and maximum walking distances, percentage fall in ankle systolic pressure after exercise.\n Significant increases were seen in ABPI in the patients treated with PTA at all assessment to 15 months. However in terms of improved walking performance, the most significant changes in claudication and maximum walking distance were seen in the exercise training group. At long term follow-up, there was no significant difference between the groups. Subgroup analysis by angiographic site of disease showed greater functional improvement in those patients with disease confined to the superficial femoral artery treated by exercise training. The overall prognosis for the whole group of patients was benign, with only two (4%) undergoing amputation.\n Exercise training confers a greater improvement in claudication and maximum walking distance than PTA, especially in patients with disease confined to the superficial femoral artery.", "Percutaneous transluminal angioplasty (PTA) is an increasingly popular invasive treatment for peripheral arterial disease, but there have been very few controlled trials to justify its use. This randomized controlled clinical trial was performed to determine in patients with mild and moderate intermittent claudication differences in outcome between PTA and conventional medical treatment after 2 years.\n Six hundred patients with claudication were screened at the Peripheral Vascular Clinic, Royal Infirmary of Edinburgh. Sixty-two patients with short femoral artery stenoses or occlusions (47 patients) and iliac stenoses (15 patients) were randomized to either PTA plus medical treatment (PTA group, 30 patients) or to medical treatment alone (control group, 32 patients). Medical treatment consisted of daily low-dose aspirin and advice on smoking and exercise. Outcome measures studied were patient-reported maximum walking distance, exercise treadmill distance until onset of claudication, treadmill maximum walking distance, ankle-brachial pressure index (ABPI), quality of life (Nottingham Health Profile), and duplex ultrasound-measured extent of occlusive disease.\n At 2 years of follow-up, the PTA group and control subjects did not differ significantly in patient-reported maximum walking, treadmill onset to claudication, treadmill maximum walking distances, or ABPI (p > 0.05). However, the PTA group had significantly fewer occluded arteries (p = 0.003) and a lesser degree of stenosis (expressed in terms of the velocity ratio; p = 0.004) in patent arteries. Quality of life was not demonstrably different between the two groups (p > 0.05).\n Two years after PTA, patients had less extensive disease than medically treated patients, but this did not translate into a significant advantage in terms of improved walking or quality of life. There are important implications for patient management and future clinical research." ]

[ "12168688", "16555138" ]

[ "A randomised, controlled study of dietary intervention in autistic syndromes.", "The gluten-free, casein-free diet in autism: results of a preliminary double blind clinical trial." ]

[ "Impaired social interaction, communication and imaginative skills characterize autistic syndromes. In these syndromes urinary peptide abnormalities, derived from gluten, gliadin, and casein, are reported. They reflect processes with opioid effect. The aim of this single blind study was to evaluate effect of gluten and casein-free diet for children with autistic syndromes and urinary peptide abnormalities. A randomly selected diet and control group with 10 children in each group participated. Observations and tests were done before and after a period of 1 year. The development for the group of children on diet was significantly better than for the controls.", "This study tested the efficacy of a gluten-free and casein-free (GFCF) diet in treating autism using a randomized, double blind repeated measures crossover design. The sample included 15 children aged 2-16 years with autism spectrum disorder. Data on autistic symptoms and urinary peptide levels were collected in the subjects' homes over the 12 weeks that they were on the diet. Group data indicated no statistically significant findings even though several parents reported improvement in their children. Although preliminary, this study demonstrates how a controlled clinical trial of the GFCF diet can be conducted, and suggests directions for future research." ]

[ "8005278", "9806261", "7593499", "17313946", "10402419", "11384805", "14585874" ]

[ "Intravenous albumin for the prevention of severe ovarian hyperstimulation syndrome in an in vitro fertilization program: a prospective, randomized, placebo-controlled study.", "Prophylactic intravenous hydroxyethyle starch solution prevents moderate-severe ovarian hyperstimulation in in-vitro fertilization patients: a prospective, randomized, double-blind and placebo-controlled study.", "Decreased incidence of severe ovarian hyperstimulation syndrome in high risk in-vitro fertilization patients receiving intravenous albumin: a prospective study.", "Human albumin does not prevent ovarian hyperstimulation syndrome in assisted reproductive technology program: a prospective randomized placebo-controlled double blind study.", "Does i.v. albumin prevent ovarian hyperstimulation syndrome?", "Intravenous albumin versus hydroxyethyl starch for the prevention of ovarian hyperstimulation in an in-vitro fertilization programme: a prospective randomized placebo controlled study.", "Intravenous albumin does not prevent moderate-severe ovarian hyperstimulation syndrome in high-risk IVF patients: a randomized controlled study." ]

[ "To evaluate the efficacy of i.v. administration of human albumin solution for the prevention of severe ovarian hyperstimulation syndrome (OHSS).\n A prospective, randomized, placebo-controlled study comparing the effects of i.v. administration of human albumin solution versus sodium chloride 0.9% solution at the time of oocyte retrieval with patients undergoing IVF-ET who are at high risk for the development of severe OHSS.\n Specialized assisted reproduction unit.\n Thirty-one patients undergoing IVF-ET who had serum E2 levels of 1,906 pg/mL (> 7,000 pmol/L) and multiple follicular development on the day of hCG administration.\n After hCG administration, patients were randomized to receive i.v., either 50 g of human albumin diluted in 500 mL of sodium chloride 0.9% or 500 mL of sodium chloride 0.9% at the time of oocyte retrieval.\n Ovarian size as measured by pelvic ultrasonography, development of ascites, serum E2 concentrations during the luteal phase, and results of the IVF-ET cycles.\n Although no patient who had received human albumin solution developed severe OHSS, there were four such cases in the control group. All four were hospitalized with marked ascites and ovarian enlargement. There were no significant differences between the two groups comparing serum E2 levels on the day of hCG administration and during the luteal phase, the number of oocytes retrieved, fertilization, and pregnancy rates.\n Our preliminary results suggest that the administration of human albumin solution may help to prevent the development of severe OHSS in high-risk patients. Further research is needed to assess the potential of this novel approach.", "A prospective, randomized, double-blind and placebo-controlled study was conducted to assess the effectiveness of i.v. administration of 6% hydroxyethyle starch solution (HES) in preventing moderate and severe ovarian hyperstimulation syndrome (OHSS) in patients in an in-vitro fertilization programme. A total of 101 women who had serum oestradiol concentrations >1500 pg/ml and/or more than 10 follicles on day of human chorionic gonadotrophin (HCG) administration were recruited into two groups: HES group (n = 51) received 1000 ml 6% HES; and the placebo group (n = 50) received 1000 ml of sodium chloride 0.9% solution at the time shortly after embryo transfer. Follow-up examinations 7 +/- 1 and 14 +/- 1 days after embryo transfer included transvaginal ultrasound (diameters of each ovary and maximum cysts, number of cysts, ascites), blood tests (serum oestradiol, progesterone, beta-HCG, C-reactive protein, blood count, plasma proteins, electrolytes, kidney function tests) and evaluation of abdominal pain, nausea, diarrhoea, abdominal swelling and weight gain. Only one moderate OHSS developed in the HES group whereas seven moderate-severe cases were observed in the placebo group (P = 0.031). Furthermore, serum oestradiol concentration, leukocyte count, increase in abdominal circumference and weight gain 14 days after embryo transfer were significantly higher in the placebo group. There were no differences between the two groups in terms of age, oestradiol concentration and number of follicles at time of HCG injection. Administration of 6% HES prevents the development of moderate-severe OHSS in risk patients.", "The administration of human serum albumin has been reported to prevent severe ovarian hyperstimulation syndrome (OHSS) while undergoing ovarian stimulation protocols for in-vitro fertilization (IVF). This prospective, randomized study investigated the effectiveness of a single dose of human serum albumin (20 g) administered i.v. immediately after oocyte retrieval. Women enrolled in the IVF programme were treated with long gonadotrophin-releasing hormone agonist, triptorelin, and an individually-adjusted human menopausal gonadotrophin protocol. The criteria for inclusion in the study were young age, non-obesity, oestradiol concentration > 9200 pmol/l on the day of human chorionic gonadotrophin administration and > 20 follicles > 14 mm diameter as observed by transvaginal sonography. The treatment group (n = 22) received albumin while the control group (n = 18) did not. Patients were followed-up using ultrasound every 3 days. There was a significantly higher number of severe OHSS cases in the control group (n = 4) than in the treatment group (n = 0) (P = 0.035). Where the data base was restricted to patients with an oestradiol concentration > 15,000 pmol/l, the difference between control and treatment groups was highly significant (P = 0.008). These findings support the use of i.v. albumin in preventing severe OHSS during IVF treatment.", "We aimed to clarify the efficiency of IV human albumin in the prevention of ovarian hyperstimulation syndrome (OHSS). We found that human albumin at the described strength does not seem to either prevent or reduce the incidence of severe OHSS in high risk patients undergoing intracytoplasmic sperm injection (ICSI).", "nan", "A prospective randomized placebo controlled clinical trial was carried out on 250 patients (cycles) considered at risk of developing OHSS in an IVF programme. Criteria for inclusion were: estradiol value of more than 3000 pg/ml or the presence of more than 20 follicles on the day of hCG administration. Patients were randomized by using a random table to receive either 20% human albumin 50 ml (n: 82); 6% hydroxyethyl starch (200/0.5) 500 ml (n: 85) or a placebo of 500 ml 0.9% NaCl solution (n: 83) over 30 min during oocyte collection. Groups were similar with respect to patients' age, estradiol levels on hCG day, body mass index, number of oocytes retrieved, number of embryos transferred and pregnancies (P>0.05). There was no severe OHSS in patients who received albumin and HES while four patients who received placebo developed severe OHSS. On the other hand moderate OHSS was encountered in four patients in the albumin group; five patients receiving HES; and 12 patients receiving placebo. There was a statistically significant difference in the incidence of moderate, severe and overall OHSS among groups (P values of <0.05, <0.05, and <0.01, respectively). Both HES and albumin significantly reduced the incidence of moderate, severe and overall incidence of OHSS. It is concluded that hydroxyethyl starch is a cheaper and safer alternative to Human Albumin in OHSS prevention.", "Intravenous albumin administration has been described for many years as a debatable, but probably useful preventive measure in ovarian hyperstimulation syndrome (OHSS). The present study details the largest randomized controlled trial to date of albumin infusion versus no treatment in IVF patients with a high risk of developing moderate to severe OHSS.\n Between March 1999 and February 2002, women undergoing IVF at the IVI Valencia with >20 retrieved oocytes were included. A total of 988 patients was initially enrolled. Immediately after oocyte retrieval, patients were allocated to two groups based on a computer randomization: the first group received 40 g human albumin; the second group received no treatment. Subjects were weighed and a blood analysis performed immediately after oocyte retrieval and again 7 days later. Women were monitored on an outpatient basis until menstruation, or until fetal heart activity was detected. Twelve subjects were excluded due to follow-up loss, leaving 976 women (377 of them oocyte donors), with 488 in each group.\n No difference was found between the two groups in terms of patient characteristics and outcome. Moderate-severe and severe-only OHSS rates were similar. The incidence of haemoconcentration and liver and renal dysfunction at 7 days after oocyte retrieval was similar in the two groups. In women who developed moderate/severe (n = 66) or only severe (n = 46) OHSS, there was no difference based on prior albumin administration between blood parameters or body weight on the day of oocyte retrieval, 7 days later, and even when comparing variation between both measurements. Moreover, the number of patients with paracentesis, hospital admissions, complications and days of OHSS until resolution did not differ.\n Albumin infusion on the day of oocyte retrieval is not a useful means of preventing the development of moderate-severe OHSS." ]

[ "19032398", "16708735", "15733717", "1298056", "8555849", "1628013", "16440428" ]

[ "Randomized study of percutaneous endoscopic gastrostomy versus nasogastric tubes for enteral feeding in head and neck cancer patients treated with (chemo)radiation.", "A prospective comparison of percutaneous endoscopic gastrostomy and nasogastric tube feeding in patients with acute dysphagic stroke.", "Effect of timing and method of enteral tube feeding for dysphagic stroke patients (FOOD): a multicentre randomised controlled trial.", "Feeding via nasogastric tube or percutaneous endoscopic gastrostomy. A comparison.", "A randomised prospective comparison of percutaneous endoscopic gastrostomy and nasogastric tube feeding after acute dysphagic stroke.", "Randomised comparison of percutaneous endoscopic gastrostomy and nasogastric tube feeding in patients with persisting neurological dysphagia.", "Effect of percutaneous endoscopic gastrostomy on gastro-esophageal reflux in mechanically-ventilated patients." ]

[ "Percutaneous endoscopic gastrostomy (PEG) tubes have largely replaced nasogastric tubes (NGT) for nutritional support of patients with head and neck cancer undergoing curative (chemo)radiotherapy without any good scientific basis. A randomized trial was conducted to compare PEG tubes and NGT in terms of nutritional outcomes, complications, patient satisfaction and cost. The study was closed early because of poor accrual, predominantly due to patients' reluctance to be randomized. There were 33 patients eligible for analysis. Nutritional support with both tubes was good. There were no significant differences in overall complication rates, chest infection rates or in patients' assessment of their overall quality of life. The cost of a PEG tube was 10 times that of an NGT. The duration of use of PEG tubes was significantly longer, a median 139 days compared with a median 66 days for NGT. We found no evidence to support the routine use of PEG tubes over NGT in this patient group.", "Dysphagia following stroke is common problem and is of particular concern because of its potental for malnutrition. Nasogastric (NG) and percutaneous endoscopic gastrostomy (PEG) tube feeding are recognized methods for nutritional support for patients with persistent neurologic dysphagia. However, the former is associated with tube dislodgement and blockage that might compromise the patients' nutritional status. There have been few randomized prospective studies to date comparing the efficacy and safety of these 2 modes of dysphagia management in stroke patients. The objective of this study was to compare PEG with NG tube feeding after acute dysphagic stroke in terms of nutritional status and treatment failure. This was a randomized prospective clinical trial. A total of 23 consecutive patients who fulfilled the criteria were recruited from the medical wards in Hospital Universiti Kebangsaan Malaysia. The diagnosis of stroke (acute cerebral infarct) was based on clinical and brain computed tomographic (CT scan) findings; and the diagnosis of dysphagia was done clinically by using the 'swallowing test'. At recruitment, upper-arm skin fold thickness (triceps and biceps) and mid-arm circumference were measured; and blood was drawn for serum albumin level. They were then followed up at 4 weeks where the above tests were repeated. A total of 22 patients completed the study (12 patients in the NG group and 10 patients in the PEG group). Serum albumin levels (p = 0.045) were significantly higher in the PEG as compared to the NG group at 4 weeks post-intervention. There were statistically significant improvements in serum albumin level (p = 0.024) in the PEG group; and statistically significant reductions in serum albumin level (p = 0.047) in the NG group 4 weeks after the intervention. However, there were no significant differences in anthropometric parameters between the two groups and no significant changes in these parameters for each group 4 weeks after the intervention. Treatment failure occurred in 5 out of 10 patients (50.0%) in the NG group, but none in PEG group (p = 0.036). PEG tube feeding is more effective than NG tube feeding in improving the nutritional status (in terms of the serum albumin level) of patients with dysphagic stroke. NG tube feeding, in fact, reduced the nutritional status (in terms of the serum albumin level) of the patients.", "Undernutrition is common in patients admitted with stroke. We aimed to establish whether the timing and route of enteral tube feeding after stroke affected patients' outcomes at 6 months.\n The FOOD trials consist of three pragmatic multicentre randomised controlled trials, two of which included dysphagic stroke patients. In one trial, patients enrolled within 7 days of admission were randomly allocated to early enteral tube feeding or no tube feeding for more than 7 days (early versus avoid). In the other, patients were allocated percutaneous endoscopic gastrostomy (PEG) or nasogastric feeding. The primary outcome was death or poor outcome at 6 months. Analysis was by intention to treat.\n Between Nov 1, 1996, and July 31, 2003, 859 patients were enrolled by 83 hospitals in 15 countries into the early versus avoid trial. Early tube feeding was associated with an absolute reduction in risk of death of 5.8% (95% CI -0.8 to 12.5, p=0.09) and a reduction in death or poor outcome of 1.2% (-4.2 to 6.6, p=0.7). In the PEG versus nasogastric tube trial, 321 patients were enrolled by 47 hospitals in 11 countries. PEG feeding was associated with an absolute increase in risk of death of 1.0% (-10.0 to 11.9, p=0.9) and an increased risk of death or poor outcome of 7.8% (0.0 to 15.5, p=0.05).\n Early tube feeding might reduce case fatality, but at the expense of increasing the proportion surviving with poor outcome. Our data do not support a policy of early initiation of PEG feeding in dysphagic stroke patients.", "When a patient needs enteral feeding, there are two methods to administer the nutrition. The method most used is the nasogastric tube (NGT), although in the literature little is published about the advantages and complications of the NGT. The second method is percutaneous endoscopic gastrostomy (PEG). A prospective randomized trial was started, and so far 90 patients have entered the study (46 NGT and 44 PEG). In four patients it was not possible to insert the NGT, and in three patients it was impossible to place the PEG. In both groups 6.5% aspiration was found. Nasal decubitus and swallowing problems were seen in 13% and 17%, respectively, in the NGT group. Intraperitoneal bleeding and abdominal pain were found in 2% and 11%, respectively, in the PEG group. Fixation of the patients was needed in 7% of the PEG and 22% in the NGT group. In eight patients in the NGT group the feeding had to be stopped owing to problems; in none of the PEG group was this necessary. The nursing staff awarded marks to each patient on a scale of 5 for the convenience of care (very good, 1; very bad, 5). This resulted in a mean score of 2.6 in the NGT and 2.0 in the PEG group. The score given by the patients was 2.3 in the NGT and 1.8 in the PEG group. There seems to be a clear preference for the PEG as a method for enteral nutrition.", "To compare percutaneous endoscopic gastrostomy and nasogastric tube feeding after acute dysphagic stroke.\n Randomised prospective study of inpatients with acute stroke requiring enteral nutrition.\n One university hospital (Nottingham) and one district general hospital (Derby).\n 30 patients with persisting dysphagia at 14 days after acute stroke: 16 patients were randomised to gastrostomy tube feeding and 14 to nasogastric tube feeding.\n Six week mortality; amount of feed administered; change in nutritional state; treatment failure; and length of hospital stay.\n Mortality at 6 weeks was significantly lower in the gastrostomy group with two deaths (12%) compared with eight deaths (57%) in the nasogastric group (P < 0.05). All gastrostomy fed patients (16) received the total prescribed feed whereas 10/14 (71%) of nasogastric patients lost at least one day's feed. Nasogastric patients received a significantly (P < 0.001) smaller proportion of their prescribed feed (78%; 95% confidence interval 63% to 94%) compared with the gastrostomy group (100%). Patients fed via a gastrostomy tube showed greater improvement in nutritional state, according to several different criteria at six weeks compared with the nasogastric group. In the gastrostomy group the mean albumin concentration increased from 27.1 g/l (24.5 g/l to 29.7 g/l) to 30.1 g/l (28.3 g/l to 31.9 g/l). In contrast, among the nasogastric group there was a reduction from 31.4 g/l (28.6 g/l to 34.2 g/l) to 22.3 g/l (20.7 g/l to 23.9 g/l) (P < 0.003). In addition, there were fewer treatment failures in the gastrostomy group (0/16 versus 3/14). Six patients from the gastrostomy group were discharged from hospital within six weeks of the procedure compared with none from the nasogastric group (P < 0.05).\n This study indicates that early gastrostomy tube feeding is greatly superior to nasogastric tube feeding and should be the nutritional treatment of choice for patients with acute dysphagic stroke.", "To compare percutaneous endoscopic gastrostomy and nasogastric tube feeding in patients with persisting neurological dysphagia.\n Randomised 28 day study of inpatients requiring long term enteral nutrition.\n Three Glasgow teaching hospitals.\n 40 patients with dysphagia for at least four weeks secondary to neurological disorders: 20 patients (10 women) were randomised to nasogastric feeding and 20 (eight women) to endoscopic gastrostomy.\n Treatment failure (blocked or displaced tubes on three or more occasions or refusal to continue treatment); duration of feeding; intake of liquid diets; complications; nutritional status at end of trial.\n One patient in each group died before starting feeding. Treatment failure occurred in 18 of the 19 nasogastric patients and in none of the gastrostomy group. The mean (SE) duration of feeding for the nasogastric group was 5.2 (1.5) days. No complications occurred in the nasogastric group but three (16%) of the gastrostomy group developed minor problems (aspiration pneumonia (two patients) wound infection (one)). Gastrostomy patients received a significantly greater proportion of their prescribed feed (93% (2%)) compared with the nasogastric group, (55% (4%); p less than 0.001) and also gained significantly more weight after seven days of feeding (1.4 (0.5) kg v 0.6 (0.1) kg; p less than 0.05). Analyses at days 14, 21, and 28 were not possible due to the small numbers remaining in the nasogastric group.\n Percutaneous endoscopic gastrostomy tube feeding is a safe and effective method of providing long term enteral nutrition to patients with neurological dysphagia and offers important advantages over nasogastric tube feeding.", "To investigate the effect of percutaneous endoscopic gastrostomy (PEG) on gastroesophageal reflux (GER) in mechanically-ventilated patients.\n In a prospective, randomized, controlled study 36 patients with recurrent or persistent ventilator-associated pneumonia (VAP) and GER > 6% were divided into PEG group (n = 16) or non-PEG group (n = 20). Another 11 ventilated patients without reflux (GER < 3%) served as control group. Esophageal pH-metry was performed by the \"pull through\" method at baseline, 2 and 7 d after PEG. Patients were strictly followed up for semi-recumbent position and control of gastric nutrient residue.\n A significant decrease of median (range) reflux was observed in PEG group from 7.8 (6.2 - 15.6) at baseline to 2.7 (0 - 10.4) on d 7 post-gastrostomy (P < 0.01), while the reflux increased from 9 (6.2 - 22) to 10.8 (6.3 - 36.6) (P < 0.01) in non-PEG group. A significant correlation between GER (%) and the stay of nasogastric tube was detected (r = 0.56, P < 0.01).\n Gastrostomy when combined with semi-recumbent position and absence of nutrient gastric residue reduces the gastroesophageal reflux in ventilated patients." ]

[ "8692505" ]

[ "Meconium-stained amniotic fluid-associated infectious morbidity: a randomized, double-blind trial of ampicillin-sulbactam prophylaxis." ]

[ "To evaluate the efficacy of intrapartum prophylactic administration of ampicillin-sulbactam in reducing intraamniotic infection and postpartum endometritis in patients with meconium-stained amniotic fluid (AF).\n Patients with intrapartum meconium-stained AF were randomized to receive either ampicillin-sulbactam or normal saline (placebo) intravenously at the time of diagnosis of meconium and every 6 hours until delivery. The outcomes of the two groups were compared with respect to intra-amniotic infection and postpartum endometritis.\n During the study period, 332 patients with meconium-stained AF were approached for participation, and 120 patients met inclusion criteria and were enrolled. Patient demographics, labor, and delivery characteristics were similar. Ampicillin-sulbactam reduced the incidence of intra-amniotic infection from 23.3 to 6.7%, (P = .02; relative risk [RR] 0.48, 95% confidence interval [CI] 0.22-0.98). The incidence of postpartum endometritis was also reduced, but the difference was statistically nonsignificant (8.3 versus 16.7%, P = .16; RR 0.64, 95% CI 0.30-1.33).\n Prophylactic intravenous ampicillin-sulbactam significantly reduces intra-amniotic infection in patients with meconium-stained AF." ]

[ "10798453", "18525288", "10990596", "8483655", "9801526", "16618375", "19628939" ]

[ "Effects of individualized versus classical \"relaxation\" music on the frequency of agitation in elderly persons with Alzheimer's disease and related disorders.", "Efficacy of music therapy in the treatment of behavioral and psychiatric symptoms of dementia.", "The impact of music therapy on language functioning in dementia.", "Effects of music on Alzheimer patients.", "Use of music to decrease aggressive behaviors in people with dementia.", "Music therapy in moderate and severe dementia of Alzheimer's type: a case-control study.", "Effect of music therapy on anxiety and depression in patients with Alzheimer's type dementia: randomised, controlled study." ]

[ "Confusion and agitation in elderly patients are crucial problems. This study tested Gerdner's mid-range theory of individualized music intervention for agitation. An experimental repeated measures pretest-posttest crossover design compared the immediate and residual effects of individualized music to classical \"relaxation\" music relative to baseline on the frequency of agitated behaviors in elderly persons with Alzheimer's disease and related disorders (ADRD). Thirty-nine subjects were recruited from six long-term-care facilities in Iowa. The sample consisted of 30 women and 9 men (mean age 82 years) with severe cognitive impairment. Baseline data were collected for 3 weeks. Findings from the Modified Hartsock Music Preference Questionnaire guided the selection of individualized music. Group A (n = 16) received individualized music for 6 weeks followed by a 2-week \"washout\" period and 6 weeks of classical \"relaxation\" music. Group B (n = 23) received the same protocol but in reverse order. Music interventions were presented for 30 minutes, two times per week. The Modified Cohen-Mansfield Agitation Inventory measured the dependent variable. A repeated measures analysis of variance with Bonferroni post hoc test showed a significant reduction in agitation during and following individualized music compared to classical music. This study expands science by testing and supporting a theoretically based intervention for agitation in persons with ADRD.", "Music therapy (MT) has been proposed as valid approach for behavioral and psychologic symptoms (BPSD) of dementia. However, studies demonstrating the effectiveness of this approach are lacking.\n To assess MT effectiveness in reducing BPSD in subjects with dementia.\n Fifty-nine persons with dementia were enrolled in this study. All of them underwent a multidimensional assessment including Mini Mental State Examination, Barthel Index and Neuropsychiatry Inventory at enrollment and after 8, 16, and 20 weeks. Subjects were randomly assigned to experimental (n=30) or control (n=29) group. The MT sessions were evaluated with standardized criteria. The experimental group received 30 MT sessions (16 wk of treatment), whereas the control group received educational support or entertainment activities.\n NPI total score significantly decreased in the experimental group at 8th, 16th, and 20th weeks (interaction time x group: F3,165=5.06, P=0.002). Specific BPSD (ie, delusions, agitation, anxiety, apathy, irritability, aberrant motor activity, and night-time disturbances) significantly improved. The empathetic relationship and the patients' active participation in the MT approach, also improved in the experimental group.\n The study shows that MT is effective to reduce BPSD in patients with moderate-severe dementia.", "Dementias, such as Alzheimer's disease, include a progressive deterioration of language functioning. While some researchers have reported an increase in patients' self-expression following music therapy, it is not clear whether these changes specifically reflect improved language skills or whether simple interpersonal interaction with a therapist could account for the improvement. In this study, the effects of music therapy were compared to conversational sessions on language functioning in dementia patients. Participants were selected according to the following criteria: (a) residing in a facility specializing in Alzheimer's and related disorders; (b) possessing sufficient verbal ability to answer simple questions and to comply with requests to speak, participate, or sit down; and (c) attaining the written consent of the patient's guardian or representative. All participants had been in music therapy twice per week for at least 3 months prior to the study onset. One week prior to the beginning of the study, subjects were assessed for cognitive functioning using the Mini-Mental State Examination (MMSE), and language ability via the Western Aphasia Battery (WAB). A within-subjects design was used, with order of condition (music or group conversation first) counter-balanced between participants. Subjects participated in groups of 2 to 4, twice per week for 20-30 minutes for a total of 8 sessions (4 music therapy and 4 conversation sessions or vice-versa), and were re-tested on the WAB at the end of each 2 week (4 session) interval. Results from 20 participants revealed that music therapy significantly improved performance on both speech content and fluency dimensions of the spontaneous speech subscale of the WAB (p =.01). While the difference in overall Aphasia Quotient (AQ) for music and conversation sessions (mean AQ = 76 vs. 70, respectively) did not reach statistical significance, data were only available for 10 participants (5 per condition). Hopefully, these findings will stimulate additional research on the use of music therapy interventions with demented patients, as it may offer a noninvasive mechanism to enhance communication between victims and their caregivers.", "From a large nursing care facility, 60 elderly patients diagnosed as having Alzheimer disease were randomly separated into three groups of equal size and given tests to measure their mood and mental state. For music Group 1, \"Big Band\" music from the 1920s and 1930s was played during their daily recreation period while Group 2 were given puzzle exercises during their activity sessions. Members of Group 3 participated in the standard recreational activities of drawing and painting. After six months, the questionnaire was again given to all participants. Analysis of variance showed the individuals in Group 1 were more alert, happier, and had higher recall of past personal history than patients in the other two groups. This suggests that music can be of therapeutic value to Alzheimer patients.", "The purpose of this study was to examine the effects of recorded, preferred music in decreasing occurrences of aggressive behavior among individuals with Alzheimer's type dementia during bathing episodes. Eighteen older adults, age 55 to 95, with severe levels of cognitive impairment, participated in the study. They were randomly scheduled for observation during bath time under either a control (no music) condition or an experimental condition in which recorded selections of preferred music were played via audiotape recorder during the bathing episode. Following a 2-week (10 episode) observation period, conditions were reversed. A total of 20 observations were recorded for each individual. Results indicated that during the music condition, decreases occurred in 12 of 15 identified aggressive behaviors. Decreases were significant (p < 0.05) for the total number of observed behaviors and for hitting behaviors. During the music condition, caregivers frequently reported improved affect and a general increase in cooperation with the bathing task. The implications of these findings for improving the overall quality of care for severely cognitively impaired older adults are discussed.", "Music therapy is a potential non-pharmacological treatment for the behavioral and psychological symptoms of dementia, but although some studies have found it to be helpful, most are small and uncontrolled.\n This case-control study was carried out by qualified music therapists in two nursing homes and two psychogeriatric wards. The participants were 38 patients with moderate or severe Alzheimer's disease (AD) assigned randomly to a music therapy group and a control group.\n The study showed a significant reduction in activity disturbances in the music therapy group during a 6-week period measured with the Behavior Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). There was also a significant reduction in the sum of scores of activity disturbances, aggressiveness and anxiety. Other symptoms rated by subscales of the BEHAVE-AD did not decrease significantly. Four weeks later the effects had mostly disappeared.\n Music therapy is a safe and effective method for treating agitation and anxiety in moderately severe and severe AD. This is in line with the results of some non-controlled studies on music therapy in dementia.", "Numerous studies have indicated the value of music therapy in the management of patients with Alzheimer's disease. A recent pilot study demonstrated the feasibility and usefulness of a new music therapy technique. The aim of this controlled, randomised study was to assess the effects of this new music therapy technique on anxiety and depression in patients with mild to moderate Alzheimer-type dementia.\n This was a single-centre, comparative, controlled, randomised study, with blinded assessment of its results. The duration of follow-up was 24 weeks. The treated group (n = 15) participated in weekly sessions of individual, receptive music therapy. The musical style of the session was chosen by the patient. The validated 'U' technique was employed. The control group (n = 15) participated under the same conditions in reading sessions. The principal endpoint, measured at weeks 1, 4, 8, 16 and 24, was the level of anxiety (Hamilton Scale). Changes in the depression score (Geriatric Depression Scale) were also analyzed as a secondary endpoint.\n Significant improvements in anxiety (p < 0.01) and depression (p < 0.01) were observed in the music therapy group as from week 4 and until week 16. The effect of music therapy was sustained for up to 8 weeks after the discontinuation of sessions between weeks 16 and 24 (p < 0.01).\n These results confirm the valuable effect of music therapy on anxiety and depression in patients with mild to moderate Alzheimer's disease. This new music therapy technique is simple to implement and can easily be integrated in a multidisciplinary programme for the management of Alzheimer's disease.\n Copyright 2009 S. Karger AG, Basel." ]

[ "7353752", "374177", "7184928", "378825" ]

[ "Successful use of bromocriptine in the treatment of chronic hepatic encephalopathy.", "Treatment of chronic portal systemic encephalopathy with bromocriptine: a double-blind controlled trial.", "Prospective randomised controlled trial of L-dopa and hydrocortisone in fulminant hepatitis.", "Controlled trial of levodopa in fulminant hepatitis." ]

[ "Six patients with cirrhosis and severe chronic hepatic encephalopathy were treated with bromocriptine. All showed significant overall improvement clinically and in 3, the electroencephalogram became normal. The cerebral blood flow increased significantly from 32.7 +/- 2.4 (mean +/- 1 SE) to 40.5 +/- 1.5 ml/100 g brain/min (P less than 0.05). Similarly, there were significant improvements in the cerebral oxygen consumption from 2.2 +/- 0.4 to 3.3 +/- 0.4 ml/100 g brain/min (P less than 0.02) and in cerebral glucose consumption from 2.1 +/- 0.6 to 6.6 +/- 1.6 mg/100 g brain/min (P less than 0.02). Cross-over to placebo produced overall deterioration, more marked in the patients who had received the active drug for the shorter time period. No serious side effects were seen; the drug was well tolerated in doses of up to 15 mg daily and is a useful treatment for chronic hepatic encephalopathy when the response to conventional therapy has been poor.", "A randomized double-blind clinical comparison of bromocriptine, a new dopamine agonist, and placebo was performed on 7 cirrhotic patients with chronic portal systemic encephalopathy (PSE). Before given either medication, patients were stabilized with a standard treatment (neomycin and cathartics). Serial semiquantitative assessments were done, including mental state, asterixis, number connection test, electroencephalogram, and ammonia blood levels. Three patients developed signs of precoma while ingesting both placebo and bromocriptine. Two patients experienced precoma only with placebo, and another patient only while taking bromocriptine. One patient remained awake throughout the study. All patients responded initially to neomycin and cathartics. Bromocriptine proved not to be significantly superior to placebo and was always inferior to standard treatment. During treatment with bromocriptine, 3 patients experienced constipation. This may be partially responsible for the ineffectiveness in the treatment of PSE.", "nan", "nan" ]

[ "8238713", "17940147", "15319103", "870782", "19317200", "15064923", "18337359", "12072853", "3056045", "11676730", "16388054", "10694106", "20117594", "19387413", "4434039", "9232977", "8365838", "10102097", "9006705" ]

[ "Prevention of running injuries by warm-up, cool-down, and stretching exercises.", "No effect of a graded training program on the number of running-related injuries in novice runners: a randomized controlled trial.", "A prospective study of the effect of foot orthoses composition and fabrication on comfort and the incidence of overuse injuries.", "Effects of frequency and duration of training on attrition and incidence of injury.", "Sock systems to prevent foot blisters and the impact on overuse injuries of the knee joint.", "Effect of bracing on the prevention of anterior knee pain--a prospective randomized study.", "Prevention of overuse injuries by a concurrent exercise program in subjects exposed to an increase in training load: a randomized controlled trial of 1020 army recruits.", "Can custom-made biomechanic shoe orthoses prevent problems in the back and lower extremities? A randomized, controlled intervention trial of 146 military conscripts.", "Prevention of lower extremity stress fractures: a controlled trial of a shock absorbent insole.", "Effects of ankle dorsiflexion range and pre-exercise calf muscle stretching on injury risk in Army recruits.", "Do shock absorbing insoles in recruits undertaking high levels of physical activity reduce lower limb injury? A randomized controlled trial.", "A randomized trial of preexercise stretching for prevention of lower-limb injury.", "Effect on injuries of assigning shoes based on foot shape in air force basic training.", "Injury reduction effectiveness of selecting running shoes based on plantar shape.", "A prospective study on the management of shin splints.", "Injuries in Australian Army recruits. Part II: Location and cause of injuries seen in recruits.", "Soreness in lower extremities and back is reduced by use of shock absorbing heel inserts.", "Increasing hamstring flexibility decreases lower extremity overuse injuries in military basic trainees.", "The role of the knee brace in the prevention of anterior knee pain syndrome." ]

[ "The purpose of this study was to evaluate the effect of a health education intervention on running injuries. The intervention consisted of information on, and the subsequent performance of, standardized warm-up, cool-down, and stretching exercises. Four hundred twenty-one male recreational runners were matched for age, weekly running distance, and general knowledge of preventing sports injuries. They were randomly split into an intervention and a control group: 167 control and 159 intervention subjects participated throughout the study. During the 16-week study, both groups kept a daily diary on their running distance and time, and reported all injuries. In addition, the intervention group was asked to note compliance with the standardized program. At the end of the study period, knowledge and attitude were again measured. There were 23 injuries in the control group and 26 in the intervention group. Injury incidence for control and intervention subjects was 4.9 and 5.5 running injuries per 1000 hours, respectively. The intervention was not effective in reducing the number of running injuries; it proved significantly effective (P < 0.05) in improving specific knowledge of warm-up and cool-down techniques in the intervention group. This positive change can perhaps be regarded as a first step on the way to a change of behavior, which may eventually lead to a reduction of running injuries.", "Although running has positive effects on health and fitness, the incidence of a running-related injury (RRI) is high. Research on prevention of RRI is scarce; to date, no studies have involved novice runners.\n A graded training program for novice runners will lead to a decrease in the absolute number of RRIs compared with a standard training program.\n Randomized controlled trial; Level of evidence, 1.\n GRONORUN (Groningen Novice Running) is a 2-armed randomized controlled trial comparing a standard 8-week training program (control group) and an adapted, graded, 13-week training program (intervention group), on the risk of sustaining an RRI. Participants were novice runners (N = 532) preparing for a recreational 4-mile (6.7-km) running event. The graded 13-week training program was based on the 10% training rule. Both groups registered information on running characteristics and RRI using an Internet-based running log. The primary outcome measure was RRIs per 100 participants. An RRI was defined as any musculoskeletal complaint of the lower extremity or back causing a restriction of running for at least 1 week.\n The graded training program was not preventive for sustaining an RRI (chi(2) = 0.016, df = 1, P = .90). The incidence of RRI was 20.8% in the graded training program group and 20.3% in the standard training program group.\n This randomized controlled trial showed no effect of a graded training program (13 weeks) in novice runners, applying the 10% rule, on the incidence of RRI compared with a standard 8-week training program.", "Foot orthoses are widely prescribed both to treat existing pathological conditions and to prevent overuse injuries, but little is known about the effect of their material composition and fabrication technique on patient comfort and the incidence of overuse injuries.\n The acceptance rates and comfort scores of soft custom, soft prefabricated, semirigid biomechanical, and semirigid prefabricated orthoses and their effect on the incidence of stress fractures, ankle sprains, and foot problems were studied in a prospective, randomized, single-blinded clinical trial among 874 infantry recruits during basic training.\n A statistically significantly lower number of recruits given soft prefabricated orthoses (53%) finished basic training in their assigned devices than in the soft custom group (72%), in the semirigid biomechanical group (75%), and in the semirigid prefabricated group (82%) (p = .003). For recruits who finished training in their assigned orthoses, the soft custom (3.54) and soft prefabricated (3.43) orthoses had significantly higher comfort scores than the semirigid biomechanical (3.23) and prefabricated (3.17) orthoses, (p = .0001). There was no statistically significant difference in the incidence of stress fractures, ankle sprains, or foot problems between recruits using the different types of orthoses.\n These findings suggest that if a foot orthosis is being dispensed as prophylaxis for overuse injuries in an active, healthy population, there is little justification for prescribing semirigid biomechanical orthoses. Their cost is high compared to other types of orthoses, without an advantage in comfort or a reduction in stress fractures, ankle sprains, and foot problems.", "Eighty-seven male inmates from a state prison and 70 inmates from a county jail volunteered as subjects. The subjects, age 20 to 35 yrs, were assigned randomly into a control or exercise group. Their Vo2max and treadmill performance values were determined before and after a 20 week jogging program. Training intensity was between 85 and 90 percent of maximum heart rate and involved workouts 3 days/week for 15, 30, or 45-min duration at the state prison and for 30-min 1, 3, or 5 days/week at the country jail. Cardiorespiratory fitness improved in direct proportion to frequency and duration of training. Injury, occurred in 22%, 24% and 54% of the 15, 30, and 45-min duration groups and in 0%, 12%, and 39% of the 1, 3, and 5-day/week groups, respectively. Attrition resulting from injury occurred in 0%, 0%, and 17% and in 0%, 4%, and 6% of the same respective groups. Attrition due to lack of interest was similar for all training groups (25%), but was significantly lower in the control groups (10%). Although the results showed a greater increase in cardiorespiratory fitness for the 45-min duration and 5-day/week groups, these programs are not recommened for beginning joggers because of the significantly greater percent of injuries.", "The incidence of foot blisters and other overuse injuries of the lower limb is very high during basic military training (BMT). One hundred and eighty-nine subjects were divided into two intervention groups wearing alternative sock systems and one control group. Overall, 57% of the 173 recruits who completed the training, developed foot blisters. Binary logistic regression revealed the type of sock, race, previous hiking or military experience, and known orthopedic foot conditions to be predictive variables for foot blisters. Fifty-three percent of the 173 recruits also developed another overuse injury of the lower limb (25.4% related to the knee joint). Previous military or hiking experience and the association of foot blisters revealed to be predictive for the overuse injuries of the knee joint. The results of the present study suggest associated foot blisters are also an important factor in the development of overuse injuries of the knee joint during BMT.", "There have been numerous reports about the use of knee braces to prevent traumatic knee injuries. Despite the frequent use of braces, very few prospective studies have been performed to study the effect of knee braces for preventing anterior knee pain syndrome (AKPS). The purpose of this study was to assess the effectiveness of a dynamic patellofemoral brace (On-Track System, dj Orthopedics) in the prevention of AKPS. 167 military recruits without history of knee pain were randomized into two groups prior to the start of their 6-week basic military training (BMT) program. The first group (brace group) consisted of 54 recruits who wore the braces for all physical activities during these 6 weeks. 113 recruits served as a control group, and followed the same 6-week strenuous training program. Chi square statistics (Fisher exact test) were used to compare the number of AKPS patients in the brace group and in the non-brace group. Our results indicated that recruits in the brace group appeared to develop significantly less anterior knee pain compared to the recruits in the control group (p=0.020). Out of the 54 recruits in the brace group, ten (18.5%) developed anterior knee pain during this study. In the control group (n=113), 42 recruits (37%) developed anterior knee pain. We conclude that the result of the present study suggests that the use of a dynamic patellofemoral brace is an effective way to prevent the development of anterior knee pain in persons undergoing a strenuous training program.", "It is unknown whether an exercise program can prevent overuse injuries in the lower extremity. An often encountered and important risk factor for the development of lower extremity overuse injuries is an abrupt increase in activity level.\n A preventive training program based on a literature review of intrinsic risk factors, and performed concurrent with an increase in physical activity, can reduce the incidence of overuse knee injuries and medial tibial stress syndrome, as well as increase running distance.\n Randomized controlled trial; Level of evidence, 1.\n A total of 1020 soldiers aged 20.9 years (range, 19-26 years) undergoing 3 months of basic military training consecutively enrolled from December 2004 to December 2005. The prevention program consisted of an exercise program of 15 minutes' duration 3 times a week, including 5 exercises for strength, flexibility, and coordination; the placebo program consisted of 5 exercises for the upper body.\n During the observation period, 223 subjects sustained an injury, with 50 and 48 of these fulfilling the study criteria for overuse knee injuries or medial tibial stress syndrome, respectively. There were no significant differences in incidence of injury between the prevention group and the placebo group (incidence, 0.22 vs 0.19; P = .162; relative risk = 1.05 [range, 0.98-1.11]). The soldiers in the prevention group had the greater improvement in running distance in 12-minute run tests (82 vs 43 m; P = .037).\n An exercise program with an emphasis on muscular strengthening, coordination, and flexibility based on intrinsic risk factors identified through a literature review did not influence the risk of developing overuse knee injuries or medial tibial stress syndrome in subjects undergoing an increase in physical activity. The program increased maximal running distance in a 12-minute test.", "Shock-absorbing and biomechanic shoe orthoses are frequently used in the prevention and treatment of back and lower extremity problems. One review concludes that the former is clinically effective in relation to prevention, whereas the latter has been tested in only 1 randomized clinical trial, concluding that stress fractures could be prevented.\n To investigate if biomechanic shoe orthoses can prevent problems in the back and lower extremities and if reducing the number of days off-duty because of back or lower extremity problems is possible.\n Prospective, randomized, controlled intervention trial.\n One female and 145 male military conscripts (aged 18 to 24 years), representing 25% of all new conscripts in a Danish regiment.\n Health data were collected by questionnaires at initiation of the study and 3 months later. Custom-made biomechanic shoe orthoses to be worn in military boots were provided to all in the study group during the 3-month intervention period. No intervention was provided for the control group. Differences between the 2 groups were tested with the chi-square test, and statistical significance was accepted at P <.05. Risk ratio (RR), risk difference (ARR), numbers needed to prevent (NNP), and cost per successfully prevented case were calculated.\n Outcome variables included self-reported back and/or lower extremity problems; specific problems in the back or knees or shin splints, Achilles tendonitis, sprained ankle, or other problems in the lower extremity; number of subjects with at least 1 day off-duty because of back or lower extremity problems and total number of days off-duty within the first 3 months of military service because of back or lower extremity problems.\n Results were significantly better in an actual-use analysis in the intervention group for total number of subjects with back or lower extremity problems (RR 0.7, ARR 19%, NNP 5, cost 98 US dollars); number of subjects with shin splints (RR 0.2, ARR 19%, NNP 5, cost 101 US dollars); number of off-duty days because of back or lower extremity problems (RR 0.6, ARR < 1%, NNP 200, cost 3750 US dollars). In an intention-to-treat analysis, a significant difference was found for only number of subjects with shin splints (RR 0.3, ARR 18%, NNP 6 cost 105 US dollars), whereas a worst-case analysis revealed no significant differences between the study groups.\n This study shows that it may be possible to prevent certain musculoskeletal problems in the back or lower extremities among military conscripts by using custom-made biomechanic shoe orthoses. However, because care-seeking for lower extremity problems is rare, using this method of prevention in military conscripts would be too costly. We also noted that the choice of statistical approach determined the outcome.", "A prospective controlled trial was carried out to determine the usefulness of a viscoelastic polymer insole in prevention of stress fractures and stress reactions of the lower extremities. The subjects were 3,025 US Marine recruits who were followed for 12 weeks of training at Parris Island, South Carolina. Polymer and standard mesh insoles were systematically distributed in boots that were issued to members of odd and even numbered platoons. The most important finding was that an elastic polymer insole with good shock absorbency properties did not prevent stress reactions of bone during a 12-week period of vigorous physical training. To control for the confounding effects of running in running shoes, which occurred for about one and one-half hours per week for the first five weeks, we also examined the association of age of shoes and cost of shoes with injury incidence. A slight trend of increasing stress injuries by increasing age of shoes was observed. However, this trend did not account for the similarity of rates in the two insole groups. In addition, we observed a strong trend of decreasing stress injury rate by history of increasing physical activity, as well as a higher stress injury rate in White compared to Black recruits. The results of the trial were not altered after controlling for these factors. This prospective study confirms previous clinical reports of the association of stress fractures with physical activity history. The clinical application of a shock absorbing insole as a preventive for lower extremity stress reactions is not supported in these uniformly trained recruits. The findings are relevant to civilian populations.", "This study investigated effects of ankle dorsiflexion range and pre-exercise calf muscle stretching on relative risk of selected injuries in 1093 male Army recruits undertaking 12 weeks of intensive training. Prior to training, ankle dorsiflexion range was measured and recruits were allocated to stretch and control groups using a quasi-random procedure. The stretch group stretched calf muscles under supervision prior to all intense exercise. The control group stretched upper limb muscles instead. Forty-eight injuries were recorded. Survival analysis indicated that ankle dorsiflexion range was a strong predictor of injury (p = 0.03). Definitive evidence of an effect of stretching on injury risk was not found (p = 0.76), but the sample size may have been insufficient to detect such an effect.", "To assess the benefits, if any, of the use of shock absorbing insoles in reducing lower limb injury among Air Force recruits, and to assess the differences, if any, in the efficacy of two commonly available shock absorbing insoles.\n Randomized controlled trial.\n RAF Halton, UK. Site of all basic training for RAF personnel.\n 1205 recruits participating in basic training between 17 September 2003 and 7 April 2004.\n Participants were randomized to receive either standard issue Saran non-shock absorbing insoles, or shock absorbing Sorbothane or Poron insoles, on a 1:1:1 basis.\n The primary outcome measure was withdrawal from training for lower limb injury. The two primary comparisons were shock absorbing insole versus non-shock absorbing insole, and Sorbothane versus Poron (comparison of different shock absorbing insoles). Secondary outcomes were medical withdrawals for reasons other than those qualifying for the primary outcome measure.\n When comparing the non-shock absorbing insole to the shock absorbing insoles 72/401 participants (18.0%) allocated to Saran insoles were removed from training because of a qualifying lower limb injury, compared with 149/804 (18.5%) allocated to the shock absorbing insole (Sorbothane or Poron), odds ratio 1.04 (95% CI 0.75 to 1.44; P=0.87). When comparing the two shock absorbing insole 73/421 participants (17.3%) randomized to Sorbothane were removed from training because of a qualifying lower limb injury, compared with 76/383 for Poron (19.8%), odds ratio 0.85 (95% CI 0.58 to 1.23; P=0.37).\n Similar rates of lower limb injuries were observed for all insoles (shock absorbing and non-shock absorbing) in the trial. The trial provides no support for a change in policy to the use of shock absorbing insoles for military recruits.", "This study investigated the effect of muscle stretching during warm-up on the risk of exercise-related injury.\n 1538 male army recruits were randomly allocated to stretch or control groups. During the ensuing 12 wk of training, both groups performed active warm-up exercises before physical training sessions. In addition, the stretch group performed one 20-s static stretch under supervision for each of six major leg muscle groups during every warm-up. The control group did not stretch.\n 333 lower-limb injuries were recorded during the training period, including 214 soft-tissue injuries. There were 158 injuries in the stretch group and 175 in the control group. There was no significant effect of preexercise stretching on all-injuries risk (hazard ratio [HR] = 0.95, 95% CI 0.77-1.18), soft-tissue injury risk (HR = 0.83, 95% CI 0.63-1.09), or bone injury risk (HR = 1.22, 95% CI 0.86-1.76). Fitness (20-m progressive shuttle run test score), age, and enlistment date all significantly predicted injury risk (P < 0.01 for each), but height, weight, and body mass index did not.\n A typical muscle stretching protocol performed during preexercise warm-ups does not produce clinically meaningful reductions in risk of exercise-related injury in army recruits. Fitness may be an important, modifiable risk factor.", "This study examined whether assigning running shoes based on the shape of the bottom of the foot (plantar surface) influenced injury risk in Air Force Basic Military Training (BMT) and examined risk factors for injury in BMT.\n Data were collected from BMT recruits during 2007; analysis took place during 2008. After foot examinations, recruits were randomly consigned to either an experimental group (E, n=1042 men, 375 women) or a control group (C, n=913 men, 346 women). Experimental group recruits were assigned motion control, stability, or cushioned shoes for plantar shapes indicative of low, medium, or high arches, respectively. Control group recruits received a stability shoe regardless of plantar shape. Injuries during BMT were determined from outpatient visits provided from the Defense Medical Surveillance System. Other injury risk factors (fitness, smoking, physical activity, prior injury, menstrual history, and demographics) were obtained from a questionnaire, existing databases, or BMT units.\n Multivariate Cox regression controlling for other risk factors showed little difference in injury risk between the groups among men (hazard ratio [E/C]=1.11, 95% CI=0.89-1.38) or women (hazard ratio [E/C]=1.20, 95% CI= 0.90-1.60). Independent injury risk factors among both men and women included low aerobic fitness and cigarette smoking.\n This prospective study demonstrated that assigning running shoes based on the shape of the plantar surface had little influence on injury risk in BMT even after controlling for other injury risk factors.\n Published by Elsevier Inc.", "Popular running magazines and running shoe companies suggest that imprints of the bottom of the feet (plantar shape) can be used as an indication of the height of the medial longitudinal foot arch and that this can be used to select individually appropriate types of running shoes. This study examined whether or not this selection technique influenced injury risk during United States Army Basic Combat Training (BCT). After foot examinations, BCT recruits in an experimental group (E: n = 1,079 men and 451 women) selected motion control, stability, or cushioned shoes for plantar shapes judged to represent low, medium, or high foot arches, respectively. A control group (C: n = 1,068 men and 464 women) received a stability shoe regardless of plantar shape. Injuries during BCT were determined from outpatient medical records. Other previously known injury risk factors (e.g., age, fitness, and smoking) were obtained from a questionnaire and existing databases. Multivariate Cox regression controlling for other injury risk factors showed little difference in injury risk between the E and C groups among men (risk ratio (E/C) = 1.01; 95% confidence interval = 0.88-1.16; p = 0.87) or women (risk ratio (E/C) = 1.07; 95% confidence interval = 0.91-1.25; p = 0.44). In practical application, this prospective study demonstrated that selecting shoes based on plantar shape had little influence on injury risk in BCT. Thus, if the goal is injury prevention, this selection technique is not necessary in BCT.", "nan", "Three hundred fifty male recruits were randomly allocated to either the standard recruit training program (N = 180) or substituted a weighted-march activity for all formal run periods (N = 170) in the physical training program. All injuries were seen at a single medical facility, and the cause, location, and severity of injury were recorded in the medical documents. Lower-limb injuries constituted 79.8% of all Run injuries and 61.1% of all Walk injuries. Foot (18.9%), knee (16.7%), ankle (13.3%), and shoulder (8.9%) were the most common sites of injury in the Walk group. In the Run group, the most common sites were knee (32.1%), ankle (18.3%), foot (11.9%), and shin (7.3%). There were two stress fractures (tibial) in the Run group and none in the Walk group, giving the Run group an incidence of 1.1%. There were 10 medical discharges in the Walk group and 16 in the Run group. Ten (62.5%) of the Run and 2 (20%) of the Walk discharges were due to lower-limb causes. Of these, only 1 (10%) of the Walk and 4 (25%) of the Run injuries were not considered to be pre-existing conditions. Marching (30.0%), physical training (25.5%), and the obstacle course (11.1%) were the most frequent causes of injury in the Walk group. In the Run group, the leading causes were running (36.6%), physical training (19.2%), and the obstacle course (14.6%). Running was the major cause of knee injury in the Run group (17/35), whereas physical training was the major cause of knee injury in the Walk group (5/15). Running was also the major cause of other lower-limb injuries in the Run group (19/58), whereas marching was the major cause in the Walk group (19/50). Lower-limb injuries were more frequent in the Run group, with running cited as the major cause of these injuries.", "Soccer referees participating in large soccer tournaments may develop overuse injuries. In this study the effect of shock absorbing heel inserts in the incidence of soreness was investigated. Forty-eight referees were randomly selected to wear shock absorbing heel inserts (SAH) in the 5 day-tournament, while 43 referees were the control group. A daily questionnaire inquiring about complaints from the locomotive system was completed for each referee and in case of any soreness they were examined by doctors to document and classify the anatomical site. Calf, thigh, back, achilles tendon and knee were the most common localizations of overuse symptoms. The incidence of soreness in achilles tendon, calf and back were significantly reduced by the use of (SAH) inserts.", "The purpose of this intervention study was to prove that increasing flexibility of the hamstring musculotendinous unit would decrease the number of lower extremity overuse injuries that occur in military infantry basic trainees. Two different companies going through basic training at the same time were used. Hamstring flexibility was checked at the beginning and at the end of the 13-week infantry basic training course. The control company (N = 148) proceeded through normal basic training. The intervention company (N = 150) followed the same program but added three hamstring stretching sessions to their already scheduled fitness program. All subsequent lower extremity overuse injuries were recorded through the troop medical clinic. Hamstring flexibility increased significantly in the intervention group compared with the control group. The number of injuries was also significantly lower in the intervention group. Forty-three injuries occurred in the control group for an incidence rate of 29.1%, compared with 25 injuries in the intervention group for an incidence rate of 16.7%. Thus, in this study, the number of lower extremity overuse injuries was significantly lower infantry basic trainees with increased hamstring flexibility.", "Our prospective study evaluates the use of a knee brace with a silicon patellar support ring as a method of preventing anterior knee pain from developing in young persons undergoing strenuous physical exercise. We studied 60 young athletes, who qualified for a strenuous physical training course and who had not suffered from anterior knee pain previously. Twenty-seven subjects were in the brace group and 33 were in the nonbrace control group. The incidence of anterior knee pain syndrome increased with the intensity of exertion as the study progressed; i.e., subjects ran 6 km in the 1st week, gradually increasing each week up to 42 km/week at the 8th week. Yet, there was a significant reduction in the incidence of the syndrome at the end of the study in male athletes who had applied the braces before exercise sessions and in the brace group as a whole, compared with the control group. Prophylactic use of the brace, as described, did not reduce the ability of the athletes who wore braces to improve their physical fitness parameters in response to exercise. These data indicate that the use of a brace may be an effective way to prevent the development of anterior knee pain syndromes in persons participating in strenuous and intensive physical exercise." ]

[ "12414200", "11022066" ]

[ "International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial.", "Outcomes of early endovascular versus surgical treatment of ruptured cerebral aneurysms. A prospective randomized study." ]

[ "Endovascular detachable coil treatment is being increasingly used as an alternative to craniotomy and clipping for some ruptured intracranial aneurysms, although the relative benefits of these two approaches have yet to be established. We undertook a randomised, multicentre trial to compare the safety and efficacy of endovascular coiling with standard neurosurgical clipping for such aneurysms judged to be suitable for both treatments.\n We enrolled 2143 patients with ruptured intracranial aneurysms and randomly assigned them to neurosurgical clipping (n=1070) or endovascular treatment by detachable platinum coils (n=1073). Clinical outcomes were assessed at 2 months and at 1 year with interim ascertainment of rebleeds and death. The primary outcome was the proportion of patients with a modified Rankin scale score of 3-6 (dependency or death) at 1 year. Trial recruitment was stopped by the steering committee after a planned interim analysis. Analysis was per protocol.\n 190 of 801 (23.7%) patients allocated endovascular treatment were dependent or dead at 1 year compared with 243 of 793 (30.6%) allocated neurosurgical treatment (p=0.0019). The relative and absolute risk reductions in dependency or death after allocation to an endovascular versus neurosurgical treatment were 22.6% (95% CI 8.9-34.2) and 6.9% (2.5-11.3), respectively. The risk of rebleeding from the ruptured aneurysm after 1 year was two per 1276 and zero per 1081 patient-years for patients allocated endovascular and neurosurgical treatment, respectively.\n In patients with a ruptured intracranial aneurysm, for which endovascular coiling and neurosurgical clipping are therapeutic options, the outcome in terms of survival free of disability at 1 year is significantly better with endovascular coiling. The data available to date suggest that the long-term risks of further bleeding from the treated aneurysm are low with either therapy, although somewhat more frequent with endovascular coiling.", "This prospective study was conducted to compare the outcomes of surgical clipping and endovascular treatment in acute (<72 hours) aneurysmal subarachnoid hemorrhage (SAH).\n One hundred nine consecutive patients were randomly assigned to either surgical (n=57) or endovascular (n=52) treatment. Clinical and neuropsychological outcome was assessed at 3 and 12 months after treatment; MRI of the brain was performed at 12 months. Follow-up angiography was scheduled after clipping and 3 and 12 months after endovascular treatment.\n One year postoperatively, 43/41 (surgical/endovascular) patients had good or moderate recovery, 5/4 had severe disability or were in a vegetative state, and 9/7 had died (NS) according to intention to treat. Patients with good clinical recovery did not differ in their neuropsychological test scores. Symptomatic vasospasm (OR 2.47; 95% CI 1.45 to 4.19; P<0.001), poorer Hunt and Hess grade (OR 2.50; 95% CI 1.31 to 4.75; P=0.005), need for permanent shunt (OR 8.90; 95% CI 1.80 to 44.15; P=0.008), and larger size of the aneurysm (OR 1. 22; 95% CI 1.02 to 1.45; P=0.032) independently predicted worsened clinical outcome regardless of the treatment modality. In MRI, superficial brain retraction deficits (P<0.001) and ischemic lesions in the territory of the ruptured aneurysm (P=0.025) were more frequent in the surgical group. Kaplan-Meier analysis (mean+/-SD follow-up 39+/-18 months) revealed equal survival in both treatment groups. No late rebleedings have occurred.\n One-year clinical and neuropsychological outcomes seem comparable after early surgical and endovascular treatment of ruptured intracranial aneurysms. The long-term efficacy of endovascular treatment in preventing rebleeding remains open." ]

[ "8757375", "19430829", "11882751" ]

[ "A randomized study comparing laparoscopic versus open repair of perforated peptic ulcer using suture or sutureless technique.", "Randomized clinical trial of laparoscopic versus open repair of the perforated peptic ulcer: the LAMA Trial.", "Laparoscopic repair for perforated peptic ulcer: a randomized controlled trial." ]

[ "This study compares laparoscopic versus open repair and suture versus sutureless repair of perforated duodenal and juxtapyloric ulcers.\n The place of laparoscopic repair of perforated peptic ulcer followed by peritoneal toilet of the peritoneal cavity has been established. Whether repair of the perforated peptic ulcer by the laparoscopic approach is better than conventional open repair and whether sutured repair is better than sutureless repair are both undetermined.\n One hundred three patients were randomly allocated to laparoscopic suture repair, laparoscopic sutureless repair, open suture repair, and open sutureless repair.\n Laparoscopic repair of perforated peptic ulcer (groups 1 and 2) took significantly longer than open repair (groups 3 and 4; 94.3 +/ 40.3 vs. 53.7 +/ 42.6 minutes: Student's test, p < 0.001), but the amount of analgesic required after laparoscopic repair was significantly less than in open surgery (median 1 dose vs. 3 doses) (Mann-Whitney U test, p = 0.03). There was no significant difference in the four groups of patients in terms of duration of nasogastric aspiration, duration of intravenous drip, total hospital stay, time to resume normal diet, visual analogue scale score for pain in the first 24 hours after surgery, morbidity, reoperation, and mortality rates.\n Laparoscopic repair of perforated peptic ulcer is a viable option. Sutureless repair is as safe as suture repair and it takes less time to perform.", "Laparoscopic surgery has become popular during the last decade, mainly because it is associated with fewer postoperative complications than the conventional open approach. It remains unclear, however, if this benefit is observed after laparoscopic correction of perforated peptic ulcer (PPU). The goal of the present study was to evaluate whether laparoscopic closure of a PPU is as safe as conventional open correction.\n The study was based on a randomized controlled trial in which nine medical centers from the Netherlands participated. A total of 109 patients with symptoms of PPU and evidence of air under the diaphragm were scheduled to receive a PPU repair. After exclusion of 8 patients during the operation, outcomes were analyzed for laparotomy (n = 49) and for the laparoscopic procedure (n = 52).\n Operating time in the laparoscopy group was significantly longer than in the open group (75 min versus 50 min). Differences regarding postoperative dosage of opiates and the visual analog scale (VAS) for pain scoring system were in favor of the laparoscopic procedure. The VAS score on postoperative days 1, 3, and 7 was significant lower (P < 0.05) in the laparoscopic group. Complications were equally distributed. Hospital stay was also comparable: 6.5 days in the laparoscopic group versus 8.0 days in the open group (P = 0.235).\n Laparoscopic repair of PPU is a safe procedure compared with open repair. The results considering postoperative pain favor the laparoscopic procedure.", "To compare the results of open versus laparoscopic repair for perforated peptic ulcers.\n Omental patch repair with peritoneal lavage is the mainstay of treatment for perforated peptic ulcers in many institutions. Laparoscopic repair has been used to treat perforated peptic ulcers since 1990, but few randomized studies have been carried out to compare open versus laparoscopic procedures.\n From January 1994 to June 1997, 130 patients with a clinical diagnosis of perforated peptic ulcer were randomly assigned to undergo either open or laparoscopic omental patch repair. Patients were excluded for a history of upper abdominal surgery, concomitant evidence of bleeding from the ulcer, or gastric outlet obstruction. Patients with clinically sealed-off perforations without signs of peritonitis or sepsis were treated without surgery. Laparoscopic repair would be converted to an open procedure for technical difficulties, nonjuxtapyloric gastric ulcers, or perforations larger than 10 mm. A Gastrografin meal was performed 48 to 72 hours after surgery to document sealing of the perforation. The primary end-point was perioperative parenteral analgesic requirement. Secondary endpoints were operative time, postoperative pain score, length of postoperative hospital stay, complications and deaths, and the date of return to normal daily activities.\n Nine patients with a surgical diagnosis other than perforated peptic ulcer were excluded; 121 patients entered the final analysis. There were 98 male and 23 female patients recruited, ages 16 to 89 years. The two groups were comparable in age, sex, site and size of perforations, and American Society of Anesthesiology classification. There were nine conversions in the laparoscopic group. After surgery, patients in the laparoscopic group required significantly less parenteral analgesics than those who underwent open repair, and the visual analog pain scores in days 1 and 3 after surgery were significantly lower in the laparoscopic group as well. Laparoscopic repair required significantly less time to complete than open repair. The median postoperative stay was 6 days in the laparoscopic group versus 7 days in the open group. There were fewer chest infections in the laparoscopic group. There were two intraabdominal collections in the laparoscopic group. One patient in the laparoscopic group and three patients in the open group died after surgery.\n Laparoscopic repair of perforated peptic ulcer is a safe and reliable procedure. It was associated with a shorter operating time, less postoperative pain, reduced chest complications, a shorter postoperative hospital stay, and earlier return to normal daily activities than the conventional open repair." ]

[ "21290830", "19276620", "15733717", "15733716", "16544087", "20176418", "20138037", "20667840", "21441148", "19229451", "18782484", "10921166", "16361020", "16364933", "16708735", "18946003", "8555849", "18771521" ]

[ "[Dysphagia after stroke treated with acupuncture or electric stimulation: a randomized controlled trial].", "Is antioxidant and n-3 supplementation able to improve functional status in poststroke patients? Results from the Nutristroke Trial.", "Effect of timing and method of enteral tube feeding for dysphagic stroke patients (FOOD): a multicentre randomised controlled trial.", "Routine oral nutritional supplementation for stroke patients in hospital (FOOD): a multicentre randomised controlled trial.", "Evaluating oral stimulation as a treatment for dysphagia after stroke.", "Individual, nutritional support prevents undernutrition, increases muscle strength and improves QoL among elderly at nutritional risk hospitalized for acute stroke: a randomized, controlled trial.", "Adjunctive functional pharyngeal electrical stimulation reverses swallowing disability after brain lesions.", "Does looped nasogastric tube feeding improve nutritional delivery for patients with dysphagia after acute stroke? A randomised controlled trial.", "Noninvasive brain stimulation may improve stroke-related dysphagia: a pilot study.", "Neuromuscular electrical and thermal-tactile stimulation for dysphagia caused by stroke: a randomized controlled trial.", "Effect of calorie-protein supplementation on the cognitive recovery of patients with subacute stroke.", "Acupuncture treatment of bulbar palsy--a report of 54 cases.", "Behavioural intervention for dysphagia in acute stroke: a randomised controlled trial.", "The role of selective decontamination of the digestive tract in acute stroke.", "A prospective comparison of percutaneous endoscopic gastrostomy and nasogastric tube feeding in patients with acute dysphagic stroke.", "Intensive nutritional supplements can improve outcomes in stroke rehabilitation.", "A randomised prospective comparison of percutaneous endoscopic gastrostomy and nasogastric tube feeding after acute dysphagic stroke.", "Treatment of post-stroke dysphagia with repetitive transcranial magnetic stimulation." ]

[ "To compare the therapeutic effects between acupuncture and electric stimulation on post-stroke dysphagia on the basis of rehabilitation training.\n Ninety-seven patients with post-stroke dysphagia were randomly divided into an acupuncture group (group A, n = 32), an electric stimulation group (group B, n = 35) and a rehabilitation training group (group C, n = 30). In group C, the conventional therapy (conventional therapy of neurologic internal medicine and rehabilitation training) was applied. In group A, the combination of conventional therapy and acupuncture was applied. The acupoints of Fengchi (GB 20), Futu (LI 18), three-needles on the forehead, etc. were selected. In group B, the combination of conventional therapy and electric stimulation was adopted. Watian drinking water experiment, stethocatharsis function scoring and video fluoroscopic swallowing study (VFSS) were used to evaluate swallowing function of patients.\n After treatment, the total effective rate was 96.95 (31/32) in group A and was 94.3% (33/35) in group B, which was superior to that of 66.7% (20/30) in group C (P < 0.01). After treatment, the swallowing function in group A, group B and group C were all improved significantly as compared with that before treatment (all P < 0.05). After treatment, the effects in group A and B were superior to that in group C (both P < 0.05).\n The therapeutic effect of the combination of either acupuncture or electric stimulation with rehabilitation training is better than that of simple rehabilitation training. The efficacy on dysphagia is equal between acupuncture and electric stimulation.", "To test whether supplementary antioxidants and n-3 fatty acids, alone or in combination, could improve functional status in stroke survivors.\n We performed a randomized, double-blind, placebo-controlled clinical trial in 72 stroke patients (47 males; age 65.3 +/- 12.9 years) admitted to a rehabilitation hospital for sequelae of first-ever ischemic stroke, and divided them into 4 subgroups. Group 1 patients received daily oral antioxidants, group 2 received n-3 polyunsaturated fatty acids, group 3 both supplements, and group 4 placebo, all for 12 months. No difference at baseline was observed among groups in neurological severity or in disability. All measures were repeated after 6 and 12 months of treatment. All major clinical events were recorded.\n At baseline, 25% of the patients had a low plasma vitamin status, and 48.5% was at risk of undernutrition. At the 1-year follow-up, we observed a trend for lower mortality (p = 0.060) in subgroups treated with n-3 fatty acids, but without significant differences in rehabilitation result status among groups.\n Malnutrition is widely observed in patients admitted to a rehabilitative hospital for stroke rehabilitation, and dietary supplementation, even if not able to improve rehabilitation results, is likely to reduce mortality at the 1-year follow-up.\n Copyright 2009 S. Karger AG, Basel.", "Undernutrition is common in patients admitted with stroke. We aimed to establish whether the timing and route of enteral tube feeding after stroke affected patients' outcomes at 6 months.\n The FOOD trials consist of three pragmatic multicentre randomised controlled trials, two of which included dysphagic stroke patients. In one trial, patients enrolled within 7 days of admission were randomly allocated to early enteral tube feeding or no tube feeding for more than 7 days (early versus avoid). In the other, patients were allocated percutaneous endoscopic gastrostomy (PEG) or nasogastric feeding. The primary outcome was death or poor outcome at 6 months. Analysis was by intention to treat.\n Between Nov 1, 1996, and July 31, 2003, 859 patients were enrolled by 83 hospitals in 15 countries into the early versus avoid trial. Early tube feeding was associated with an absolute reduction in risk of death of 5.8% (95% CI -0.8 to 12.5, p=0.09) and a reduction in death or poor outcome of 1.2% (-4.2 to 6.6, p=0.7). In the PEG versus nasogastric tube trial, 321 patients were enrolled by 47 hospitals in 11 countries. PEG feeding was associated with an absolute increase in risk of death of 1.0% (-10.0 to 11.9, p=0.9) and an increased risk of death or poor outcome of 7.8% (0.0 to 15.5, p=0.05).\n Early tube feeding might reduce case fatality, but at the expense of increasing the proportion surviving with poor outcome. Our data do not support a policy of early initiation of PEG feeding in dysphagic stroke patients.", "Undernutrition is common in hospital patients with stroke, can develop or worsen in hospital, and is associated with poor outcomes. We aimed to establish whether routine oral nutritional supplements improve outcome after stroke.\n The FOOD trials are a family of three pragmatic, multicentre, randomised controlled trials. We measured the outcomes of stroke patients who could swallow and who were randomly allocated normal hospital diet or normal hospital diet plus oral nutritional supplements until hospital discharge. The primary outcome was death or poor outcome (modified Rankin scale [MRS] grade 3-5), 6 months after enrollment, measured unaware of treatment allocation. Analysis was by intention to treat.\n Between Nov 1, 1996, and July 31, 2003, 4023 patients were enrolled by 125 hospitals in 15 countries. Only 314 (8%) patients were judged to be undernourished at baseline. Vital status and MRS at the end of the trial were known for 4012 and 4004 patients, respectively. Supplemented diet was associated with an absolute reduction in risk of death of 0.7% (95% CI -1.4 to 2.7) and an increased risk of death or poor outcome of 0.7% (-2.3 to 3.8).\n We could not confirm the anticipated 4% absolute benefit for death or poor outcome from routine oral nutritional supplements for mainly well nourished stroke patients in hospital. Our results would be compatible with a 1% or 2% absolute benefit or harm from oral supplements. These results do not support a policy of routine oral supplementation after stroke.", "Deglutitive aspiration is common after stroke and can have devastating consequences. While the application of oral sensory stimulation as a treatment for dysphagia remains controversial, data from our laboratory have suggested that it may increase corticobulbar excitability, which in previous work was correlated with swallowing recovery after stroke. Our study assessed the effects of oral stimulation at the faucial pillar on measures of swallowing and aspiration in patients with dysphagic stroke. Swallowing was assessed before and 60 min after 0.2-Hz electrical or sham stimulation in 16 stroke patients (12 male, mean age = 73 +/- 12 years). Swallowing measures included laryngeal closure (initiation and duration) and pharyngeal transit time, taken from digitally acquired videofluoroscopy. Aspiration severity was assessed using a validated penetration-aspiration scale. Preintervention, the initiation of laryngeal closure, was delayed in both groups, occurring 0.66 +/- 0.17 s after the bolus arrived at the hypopharynx. The larynx was closed for 0.79 +/- 0.07 s and pharyngeal transit time was 0.94 +/- 0.06 s. Baseline swallowing measures and aspiration severity were similar between groups (stimulation: 24.9 +/- 3.01; sham: 24.9 +/- 3.3, p = 0.2). Compared with baseline, no change was observed in the speed of laryngeal elevation, pharyngeal transit time, or aspiration severity within subjects or between groups for either active or sham stimulation. Our study found no evidence for functional change in swallow physiology after faucial pillar stimulation in dysphagic stroke. Therefore, with the parameters used in this study, oral stimulation does not offer an effective treatment for poststroke patients.", "Undernutrition after an acute stroke increases the risk of poor outcome. We wanted to examine the effect of individualized, nutritional support on weight loss and functional outcomes in stroke patients.\n Acute stroke patients at nutritional risk were randomized to either individualized, nutritional care or routine care while in hospital. Patients in the intervention group received an individualized treatment plan aiming to prevent weight loss. In accordance with routine care, the controls did not have such a treatment plan. Patients were reviewed at follow-up after three months. Primary outcome measure was the percentage of patients with weight loss ≥5%. Secondary outcomes measures were quality of life (QoL), handgrip strength and length of hospital stay. This trial is registered with ClinicalTrials.gov, number NCT00163007.\n At follow-up, 20.7% of the intervention group (n = 58) lost ≥5% weight compared with 36.4% in the control group (n = 66) (P = 0.055). The intervention group had a significantly higher increase in QoL score (P = 0.009) and in handgrip strength (P = 0.002). There was no difference in length of hospital stay.\n Individualized, nutritional treatment strategy can prevent clinically significant weight loss and improve QoL in elderly acute stroke patients at nutritional risk.\n Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.", "Oropharyngeal dysphagia is an important disability that occurs after stroke; it contributes to aspiration pneumonia and death, and current modalities for rehabilitation of dysphagia have uncertain efficacy. We therefore examined the role of pharyngeal electrical stimulation (PES) in expediting human swallowing recovery after experimental (virtual) and actual (stroke) brain lesions.\n First, healthy subjects (n = 13) were given 1-Hz repetitive transcranial magnetic stimulation to induce a unilateral virtual lesion in pharyngeal motor cortex followed by active or sham (control) PES. Motor-evoked potentials and swallow accuracy were recorded before and after the lesion to assess PES response. Thereafter, 50 acute dysphagic stroke patients underwent either a dose-response study, to determine optimal parameters for PES (n = 22), or were assigned randomly to groups given either active or sham (control) PES (n = 28). The primary end point was the reduction of airway aspiration at 2 weeks postintervention.\n In contrast to sham PES, active PES reversed the cortical suppression induced by the virtual lesion (F(7,70) = 2.7; P = .015) and was associated with improvement in swallowing behavior (F(3,42) = 5; P = .02). After stroke, 1 PES treatment each day (U = 8.0; P = .043) for 3 days (U = 10.0) produced improved airway protection compared with controls (P = .038). Active PES also reduced aspiration (U = 54.0; P = .049), improved feeding status (U = 58.0; P = .040), and resulted in a shorter time to hospital discharge (Mantel-Cox log-rank test, P = 0.038).\n This pilot study of PES confirms that it is a safe neurostimulation intervention that reverses swallowing disability after virtual lesion or stroke.\n Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.", "nasogastric tube (NGT) feeding is commonly used after stroke, but its effectiveness is limited by frequent dislodgement.\n the objective of the study was to evaluate looped NGT feeding in acute stroke patients with dysphagia.\n this was a randomised controlled trial of 104 patients with acute stroke fed by NGT in three UK stroke units. NGT was secured using either a nasal loop (n = 51) or a conventional adhesive dressing (n = 53). The main outcome measure was the proportion of prescribed feed and fluids delivered via NGT in 2 weeks post-randomisation. Secondary outcomes were frequency of NGT insertions, treatment failure, tolerability, adverse events and costs at 2 weeks; mortality; length of hospital stay; residential status; and Barthel Index at 3 months.\n participants assigned to looped NGT feeding received a mean 17% (95% confidence interval 5-28%) more volume of feed and fluids, required fewer NGTs (median 1 vs 4), and had fewer electrolyte abnormalities than controls. There was more minor nasal trauma in the loop group. There were no differences in outcomes at 3 months. Looped NGT feeding cost 88 pounds sterling more per patient over 2 weeks than controls.\n looped NGT feeding improves delivery of feed and fluids and reduces NGT reinsertion with little additional cost.", "Treatment options for stroke-related dysphagia are currently limited. In this study, we investigated whether noninvasive brain stimulation in combination with swallowing maneuvers facilitates swallowing recovery in dysphagic stroke patients during early stroke convalescence.\n Fourteen patients with subacute unilateral hemispheric infarction were randomized to anodal transcranial direct current stimulation (tDCS) versus sham stimulation to the sensorimotor cortical representation of swallowing in the unaffected hemisphere over the course of 5 consecutive days with concurrent standardized swallowing maneuvers. Severity of dysphagia was measured using a validated swallowing scale, Dysphagia Outcome and Severity scale, before the first and after the last session of tDCS or sham. The effect of tDCS was analyzed in a multivariate linear regression model using changes in Dysphagia Outcome and Severity Scale as the outcome variable after adjusting for the effects of other potential confounding variables such as the National Institutes of Health Stroke Scale and Dysphagia Outcome and Severity scale scores at baseline, acute ischemic lesion volumes, patient age, and time from stroke onset to stimulation.\n Patients who received anodal tDCS gained 2.60 points of improvement in Dysphagia Outcome and Severity scale scores compared to patients in the sham stimulation group who showed an improvement of 1.25 points (P=0.019) after controlling for the effects of other aforementioned variables. Six out 7 (86%) patients in tDCS stimulation group gained at least 2 points of improvement compared with 3 out 7 (43%) patients in the sham group (P=0.107).\n Because brain stem swallowing centers have bilateral cortical innervations, measures that enhance cortical input and sensorimotor control of brain stem swallowing may be beneficial for dysphagia recovery.", "The aim of this study was to assess the effectiveness of neuromuscular electrical stimulation in patients with dysphagia caused by stroke.\n Thirty-six subjects were randomized into experimental and control groups. The control group was given thermal-tactile stimulation treatment only, while in the experimental group neuromuscular electrical stimulation and thermal-tactile stimulation treatments were applied simultaneously. Swallowing function was assessed before and 4 weeks after treatment, and evaluated via the swallow function scoring system, penetration-aspiration scale, and pharyngeal transit time. In addition, the discomfort score during the treatments and the satisfaction score 4 weeks after the treatments were measured.\n Twenty-eight persons with dysphagia completed the study, 16 in the experimental group and 12 in the control group. Both groups showed improvement, but the experimental group showed more significant improvement in the swallow function scoring system, penetration-aspiration scale and pharyngeal transit time than the control group. The patient's discomfort score did not show statistically significant differences in either group, but the satisfactory score was higher in the experimental group.\n The results suggest that neuromuscular electrical stimulation combined with thermal-tactile stimulation is a better treatment for patients with swallowing disorders after stroke than thermal-tactile stimulation alone.", "The objective of this study was to investigate whether protein-calorie supplementation may enhance the cognitive retrieval of patients with stroke.\n A randomized, double-blind, controlled pilot clinical trial was performed comparing diet and diet plus protein-calorie supplementation regimens. The subjects were 48 patients with subacute stroke (>or14 days from index event). Anthropometric and nutritional (3-day diary) variables, cognitive function (Mini-Mental State Examination; MMSE) were determined before and 21 days after randomization in control and daily supplemented group (formula providing 250 kcal + 20 g protein).\n At day 21 after starting the protocol, only the supplemented group significantly improved their performance to MMSE (log(10)MMSE +0.6+/-0.4 score; P=0.01 from baseline).\n Protein-calorie supplementation may enhance the recovery of cognitive function in subacute stroke patients.", "nan", "Swallowing dysfunction after stroke is common, but there is little reliable evidence for how the disorder should be managed. This study compared standard low-intensity and high-intensity behavioural interventions with usual care for dysphagia.\n 306 patients with clinical dysphagia admitted to hospital with acute stroke were randomly assigned to receive usual care (n=102), prescribed by the attending physician; standard low-intensity intervention (n=102), comprising swallowing compensation strategies and diet prescription three times weekly for up to a month; or standard high-intensity intervention and dietary prescription (n=102), at least daily for up to a month. The primary outcome measure was survival free of an abnormal diet at 6 months. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00257764.\n 60 patients died and three patients were lost to follow up before the 6-month analysis. Of patients randomly allocated usual care, 56% (57/102) survived at 6 months free of an abnormal diet compared with 67% (136/204) allocated standard swallowing therapy (relative risk 1.19, 95% CI 0.98-1.45). Standard swallowing therapy was associated with a non-significant trend toward a reduction in death (0.80, 0.5-1.3), institutionalisation (0.69, 0.4-1.1), and dependency (1.05, 0.8-1.3); a significant reduction in swallowing-related medical complications (0.73, 0.6-0.9), chest infection (0.56, 0.4-0.8), and death or institutionalisation (0.73, 0.55-0.97); and a significant rise in the proportion of patients regaining swallowing function (1.41, 1.03-1.94) by 6 months. Compared with usual care and low-intensity therapy, high-intensity therapy was associated with an increased proportion of patients who returned to a normal diet (p=0.04) and recovered swallowing (p=0.02) by 6 months.\n These data show a consistent trend towards more favourable outcomes in dysphagic stroke patients who are assigned a standard programme of early behavioural swallowing intervention, including active therapeutic approaches and dietary modification.", "following a stroke, morbidity and mortality is high, with aspiration pneumonia being a common complication.\n to determine the levels of colonisation by and isolation of aerobic Gram-negative bacteria (AGNB) in acute stroke patients and determine the effect of selective decontamination of the digestive tract (SDD) on oral flora and whether it reduces both morbidity and mortality after an acute stroke.\n a prospective, randomised, placebo-controlled double blind trial.\n acute stroke assessment units of three hospitals in the northwest of England.\n 203 patients admitted to hospital following a first acute stroke.\n participants were randomised to SDD oral gel or placebo. Swallow was assessed on admission to hospital, and oral swabs were obtained thrice weekly. Demographic and clinical data were recorded.\n 203 patients (106 males and 97 females) participated, of whom 20 died during their hospitalisation, 19 withdrew and full follow-up was obtained for the remaining 164. A total of 122 AGNB were isolated in 105 samples from 48 patients. Abnormal swallow on admission was found in 58 patients (29%). A total of 34 patients carried a single gram-negative micro-organism that was present on one or more occasions. More than one AGNB was carried in 14 patients, and organisms were significantly more likely to be isolated from the placebo group than the active group during weeks 2 and 3 of treatment (P = 0.034, chi-squared). Seven patients in the placebo group and one in the treatment group developed pneumonia (P = 0.029, Fisher's exact test).\n high carriage of and colonisation by AGNB was found within this study, which was reduced by the addition of SDD. Although SDD reduced the presence of both organisms and documented episodes of pneumonia, mortality remained unchanged.", "Dysphagia following stroke is common problem and is of particular concern because of its potental for malnutrition. Nasogastric (NG) and percutaneous endoscopic gastrostomy (PEG) tube feeding are recognized methods for nutritional support for patients with persistent neurologic dysphagia. However, the former is associated with tube dislodgement and blockage that might compromise the patients' nutritional status. There have been few randomized prospective studies to date comparing the efficacy and safety of these 2 modes of dysphagia management in stroke patients. The objective of this study was to compare PEG with NG tube feeding after acute dysphagic stroke in terms of nutritional status and treatment failure. This was a randomized prospective clinical trial. A total of 23 consecutive patients who fulfilled the criteria were recruited from the medical wards in Hospital Universiti Kebangsaan Malaysia. The diagnosis of stroke (acute cerebral infarct) was based on clinical and brain computed tomographic (CT scan) findings; and the diagnosis of dysphagia was done clinically by using the 'swallowing test'. At recruitment, upper-arm skin fold thickness (triceps and biceps) and mid-arm circumference were measured; and blood was drawn for serum albumin level. They were then followed up at 4 weeks where the above tests were repeated. A total of 22 patients completed the study (12 patients in the NG group and 10 patients in the PEG group). Serum albumin levels (p = 0.045) were significantly higher in the PEG as compared to the NG group at 4 weeks post-intervention. There were statistically significant improvements in serum albumin level (p = 0.024) in the PEG group; and statistically significant reductions in serum albumin level (p = 0.047) in the NG group 4 weeks after the intervention. However, there were no significant differences in anthropometric parameters between the two groups and no significant changes in these parameters for each group 4 weeks after the intervention. Treatment failure occurred in 5 out of 10 patients (50.0%) in the NG group, but none in PEG group (p = 0.036). PEG tube feeding is more effective than NG tube feeding in improving the nutritional status (in terms of the serum albumin level) of patients with dysphagic stroke. NG tube feeding, in fact, reduced the nutritional status (in terms of the serum albumin level) of the patients.", "Poor nutrition is a common complication of strokes severe enough to require inpatient rehabilitation. We therefore tested whether intensive nutritional supplements given to undernourished patients from the time of their admission to a specialized stroke rehabilitation service would improve patient outcomes.\n Randomized, prospective, double-blind, single center study comparing intensive nutritional supplementation to routine nutritional supplementation in 116 undernourished patients admitted to a stroke service. The analysis included the 90% of patients who were not lost to follow-up due to acute or subacute hospitalization (n = 102; 51 in each group). The nutritional supplements are commercially available and Food and Drug Administration approved. The primary outcome variable was change in total score on the Functional Independence Measure (FIM). The secondary outcome measurements included the FIM motor and cognitive subscores, length of stay (taken from day of admission), 2-minute and 6-minute timed walk tests measured at admission and on discharge, and discharge disposition (home/not home).\n Patients receiving intensive nutritional supplementation improved more than those on standard nutritional supplements on measures of motor function (total FIM, FIM motor subscore, 2-minute and 6-minute timed walk tests, all significant at p < 0.002). They did not, however, improve on measures of cognition (FIM cognition score). A higher proportion of patients who received the intensive nutritional supplementation went home compared to those on standard supplementation (p = 0.05).\n Intensive nutritional supplementation, using readily available commercial preparations, improves motor recovery in previously undernourished patients receiving intensive in-patient rehabilitation after stroke.", "To compare percutaneous endoscopic gastrostomy and nasogastric tube feeding after acute dysphagic stroke.\n Randomised prospective study of inpatients with acute stroke requiring enteral nutrition.\n One university hospital (Nottingham) and one district general hospital (Derby).\n 30 patients with persisting dysphagia at 14 days after acute stroke: 16 patients were randomised to gastrostomy tube feeding and 14 to nasogastric tube feeding.\n Six week mortality; amount of feed administered; change in nutritional state; treatment failure; and length of hospital stay.\n Mortality at 6 weeks was significantly lower in the gastrostomy group with two deaths (12%) compared with eight deaths (57%) in the nasogastric group (P < 0.05). All gastrostomy fed patients (16) received the total prescribed feed whereas 10/14 (71%) of nasogastric patients lost at least one day's feed. Nasogastric patients received a significantly (P < 0.001) smaller proportion of their prescribed feed (78%; 95% confidence interval 63% to 94%) compared with the gastrostomy group (100%). Patients fed via a gastrostomy tube showed greater improvement in nutritional state, according to several different criteria at six weeks compared with the nasogastric group. In the gastrostomy group the mean albumin concentration increased from 27.1 g/l (24.5 g/l to 29.7 g/l) to 30.1 g/l (28.3 g/l to 31.9 g/l). In contrast, among the nasogastric group there was a reduction from 31.4 g/l (28.6 g/l to 34.2 g/l) to 22.3 g/l (20.7 g/l to 23.9 g/l) (P < 0.003). In addition, there were fewer treatment failures in the gastrostomy group (0/16 versus 3/14). Six patients from the gastrostomy group were discharged from hospital within six weeks of the procedure compared with none from the nasogastric group (P < 0.05).\n This study indicates that early gastrostomy tube feeding is greatly superior to nasogastric tube feeding and should be the nutritional treatment of choice for patients with acute dysphagic stroke.", "Up to one-third of patients experience swallowing problems in the period immediately after a stroke.\n To investigate the therapeutic effect of repetitive transcranial magnetic stimulation (rTMS) on post-stroke dysphagia.\n Twenty-six patients with post-stroke dysphagia due to monohemispheric stroke were randomly allocated to receive real (n = 14) or sham (n = 12) rTMS of the affected motor cortex. Each patient received a total of 300 rTMS pulses at an intensity of 120% hand motor threshold for five consecutive days. Clinical ratings of dysphagia and motor disability were assessed before and immediately after the last session and then again after 1 and 2 months. The amplitude of the motor-evoked potential (MEP) evoked by single-pulse TMS was also assessed before and at 1 month in 16 of the patients.\n There were no significant differences between patients who received real rTMS and the sham group in age, hand grip strength, Barthel Index or degree of dysphagia at the baseline assessment. Real rTMS led to a significantly greater improvement compared with sham in dysphagia and motor disability that was maintained over 2 months of follow-up. This was accompanied by a significant increase in the amplitude of the oesophageal MEP evoked from either the stroke or non-stroke hemisphere.\n rTMS may be a useful adjunct to conventional therapy for dysphagia after stroke." ]

[ "6461943", "2532229", "2874047", "2531051", "2958950", "7016106", "6240599", "6236727" ]

[ "Ipratropium bromide in children with asthma.", "Long-term effect of ipratropium bromide and fenoterol on the bronchial hyperresponsiveness to histamine in children with asthma.", "Combined treatment with ipratropium bromide and beta-2-adrenoceptor agonists in childhood asthma.", "The effects of ipratropium bromide and fenoterol nebulizer solutions in children with asthma.", "Failure of ipratropium bromide to modify the diurnal variation of asthma in asthmatic children.", "Long term atropine in chronic severe childhood asthma.", "[Bronchial asthma in childhood. Therapy with fenoterol and ipratropium bromide powder].", "[Effectiveness of disodium cromoglycate, salbutamol, and ipratropium bromide in the inhibition of exercise-induced bronchospasm]." ]

[ "Eighteen children between 6 and 14 years of age with perennial asthma were studied over two four-week treatment periods. Ipratropium bromide, given in addition to their current treatment, was compared with placebo using a double-blind crossover technique. The period of treatment with ipratropium was associated with a significant reduction in symptoms during both day and night and significantly higher morning peak expiratory flow rates.", "We studied the effects of the anticholinergic ipratropium bromide (40 micrograms three times daily) and the beta-agonist, fenoterol (0.2 mg three times daily), both administered by powder inhaler, on bronchial hyperresponsiveness (BHR) to histamine in children, aged 7 to 15 years with mild stable asthma and limited bronchoconstriction who had a highly increased BHR. The double-blind, randomized, parallel study was conducted and performed in spring and early summer. BHR and FEV1 were measured on two occasions, before the start of treatment and monthly thereafter for 4 months. Symptoms, peak expiratory flow, and concomitant medication were registered daily. Nine of the 12 patients receiving ipratropium bromide and all eight patients receiving fenoterol completed the study. Patients completing treatment had few symptoms and were in a stable condition throughout the treatment period. Neither the administration of ipratropium bromide nor fenoterol resulted in a significant change of BHR. We concluded that long-term treatment with ipratropium bromide or fenoterol had no effect on BHR in children with mild stable asthma.", "The effect of adding ipratropium bromide to treatment with beta-2-adrenoceptor agonists was studied in 13 asthmatic children in a double-blind cross-over trial. In the acute phase of the study inhalation of salbutamol 0.1 mg/kg followed by inhalation of 0.25 mg of ipratropium bromide was found to improve pulmonary function variables to a significantly greater extent than salbutamol followed by placebo. The combined therapy also provided significantly better protection than salbutamol plus placebo against exercise-induced asthma. Maintenance treatment with ipratropium bromide (two inhalations four times daily, 20 micrograms per inhalation) in combination with oral terbutaline and aerosolized salbutamol did not alleviate asthmatic symptoms or pulmonary function variables to a degree beyond that achieved with the beta-stimulants alone. There were no side effects associated with the ipratropium bromide treatment. These data suggest that higher doses of ipratropium bromide than are presently used should be tested for maintenance treatment of chronic asthma.", "The effects of nebulized solutions of ipratropium bromide and fenoterol combined were compared with the response to either preparation alone in single dose and longer-term administration in children who had asthma. The combination produced a slightly greater response than either alone, especially in peak expiratory flow. Over a 1-month period, there were no significant differences in symptom scores or lung function parameters between the combination of ipratropium bromide and fenoterol and fenoterol alone in a group of children who had asthma. It is possible that the addition of ipratropium bromide to a sympathomimetic drug may be useful in a subgroup of asthmatics, particularly if there is a considerable large airway contribution to bronchial narrowing.", "Thirty one children with asthma were given 40 micrograms of ipratropium bromide and identical placebo by inhalation three times a day in a double blind, randomised crossover study to test the ability of an anticholinergic drug to modify the diurnal variation in airway calibre and bronchial reactivity. Subjects measured peak expiratory flow rate approximately eight hourly, before and after inhaled salbutamol, for four week periods. Paired t tests and cosinor analysis were used to assess the diurnal variation in airway calibre from the peak expiratory flow rate recorded before salbutamol and to assess the diurnal variation in bronchodilator responsiveness from the increase in peak expiratory flow rate after salbutamol. Maintenance treatment with ipratropium bromide 40 micrograms three times daily reduced the provocative dose of histamine which caused a 20% fall in FEV1 (geometric mean PD20 = 0.78 v 0.49 mg/ml, p less than 0.05), despite an eight to 12 hour gap between the last dose of ipratropium and histamine challenge. It did not, however, diminish the diurnal variation in airway calibre (mean amplitude = 12.7 v 10.1) or in bronchodilator responsiveness (mean amplitude = 62.4 v 63.5). There was no improvement in the clinical state of subjects while they were taking ipratropium bromide.", "nan", "In a double blind randomized study during a period of 2 weeks we compared the therapeutic effectiveness and side effects of IK-6-Inhaletten (0.1 mg Fenoterol + 0.04 mg Ipratropiumbromide) and SCH 1000-Inhaletten (0.2 mg Ipratropiumbromide) in 39 children (4-14 years) suffering from mild, moderate or severe asthma bronchiale. All measurements were performed with a whole body plethysmograph. In contrast to SCH 1000-inhalation after inhalation of IK-6-Inhaletten, we found a good improvement of the total airway resistance Rtot, the specific airway resistance SRaw and the forced exspiratory volume FEV1. Especially SRaw was significantly diminished compared to the less effective SCH 1000-inhalation. IK-6-inhalation allowed to decrease the amount of bronchospasmolytic therapy in our group of patients. We did not observe any severe side effects after inhalation of IK-6 or SCH 1000. In summary, we recommend the application of the IK-6-Inhaletten in children suffering from mild and moderate asthma bronchiale.", "Forty-nine asymptomatic asthmatic children who showed exercise induced bronchospasm (EIB), received in a randomized double-blind fashion one of the four following drugs administered through nebulizer and facial mask: salbutamol 4 mg (13 patients), disodium chromoglycate 20 mg (12 patients), ipratroprium bromide 0.4 mg (12 patients), placebo (12 patients). They performed exercise fifteen minutes after receiving the drugs and spirometries were done 0, 5, 10, 15 and 20 minutes after the end of the exercise. Bronchodilation was noticed 15 minutes after the administration of salbutamol and ipratroprium bromide but not after cromoglycate or placebo. No patient receiving either salbutamol or cromoglycate had EIB whereas it occurred in 50% of those receiving ipratroprium bromide and 91.6% of those receiving placebo." ]

[ "12130413", "10424554", "10401657" ]

[ "A prospective, randomized evaluation of arthroscopic stabilization versus nonoperative treatment in patients with acute, traumatic, first-time shoulder dislocations.", "Prospective randomized clinical trial comparing the effectiveness of immediate arthroscopic stabilization versus immobilization and rehabilitation in first traumatic anterior dislocations of the shoulder.", "Arthroscopic lavage reduced the recurrence rate following primary anterior shoulder dislocation. A randomised multicentre study with 1-year follow-up." ]

[ "Nonoperative treatment of traumatic shoulder dislocations leads to a high rate of recurrent dislocations.\n Early arthroscopic treatment for shoulder dislocation will result in a lower recurrence rate than nonoperative treatment.\n Prospective, randomized clinical trial.\n Two groups of patients were studied to compare nonoperative treatment with arthroscopic Bankart repair for acute, traumatic shoulder dislocations in young athletes. Fourteen nonoperatively treated patients underwent 4 weeks of immobilization followed by a supervised rehabilitation program. Ten operatively treated patients underwent arthroscopic Bankart repair with a bioabsorbable tack followed by the same rehabilitation protocol as the nonoperatively treated patients. The average follow-up was 36 months.\n Three patients were lost to follow-up. Twelve nonoperatively treated patients remained for follow-up. Nine of these (75%) developed recurrent instability. Six of the nine have required subsequent open Bankart repair for recurrent instability. Of the nine operatively treated patients available for follow-up, only one (11.1%) developed recurrent instability.\n Arthroscopic stabilization of traumatic, first-time anterior shoulder dislocations is an effective and safe treatment that significantly reduces the recurrence rate of shoulder dislocations in young athletes when compared with conventional, nonoperative treatment.", "Our purpose was to compare the effectiveness of traditional treatment with immediate arthroscopic stabilization in young patients who have sustained a first traumatic anterior dislocation of the shoulder. Forty skeletally mature patients younger than 30 years of age were randomly allocated to immobilization for 3 weeks followed by rehabilitation (group T) or arthroscopic stabilization (within 4 weeks of injury) followed by an identical immobilization and rehabilitation protocol (group S). A blinded research assistant performed all follow-up evaluations. The dominant arm was involved in 35% of subjects. The injury occurred in a sporting event in 70% of subjects. At 24 months, there was a statistically significant difference in the rate of redislocation (T = 47%, S = 15.9%, P = .03). An intention-to-treat analysis comparing disease-specific quality of life using the validated Western Ontario Shoulder Instability (WOSI) index showed statistically significantly better results in the surgically treated group at the 33 months (T = 633.93 v S = 287.1, P = .03) and no significant difference in range of motion. At an average 32 months follow-up, a significant reduction in redislocation and improvement in disease-specific quality of life is afforded by early arthroscopic stabilization in patients less than 30 year of age with a first, traumatic, anterior dislocation of the shoulder.", "Young individuals have a high recurrence rate following non-operative treatment of traumatic primary anterior shoulder dislocation. The present multicentre study was undertaken to find out whether the results could be improved by using arthroscopic lavage as treatment. Sixty patients aged 16-30 years, with traumatic primary anterior shoulder dislocation were randomised into two groups. One group was treated with arthroscopic lavage within 10 days, while the other group was treated non-operatively. Rehabilitation was otherwise identical. At 1-year follow-up, 4 of 30 patients (13%) in the lavage group had had redislocation compared with 13 of 30 (43%) in the group treated non-operatively (P = 0.01). The difference in recurrence rate was more pronounced in younger patients. The functional outcome according to the Rowe shoulder score was better in the lavage group (P = 0.003), as was the anterior stability according to the apprehension test (P = 0.008). We conclude that arthroscopic lavage reduced the recurrence rate and produced a better functional outcome at 1-year follow-up than the non-operative treatment in young individuals." ]

[ "15672012", "10535343", "9764616", "11004356", "15695985", "8018638" ]

[ "Use of mifepristone to ripen the cervix and induce labor in term pregnancies.", "Induction of labor with mifepristone--a randomized, double-blind study versus placebo.", "Cervical ripening with mifepristone before labor induction: a randomized study.", "Mifepristone for preinduction cervical ripening beyond 41 weeks' gestation: a randomized controlled trial.", "A randomized comparison of oral mifepristone to intravenous oxytocin for labor induction in women with prelabor rupture of membranes beyond 36 weeks' gestation.", "Mifepristone for labour induction after previous caesarean section." ]

[ "This study was undertaken to determine the efficacy of mifepristone for ripening the cervix and inducing labor in term pregnancies.\n In a double-blind placebo-controlled dose-finding study, 346 women received 50, 100, 200, 400, or 600 mg of mifepristone or placebo. The main endpoint for efficacy was the number of patients in whom labor occurred between 12 and 45 and 54 hours after treatment or who had a Bishop score 6 or greater. Maternal and fetal tolerability was also studied.\n No significant efficacy was observed whatever the dose of mifepristone. Mifepristone was well tolerated by the mother and fetus.\n Mifepristone, at doses up to 600 mg, does not induce labor within 54 hours in patients with unfavourable cervical status.", "To evaluate the efficacy of mifepristone in inducing labor in women with an unripe cervix, its effect on the cervix and on the status of the newborn.\n In a prospective double-blind study, 36 post-term pregnant women with a Bishop score of 5 or less received either 400 mg mifepristone (n=24) or placebo (n=12). If, 48 hours after the treatment was started, labor had not begun or the Bishop score was 5 or less, the women were given 0.5 mg prostaglandin E2 intracervically, a treatment which was repeated 12 hours later, if necessary.\n During the first 48 hours following treatment, 19 (79.2%) of the women treated with mifepristone and two of the women (16.7%) treated with placebo went into labor. In addition, one and three women, respectively, had a ripe cervix at the end of the 48h period. The overall success rate was thus 83.3% for mifepristone and 41.7% for placebo (p=0.008; OR 14.8; 95% CI 2.1-107.6). The median time from the start of treatment to delivery was also shorter (mifepristone 36h23' and placebo 53h17'). Treatment with intracervical PGE2 was needed more often after the placebo. The duration of labor, however, tended to be shorter after placebo than after mifepristone in the women who delivered vaginally. The frequencies of instrumental delivery were similar in both treatment groups. The median Apgar score was slightly lower at 1 minute (p<0.05) following mifepristone treatment, but did not differ at 5 and 10 minutes. There was no difference between the two treatment groups in the umbilical pH at delivery.\n The results of the present study show that mifepristone is a simple and effective treatment for inducing labor in post-term women with an unripe cervix.", "To determine the efficacy and safety of mifepristone for cervical ripening in post-term pregnancies.\n Women with post-term pregnancies and Bishop scores less than 6 were assigned randomly to mifepristone (41 patients) or placebo (42 patients). Mifepristone was given orally in a dose of 400 mg. Efficacy was assessed by change in the Bishop score within 48 hours after treatment; a score of 6 or greater was considered a \"strict\" success. An \"extended\" success rate was defined, including all patients with scores of at least 6 or those who delivered within 48 hours of treatment. Antenatal safety was assessed by fetal heart rate testing before and throughout labor. Neonatal safety was assessed by Apgar score, arterial or venous pH of cord blood, and blood glucose level during the first 48 hours. Analysis used Student t test for continuous variables, Kruskal-Wallis test for ordinal data, and chi2 for categoric variables.\n Strict success was achieved in 10 of 18 mifepristone patients (55%) evaluated for Bishop score on day 2 versus 8 of 29 placebo patients (27.5%) (P=.004). Extended success was achieved in 33 mifepristone patients (80.5%) and 21 placebo patients (50.0%) (P=.004). There were no statistical differences with regard to number of cesareans or fetal and neonatal safety.\n Mifepristone proved effective for cervical ripening and reduced the time to delivery compared with placebo, but it did not improve the rate of cesarean. Our study did not include enough pregnancies to reach conclusions about fetal or neonatal safety.", "To compare the effect of mifepristone with placebo on cervical ripening before labor induction in prolonged pregnancies.\n One hundred eighty women with pregnancies beyond 41 weeks and undilated, uneffaced cervices were assigned randomly to receive mifepristone 200 mg or placebo and observed for 24 hours. We then gave intravaginal misoprostol 25 microg every 4 hours or intravenous oxytocin. We expected 60% of placebo-treated and 80% of mifepristone-treated women to deliver vaginally within 48 hours.\n Among 180 subjects, 97 received mifepristone and 83 received placebo. The mean interval (+/- standard deviation [SD]) from start of induction to delivery was 2209 +/- 698 minutes for mifepristone-treated subjects and 2671 +/- 884 minutes for placebo-treated subjects (P <.001, log-transformed data). Twelve (13. 6%) mifepristone-treated women and seven (10.8%) placebo-treated women delivered vaginally on day 1 (P =.60). After 24 hours, the median Bishop score for both groups was 3 (0-11) (P =.51). One hundred thirty-one subjects required misoprostol, 65 (67.0%) were mifepristone-treated women, and 66 (79.5%) placebo-treated women (P =.06). The median (range) oxytocin dose was 871.5 (0-22,174) mU for mifepristone-treated women and 2021.0 (0-24,750) mU for placebo-treated women (P =.02). Seventy-seven (87.5%) mifepristone-treated women and 46 (70.8%) placebo-treated women delivered vaginally 48 hours after the start of treatment (P =.01). There were nine cesareans in the mifepristone group and 18 in the placebo group (P =.02). More nonreassuring fetal heart rate patterns and uterine contractile abnormalities occurred in mifepristone-treated subjects. There were no statistically significant differences in neonatal outcomes between groups.\n Mifepristone had a modest effect on cervical ripening when given 24 hours before labor induction, appearing to reduce the need for misoprostol and oxytocin compared with placebo.", "This study was undertaken to compare the use of oral mifepristone with intravenous oxytocin for labor induction in women with prelabor rupture of membranes (PROM) at 36 weeks' or greater gestational age.\n Sixty-five women with spontaneous PROM were randomly assigned to receive orally administered mifepristone or oxytocin infusion. Two hundred milligrams of mifepristone was administered, and subjects were observed for 18 hours, or intravenous oxytocin was administered.\n Thirty-three women received mifepristone and 32 received oxytocin. The average interval from start of induction to delivery was 1194.1 +/- 568.7 minutes for mifepristone-treated subjects and 770.8 +/- 519.9 minutes for oxytocin-treated subjects ( P = .001, log-transformed data). Of 33 mifepristone-treated subjects and 32 oxytocin-treated subjects, 25 (78.1%) and 17 (51.5%), respectively, achieved successful induction (defined as vaginal delivery within 24 hours) (relative risk [RR] 0.66, 95% CI 0.45-0.96, P = .01). There was more fetal distress in the mifepristone-treated group (9 vs 2, RR 4.36, 95% CI 1.02-18.66, P = .02), and a trend toward more cesarean births (7 vs 3, RR 2.26, 95% CI 0.64-7.99, P = .19). Eleven infants of mifepristone-treated women (33.3%) and 3 infants of oxytocin-treated women (9.4%) were admitted to the neonatal intensive care unit (RR 3.56, 95% CI 1.09-11.58, P = .02).\n Oral mifepristone administration 18 hours before oxytocin infusion did not improve labor stimulation in women with PROM near term, and was associated with more adverse fetal outcomes.", "To evaluate the efficacy and tolerance of mifepristone in women undergoing induction of labour at term after previous caesarean section.\n A prospective double blind placebo controlled trial.\n Thirty-two women at term (after 37.5 weeks' amenorrhea) who had had a previous caesarean delivery with a low transverse uterine incision. All women had a clear clinical indication for induction of labour with unfavourable cervical conditions (Bishop's score < 4). They were randomised to receive either 200 mg of mifepristone or placebo on days one and two of a four-day observation period.\n Thirteen women entered spontaneous labour: 11 were treated with mifepristone and two were in the control group (P < 0.01). Thirteen women, still with an unfavourable cervix on day four needed cervical ripening with vaginal tablets of prostaglandins. Of these, four had received mifepristone and nine the placebo. Mean oxytocin requirements were lower in the mifepristone group (P < 0.01) and the mean time interval between day one and start of labour was also significantly shorter in this group. Mode of delivery and neonatal outcome were similar in both groups.\n Induction of labour is facilitated in term women with prior caesarean section by the use of mifepristone. This induction agent appears safe and useful with no adverse events on the fetus or mother." ]

[ "18663117", "16984453", "1785031", "9228227", "2263919", "2885650", "15764050" ]

[ "The use of therapeutic ultrasound in venous leg ulcers: a randomized, controlled clinical trial.", "Low-frequency ultrasound treatment of chronic venous ulcers.", "A placebo controlled trial of ultrasound therapy in chronic leg ulceration.", "Low-frequency ultrasound treatment of chronic venous leg ulcers in an outpatient therapy.", "Pulsed ultrasound does not improve healing of venous ulcers.", "A controlled trial of weekly ultrasound therapy in chronic leg ulceration.", "Application of various power densities of ultrasound in the treatment of leg ulcers." ]

[ "To estimate the usefulness of therapeutic ultrasound for healing of venous leg ulcers.\n Eighty-one patients were included in this study. Patients in groups 1 and 2 were treated surgically. Patients in groups 3 and 4 were treated conservatively. Patients in groups 1 and 3 were additionally treated with the ultrasound (1 MHz, 0.5 W/cm(2)) once daily, six times a week for seven weeks.\n Comparison of the number of complete healed wounds indicated statistically significant differences between groups 1 and 4 (P = 0.03), 2 and 4 (P = 0.03), 3 and 4 (P = 0.03) in favour of groups 1, 2 and 3. Comparison of the other parameters also demonstrated more efficient therapy effects in groups 1, 2 and 3 than in group 4. There were no statistical differences in all examined parameters between groups 1, 2 and 3 (P > 0.05).\n The ultrasound is an efficient and useful method only in conservatively treated venous leg ulcers. There are no special reasons for application of the ultrasound in surgically treated patients. A well-conducted surgical operation is much more effective for a healing process than conservative pharmacological procedures.", "In a randomized controlled clinical trial, the properties of low-frequency ultrasound in the treatment of chronic venous ulcers were investigated. Thirty-eight patients with chronic ulcerations of the legs caused by chronic venous insufficiency were randomly assigned to receive either conventional therapy alone or conventional therapy plus additional 30 kHz ultrasound treatment. Patients with other conditions that may impair wound healing such as diabetes mellitus or arterial disease were excluded. The ultrasound treatment consisted of 10 minutes of foot bathing with application of 30 kHz ultrasound 100 mW/cm(2) three times a week. Response was evaluated with the use of planimetry of the ulcer area and compared with controls after 3 and 8 weeks. After 3 weeks of treatment (and to a greater extent after 8 weeks of treatment) the ultrasound group showed a markedly better response than the control group. Although the control group showed a mean decrease of 11% in the ulcerated area after 8 weeks, in the ultrasound group the mean ulcerated area decreased by 41% (p < 0.05). There were only mild side effects in some of the patients treated with ultrasound. In conclusion, application of low-frequency ultrasound may be a helpful treatment option in chronic venous leg ulcers.", "A controlled study of the effects of ultrasound on healing chronic leg ulcers was carried out in conjunction with standard treatment on 38 patients divided randomly into two groups. All patients received standard treatment (paste impregnated bandage and a self-adhesive elastic bandage plus placebo ultrasound or ultrasound (1.0 watt/cm2 at 1 MHz, for 10 min) twice weekly for 8 weeks. Percentage healed ulcer area and number of healed ulcers were compared after 2, 4, 6 and 8 weeks. There were no significant differences in the proportion of healed ulcers or ulcer area in the ultrasound group as compared with the placebo group.", "Low-dose ultrasound seems to be an effective method to enhance wound healing, particularly in chronic venous leg ulcers. The aim of our investigation was to examine the effect of 30 kHz low-dose ultrasound in local treatment of chronic venous leg ulcers, when added to conventional therapy of outpatients. Twenty-four patients with chronic ulcerations of the leg due to chronic venous insufficiency were randomised in placebo-controlled parallel groups in a single-blind clinical study. Patients were randomised to conventional therapy with topical application of hydrocolloid dressings and compression therapy or conventional therapy with additional ultrasound treatment for 12 weeks. The ultrasound treatment consisted of 10 min of footbathing, with application of 30 kHz continuous ultrasound 100 mW/cm2 three times a week. The ulcer area was measured by planimetry, using a millimeter grid before treatment and after 2, 4, 6, 8, 10 and 12 weeks of therapy. The ulcer radius and the daily ulcer radius reduction were calculated. Colour photographs of the ulcers were taken under standard conditions at the same time. After each treatment local findings and side effects were recorded. After 12 weeks of treatment the control group showed a mean decrease of 16.5% in the ulcerated area. In contrast the mean ulcerated area decreased by 55.4% in the ultrasound group (p<0.007). The daily ulcer reduction in the ultrasound-treated patients was 0.08 mm+/-0.04 mm and in the placebo patients 0.03 mm+/-0.03 mm. Patients recorded only minor side-effects such as a tingling feeling and occasionally pinhead-sized bleeding in the ulcer area. The application of low-frequency and low-dose ultrasound is a helpful treatment option in chronic venous leg ulcers, especially if they do not respond to conventional ulcer treatment.", "A controlled study of the effects of pulsed ultrasound was carried out in conjunction with a standard treatment for healing chronic leg ulcers on 44 patients divided randomly into two groups. All patients received standard treatment (paste impregnated bandage and a self-adhesive elastic bandage) plus placebo-ultrasound or pulsed ultrasound (1:9, 0.5 watt/cm2 at 1 MHz, for 10 min) 3 days a week for 4 weeks, thereafter twice weekly for 4 weeks and once weekly for the following 4 weeks. Percentage healed ulcer area and comparison of percentage healed ulcers were examined after 4, 8 and 12 weeks. There were no significant differences in the proportion of healed ulcers or ulcer area in the pulsed ultrasound group as compared with the placebo group.", "In a controlled trial to ascertain whether ultrasound given weekly in conjunction with a standard treatment for chronic leg ulcers improves the rate of healing 56 patients were randomised to standard treatment (paste impregnated bandage and a self-adhesive elastic bandage) and 52 to standard treatment plus pulsed ultrasound given weekly. After 12 weeks the proportion of ulcers healed was 20% greater in the ultrasound than in the control group.", "The objective of our study was to determine which ultrasound power density (0.5 W/cm(2) or 1 W/cm(2)) is more effective at reducing the area and volume of leg ulceration.\n A total of 65 patients with venous ulcers were randomly divided into three groups: A, B and C. In group A, 22 patients were treated with ultrasound rated at 1 W/cm(2) and with compressive therapy. In group B, 21 patients were treated with ultrasound rated at 0.5 W/cm(2) and with compressive therapy. In both groups the patients were treated with a pulsed wave of a duty cycle of 1/5 (impulse time=2 ms, pause time=8 ms) and frequency of 1 MHz. The 22 patients in group C (control group) were subjected to topical pharmacological treatment.\n We found a statistically significant reduction of the ulcer area, volume and linear dimensions in all three groups of patients. The ulcer area reduction rate was highest in group B. The volume reduction rate in group B was higher than in group A only. The rate of reduction of suppurate area was highest in group B.\n We have demonstrated that ultrasound rated at 0.5 W/cm(2) causes greater and faster changes in the healing process than ultrasound rated at 1 W/cm(2)." ]

[ "9361539", "11881887" ]

[ "Intraoperative intravascular volume optimisation and length of hospital stay after repair of proximal femoral fracture: randomised controlled trial.", "Randomized controlled trial to investigate influence of the fluid challenge on duration of hospital stay and perioperative morbidity in patients with hip fractures." ]

[ "To assess whether intraoperative intravascular volume optimisation improves outcome and shortens hospital stay after repair of proximal femoral fracture.\n Prospective, randomised controlled trial comparing conventional intraoperative fluid management with repeated colloid fluid challenges monitored by oesophageal Doppler ultrasonography to maintain maximal stroke volume throughout the operative period.\n Teaching hospital, London.\n 40 patients undergoing repair of proximal femoral fracture under general anaesthesia.\n Patients were randomly assigned to receive either conventional intraoperative fluid management (control patients) or additional repeated colloid fluid challenges with oesophageal Doppler ultrasonography used to maintain maximal stroke volume throughout the operative period (protocol patients).\n Time declared medically fit for hospital discharge, duration of hospital stay (in acute bed; in acute plus long stay bed), mortality, perioperative haemodynamic changes.\n Intraoperative intravascular fluid loading produced significantly greater changes in stroke volume (median 15 ml (95% confidence interval 10 to 21 ml)) and cardiac output (1.2 l/min (0.1 to 2.3 l/min)) than in the conventionally managed group (-5 ml (-10 to 1 ml) and -0.4 l/min (-1.0 to 0.2 l/min)) (P < 0.001 and P < 0.05, respectively). One protocol patient and two control patients died in hospital. In the survivors, postoperative recovery was significantly faster in the protocol patients, with shorter times to being declared medically fit for discharge (median 10 (9 to 15) days v 15 (11 to 40) days, P < 0.05) and a 39% reduction in hospital stay (12 (8 to 13) days v 20 (10 to 61) days, P < 0.05).\n Proximal femoral fracture repair constitutes surgery in a high risk population. Intraoperative intravascular volume loading to optimal stroke volume resulted in a more rapid postoperative recovery and a significantly reduced hospital stay.", "A prospective, randomized controlled trial comparing conventional intraoperative fluid management with two differing methods of invasive haemodynamic monitoring to optimize intraoperative fluid therapy, in patients undergoing proximal femoral fracture repair under general anaesthesia.\n Ninety patients randomized to three groups; conventional intraoperative fluid management (Gp CON, n=29), and two groups receiving additional repeated colloid fluid challenges guided by central venous pressure (Gp CVP, n=31) or oesophageal Doppler ultrasonography (Gp DOP, n=30). Primary outcome measures were time to medical fitness to discharge, hospital stay and postoperative morbidity.\n The fluid challenge resulted in significantly greater perioperative changes in central venous pressure between Gp CVP and Gp CON (mean 5 (95% confidence interval 3-7) mm Hg) (P<0.0001). Important perioperative changes were also shown in Gp DOP with increases of 49.4 ms (19.7-79.1 ms) in the corrected flow time, 13.5 ml (7.4-19.6 ml) in stroke volume, and 0.9 (0.49-1.39) litre min(-1) in cardiac output. As a result, fewer patients in Gp CVP and Gp DOP experienced severe intraoperative hypotension (Gp CON 28% (8/29), Gp CVP 9% (3/31), Gp DOP 7% (2/30), P=0.048 (chi-squared, 2 degrees of freedom (df). No differences were seen between the three groups when major morbidity and mortality were combined, P=0.24 (chi-squared, 2 df). Postoperative recovery for survivors, as defined by time to be deemed medically fit for discharge, was significantly faster, in comparison with Gp CON, in both the Gp CVP (10 vs 14 (95% confidence interval 8-12 vs 12-17) days, P=0.008 (t-test)), and Gp DOP (8 vs 14 (95% confidence interval 6-12 vs 12-17) days, P=0.023 (t-test). There were no significant differences between groups, for survivors, with respect to acute orthopaedic hospital and total hospital stay.\n Invasive intraoperative haemodynamic monitoring with fluid challenges during repair of femoral fracture under general anaesthetic shortens time to being medically fit for discharge." ]

[ "10827226", "669832", "8320931", "710967", "3280388", "2554450", "9726220", "8106686", "2812168", "10098582", "4118558", "8938179", "7759146", "12297843" ]

[ "Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial.", "Experiences in the treatment of fulminant hepatic failure by conservative therapy, charcoal haemoperfusion, and polyacrylonitrile haemodialysis.", "Effect of renal replacement therapy on patients with combined acute renal and fulminant hepatic failure.", "Treatment of encephalopathy during fulminant hepatic failure by haemodialysis with high permeability membrane.", "Controlled trials of charcoal hemoperfusion and prognostic factors in fulminant hepatic failure.", "Temporary organ substitution by hemoperfusion through suspension of active donor hepatocytes in a total complex of intensive therapy in patients with acute hepatic insufficiency.", "Hemodiabsorption in treatment of hepatic failure.", "Atracurium infusions in patients with fulminant hepatic failure awaiting liver transplantation.", "Changes in intracranial pressure during haemofiltration in oliguric patients with grade IV hepatic encephalopathy.", "Temporary extracorporeal liver support for severe acute alcoholic hepatitis using the BioLogic-DT.", "Controlled trial of exchange-transfusion therapy in fulminant hepatitis.", "Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure.", "Evaluation of the BioLogic-DT sorbent-suspension dialyser in patients with fulminant hepatic failure.", "Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study." ]

[ "In hepatorenal syndrome (HRS), renal insufficiency is often progressive, and the prognosis is extremely poor under standard medical therapy. The molecular adsorbent recirculating system (MARS) is a modified dialysis method using an albumin-containing dialysate that is recirculated and perfused online through charcoal and anion-exchanger columns. MARS enables the selective removal of albumin-bound substances. A prospective controlled trial was performed to determine the effect of MARS treatment on 30-day survival in patients with type I HRS at high risk (bilirubin level, > or =15 mg/dL) compared with standard treatment. Thirteen patients with cirrhosis with type I HRS were included from 1997 to 1999. All were Child's class C, with Child-Turcotte-Pugh scores of 12.4 +/- 1. 0, United Network for Organ Sharing status 2A, and total bilirubin values of 25.7 +/- 14.0 mg/dL. Eight patients were treated with the MARS method in addition to hemodiafiltration (HDF) and standard medical therapy, and 5 patients were in the control group (HDF and standard medical treatment alone). None of these patients underwent liver transplantation or received a transjugular intrahepatic portosystemic shunt or vasopressin analogues during the observation period. In the MARS group, 5.2 +/- 3.6 treatments (range, 1 to 10 treatments) were performed for 6 to 8 hours daily per patient. A significant decrease in bilirubin and creatinine levels (P <.01) and increase in serum sodium level and prothrombin activity (P <.01) were observed in the MARS group. Mortality rates were 100% in the control group at day 7 and 62.5% in the MARS group at day 7 and 75% at day 30, respectively (P <.01). We conclude that the removal of albumin-bound substances with the MARS method can contribute to the treatment of type I HRS.", "nan", "The mortality of patients with combined acute hepatic and renal failure remains high. Previous studies have reported both patient morbidity and mortality directly attributable to the use of extracorporeal circuits used to treat renal failure. We investigated the effect of various modes of renal replacement therapy in 30 consecutive patients referred with both fulminant hepatic and acute renal failure. Cardiac output decreased during the first hour of 30 intermittent machine haemofiltration treatments, by 15 +/- 3%, as did tissue oxygen delivery, 16 +/- 3% and tissue oxygen uptake, 13 +/- 4%, whereas there was no significant change during 30 continuous hemofiltration and/or dialysis treatments. Intracranial pressure remained stable during the continuous modes but increased from 9 +/- 2 mm Hg to 17 +/- 2 mm Hg, P < 0.01, during intermittent machine hemofiltration, with the greatest increase of 55 +/- 9% within the first hour. Mean arterial blood pressure was stable during treatment with the continuous modes, but decreased by 20 +/- 3% during the first hour of intermittent machine hemofiltration, resulting in a maximum reduction in cerebral perfusion pressure of 35 +/- 8%. In this group of critically ill patients continuous modes of renal replacement therapy resulted in superior cardiac and intracranial stability compared to standard intermittent modes of treatment.", "Forty-one patients with fulminant hepatic failure and coma underwent 180 periods of haemodialysis with polyacrylonitrile membrane (AN 69 HD). Hepatic failure was due to viral hepatitis in 40 and drugs in one. Total recovery of consciousness occurred in 17 patients (43.6%), and partial in seven (17.9%)--that is, an overall figure of 61.5%. Regain of consciousness was not related to liver regeneration as assessed by levels of factor V and hepatocyte volume fraction. At the time of the first haemodialysis, neurological status was significantly impaired in the patients who could not be aroused. Mean duration of coma grade IV averaged 6.1 +/- 4.3 days and mean duration of illness until death or decerebration 8.6 +/- 8.3 days. Of the 17 patients who totally regained consciousness, nine recovered and eight died (three from intercurrent complications and five with no liver regeneration).", "One hundred thirty-seven patients with fulminant hepatic failure were entered into two controlled trials of charcoal hemoperfusion carried out concurrently. In trial A, 75 patients with grade 3 encephalopathy were randomized to receive 5 or 10 h of hemoperfusion daily. Overall survival rates for the two groups were similar (51.3% vs. 50.0%) as was the frequency of major complications including cerebral edema and renal failure. In trial B, in which 62 patients with established grade 4 encephalopathy on admission were randomized to a no-perfusion group or to have 10 h of hemoperfusion daily, overall survival rates for the two groups were again similar (39.3% and 34.5%, respectively). There was in both trials a significant relationship between survival and etiology quite independent of the use or duration of hemoperfusion. Thus, percentage survival for the acetaminophen-overdose cases was 52.9%, for hepatitis A 66.7%, for hepatitis B 38.9%, for presumed non-A, non-B hepatitis 20%, and for halothane or drug reaction 12.5%. Within the etiologic subgroups survival was also influenced by the three major complications that developed, being inversely related to their frequency and combination, except in the non-A, non-B hepatitis and halothane or drug reaction subgroups, which had a high mortality throughout. In the latter cases particularly, orthotopic liver transplantation merits early consideration and in the group with better \"intrinsic\" survival (acetaminophen, hepatitis A and B) intensive management of complications (rather than charcoal hemoperfusion) would appear to be of major importance.", "The results of intensive therapy and temporary organ substitution by hemoperfusion through a suspension of active hepatocytes in 126 patients suffering from acute hepatic insufficiency (AHI) induced by virus B hepatitis, virus non-A, non-B hepatitis, acute toxic hepatitis, active liver cirrhosis, sepsis leptospirosis long-term subhepatic jaundice are presented in this paper. Hepatic encephalopathia confirmed both clinically and electroencephalographically was registered in all the patients. The patients were subdivided into two groups: a complex of commonly used curative measures according to the intensive therapy for AHI was applied in Group A (67 patients); in Group B (59 patients), alongside with the above measures, temporary organ substitution by hemoperfusion through a suspension of active porky hepatocytes was also performed. The lethality in Group A made up 59% and that in Group B was 37%.", "Conducted at the University of California, Los Angeles, this randomized, prospectively controlled study was designed to measure the effects of a hemodiabsorption device in the treatment of 11 patients with hepatic failure and stage III to IV encephalopathy. The results of 5 days of treatment with the hemodiabsorption device were compared with those of standard intensive care procedures. The BioLogic-DT System, a simple sorbent-based system, demonstrated a slight improvement in the neurologic status of patients, a significant improvement in the physiologic status of patients, and an improved outcome for treated patients as opposed to nontreated patients.", "To determine the pharmacokinetics and pharmacodynamics of the neuromuscular blocking agent atracurium besylate in patients with fulminant hepatic failure (FHF).\n Open study of patients receiving atracurium infusions to facilitate mechanical ventilation.\n Intensive care unit in a tertiary referral university teaching hospital.\n Ten encephalopathic patients with FHF requiring mechanical ventilation while awaiting orthotopic liver transplantation. Three patients died before transplantation could be performed, three died after transplantation, and four survived following successful transplantation.\n Plasma, urine and dialysate fluid were analysed for atracurium and its metabolites using HPLC. Neuromuscular blockade was measured using transcutaneous ulnar nerve stimulation and an accelerometer. Electroencephalography and liver function tests were performed daily.\n Patients received atracurium infusions for a period ranging from 38 to 217 h. Six patients required continuous arteriovenous haemodiafiltration (CAVHD) to replace renal function. Atracurium mean steady state clearance was 8.6 ml/min/kg, and train-of-four recovery ratio to 75% took 63 min (range 32-108). Laudanosine clearance was markedly reduced in the non-survivors; the half-life was 38.5 hrs compared with 5.3 h in the 4 patients who underwent successful transplantation. Laudanosine accumulation could be observed in all patients before transplantation, but kinetics returned to normal after successful transplantation. The highest laudanosine level recorded was 6,860 ng/ml. There was no evidence of adverse central neurological effects attributable to laudanosine. CAVHD did not contribute significantly to clearance of atracurium or its metabolites.\n Atracurium kinetics and dynamics are near-normal even in patients with fulminant hepatic failure and renal failure; laudanosine accumulation will occur, but this is not associated with measurable central neurological effects. Implantation of a functioning liver graft results in clearance of laudanosine, which seems to be independent of renal function. Atracurium is an appropriate choice for producing neuromuscular blockade for periods of several days in patients with fulminant hepatic failure and renal impairment.", "Seven consecutive patients with grade IV hepatic encephalopathy, due to fulminant hepatic failure complicated by oliguric renal failure were allocated at random to treatment with daily machine haemofiltration (MHF) or continuous arteriovenous haemofiltration (CAVHF). Intracranial pressure (ICP) was continuously monitored using a subdural catheter. Four patients received 17 treatments by MHF, and ICP increased from 8.4 +/- 1.5 mm Hg (mean + SEM) prior to treatment to 12.6 +/- 1.8 mm Hg on completion (p less than 0.05). Active intervention was required on twenty occasions to treat sustained increases in ICP (greater than 25 mm Hg maintained for 5 min or longer). A total of 12 haemofilters were used in the treatment of 3 patients by CAVHF. The ICP showed greater stability during CAVHF therapy, the mean pressure prior to treatment was 15.6 +/- 5.2 mm Hg and fell to 11.7 +/- 2.3 mm Hg at 4 h. Sustained increases in ICP occurred in only 1 patient as a preterminal event. These findings suggest that CAVHF is the preferred method of treatment in patients with fulminant hepatic failure complicated by oliguric renal failure who are at risk of developing cerebral oedema.", "Patients with severe acute alcoholic hepatitis develop multiple organ failure which is associated with production of inflammatory cytokines and a poor prognosis. The aim of the present pilot study was to evaluate the effects of the BioLogic-DT sorption-suspension dialyser in patients with severe acute alcoholic hepatitis. Ten patients with encephalopathy (grade II-IV) were entered into the study, 5 received treatment with the BioLogic-DT for 6 hours daily for 3 days and 5 received conventional treatment as controls. The system was biocompatible with no adverse effects on blood pressure or platelet counts, factor V, fibrinogen or antithrombin III. No bleeding episodes were observed even with the use of small doses of heparin. After 3 days, blood ammonia was lower in the BioLogic-DT treated patients than in the controls, although blood lactate was higher. There were slight increases in plasma TNF and IL-8 during treatment over and above the higher levels present initially, possibly as a result of activation of white cells in the extracorporeal circuit. The further development of the BioLogic-DT dialyser with the addition of a plasma treatment module capable of removing cytokines would be worth evaluating in acute alcoholic hepatitis.", "nan", "The objective of this pilot controlled study was to evaluate the extracorporeal liver assist device (ELAD) in patients with acute liver failure who were judged to still have a significant chance of survival (approximately 50%) and in those who had already fulfilled criteria for transplantation. Twenty-four patients were divided into two groups, 17 with a potentially recoverable lesion (group I) and 7 listed for transplantation (group II), and then randomly allocated to ELAD haemoperfusion or control. The median period of ELAD haemoperfusion was 72 hours (range 3-168 h). Biocompatibility of the device was good, with no acceleration in platelet consumption, and haemodynamic stability was maintained. Two patients were withdrawn from the study because of worsening of preexisting disseminated intravascular coagulation in one case and a hypersensitivity reaction in the other. Deterioration with respect to encephalopathy grade was more frequent in the control patients, 7 of 12 (58%), than in the ELAD-treated patients, 3 of 12 (25%). In group I where survival for the ELAD cases was 7 of 9 (78%), there was a higher than expected survival in the controls, 6 of 8 (75%). For group II cases, survival was 1 of 3 (33%) for the ELAD-treated patients, and 1 of 4 (25%) for the controls. Both of the survivors underwent transplantation. Assessment of additive function for the device revealed an improvement in galactose elimination capacity after 6 hours of haemoperfusion. Based on the results of this pilot-controlled trial, better indices of prognosis will be required, in addition to those used to select for transplantation, if patients at an earlier stage of clinical deterioration are to be included in future studies.", "The BioLogic-DT sorbent suspension dialyser was developed to remove toxic substances from the blood of patients with liver failure. In the present study a randomised controlled trial was carried out in 10 patients with fulminant hepatic failure who had developed grade 4 encephalopathy to evaluate the safety and biocompatibility of the dialyser in such severely ill patients. A total of 18 treatments were performed in 5 patients. Haemodynamic stability was maintained throughout. There was a significant loss of platelets (163 +/- 34 to 101 +/- 13 x 10(9)/l) and decrease in plasma fibrinogen (0.53 +/- 0.09 to 0.31 +/- 0.08 g/l) with a rise in blood activated clotting time (190 +/- 17 to 223 +/- 22 sec)--not seen in the controls--, which was a result of the dialysis being carried out without the use of heparin as anticoagulant. Removal of metabolites by treatment was limited, with no significant effect on blood ammonia level and further developments of the system will be needed for this very sick group of patients.", "Patients with liver cirrhosis and a superimposed acute injury with progressive hyperbilirubinemia have a high mortality. A prospective, controlled study was performed to test whether hyperbilirubinemia, 30-day survival, and encephalopathy would be improved by extracorporeal albumin dialysis (ECAD). Twenty-four patients were studied; 23 patients had cirrhosis; 1 had a prolonged cholestatic drug reaction and was excluded from per protocol (PP) analysis. Patients had a plasma bilirubin greater than 20 mg/dL and had not responded to prior standard medical therapy (SMT). Patients were randomized to receive SMT with ECAD or without (control). ECAD was performed with an extracorporeal device that dialyzes blood in a hollow fiber dialyzer (MW cutoff < 60 kd) against 15% albumin. Albumin-bound molecules transfer to dialysate albumin that is regenerated continuously by passage through a charcoal and anion exchange column and a conventional dialyzer. ECAD was associated with improved 30-day survival (PP, 11 of 12 ECAD, 6 of 11 controls; log rank P <.05). Plasma bile acids and bilirubin decreased on average by 43% and 29%, respectively, in the ECAD group after 1 week of treatment, but not in the control group. Renal dysfunction and hepatic encephalopathy improved in the ECAD group, but worsened significantly in the control group. ECAD was safe, with adverse events being rare and identical in both groups. In conclusion, ECAD appears to be effective and safe for the short-term treatment of patients with cirrhosis and superimposed acute injury associated with progressive hyperbilirubinemia and may be useful for increasing survival in such patients awaiting liver transplantation." ]

[ "2000278", "9120744", "3895150", "2057245", "3900906", "3054783", "2187176" ]

[ "Bovine surfactant replacement therapy in neonates of less than 30 weeks' gestation: a randomized controlled trial of prophylaxis versus treatment.", "Prophylaxis of respiratory distress syndrome by treatment with modified porcine surfactant at birth: a multicentre prospective randomized trial.", "Prevention of neonatal respiratory distress syndrome by tracheal instillation of surfactant: a randomized clinical trial.", "Improved neonatal survival following multiple doses of bovine surfactant in very premature neonates at risk for respiratory distress syndrome.", "Double-blind clinical trial of calf lung surfactant extract for the prevention of hyaline membrane disease in extremely premature infants.", "Surfactant replacement therapy at birth: final analysis of a clinical trial and comparisons with similar trials.", "Multicenter trial of single-dose modified bovine surfactant extract (Survanta) for prevention of respiratory distress syndrome. Ross Collaborative Surfactant Prevention Study Group." ]

[ "The influence of the timing of surfactant replacement therapy for the treatment of neonatal respiratory distress syndrome was evaluated in a study of 182 neonates of less than 30 weeks' gestation who were randomly assigned prior to delivery to one of three study groups: control (dummy instillation of air given at birth), early surfactant (surfactant given at birth), or late surfactant (surfactant given at less than 6 hours of age). Subjects in the late surfactant group could avoid treatment if they had a clear chest roentgenogram and required no supplemental oxygen at a mean airway pressure of less than 7 cm of water. All treated neonates were eligible to receive up to three additional doses during the first 5 days of life. The three groups were comparable with respect to birth weight, gestational age, and other perinatal parameters with the exception of a lower cord arterial pH and 1-minute Apgar score in the early surfactant group. Of the 60 neonates randomly assigned to late treatment, 29 (48%) were deemed surfactant sufficient and thereby avoided treatment; the other 31 received their first dose at a mean age of 2.9 hours. There was a significant improvement in gas exchange during the first week of life in both surfactant groups compared with the control group, reflected by differences in fraction of inspired oxygen, arterial/alveolar PO2, and ventilation index (peak pressure x rate on the ventilator) (P less than .001). Surfactant therapy also resulted in a lower incidence of pulmonary air leak and severe chronic lung disease (defined as requirement for respiratory support beyond 36 weeks post-conceptional age). There were no differences between early and late surfactant groups in any of these parameters. The only statistically significant difference between the surfactant groups was that the early group had a higher incidence of mild chronic lung disease (respiratory support beyond 28 days of age) than the late treatment group (P less than .005). Neonates in the late treatment group were extubated earlier and had a shorter neonatal intensive care unit stay than control neonates (P less than .05), whereas those in the early group were not significantly different from control neonates in these parameters. It is concluded that replacement therapy with bovine lung surfactant extract in neonates of less than 30 weeks' gestation results in decreased oxygen and ventilatory requirements during the first week of life and a lower incidence of pulmonary air leak and severe chronic lung disease.(ABSTRACT TRUNCATED AT 400 WORDS)", "The objective of this prospective, multicentre trial, carried out at 18 third level hospitals in Italy, was to evaluate efficacy of modified porcine surfactant (Curosurf), administered at birth to prevent the development of respiratory distress syndrome (RDS) in premature infants. 287 babies with a gestational age of 24-30 weeks were randomized to prophylactic treatment with Curosurf (80 mg/ml; dose 20 mg/kg) or to a control group receiving no surfactant treatment in the delivery-room. Babies in both groups were eligible for rescue treatment with surfactant (200 mg/kg) if they developed clinical symptoms of RDS and required mechanical ventilation. The main end-point was to obtain, in the prophylaxis group, a 30% reduction in the incidence of grade 3-4 RDS. Median gestational age was 28 weeks in both groups and mean birth weight 1010 and 1002 g, respectively for prophylaxis and control babies. There was a 32% reduction in the incidence of grade 3-4 RDS in the prophylaxis group (p < 0.05). This was associated with a significant reduction in mean maximum fraction of inspired oxygen (0.57 vs 0.66%; p < 0.01), a decreased incidence of pulmonary interstitial emphysema (7 vs 14%; p < 0.05) and a lowered mortality (21 vs 35%; p < 0.01). Combined unfavourable outcome (mortality + bronchopulmonary dysplasia and/or grade 3-4 intraventricular hemorrhage and/or grade 2-4 retinopathy of prematurity) was significantly lower in the prophylaxis than in the second group (41 vs 58%; p < 0.01). The favourable effects of prophylactic treatment were equally recorded in all the age groups, including the babies with the lowest gestational age (24-25 weeks). Multiple and logistic regression analysis confirmed that high gestational age and surfactant prophylaxis were, independently, associated with a lower degree of RDS (p = 0.0001 and p = 0.0008, respectively) and a lower mortality (p = 0.0001 and p = 0.0045, respectively). We conclude that prophylaxis with modified natural surfactant effectively prevents RDS in newborn babies between 24 and 30 weeks' gestation.", "With a randomized clinical trial, the possibility was assessed that a tracheal instillation of pulmonary surfactant prior to the first breath might prevent the development of some of the signs of neonatal respiratory distress syndrome. Of the 72 infants in the trial, all born at a gestational age of less than 30 weeks, 39 received 3 or 4 mL of surfactant, prepared from the lipids extracted from calf lung lavage. The treatment resulted in a significantly improved gas exchange during the first 72 hours of life. On the average, the arterial/alveolar PO2 ratio was 0.15 higher for the treated infants, and only about half as much extra oxygen had to be supplied. The respiratory support (peak inspiratory pressure X frequency) could be lowered significantly. Pulmonary interstitial emphysema occurred in 13 of the 33 control infants, but in only three of the 39 treated infants. Six of the control infants died in the neonatal period, but only one treated infant died. It is concluded that surfactant supplementation prior to the first breath is feasible and is of value as protection against the respiratory distress syndrome and the negative effects of hypoxia and ventilatory support.", "To determine whether multiple doses of bovine surfactant would improve neonatal mortality in very premature neonates, we conducted two multicenter controlled trials under identical protocols; the results were combined for analysis. Four hundred and thirty neonates born between 23 and 29 weeks gestation and weighing 600 to 1250 g at birth were assigned randomly at birth to receive either 100 mg of phospholipids/kg of Survanta, a modified bovine surfactant (n = 210), or a sham air placebo (n = 220) within 15 minutes of birth. Neonates who developed respiratory distress syndrome and required mechanical ventilation with at least 30% oxygen could be given up to three more doses in the first 48 hours after birth. Dosing was performed by investigators not involved in the clinical care of the neonates; nursery staff were kept blinded as to the treatment assignment. Cause of death was determined by a panel of three independent, board-certified neonatologists after blindly reviewing case report forms and autopsy reports. Fewer Survanta-treated neonates died of any cause (11.4% vs 18.8%, P = .031), died of respiratory distress syndrome (1.9% vs 15.6%, P less than .001), and either died or developed bronchopulmonary dysplasia due to respiratory distress syndrome (39.5% vs 49.1%, P = .044). The incidence of respiratory distress syndrome was also lower in Survanta-treated neonates (28.0% vs 56.9%, P less than .001), and the Survanta-treated neonates' oxygenation and ventilatory status were improved significantly at 72 hours. Survanta-treated neonates were also at lowered risk of developing pulmonary interstitial emphysema (23.3% vs 36.9%, P = .002) and other forms of pulmonary air leaks (9.6% vs 20.8%, P .002).(ABSTRACT TRUNCATED AT 250 WORDS)", "A prospective, double-blind, controlled trial was conducted to determine whether instillation of an exogenous surfactant into the lungs before the first breath could prevent hyaline membrane disease. The surfactant is calf lung lipid extracted from saline lung lavage. Entry was limited to infants who were 24 to 28 weeks' gestation, who were born at Children's Hospital of Buffalo, and whose mothers had not received betamethasone for more than 24 hours before birth. Treated infants received 3 mL (90 mg) of calf lung surfactant extract instilled into their trachea before the first breath; control infants received 3 mL of normal saline. A prospective scoring system and respiratory support variables were used to compare the groups. At 48 hours of age, only two of 14 calf lung surfactant extract-treated infants (14%) had hyaline membrane disease compared with seven of 13 control infants (54%) (P = .033). Inspired oxygen, mean airway pressure, ventilator rate and ventilator efficiency index were also lower in the treated group during the first 48 hours of life (P less than .01 to P less than .001). Calf lung surfactant extract instillation at birth appears to be an effective material and method of preventing hyaline membrane disease in extremely premature infants.", "A randomized trial of surfactant replacement therapy at birth was conducted at the University of Rochester between June 1983 and November 1985. Thirty-four premature infants, 25 to 29 weeks' gestational age, received a preventilatory dose of a calf lung surfactant extract in saline prepared at the University of Rochester. A control group of 31 infants received a preventilatory dose of saline alone. The major finding of this trial is that a single preventilatory dose of calf lung surfactant extract reduces the severity of the respiratory distress syndrome during the first 24 hours of life. The beneficial effects, however, are not sustained in many infants and diminish after 24 hours of life. The survival rate was 71% in both the control and surfactant-treated groups. There was a lower incidence of pneumothorax in the surfactant-treated group. There were no differences in the incidence of bronchopulmonary dysplasia, patent ductus arteriosus, and intraventricular hemorrhage. No adverse effects of surfactant replacement therapy were identified. Results of this study suggest that multiple postventilatory doses of surfactant will be required for optimal therapy.", "A multicenter, prospective randomized controlled trial was performed comparing the efficacy of a single intratracheal dose of modified bovine surfactant extract (Survanta, 100 mg/kg, Abbott Laboratory, North Chicago, IL) with air placebo in preventing respiratory distress syndrome. Infants were enrolled if they were estimated to be between 24 and 30 weeks' gestation, weighed between 750 and 1250 g, and were intubated and stabilized within 15 minutes after birth. A total of 160 infants were treated (79 with surfactant, 81 with air placebo) between 4 and 37 minutes after birth (median time 12 minutes). Of these, 5 infants were excluded from the final analysis. The 72-hour average values for the arterial-alveolar oxygen ratio, fraction of inspired oxygen, and mean airway pressure were calculated from the area under the curve of scheduled values measured throughout 72 hours. Clinical status was classified using five ordered categories (no supplemental oxygen or assisted ventilation, supplemental oxygen only, continuous positive airway pressure or assisted ventilation with intermittent mandatory ventilation less than or equal to 6 breaths/min, assisted ventilation with intermittent mandatory ventilation greater than 6 breaths/min, death). Chest radiographs at 24 hours were graded for severity of respiratory distress syndrome. Infants receiving Survanta had less severe radiographic changes at 24 hours of age and decreased average fraction of inspired oxygen (31% vs 42%, P = .002) compared with control infants. No differences were noted in the average arterial-alveolar oxygen ratio, mean airway pressure, or clinical status on days 7 and 28. A beneficial effect was noted in the incidence of pneumothorax (P = .057) and an increase was noted in the incidence of necrotizing enterocolitis (P = .052). No differences in incidence of patent ductus arteriosus, intraventricular hemorrhage, sepsis, or bronchopulmonary dysplasia were seen. According to results of a secondary analysis, there was improvement in the fraction of inspired oxygen and a greater number of survivors without bronchopulmonary dysplasia in the subgroup of infants weighing less than 1000 g who were treated with surfactant. It was concluded that a single dose of Survanta given shortly after birth resulted in decreased severity of chest radiographic findings 24 hours after treatment and improved oxygenation during 72 hours after treatment, but did not improve other acute measures of disease severity or clinical status later in the neonatal period. The group at highest risk for respiratory distress syndrome (infants with birth weights between 750 and 999 g) may benefit the most from preventive therapy." ]

[ "15543373", "16519632", "10344682", "14972218", "14605927", "15368794", "11744979", "10668875", "11875680", "11878300", "12380728", "12473883", "16007352", "12972959" ]

[ "Radiofrequency fistulotomy: a better alternative for treating low anal fistula.", "Marsupialization of fistulotomy and fistulectomy wounds improves healing and decreases bleeding: a randomized controlled trial.", "Repair of fistulas-in-ano using autologous fibrin tissue adhesive.", "Radiosurgical fistulotomy; an alternative to conventional procedure in fistula in ano.", "Conventional cutting vs. internal anal sphincter-preserving seton for high trans-sphincteric fistula: a prospective randomized manometric and clinical trial.", "Radiofrequency fistulectomy vs. diathermic fistulotomy for submucosal fistulas: a randomized trial.", "KTP-Laser and fibrin glue for treatment of fistulae in ano.", "Repair of chronic anorectal fistulae using commercial fibrin sealant.", "Prospective randomised trial comparing ayurvedic cutting seton and fistulotomy for low fistula-in-ano.", "Preliminary results of using a commercial fibrin sealant in the treatment of fistula-in-ano.", "Routine use of setons for the treatment of anal fistulae.", "A randomized, controlled trial of fibrin glue vs. conventional treatment for anal fistula.", "Controlled, randomized trial of island flap anoplasty for treatment of trans-sphincteric fistula-in-ano: early results.", "Efficacy of fibrin sealant in the management of complex anal fistula: a prospective trial." ]

[ "Wide varieties of approaches are employed in dealing with low anal fistula. However, the simple method of laying open the fistula tract (fistulotomy) is still considered to be the favored one.\n A modified approach to the procedure of fistulotomy is discussed. This study describes the procedure, which used a technique of radiofrequency surgery, and its outcome in 232 patients with low anal fistula. The patients were followed for a period of 15 months.\n The patients were discharged on the same day as the procedure. The mean period off work was four days. The average healing time recorded was 67 days. Four wound complications in the form of premature closure of the external wound were noted, which required trimming of the edges. Two of these wounds remained unhealed. The recurrence rate was 1.7%.\n In this era when the emphasis is on criteria like the minimization of hospital stay, reduction of postoperative pain, early resumption of work and low and comparable recurrence rates, there is a future for the procedure of radiofrequency fistulotomy.", "Marsupialization of anal fistulotomy/fistulectomy wound leaves less raw unepithelialized tissue. The suture results in a more rapid healing and is likely to reduce the risk of bleeding but at the cost of an increased pain and infection. The aim of this prospective study was to compare the outcomes of marsupialization and open wound.\n Forty-six consecutive patients with anal fistulae were recruited in a randomized controlled trial. Fistula tracks were treated by fistulotomy and/or fistulectomy. The resulting wounds were marsupialized to the skin edges with locking continuous absorbable sutures (M group) or left open (O group). The clinical outcome was then evaluated. The intra-operative effect of the suture on wound size was recorded as well as the postoperative pain using a 0-10 visual analogue scale (VAS) and the occurrence of both wound bleeding and infection.\n Twenty-two patients were randomized to the M group and 24 to the O group. There were no differences in the age, sex and fistula type between the groups. Mean follow-up times were 10.5 and 13.8 months, respectively. No significant difference was observed in postoperative pain, the VAS being 3.5 +/- 1.5 in the M group and 3.4 +/- 1.6 in the O group at 12 h (mean +/- s.e.m.; n.s). The marsupialization nearly halved the size of the wound intra-operatively from an area of 1749 +/- 66 mm2 to 819 +/- 38 mm2 (P < 0.001), which subsequently decreased to 217 +/- 15 mm2 after 4 weeks (P < 0.01). No significant reduction of wound size was observed in the O group (from 1171 +/- 31 mm2 to 543 +/- 19; n.s). Bleeding occurred less frequently in M group than in O group (36%vs 46%, P < 0.05), whereas the difference in the postoperative sepsis rate was not significant, being 14% in M vs 21% in the O group. Three reinterventions were needed in both groups due to wound sepsis.\n Marsupialization after fistulotomy/fistulectomy significantly reduces the size of the wound and the risk of bleeding, without increasing postoperative pain and sepsis.", "Our goal was to determine if autologous fibrin tissue adhesive derived from the precipitation of fibrinogen using a combination of ethanol and freezing, could be used to completely close both simple and complex fistulas-in-ano.\n A 26-patient pilot study was performed in which 100 ml of a patient's blood was drawn 90 minutes before surgery. Autologous fibrin tissue adhesive was prepared. In the operating room the patient underwent an examination under anesthesia, and the primary and secondary fistula tract openings were attempted to be identified. The fistula tract was curetted, and autologous fibrin tissue adhesive was injected into the secondary fistula tract opening until fibrin glue was seen coming from the primary opening. A petroleum jelly gauze was then applied over the secondary opening, and the patient was sent home. Follow-up visits were scheduled for one week, one month, three months, and one year later.\n Twenty-six patients received autologous fibrin tissue adhesive fistula injections, with a mean follow-up of 3.5 months. Initial results were encouraging. Twenty-one of 26 patients (81 percent) had successful initial closure of their fistulas. Two of five failures were injected a second time, and one closed, giving an overall successful closure rate of 85 percent (22/26 patients). Of five patients who failed, mean time to failure was 3.8 weeks. In addition, there was no evidence of infection or complications related to the procedure.\n Our initial results are optimistic and require further support through longer follow-up data. Fibrin glue treatment of anorectal fistulas offers a unique mode of management that is safe, simple, and easy for the surgeon to perform. By using autologous fibrin tissue adhesive the patient avoids the risk of anal incontinence and the discomfort of prolonged wound healing which may be associated with fistulotomy.", "Most surgeons continue to prefer the classic lay open technique [fistulotomy] as the gold standard of treatment in anal fistula. In this randomized study, a comparison is made between conventional fistulotomy and fistulotomy performed by a radio frequency device.\n One hundred patients of low anal fistula posted for fistulotomy were randomized prospectively to either a conventional or radio frequency technique. Parameters measured included time taken for the procedure, amount of blood loss, postoperative pain, return to work, and recurrence rate.\n The patient demographic was comparable in 2 groups. The radio frequency fistulotomy was quicker as compared to a conventional one [22 versus 37 minutes, p = 0.001], amount of bleeding was significantly less [47 ml versus 134 ml, p = 0.002], and hospital stay was less when patient was operated by radio frequency method [37 hours versus 56 hours in conventional method, p = 0.001]. The postoperative pain in the first 24 hours was more in conventional group [2 to 5 versus 0 to 3 on visual analogue scale]. The patients from radio frequency group resumed their duties early with a reduced healing period of the wounds [47 versus 64 days, p = 0.01]. The recurrence or failure rates were comparable in the radio frequency and conventional groups [2% versus 6%].\n Fistulotomy procedure using a radio frequency technique has significant advantages over a conventional procedure with regard to operation time, blood loss, return to normal activity, and healing time of the wound.", "Cutting setons have been used in complicated perirectal sepsis with good effect, although there is a moderately high incidence of fecal leakage after their use. The aim of this study was to compare a modified cutting seton, which repaired the internal anal sphincter muscle and re-routed the seton through the intersphincteric space, with a conventional cutting seton.\n A total of 34 patients were randomized between 1998 and 2002. They were prospectively assessed by continence score and anorectal manometry, and for anal function, clinical sepsis and fistula recurrence.\n There was no difference in postoperative continence score, incidence of recurrent fistula or healing time between groups after a mean follow-up of 12 months. Resting anal manometric pressures and vector volumes were consistently higher with the modified seton (although not statistically significant), as was the area under the inhibitory curve during elicitation of the rectoanal inhibitory reflex across the full sphincter length. ( p<0.05).\n A larger prospective study of internal anal sphincter-preserving seton use in cryptogenic high transshincteric fistula-in-ano appears justified.", "Anal fistula represents one of the most frequent anorectal disease. Fistulotomy is considered the gold standard treatment but related problems are numerous (postoperative pain, bleeding, delayed or impaired wound healing). Fistulectomy lowers the recurrences but is less feasible with longer operating time and healing process. We applied the radiofrequencies to fistulectomy and compared the early and late results with those obtained from traditional fistulotomy.\n Twenty patients were randomized to undergo radiofrequency fistulectomy (10 patients, Group A) or conventional fistulotomy (10 patients, Group B). We analysed the first postoperative day pain, intra- and postoperatory bleeding, operating time, complications (impaired or delayed wound healing, fecal incontinence) and any recurrences.\n The mean values for operative time have been 18.3 min for group A (range 15-26 min) and 17.9 min for group B (range 13-21 min). According to VAS scale, first postoperative day pain mean values were 2.8 for group A (range 2-4) and 4.1 for group B (range 3-5). Intra- and post-operative bleeding has always been negligible and faecal incontinence was never observed. Healing time mean values have been 3.5 weeks for group A (range 3-5) and 5.9 weeks for group B (range 4-8 weeks). Long-term results did not evidence complications or recurrences for both groups.\n The application of radiofrequencies to fistulectomy renders more feasible and easies the operation. Postoperative pain is smaller than traditional fistulotomy because of the lower temperatures used and for the shorter time spent in coagulating. This gives a faster wound healing. In conclusion we think that radiofrequency fistulectomy is technically more advantageous than traditional fistulotomy and furnishes better results.", "Fistulae-in-ano remains a significant surgical problem due to the limitations pertinent to accurate assessment and the magnitude, shortcomings and side effects of the various procedures currently employed for their management. Six consecutive fistulae-in-ano patients (males, age range 30 to 58 years) were successfully treated by KTP laser (20-watt continuous aim for 20 to 30 seconds delivering a total energy of 400 to 600 joules) with rapid solidification fibrin glue then followed up for 3 months without recurrence. This approach offers a simple, expeditious and effective treatment for fistulae-in-ano thereby overcoming many of the restrictions associated with other methods.", "Commercially produced fibrin sealant can be used to completely close both simple and complex fistulae in ano.\n A 29-patient prospective nonrandomized clinical trial was performed. In the operating room, the patient underwent an examination with anesthesia and the primary and secondary fistula tract openings were attempted to be identified. The fistula tract was curetted and fibrin sealant was injected into the secondary fistula tract opening until fibrin sealant was seen coming from the primary opening. A petroleum jelly gauze was then applied over the secondary opening and the patient was sent home. Follow-up visits were scheduled for 1 week, 1 month, 3 months, and 1 year later.\n Twenty-nine consecutive patients received fibrin sealant injections for their fistulae in ano, with a mean follow-up of 6 months. Two patients had a history of Crohn disease (regional enteritis) and 2 patients had human immunodeficiency virus infection. Overall, 17 (68%) of 25 patients have had successful closure of their fistula with 4 patients lost to follow-up. Two patients required reinjection with fibrin sealant, and neither of these subsequently had closure. One of the 2 patients with Crohn disease had closure, as well as 1 human immunodeficiency virus-positive patient. In addition, there has been no evidence of incontinence or complications related to the use of fibrin sealant in this procedure.\n Initial results in the treatment of chronic anorectal fistulae using commercial fibrin sealant are optimistic, but require further support through longer follow-up data. Fibrin sealant treatment of anorectal fistulae offers a unique mode of management which is safe, simple, and easy for the surgeon to perform. By using fibrin sealant, the patient avoids the risk of fecal incontinence and the discomfort of prolonged wound healing that may be associated with fistulotomy.", "The aim of this study was to evaluate the role of ayurvedic setons in the treatment of low fistula-in-ano. One hundred and eight patients were randomised into either conventional fistulotomy (F) or ayurvedic cutting seton insertion (C). Endpoints investigated included time to wound healing and complications of surgery. Post-operative pain scores were measured daily using a visual analog scale. Anal function was compared using a continence score. Pre- and postoperative manometry and ultrasound were also performed. After exclusions, there were 54 patients in group F and 46 in group C. There were no differences in age, sex or follow-up duration between the two groups. Healing time was similar between the groups. Group C reported more pain following operation and on the first 2-4 postoperative days, but both groups experienced the same amount of pain subsequently. In conclusion, chemical seton was more painful than conventional fistulotomy in the first few days following surgery. However, there was no difference in time to wound healing, complications or functional outcome.", "A prospective non-randomised study fibrin sealant injection to manage patients with fistula-in-ano, with magnetic resonance imaging (MRI) monitoring, was performed during the period 5/6/1999 to 28/2/2000. The aim was to determine whether a fibrin sealant could be used as a treatment modality for anorectal fistula and the usefulness of MRI perineum to monitor the disease activity. Ten patients were included in the study. Mean age was 47 years (range 7 months to 70 years). Male: female ratio was 9:1. Mean follow-up duration was 26.4 weeks. The overall success rate was 60%. The success rate of different fistula types were different (60%, 0%, 100% for intersphincteric, transphincteric, subcutaneous, respectively). Variable decrease in signal on STIR images and contrast enhancement was noted in the patients with successful and failure of fibrin sealant injection. In conclusion, fibrin sealant injection is a useful alternative treatment in the management of fistula-in-ano. MRI is helpful in delineating the anatomy of fistula-in-ano but not a useful tool to follow-up disease activity.", "Anal fistula is usually treated by either fistulotomy or fistulectomy. We described the routine use of setons to treat anal fistula without any surgery.\n Forty-seven consecutive patients with diagnosed anal fistulae were treated using setons alone.\n The median age of the patients was 41 (range: 18-70). Of the 47 patients, 15 had surgery previously for fistula and perianal abscess. At least two setons were inserted through each fistula. One was tied tightly to function as a cutting seton and this was sequentially tightened by the patient and another was tied loosely for drainage. Of the 47 patients, 33 (70%) had the placement of setons in the clinic without any anaesthesia. The remaining 14 patients had the setons inserted in the operating room, with one patient having a complex anal fistula and 13 patients having perianal abscess requiring drainage at the same time. There were no post procedure complications in the series. Forty-one patients had completed follow up at clinic within a median duration of 15 weeks (range: two to 67 weeks). The fistula was completely healed by this method in 37 patients (78%). The median healing time was nine weeks (range: four to 62 weeks). One patient developed recurrent fistula and was healed after another seton placement. No patient developed any faecal incontinence and all patients were satisfied with this treatment.\n The routine seton method is safe, cheap and effective in the treatment of anal fistula regardless of type. It does not leave an open wound and most patients are satisfied with the treatment.", "Fibrin glue is a novel treatment for anal fistulas and possesses many advantages in the treatment of difficult high fistulas. Fibrin glue treatment is simple and repeatable; failure does not compromise further treatment options; and sphincter function is preserved. We aimed to compare the outcomes of patients with low and high anal fistulas randomly assigned to either fibrin glue or conventional treatment.\n Patients with simple fistulas (low fistulas) and complex fistulas (high, Crohn's, and low fistulas with compromised sphincters) were randomly assigned to either fibrin glue or conventional treatment (fistulotomy or loose seton insertion with or without subsequent advancement flap). Patients with rectovaginal fistulas and anal fistulas associated with chronic cavities, acute sepsis, and side branches were excluded. The primary end point was fistula healing. Secondary end points were complications, changes in preoperative continence score, changes in maximum resting and squeeze pressure, satisfaction scores, and pain scores and time off work (simple fistulas only).\n Patients in the fibrin glue and conventional treatment arms were well matched for gender, median age, duration of fistula symptoms, and follow-up. Fibrin glue healed three (50 percent) of six and fistulotomy seven (100 percent) of seven simple fistulas (difference, 50 percent; confidence interval, 10 to 90 percent; P= 0.06, Fisher's exact probability test). There was no change in baseline incontinence score, maximum resting pressures, or squeeze pressures between the study arms. Return to work was quicker in the glue arm, but pain scores were similar and satisfaction scores higher in the fistulotomy group. Fibrin glue healed 9 (69 percent) of 13 and conventional treatment 2 (13 percent) of 16 complex fistulas (difference, 56 percent; 95 percent confidence interval, 25.9 to 86.1 percent; P= 0.003, Fisher's exact probability test). There was no change in baseline incontinence score, maximum resting pressures, or squeeze pressures in either study arm. Satisfaction scores were higher in the fibrin glue group.\n No advantage was found for fibrin glue over fistulotomy for simple fistulas, but fibrin glue healed more complex fistulas than conventional treatment and with higher patient satisfaction.", "Treatment of trans-sphincteric fistula is usually a compromise between recurrence and incontinence. Dermal island flap anoplasty has been found to be useful in the treatment of these fistulas. We performed a randomized trial to compare dermal island flap anoplasty with conventional treatment for trans-sphincteric fistula-in-ano. Seventy nine patients with fistula-in-ano were recruited; twenty patients with trans-sphincteric fistula confirmed by endoanal ultrasound were prospectively randomized to receive either dermal island flap anoplasty (IFA) or conventional treatment (CVN) for trans-sphincteric fistula-inano. Conventional treatment consisted of lay open fistulotomy or seton insertion if deemed unsuitable for fistulotomy. Dermal island flap anoplasty involved a cutaneous advancement flap into the rectum. Pain scores, fecal incontinence scores, operative complications, wound healing and recurrence rates were charted. Two patients in the CVN group required seton insertions, which were still intact at the 9-month follow-up. Two patients with similar high trans-sphincteric fistula in the IFA group avoided having a long-term seton. There were no differences in the postoperative pain score, incontinence score, complications, wound healing and recurrence rates between the two groups. IFA is a safe and useful method for treating transsphincteric fistula. It can be considered when a suprasphincteric extension is suspected, thus avoiding risk of incontinence or the discomfort of a long-term seton.", "A prospective trial was conducted to establish long-term healing of complex idiopathic anorectal fistula, without extension, after fibrin glue treatment, with clinical assessment and magnetic resonance imaging to determine tract healing.\n Twenty-two patients undergoing glue instillation after fistula curettage and irrigation were followed up for a median of 14 months. Clinical assessment, short tau inversion recovery sequence magnetic resonance imaging, and combined short tau inversion recovery and dynamic contrast-enhanced magnetic resonance imaging were performed at a median of three months postoperatively, and their ability to predict outcome in the presence of early skin healing was determined.\n Of 22 patients, 19 (86.5 percent) had transsphincteric fistulas, 1 (4.5 percent) had a suprasphincteric fistula, 1 (4.5 percent) had an extrasphincteric fistula, and 1 (4.5 percent) had a rectovaginal fistula. None had clinical or radiologic evidence of secondary extension. Despite skin healing in 17 (77 percent) of 22 patients at a median of 14 days after treatment, only 3 (14 percent) remained healed at 16 months. Magnetic resonance imaging with short tau inversion recovery sequences in combination with dynamic contrast-enhanced magnetic resonance imaging predicted outcome in all 10 assessments (100 percent), compared with short tau inversion recovery sequence alone in 16 (94 percent) of 17 assessments or clinical examination in 12 (71 percent) of 17 (P = 0.02).\n The success rate of fibrin glue application for complex anorectal fistulas without extension is 14 percent. Magnetic resonance imaging predicts outcome at an earlier stage than clinical examination." ]

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[ "Subsittution of inhaled beclomethasone dipropionate for ingested prednisone in steroid-dependent asthmatics.", "A comparison of triamcinolone acetonide MDI with a built-in tube extender and beclomethasone dipropionate MDI in adult asthmatics.", "A comparison of double-strength beclomethasone dipropionate (84 microg) MDI with beclomethasone dipropionate (42 microg) MDI in the treatment of asthma.", "Aerosol beclomethasone dipropionate in chronic bronchial asthma.", "Beclomethasone dipropionate aerosol in the treatment of steroid-dependent asthma. A 12-week double-blind study comparing beclomethasone dipropionate and a vehicle aerosol.", "Effect of inhaled beclomethasone dipropionate on isocapnic hyperventilation with cold air in asthmatics, measured with forced oscillation technique.", "Changes in bronchial reactivity in asthmatic children after treatment with beclomethasone alone or in association with salbutamol.", "Effects of inhaled beclomethasone on airway responsiveness in occupational asthma. Placebo-controlled study of subjects sensitized to toluene diisocyanate.", "Steroid-dependent asthma treated with inhaled beclomethasone dipropionate. A long-term study.", "Inhaled corticosteroids decrease vascularity of the bronchial mucosa in patients with asthma.", "Effect of beclomethasone dipropionate on bronchial responsiveness to histamine in controlled nonsteroid-dependent asthma.", "High-dose beclomethasone: oral steroid-sparing effect in severe asthmatic patients.", "Comparative clinical study of inhaled beclomethasone dipropionate and triamcinolone acetonide in persistent asthma.", "Systemic side effects of beclomethasone dipropionate aerosols (becotide, aldecine, sanasthmyl) in otherwise non steroid treated asthmatic patients.", "Effect of beclomethasone dipropionate on the bronchial responsiveness to propranolol in asthmatics.", "Beclomethasone dipropionate aerosol in asthma--a double blind study.", "Inhaled beclomethasone dipropionate (BDP) prevents seasonal changes in atopic asthmatics.", "Effectiveness of low doses (50 and 100 microg b.i.d) of beclomethasone dipropionate delivered as a CFC-free extrafine aerosol in adults with mild to moderate asthma. Study Group.", "Effect of inhaled beclomethasone dipropionate on bronchial hyperreactivity in asthmatic children during maximal allergen exposure.", "A controlled trial of inhaled corticosteroids in patients receiving Prednisone tablets for asthma.", "Dose-dependent inhibitory effect of inhaled beclomethasone on late asthmatic reactions and increased responsiveness to methacholine induced by toluene diisocyanate in sensitised subjects.", "Effects of regular inhalation of beclomethasone dipropionate and sodium cromoglycate on bronchial hyperreactivity in asthmatic children.", "Increased airway responsiveness in children of low birth weight at school age: effect of topical corticosteroids.", "Preventive effects of beclomethasone on histamine-induced changes in breathing pattern in asthma.", "Efficacy of chlorofluorocarbon-free beclomethasone dipropionate 400 micrograms day-1 delivered as an extrafine aerosol in adults with moderate asthma.", "Placebo-controlled immunopathologic study of four months of inhaled corticosteroids in asthma.", "A controlled trial of beclomethasone dipropionate in asthma.", "Comparison of the effects of inhaled corticosteroids on the airway response to histamine, methacholine, hyperventilation, and sulfur dioxide in subjects with asthma.", "Hydrofluoroalkane-134a beclomethasone dipropionate, 400 microg, is as effective as chlorofluorocarbon beclomethasone dipropionate, 800 microg, for the treatment of moderate asthma.", "Beclomethasone dipropionate aerosol in adult steroid-dependent obstructive lung disease.", "A comparison of betamethasone valerate, beclomethasone dipropionate and placebo by inhalation for the treatment of chronic asthma.", "A clinical trial of beclomethasone dipropionate aerosol in children and adolescents with asthma.", "A graded dose assessment of the efficacy of beclomethasone dipropionate aerosol for severe chronic asthma.", "Efficacy and safety of beclomethasone dipropionate extrafine aerosol in childhood asthma: a 12-week, randomized, double-blind, placebo-controlled study.", "Treatment of chronic childhood asthma with beclomethasone dipropionate aerosol: I. A double-blind crossover trial in nonsteroid-dependent patients.", "Anti-inflammatory effects of salmeterol compared with beclomethasone in eosinophilic mild exacerbations of asthma: a randomized, placebo controlled trial.", "Effect of low-dose beclomethasone dipropionate on asthma control and airway inflammation.", "A controlled trial of beclomethasone dipropionate for asthma.", "A placebo-controlled blinded comparison of nedocromil sodium and beclomethasone dipropionate in bronchial asthma.", "Effect of inhaled beclomethasone dipropionate on expression of proinflammatory cytokines and activated eosinophils in the bronchial epithelium of patients with mild asthma.", "Beclomethasone dipropionate aerosol in asthma. Transfer of steroid-dependent asthmatic patients from oral prednisone to beclomethasone dipropionate aerosol.", "Substitution of beclomethasone aerosol for oral prednisolone in the treatment of chronic asthma.", "Effect of inhaled beclomethasone dipropionate on bronchial responsiveness in patients with asthma.", "Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized, controlled trial. Montelukast/Beclomethasone Study Group.", "A comparison of bronchodilator therapy with or without inhaled corticosteroid therapy for obstructive airways disease. Dutch Chronic Non-Specific Lung Disease Study Group.", "Effects of inhaled steroids on blood eosinophils in moderate asthma.", "Beclomethasone dipropionate by aerosol in the treatment in asthmatic children.", "Montelukast added to inhaled beclomethasone in treatment of asthma. Montelukast/Beclomethasone Additivity Group.", "High doses of inhaled corticosteroids in unstable chronic asthma. A multicenter, double-blind, placebo-controlled study.", "A controlled trial of beclomethasone dipropionate by aerosol in chronic asthmatics.", "The long-term effects of nedocromil sodium and beclomethasone dipropionate on bronchial responsiveness to methacholine in nonatopic asthmatic subjects." ]

[ "The effect of inhaled beclomethasone dipropionate (dose, 400 mug daily) was investigated in 31 prednisone-dependent asthmatics. In a double-blind noncrossover study of 25 patients dependent on a daily prednisone dose of 17.5 mg or less, the dose of ingested prednisone was significantly diminished through the use of beclomethasone as compared with placebo (P < 0.001). In a subsequent single-blind study of the 12 patients who had received placebo, a similar decrease in prednisone dose was possible when these patients received beclomethasone. In all 25 patients the effect of beclomethasone was maintained for 2 years; 9 came to require less beclomethasone and 1 required more. In an additional single-blind study of six patients with severe asthma, dependent on prednisone in a dose of 20 to 25 mg/d, the response to beclomethasone was more variable and less significant (P < 0.01). However, at 2 years there was no significant benefit (P > 0.05) and there were two treatment failures.In patients in whom reduction of dose or discontinuation of prednisone was possible plasma cortisol values before and after corticotropin administration increased significantly (P < 0.001). Prednisone reduction was associated with the appearance of mild musculoskeletal steroid-withdrawal symptoms of short duration in 15 patients, and recurrence of symptoms of rhinitis in 15 patients. Side effects of beclomethasone included episodes of hoarseness in 6 and easily treated oropharyngeal Candida albicans infection in 14.", "In this study, the efficacy and safety of triamcinolone acetonide (TA) metered-dose inhaler with a built-in tube extender and beclomethasone dipropionate (BDP) metered-dose inhaler without a spacer device were compared. Both treatments were dosed at their most commonly used daily doses (within labeling).\n A 56-day, randomized, double-blind, double-dummy, placebo-controlled trial.\n Seventeen asthma/allergy centers.\n We enrolled 339 patients 18 to 65 years of age, with a documented history of bronchial asthma (FEV1, 50 to 90% of predicted value) for > or = 2 years who required inhaled corticosteroid therapy.\n Patients were randomized to receive BDP 336 microg/d (4 puffs bid) plus TA placebo (4 puffs bid), TA 800 microg/d (4 puffs bid) plus BDP placebo (4 puffs bid), or TA and BDP placebos (4 puffs of each bid). The only other asthma medication permitted was inhaled albuterol that was used as a rescue medication. All medications were administered via the closed-mouth inhalation technique.\n At 8 weeks and at study end point, both active treatment groups had statistically significant and comparable improvements in FEV1 relative to baseline, and statistically significant increases relative to placebo. At study end point, improvements in forced expiratory flow (FEF25.75%), clinic peak expiratory flow (PEFR), and FVC were statistically significant for the active treatment groups compared with placebo. At end point, the mean difference between BDP and TA for mean change in FEV1 from baseline in the efficacy population was 0.02 and the 95% confidence interval was -0.11, 0.15. Asthma symptoms recorded at clinic visits showed statistically significant improvements for the BDP and TA groups compared with the placebo group. Treatment-related adverse events occurred with similar frequency in all patient groups-25.5% of placebo-treated patients, 22.3% of BDP patients, and 20.4% of TA patients. The incidence of oropharyngeal adverse events, including cough, thrush, and dysphonia, was not statistically different between the two active treatment groups.\n In this randomized, double-blind, placebo-controlled study of adult asthmatics treated with either BDP without a spacer or TA with its built-in tube extender, BDP and TA were comparable in efficacy as measured by FEV1 and other pulmonary function tests, and by improvement in asthma symptoms. Both active treatments were significantly more effective than placebo. All treatment groups were comparable in safety as measured by the incidence of adverse events.", "To compare the efficacy and safety of a double-strength formulation of beclomethasone dipropionate (BDP 84) metered-dose inhaler (MDI) with that of beclomethasone dipropionate (BDP 42) MDI in the treatment of chronic asthma.\n A 28-day, randomized, double-blind, double-dummy, placebo-controlled, multicenter study.\n Outpatient.\n A total of 423 patients aged 12 to 65 years (mean range, 34 to 36 years) with moderate asthma (FEV1, 50 to 80% of predicted) who required long-term inhaled corticosteroids were enrolled.\n Patients were randomized to receive BDP 84, two oral inhalations bid (336 microg/d), BDP 42, four oral inhalations bid (336 microg/d), or placebo. A fourth treatment arm administering BDP 84, eight oral inhalations bid (HD BDP 84; 1,344 microg/d) was also included to determine whether a dose-response relationship could be demonstrated.\n Spirometry, clinical observations.\n The three active treatments were significantly more effective (p < or = 0.01) than placebo at all time points in improving FEV1, the primary efficacy parameter; BDP 42 and BDP 84 were comparable to each other at every time point. Secondary pulmonary function tests (FVC, forced expiratory flow at 25 to 75% of FVC, and peak expiratory flow rate) showed similar results. All three active treatments were well tolerated. A dose response between 336 microg/d and 1,344 microg/d was demonstrated.\n In this well-controlled 28-day study, BDP 42 and BDP 84 were shown to be comparable in efficacy and safety on a microgram-for-microgram basis.", "nan", "In a randomized double-blind 12-week trial of steroid-dependent patients with chronic asthma, ten (59 percent) out of 17 patients receiving beclomethasone dipropionate aerosol in a total daily dose of 400mug were able to discontinue systemic corticosteroid therapy successfully, compared to two (13 percent) out of 15 patients in the placebo group (P=0.002). At the end of the trial, the average 8 am plasma cortisol level in the group receiving beclomethasone was more than twice the pretherapy value, whereas the level in the placebo group showed no significant change. There was no significant difference between the beclomethasone group and the placebo group in the overall incidence of side effects related to the aerosol and the effects of systemic corticosteroid withdrawal. Oral candidiasis was not found in any patient receiving beclomethasone dipropionate aerosol. Allergic nasal symptoms were disabling in many patients when the oral dosage of corticosteroids was tapered.", "Isocapnic hyperventilation with cold air (IHCA) is a reliable technique for assessing indirect bronchial hyperresponsiveness in patients with asthma. Impedance measurement of the respiratory system by the forced pseudorandom noise oscillation technique is a sensitive technique to assess changes in bronchial tone after IHCA. The aim of this study was to evaluate the effect of 6 weeks of treatment with beclomethasone dipropionate, 1,000 microg x day-1, on IHCA in asthmatic patients, measured with both forced oscillation technique and flow-volume recordings. Forty patients with mild asthma were included in this double-blind, placebo-controlled parallel-group study. Stratification on the basis of sex was performed to overcome differences in airway diameter. At entry and every 2 weeks during the treatment period, IHCA was performed and patient diaries were evaluated. Characteristic changes in forced oscillation parameters after IHCA were observed in all patients. After 6 weeks of treatment, BDP-treated patients showed statistically significant differences in impedance measurements after IHCA, manifested by significant attenuation of resistance at 8 Hz (p<0.01), slope of the frequency-resistance curve (p<0.01), reactance at 8 Hz (p=0.01), and resonant frequency (f0) (p<0.02). Flow-volume recordings showed only a statistically significant change in the decrease of inspiratory vital capacity (IVC) (p=0.01). Furthermore, a significant correlation was observed between serum immunoglobulin E (IgE) levels and the effect of BDP on IHCA, measured with forced oscillation technique. In this study, beclomethasone dipropionate, 1,000 microg x day(-1) for 6 weeks, decreased indirect bronchial hyperresponsiveness as assessed by cold air bronchoprovocation in asthmatic patients. The forced oscillation technique proved a more sensitive method of detecting changes in bronchial tone than flow-volume recordings.", "Airway inflammation is consistently present in patients with severe asthma. The combination of inhaled steroids and bronchodilators may be useful both for treating symptoms and improving the underlying inflammatory condition. We have compared the effect of beclomethasone dipropionate (BDP) combined with salbutamol (S), BDP alone, and placebo, on the severity of bronchial responsiveness in 30 children with allergic asthma during the period of specific allergen exposure. In children treated with BDP alone, PC20-FEV1 methacholine was 0.66 +/- 0.54 at the beginning and 1.91 +/- 2.11 at the end of the study period (p greater than 0.05). In children treated with BDP + S PC20, methacholine was 1.21 +/- 1.43 at the beginning and 4.22 +/- 3.88 at the end of the study (p less than 0.05). The group of children treated with placebo had a PC20-FEV1 methacholine of 0.79 +/- 0.61 at the beginning of the study and 0.80 +/- 0.46 at the end of the study. The results of the present study show that maintenance treatment with inhaled beclomethasone combined with salbutamol may lead to greater improvement in bronchial hyperreactivity than treatment with inhaled beclomethasone dipropionate alone.", "We investigated the effect of 5 months of treatment with inhaled beclomethasone dipropionate (BDP) on the airway responsiveness to methacholine (PD20 FEV1) and to toluene diisocyanate (TDI) in 15 sensitized asthmatic subjects who had been removed from occupational exposure to TDI. After the diagnosis was established by a positive inhalation challenge with TDI, each subject was removed from occupational exposure to isocyanates and treated with either BDP (1 mg twice per day, n = 7) or placebo (n = 8) for 5 months. The study was double blind for parallel groups. P20 FEV1 methacholine was measured before and three times during treatment and then at 6 months, that is, 4 wk after cessation of treatment. Airway sensitivity to TDI was assessed with specific inhalation challenge before treatment and at 6 months. Beclomethasone reduced the airway hyperresponsiveness to methacholine but did not affect the response to TDI. In fact, in the subjects on BDP, P20 FEV1 increased from 0.145 to 0.485 mg (p < 0.05) after 2 months of treatment. A further increase was observed at 4 and 5 months (0.548 and 0.629 mg, respectively, p < 0.01), and the improvement in nonspecific airway responsiveness was maintained after a 1-month washout period (0.637 mg, p < 0.01). In contrast, in the subjects on placebo, P20 FEV1 did not change significantly. At the end of the study, the severity of asthmatic reactions induced by bronchial challenge with TDI was significantly reduced in both groups, but no differences were observed between placebo and BDP.(ABSTRACT TRUNCATED AT 250 WORDS)", "The efficacy of inhaled beclomethasone dipropionate has been examined in 44 steroid-dependent asthmatics observed for 9 months to 2 years. A 3-month double-blind trial found that subjects treated with beclomethasone had a significant diminution in symptoms, were able to reduce their use of medication, and had improved maximum expiratory flow rates. Approximately one half were able to discontinue the use of oral prednisone within 9 months after starting beclomethasone, and a further one third reduced their dose by at least 50%. No characteristics could be defined to predict responsiveness to beclomethasone. The effectiveness of beclomethasone was sustained for as long as 2 years and was not associated with any abnormal urine, blood, or serum values or chest X-ray findings. Candidiasis of the palate appeared in approximately one third of the subjects and was usually transient. The chronic use of beclomethasone did not result in endocrine suppression.", "Increased vascularity in airway mucosa is a distinctive feature of airway remodelling in asthma. While corticosteroids have proved most effective in modifying airway inflammation, the effect of inhaled corticosteroids on increased airway mucosal vascularity in asthmatics has been little studied.\n We examined the effect of inhaled corticosteroid on airway vascularity in bronchial biopsy specimens taken from asthmatic patients.\n We studied bronchial biopsies from 28 asthmatic patients before and after treatment with inhaled beclomethasone dipropionate (BDP) 800 microg/daily, or placebo, for 6 months in a double-blind manner. Biopsy specimens were evaluated for number of vessels and percentage of area occupied by vessels, using computerized image analysis after staining for type IV collagen in vessel walls. Specimens were also examined for extent of collagen III in the subepithelial basement membrane. In addition, we compared asthmatic specimens with biopsy specimens taken from non-asthmatic control subjects.\n There was a significant increase in number of vessels (P < 0.01) and percent vascularity (P < 0.001) in the submucosa of asthmatic patients compared with control subjects. After 6 months of treatment, we observed significant improvements in forced expiratory volume in 1 s (FEV1), FEV1% and airway responsiveness (P < 0.05, each) in the BDP treatment group compared with the placebo group. This was accompanied by significant decreases in both vessel number and percent vascularity in the airways of BDP-treated patients (P < 0.05, each). We also observed a significant correlation between change in percent vascularity and change in collagen III thickness in the BDP-treated patients (rs = 0.90, P < 0.001). Furthermore, the change in percent vascularity was inversely correlated with both FEV1 (rs = -0.49, P < 0.05) and airway responsiveness (rs = -0.36, P < 0.05).\n These findings suggest that inhaled corticosteroid treatment of asthma reduced airway wall vascularity during airway remodelling.", "We investigated the possibility that corticosteroids can reduce bronchial responsiveness to histamine by mechanisms other than change in airway caliber. Ten adult asthmatic subjects were selected because their symptoms were controlled by bronchodilators alone, they had no recent respiratory infection or allergen exposure that might have temporarily altered responsiveness, their spirometry was more than 70% predicted, and they had a range of histamine bronchial hyperresponsiveness. They received, in random order and double-blind manner, beclomethasone dipropionate (400 micrograms daily) or placebo for 4 wk and then, after a 2-week washout period, they crossed over to the other treatment for 4 wk. Treatment with beclomethasone induced a small but significant reduction in bronchial responsiveness to histamine (p = 0.014). Although the improvement was too small to be considered of clinical significance, its importance lies in the mechanisms by which it was produced. Part of the improvement was related to improvement in airway caliber, but, even when the data was adjusted for this, there was still a significant difference between beclomethasone and placebo treatment (p = 0.018). The results suggest that regular treatment with corticosteroids can alter bronchial responsiveness through mechanisms other than change in airway caliber.", "One hundred and twenty four patients with severe asthma requiring maintenance treatment with oral corticosteroids were included in a multicentre, double-blind, randomized study comparing the effects of inhaled beclomethasone dipropionate (BDP) (250 micrograms.puff-1), beginning with 1,000 micrograms daily, vs placebo (P). Pulmonary function was assessed and dosage of prednisone and BDP (or P) were adjusted every 15 days according to a clinical score. Our results showed, after 3 months: 1) A greater drop-out rate in the P group than in the BDP group (36 vs 6%, respectively, p less than 0.01); 2) A total weaning from prednisone in 76% of patients in the BDP group (mean BDP dosage = 1,270 +/- 340 micrograms.day-1, mean +/- SD), vs 34% in the P group (p less than 0.001). The mean daily dosage of prednisone was reduced from 17 +/- 7.5 mg to 3.1 +/- 7.4 mg in the BDP group vs 15.6 +/- 7.7 mg to 9.1 +/- 9.4 mg in the P group (p less than 0.001) without any relationship between the steroid-sparing effect and the initial dosage of prednisone; 3) Mean change in forced expiratory volume in one second (FEV1) was +7 +/- 21% from the initial value in the BDP group vs -6 +/- 20% in the P group; p less than 0.01. Thus, in patients with severe asthma requiring oral corticosteroids, high-dose BDP has an important oral steroid-sparing effect not related to the initial dosage of oral steroids and allows a better control of airway obstruction than oral corticosteroids alone.", "At this time, no placebo-controlled studies in the clinical literature compare the efficacy and safety of the most widely prescribed oral inhaled corticosteroids when dosed at their recommended daily doses. This study compared the efficacy and safety of beclomethasone dipropionate (BDP) 336 microg/day administered by metered dose inhaler (MDI) alone, and triamcinolone acetonide (TA) 800 microg/day by MDI with a built-in tube extender in adults with persistent asthma.\n This 56-day, randomized, double-blind, double-dummy, placebo-controlled, multicenter trial was conducted in 328 adults with mild to moderately severe asthma (FEV1 50% to 90% of predicted while maintained on inhaled corticosteroids). Patients were seen at a baseline visit and on study days 28 and 56. Efficacy variables included pulmonary function tests, physician and patient assessments of asthma condition, and use of rescue medication.\n Statistically significant improvements from baseline in most efficacy measures were demonstrated for both active treatments versus placebo, and with the following exception were the same between active treatments: mean increase in FEV1 in the beclomethasone dipropionate group was statistically significantly greater than in the triamcinolone acetonide group on day 28. Throughout the study, BDP was statistically superior to TA with respect to mean change from baseline in total asthma symptom scores and for 3 of 8 weeks in reducing the mean average weekly use of rescue albuterol (the two active treatments were comparable for this variable at all other time points). Beclomethasone dipropionate and TA were comparable in safety.\n In adult patients with mild to moderately severe persistent asthma, treatment with BDP consistently conferred greater improvement from baseline in mean FEV1 than TA. This difference achieved statistical significance after 28 days of therapy but was not maintained to endpoint. Decreases in overall asthma symptom scores and in the use of rescue albuterol were statistically significantly greater for the BDP group compared with the TA group. Based on these findings, we conclude that BDP is at least as effective as TA in the treatment of persistent asthma in adults, and judged by some measures, may be superior.", "nan", "The effect of four weeks of treatment with beclomethasone dipropionate (BDP, 500 micrograms twice daily) on the bronchial responsiveness to propranolol was examined in 16 patients with mild asthma in a placebo-controlled, double-blind crossover study. Propranolol was inhaled in doubling concentrations and the results were expressed as the cumulative dose producing a 20 percent fall in FEV1 (PC20). After four weeks of treatment with BDP, the mean FEV1 increased from 82.0 percent predicted to 88.1 percent predicted. The difference was significant (p less than 0.001). Treatment with BDP did not significantly change the responsiveness to propranolol, the geometric mean PC20 being 3.17 mg/ml before and 3.64 mg/ml after BDP treatment. The recovery of FEV1 was faster after 60 minutes of BDP treatment in comparison with placebo treatment (beyond 90 minutes). This study suggests that BDP treatment is unable to reduce bronchial responsiveness to propranolol but can accelerate the recovery of bronchoconstriction induced by propranolol in asthmatic patients.", "nan", "Inhaled corticosteroids are most effective drugs currently available for the treatment of bronchial asthma. They have been shown to reduce airway inflammation and hyperresponsiveness. The aim of this study was to assess the preventive effect of inhaled steroid therapy in seasonal asthma. In a double-blind study, two groups of 10 allergic asthmatics were randomly assigned to receive inhaled beclomethasone dipropionate (BDP), 500 micrograms b.i.d., or a matched placebo, two puffs b.i.d. The patients used inhaled salbutamol as needed. At the beginning of the study, and every month between February and June, the following parameters were assessed: lung function (forced expiratory volume in one second (FEV1); airway responsiveness (provocative dose of methacholine producing a 20% fall in forced expiratory volume in one second (PD20)), serum eosinophil cationic protein (ECP); and blood eosinophil count. All subjects recorded daily asthma symptoms, beta 2-agonist consumption and peak expiratory flow (PEF) values. In the placebo group, all parameters except FEV1 worsened significantly during the pollen season compared with preseasonal values (p < 0.001). BDP produced complete protection, although a slight change from baseline was found for symptom score (p < 0.01), beta 2-agonist consumption (p < 0.01), and eosinophil number (p < 0.05) in May, when the pollen load was highest. These data provide evidence that beclomethasone dipropionate treatment is able to inhibit the seasonal changes occurring during natural exposure in asthmatics. This preventive effect is probably due to the anti-inflammatory action of beclamethasone dipropionate, as documented by its effect on serum markers of airway inflammation.", "The objective of this study was to evaluate the efficacy and safety of low doses (50 and 100 microg b.i.d.) of hydrofluoroalkane-134a (HFA) beclomethasone dipropionate (BDP) extrafine aerosol in improving asthma control. Reformulation of BDP in a new chlorofluorocarbon (CFC)-free propellant (HFA) has produced an extrafine aerosol with increased delivery of the drug to the airways of the lung. The study population comprised 270 steroid-naive patients with mild to moderate asthma (mean baseline forced expiratory volume in 1 sec [FEV1] as a percentage of predicted normal of 65%-85%). This was a 6-week, blinded, placebo-controlled, multicenter study. Patients were randomized to receive 50 or 100 microg b.i.d. HFA-BDP or HFA-placebo. Treatment with either 50 or 100 microg b.i.d. HFA-BDP resulted in a significantly greater improvement compared with placebo in FEV1 (mean change from baseline as percentage of predicted normal of 6.7%, 8.6%, and 0.4%, respectively; p < or = 0.01 active treatment groups vs. placebo), with a significant trend toward increasing improvement with increasing doses (p < or = 0.0001). Treatment also resulted in significantly greater mean changes from baseline in morning peak expiratory flow compared with placebo (29.5, 33.8, and 5.0 L/min, respectively; p < or = 0.01 active treatment groups vs. placebo). All other pulmonary function and asthma symptom measures supported these data. The study treatments were well tolerated. These results show that low doses of HFA-BDP extrafine aerosol effectively improve asthma control in adult patients with mild to moderate asthma. However, it is important that inhaled corticosteroid therapy is still given at a dose high enough to control airway inflammation as well as asthma symptoms.", "In this double blind study we evaluated the effect of a 2 months long treatment with inhaled beclomethasone dipropionate (300 micrograms/day) on methacholine responses in asthmatic children, during a period of maximal allergen exposure. Baseline values of methacholine PC20-FEV1 were 0.66 +/- 0.22 mg/mL (mean +/- SEM) in 10 children treated with the active drug and 0.78 +/- 0.21 mg/mL in 10 children treated with placebo. After 1 month of treatment PC20-FEV1 was 1.91 +/- 0.64 and 0.80 +/- 0.33 mg/mL, respectively, in the groups treated with beclomethasone versus placebo. A statistically significant reduction in bronchial hyperreactivity (PC20-FEV1, 5.49 +/- 1.86 mg/mL) but no systemic side effects were observed after 2 months of treatment with beclomethasone dipropionate. This is compared with a PC20-FEV1 of 1.38 +/- 0.52 mg/mL in the placebo group. The results confirm the effect of inhaled corticosteroids in reducing bronchial hyperreactivity, even during a period of maximal allergen exposure.", "The theraprutic efficacy of inhaled beclomethasone dipropionate and inhaled betamethasone valerate in chronic asthma has been studied in 14 treatment centres in 158 patients who had previously been taking prednisone tablets regularly. Doses of 400 mug daily of beclomethasone dipropionate and a dose of 800 mug daily of betamethasone valerate allowed approximately 80% of patients to discontinue prednisone initially and 60% to remain off daily prednisone for 24 weeks. A mean reduction in daily prednisone dose of 8 mg was achieved by patients inhaling corticosteroids whilst placebo inhaler permitted a 5 mg reduction. The three inhaled corticosteroid preparations were equally effective in facilitating prednisone reduction and provided equally good control of asthma, alone or as an ancillary to prednisone. The higher dose of beclomethasone dipropionate was superior to the lower in permitting more patients to remain off daily prednisone for the period of the trial. Although 82% of patients recovered a normal adrenal response to tetracosactrin 24 weeks after prednisone was discontinued and inhaled corticosteroids subsituted, 18% still showed some suppression of adrenal function. There was no significant difference between the treatment groups in this.", "To determine whether inhaled beclomethasone, both at low and at high doses, inhibits late asthmatic reactions and the associated increase in airway responsiveness induced by toluene diisocyanate (TDI), we studied 9 sensitised subjects. Low dose beclomethasone (200 micrograms bid), high dose beclomethasone aerosol (1000 micrograms bid), and placebo were administered for 7 days before TDI inhalation challenge to each subject, according to a double-blind, crossover study design. The washout period between the treatments was at least 1 week. When the subjects were treated with placebo, forced expiratory volume in 1 sec (FEV1) markedly decreased after exposure to TDI. By contrast, high dose beclomethasone prevented the late asthmatic reaction and the low dose partially inhibited the reaction. With placebo the mean (+/- SE) value of FEV1 4 h after exposure to TDI was 2.6 +/- 0.17 L, which went to 3.3 +/- 0.12 after low dose beclomethasone, and to 3.5 +/- 0.15 L after high dose of beclomethasone (significant difference in the decrease of FEV1 in the 8 h after exposure to TDI, between treatments: F = 9.87, (P less than 0.001), After treatment with placebo or with low dose beclomethasone, airway responsiveness to methacholine increased 8 h after exposure to TDI. With placebo, the PD20 decreased from 0.66 mg (Geometric Standard Error of the Mean [GSEM], 1.38) to 0.18 mg (GSEM, 1.46); with low dose inhaled beclomethasone, the PD20 decreased from 0.93 mg (GSEM, 1.42) to 0.36 mg (GSEM, 1.63).(ABSTRACT TRUNCATED AT 250 WORDS)", "The efficacy of beclomethasone dipropionate (BDP) was compared with sodium cromoglycate (SCG) and placebo in a double-blind parallel group study of 30 asthmatic children over a two-month period. All the three treatment groups received salbutamol concomitantly. Lung volumes, airway mechanics and the nonspecific bronchial hyperreactivity to carbachol were measured at the beginning and the end of the study. Two patients were excluded because of unequal clinical conditions at the entry and the end of the study and three because of lack of co-operation. Three patients (1 on SCG, 2 on placebo) dropped out because of worsening clinical symptoms. The improvement in airway mechanics shown by the group treated with BDP (n = 7) was significantly greater (p less than 0.01) than in the group treated with SCG (n = 8). Nonspecific hyperreactivity to carbachol improved significantly in the BDP group (factor 5.9) compared to the SCG group (factor 1.9). Childhood asthma seems to be better controlled by a combination of BDP and salbutamol, than by SCG and salbutamol.", "The effect of treatment with topical inhaled corticosteroids was assessed in 15 children of low birth weight (mean (SD) birth weight 1435 (268) g, gestational age 30.5 (2.9) weeks, age at study 8.2 (0.4) years) who were symptomatic and showed a positive airway response to histamine aerosol. The study was of a double blind, placebo controlled, crossover design with four week long treatment periods with inhaled beclomethasone dipropionate (400 micrograms daily) or placebo. Daily symptom scores were recorded and physiological measurements were performed at the beginning and end of each treatment period. There was no significant difference in respiratory symptom score, baseline airway function, or the airway response to histamine between treatment periods. The findings argue against an inflammatory basis for airway hyper-responsiveness in these children and raise questions as to its pathophysiological basis.", "Bronchial mucosa inflammation is a hallmark of asthma. Epithelial damage due to inflammatory process may contribute to induce a pattern of rapid and shallow breathing (RSB). Probably due to its effects on inflammatory process, beclomethasone dipropionate (BDP) decreases bronchial hypersensitivity (BH), as assessed in terms of histamine concentration causing a 20 percent FEV1 decrease from saline solution (PC20FEV1); however, no data are available on the effect of BDP on RSB. We studied 32 asymptomatic asthmatic subjects with a severe to moderate levels of BH (PC20FEV1 0.01 to 1.7 mg/ml). After they were randomly assigned to one month of either BDP (2 mg daily, 17 patients) or placebo (15 patients), they inhaled progressively doubling concentrations of histamine phosphate by tidal breathing method. With histamine in seven BDP-treated and in five placebo-treated patients, decrease in FEV1 > or = 20 percent from saline solution was paralleled by a significant decrease in tidal volume (VT), inspiratory time (Ti), and expiratory time (Te), and increase in respiratory frequency (RF). In the remaining patients, histamine failed to change the breathing pattern. In the seven RSB patients, BDP resulted in a smaller VT decrease (p < 0.02) and a smaller RF increase (p < 0.02) with histamine. The five RSB placebo-treated patients were then given one month BDP (2 mg daily): inhaled BDP, but not placebo, resulted both in a significant increase in PC20FEV1 and modulation in histamine-induced changes in breathing pattern. We conclude that high doses of BDP seem to be able to modulate histamine-induced RSB, an effect that might be linked to reversal of airway inflammation.", "Beclomethasone dipropionate (BDP) has been reformulated in a chlorofluorocarbon-free propellant, hydrofluoroalkane-134a (HFA), resulting in an extrafine aerosol which gives improved drug delivery to the airways. The objective of this 6 week, placebo-controlled study was to evaluate the clinical efficacy of HFA-BDP 400 micrograms day-1 in 256 adult patients with moderate asthma. This is a lower daily dose than that recommended for existing BDP inhalers in current treatment guidelines for moderate asthma (NIH publication 95-3659). Another objective was to evaluate whether delivering the 400 micrograms dose as four actuations of 50 micrograms twice daily (HFA-BDP 50 micrograms) provided equivalent asthma control to delivering the dose as two actuations of 100 micrograms twice daily (HFA-BDP 100 micrograms) without the use of a spacer or holding chamber. Both active treatments produced a significant change from baseline in morning peak expiratory flow (PEF), which was significantly larger than that in the placebo group (P < or = 0.017) throughout the study. The mean changes from baseline in morning PEF at weeks 5-6 were 47.0 l min-1 in the combined HFA-BDP group and 16.5 l min-1 in the HFA-placebo group. The two dose strengths were statistically equivalent (P = 0.017 for equivalence testing). The active treatments also produced significant improvements compared with placebo in evening PEF, forced expiratory volume in the first second, forced expiratory flow over 25-75% of vital capacity, sleep disturbance scores and daily beta-agonist use. The study medication was well tolerated, with a low incidence of adverse events. The results from this study demonstrate that a daily dose of 400 micrograms HFA-BDP (given in 50 micrograms and 100 micrograms strengths) provides dose proportionality and effective control in patients with moderate asthma.", "The effect of prolonged inhaled corticosteroid treatment on bronchial immunopathology was assessed in 25 nonsmoking mildly asthmatic subjects previously receiving intermittent inhaled beta 2-agonist alone. Inhaled beclomethasone dipropionate (BDP), 500 micrograms twice per day or placebo was administered for 4 mo in a double-blind parallel group study. Histamine bronchial provocation, fiberoptic bronchoscopic biopsy, and bronchoalveolar lavage (BAL) were performed before and after treatment. There was no difference in bronchial responsiveness or lung function between groups. In patients treated with BDP compared with placebo, there was a significant reduction in toluidine blue-staining mast cells (p = 0.028) and total (p = 0.005) and activated eosinophils (p = 0.05) in biopsies but no difference in eosinophils or eosinophil cationic protein in BAL. Granulocyte-macrophage colony-stimulating factor expression was significantly reduced in the bronchial epithelium, and the thickness of Type III collagen deposition in the bronchial lamina reticularis reduced from 29.7 +/- 4.4 to 19.8 +/- 3.4 microns (mean +/- 95% confidence interval) (p = 0.04). No change in helper or activated helper T cells occurred. Prolonged BDP treatment reduces inflammatory infiltration, proinflammatory cytokine expression, and subepithelial collagen deposition, a recognized abnormality in asthma.", "nan", "To investigate whether inhaled steroids modulate the airway response to different bronchoconstrictive stimuli, we studied 25 subjects with mild asthma with a double-blind, noncrossover design to compare the effect of a 3-week treatment with salbutamol (0.2 mg, four times a day [q.i.d.]) and placebo (N = 11) to the effect of salbutamol (0.2 mg q.i.d.) and inhaled beclomethasone dipropionate (BDP, 0.5 mg q.i.d.) (N = 14). Airway response to histamine and methacholine was assessed as the provocative concentration (in milligrams per milliliter) necessary to increase the specific airway resistance (SRaw) (in centimeters of H2O times second) by 100% (PC100 SRaw). Airway response to hyperventilation of air and to hyperventilation of 0.75 ppm of sulfur dioxide (SO2) was determined as the provocative ventilation (in liters per minute) necessary to increase SRaw by 75% (PV75 SRaw). Challenges were performed on separate days before and after treatment, and salbutamol inhalation was withheld at least 6 hours before each challenge. Salbutamol and placebo did not change perchallenge baseline SRaw nor did they have any significant effect on the airway response to the stimuli. Salbutamol and BDP decreased the mean prechallenge baseline SRaw (SEM) from 7.7 (0.37) to 5.9 (0.28) (p less than 0.01) and significantly (p less than 0.01) increased geometric mean (SEM) PC100 SRaw for histamine from 0.5 (1.42) to 0.9 (1.53) mg/ml; for methacholine, from 0.2 (1.47) to 0.5 (1.51) mg/ml; and mean (SEM) PV75 SRaw for hyperventilation of air from 51.8 (2.32) to 58.4 (1.86) L/min. In contrast, the change of PV75 SRaw during hyperventilation of SO2 from 26.2 (2.29) to 31.4 (3.30) L/min was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)", "The improved lung deposition of hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) extrafine aerosol compared with chlorofluorocarbon beclomethasone dipropionate (CFC-BDP) suggests that lower doses of HFA-BDP may be required to provide equivalent asthma control. The present study was undertaken to test this hypothesis.\n A 10- to 12-day run-in period confirmed that patients met established criteria of at least moderate asthma and the asthma was inadequately controlled by current therapy (inhaled beta-agonist and CFC-BDP [< or = 400 microg/d]). A short course of oral prednisone, 30 mg/d for 7 to 12 days, was followed to establish the patients were steroid responsive and to provide an \"in-study\" baseline of \"optimal\" asthma control.\n A total of 347 patients were then randomized to HFA-BDP 400 microg/d, CFC-BDP 800 microg/d, or HFA-placebo for 12 weeks.\n Morning peak expiratory flow (AM PEF) measurements showed that HFA-BDP 400 microg/d achieved equivalent control of asthma to CFC-BDP 800 microg/d at all time intervals after oral steroid treatment. All other efficacy variables supported the AM PEF results and both active treatments were more effective than placebo. The safety profile of HFA-BDP compared favorably with that of CFC-BDP with no unexpected adverse events reported.\n These findings demonstrate that HFA-BDP provides equivalent control of moderate or moderately severe asthma as CFC-BDP in the population studied, but at half the total daily dose.", "nan", "nan", "nan", "In a 26-wk double-blind controlled study of 34 patients whose asthma had been poorly controlled despite oral steroids, valuable clinical and pulmonary function improvement was derived by adding beclomethasone aerosol to the prednisone regimen. The amount of improvement correlated linearly with beclomethasone dosage over the range 200 to 1,600 microng/day. These patients required relatively high dosage. Success in achieving asymptomatic status was only 26% with the conventional 400 microng/day and 60% at 1,600 microng/day. Oropharyngeal candidiasis was also dose-related but did not prohibit the use of high-dosage beclomethasone. Respiratory infections, physical signs, blood glucose, and electrolytes were unaffected by the drug. A dose-related suppression of cortisol secretion was demonstrated, but about 1/4 of the group had normal plasma cortisol even at 1,600 microng/day plus the oral prednisone. An individualized risk-benefit assessment seems a better basis for choosing an optimal beclomethasone regimen for each patient than adherence to a conventionalized fixed dosage of 400 microng/day. This requires definition of: (1) a specific goal of treatment in the individual patient and the beclomethasone dosage required to achieve it; (2) the adrenocortical functional response of that particular patient to the desired dose of beclomethasone; and (3) the presence and degree of any dose-limiting constraints such as preexisting complications of steroid use.", "Beclomethasone dipropionate (BDP) has been formulated as an extrafine aerosol (hydrofluoroalkane-134a [HFA]-BDP) [QVAR; 3M Pharmaceuticals; St Paul, MN], which gives improved lung deposition compared with chlorofluorocarbon (CFC)-BDP. The clinical efficacy of HFA-BDP has been established in adult asthma at a required dose below that of CFC-BDP, but has not been evaluated in children.\n To examine the efficacy and safety of HFA-BDP in childhood asthma.\n A 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study involving 353 children aged 5 to 12 years with moderate, symptomatic asthma. After a 2-week run-in period, patients were randomized to HFA-BDP, 80 micro g/d (n = 120); HFA-BDP, 160 micro g/d (n = 117); or HFA-placebo (n = 116) administered twice daily.\n Hospital outpatient.\n HFA-BDP, 80 micro g/d and 160 micro g/d, produced a significant, dose-related increase from baseline in FEV(1) percent predicted compared with placebo. At week 12, mean changes from baseline in FEV(1) percent predicted were 9.2% (p < or = 0.01 vs placebo), 10% (p < or = 0.01 vs placebo), and 3.9% for the HFA-BDP 80 micro g/d, HFA-BDP 160 micro g/d, and placebo groups, respectively. There was also a significant decrease in daily beta-agonist use, improvement in peak expiratory flow, and increase [correction] in the percentage of days free from asthma symptoms (p < or = 0.05 for HFA-BDP, 160 micro g/d, vs placebo at weeks 11 to 12). HFA-BDP was well tolerated, with no significant differences in the incidence or nature of adverse events between HFA-BDP and placebo groups. Neither were there significant differences between groups in mean percentage change from baseline in the morning plasma cortisol level at week 12 or in the percentage of patients with morning plasma cortisol levels below the reference range at baseline and week 12. In a subgroup tested, the percentage of patients with an abnormal response to low-dose adrenocorticotropic hormone stimulation at week 12 was low and similar among all groups.\n HFA-BDP, 80 to 160 micro g/d, is effective and safe in childhood asthma.", "nan", "Salmeterol is a potent long acting beta-agonist that is effective in relieving the symptoms and airflow limitation of asthma.\n To determine whether the effect of salmeterol on clinical parameters in a mild eosinophilic exacerbation of asthma was similar to that of beclomethasone dipropionate (BDP) and, thus, is due to an anti-inflammatory property.\n Thirty-four asthmatics with a persistent increase in symptoms for at least two weeks and an increase of sputum eosinophils of 4% or more were randomized in a double-blind fashion to one of three groups that received daily treatment with 100 mg salmeterol, 1 mg BDP or placebo in divided doses using identical pressurized inhalers. Patients were treated with study medications for three weeks, followed by one week of open label BDP (500 mg bid). Patients were seen at weekly intervals, and sputum and blood were obtained on each visit. The primary outcome measure was a change in sputum eosinophils, and secondary outcomes were changes in blood eosinophils, eosinophilic cationic protein (ECP) and clinical parameters. Three patients (one in each group) could not produce any sputum after randomization and were excluded from the analysis.\n Twelve patients received salmeterol, 10 received BDP and nine received placebo. Salmeterol treatment had no effect on sputum eosinophils geometric mean, (from 35.5 [24.9] to 26.9% [25.8]), blood eosinophils (from 7.6 [4.8] to 7.2% [3.9]) or ECP (from 33.1 [18.1] to 27.8 [16.3] mg/L) but improved morning peak expiratory flow (PEF) and diurnal variation of PEF, and decreased the use of rescue medication more than placebo (P<0.05 for all comparisons). In contrast, BDP improved both inflammatory indexes (sputum eosinophils from 22.5 [17.9] to 5.7% [6.8], blood eosinophils from 9.0 [5.5] to 2.1% 1.0, and serum ECP from 36.5 [22.0] to 16.1 [10.1] mg/L) as well as clinical parameters.\n These results show that salmeterol improves the symptoms and airway function of patients with asthma, but has no effect on eosinophilic airway infiltration. These findings support current asthma guidelines, which recommend the initial use of inhaled steroid to maximize clinical improvement. While salmeterol also produces clinical improvement, it does not suppress sputum eosinophilia. The analysis of induced or spontaneous sputum for inflammatory indexes may be a valuable clinical test to guide the use of inhaled steroid and/or a long acting beta-agonist.", "The effects of usual or low doses of inhaled corticosteroids on airway mucosal inflammation have not yet been examined. We therefore, compared the effects of inhaled beclomethasone dipropionate (BDP) 336 microg x day(-1) on asthma control outcomes and markers of airway inflammation. Twenty-four adult subjects with mild and moderate asthma were randomized to receive either BDP or placebo for four weeks; then subjects entered a single blind four week placebo run-in period. We found that the BDP group had significantly greater improvements in forced expiratory volume in one second (FEV1), morning peak flow, and rescue salbutamol use than the placebo-treated group. The improvement in FEV1 largely reversed one week after treatment was stopped. The decrease in the median percentage of eosinophils in induced sputum in the BDP group from 3.8% to 3.4% was not significant, but because eosinophils increased from 8.4% to 12.7% in the placebo group, there was a significant difference between treatment groups (p=0.03). There was no significant difference between groups during treatment in the levels of eosinophil cationic protein (ECP), tryptase mucin-like glycoprotein, or fibrinogen in induced sputum. The change in FEV1 in the BDP group did not correlate significantly with the change in eosinophil percentage or ECP levels. We concluded that four weeks of treatment with inhaled beclomethasone dipropionate 336 microg x day(-1) was associated with significant improvements in peak flow, forced expiratory volume in one second, and rescue salbutamol use in asthmatic subjects but was not associated with large reductions in markers of eosinophilic inflammation, bronchovascular permeability, or mucus hypersecretion.", "nan", "Two hundred and two patients aged 12-78 with chiefly moderate to severe asthma took part in a multicenter randomized blinded group comparison of nedocromil sodium (NS) 4 mg four times daily, beclomethasone dipropionate (BD) 0.1 mg four times daily, and placebo. Patients were assessed at the start and end of a two week baseline and after three and six weeks of treatment. Compared with placebo, both NS and BD significantly improved daytime dyspnoea and day and nighttime cough, as assessed by diary card scores. Lung function (FEV1) was significantly improved in the BD group. In the NS group there was also a significant reduction in concomitant use of inhaled beta 2-agonists. Overall opinions of efficacy by clinicians and patients were significantly in favor of both active treatments over placebo. There were no significant differences between the three treatments for peak expiratory flow rates, morning tightness or nighttime dyspnoea. Comparison between the two active treatments showed no significant differences in any of the variables.", "Increasing evidence suggests that cytokines play a role in airway inflammation by attracting and activating inflammatory cells. This may lead to epithelial cell damage and airway hyperresponsiveness. Bronchial provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 second was measured in patients with mild asthma, and bronchial biopsy specimens were stained for granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-8, and activated eosinophils (EG2) in the bronchial epithelium. The effect of inhaled beclomethasone dipropionate was also assessed in a placebo-controlled double-blind manner. There was a correlation between GM-CSF expression and EG2-staining cells (r = 0.484 p < 0.05) in the epithelium. Provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 second was correlated with GM-CSF expression (r = -0.462, p < 0.05). Treatment with inhaled beclomethasone dipropionate 500 micrograms twice a day led to a significant decrease in both the expression of GM-CSF (p < 0.01) and IL-8 (p < 0.02) and the number of EG2-staining cells (p < 0.01) in the epithelium. The changes in GM-CSF (r = 0.798, p < 0.01) and IL-8 (r = 0.653, p < 0.02) expression were correlated with the changes in EG2-staining cells after treatment. These results suggest that GM-CSF may influence eosinophil activation in the epithelium in vivo and participate in the etiology of bronchial hyperresponsiveness in mild asthma. Also, beclomethasone dipropionate may inhibit eosinophil activation partly by downregulating the expression of GM-CSF and IL-8 in the bronchial epithelium.", "nan", "In a double-blind study 10 patients with chronic asthma received beclomethasone dipropionate 400 mug daily in a Freon propellant from a pressurized dispenser, and 10 patients received the Freon propellant alone. At the start of the trial each patient was receiving long-term maintenance treatment with oral prednisolone in a dose of 7.5 to 15 mg daily. The daily dose of prednisolone was reduced by 1 mg every four weeks and the patient's progress followed by regular clinical assessment and studies of pituitary-adrenal function. The trial was continued until the dose of prednisolone was reduced to zero or until asthmatic symptoms increased to an unacceptable level.In the 10 patients who received beclomethasone the mean maintenance dose of oral prednisolone was reduced by 5.6 mg/day but in only two cases could this drug be withdrawn completely. In the placebo group the mean reduction in dose was only 1.3 mg, thus there was a significant difference between the two groups (P <0.01). Studies of pituitary-adrenal function showed that a normal adrenal response to tetracosactrin stimulation returned only in the two patients from whom prednisolone was withdrawn.Hence the addition of beclomethasone dipropionate by inhalation to systemic corticosteroid therapy allows useful reductions to be made in the oral maintenance doses of corticosteroid. Reductions must be made with caution since there is wide individual variation in response to beclomethasone and in only a minority of patients can oral treatment by completely withdrawn.", "We investigated the effect of 300 micrograms of inhaled beclomethasone dipropionate (BDP) daily on bronchial responsiveness to methacholine and pulmonary function of 22 subjects with asthma in a single-blind, crossover study. The severity of bronchial hyperresponsiveness lessened significantly during treatment with BDP (P < .01). No significant changes occurred in FEV1 or in the control value of airway conductance. We conclude that a 300-micrograms total daily dose of BDP is an efficacious treatment for patients with asthma. Because suppression of adrenal function and systemic adverse effects can occur in asthmatic patients treated with inhaled corticosteroids, especially children, long-term treatment with inhaled steroids should employ minimal daily doses necessary.", "Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma.\n To compare the clinical benefit of montelukast, a once-daily oral leukotriene receptor antagonist; placebo; and inhaled beclomethasone.\n Randomized, double-blind, double-dummy, placebo-controlled, parallel-group, 12-week study.\n 36 sites worldwide.\n 895 patients 15 to 85 years of age with chronic asthma and an FEV1 50% to 85% of predicted.\n Montelukast, 10 mg once daily at bedtime; inhaled beclomethasone, 200 microg twice daily, administered with a spacer device; or placebo.\n Primary end points were daytime asthma symptom score and FEV1. Secondary end points were peak expiratory flow rates in the morning and evening, as-needed beta-agonist use, nocturnal awakenings, asthma-specific quality of life, and worsening asthma episodes.\n Over the 12-week treatment period, the average percentage change from baseline in FEV1 was 13.1% with beclomethasone, 7.4% with montelukast, and 0.7% with placebo (P < 0.001 for each active treatment compared with placebo; P < 0.01 for beclomethasone compared with montelukast). The average change from baseline in daytime symptom score was -0.62 for beclomethasone, -0.41 for montelukast, and -0.17 for placebo (P < 0.001 for each active treatment compared with placebo; P < 0.01 for beclomethasone compared with montelukast). Each agent improved peak expiratory flow rates and quality of life, reduced nocturnal awakenings and asthma attacks, increased the number of asthma-control days, and decreased the number of days with asthma exacerbations (P < 0.001 for each active treatment compared with placebo for each end point; P < 0.01 for beclomethasone compared with montelukast for each end point). Although beclomethasone had a greater mean clinical benefit than montelukast, montelukast had a faster onset of action and a greater initial effect. The two agents caused similar decreases in peripheral blood eosinophil counts (P < 0.05 for each agent compared with placebo). Both agents had tolerability profiles similar to that of placebo over the 12-week study.\n Although beclomethasone had a larger mean effect than montelukast, both drugs provided clinical benefit to patients with chronic asthma. This finding is consistent with the use of these agents as controller medications for chronic asthma.", "The morbidity from obstructive airways disease (asthma and chronic obstructive pulmonary disease) is considerable, and the mortality rate is rising in several countries. It has been hypothesized that long-term improvement in prognosis might result from vigorous bronchodilator or antiinflammatory therapy.\n In a multicenter trial we compared three inhalation regimens in which a beta 2-agonist (terbutaline, 2000 micrograms daily) was combined with a corticosteroid (beclomethasone, 800 micrograms daily), an anticholinergic bronchodilator (ipratropium bromide, 160 micrograms daily), or placebo. Patients with airways hyperresponsiveness and obstruction who were 18 to 60 years old were followed for 2 1/2 years.\n Of the 274 patients enrolled, 56 percent had allergies. The mean forced expiratory volume in one second (FEV1) was 64 percent of the predicted value. The mean PC20 (the concentration of inhaled histamine causing a 20 percent decrease in FEV1, a measure of hyperresponsiveness) was 0.26 mg per milliliter. Withdrawal from the study, due mainly to pulmonary symptoms, was less frequent in the corticosteroid group (12 of 91 patients) than in the anticholinergic-drug group (45 of 92 patients) or the placebo group (44 of 91 patients; P < 0.001). The mean FEV1 (+/- SE) increased by 10.3 +/- 1.3 percent of the predicted value in the corticosteroid group within three months and remained stable thereafter, whereas it did not change in the other two groups (P < 0.001). The PC20 increased by 2.0 doubling concentrations in the corticosteroid group but did not change in the other groups (P < 0.001). In the corticosteroid group, patients who did not smoke, who had allergies, or who were less than 40 years old benefited more from their treatment than did those who smoked, did not have allergies, or were over 40, but all subgroups of the corticosteroid group had improvement as compared with the anticholinergic-drug or placebo group.\n The addition of an inhaled corticosteroid--but not an inhaled anticholinergic agent--to maintenance treatment with a beta 2-agonist (terbutaline) substantially reduced morbidity, hyperresponsiveness, and airways obstruction in patients with a spectrum of obstructive airways disease.", "nan", "nan", "The primary objective of this study was to determine whether montelukast, an oral leukotriene receptor antagonist, provides additional clinical benefit to the effect of inhaled corticosteroids. A total of 642 patients with chronic asthma (FEV(1) 50 to 85% of predicted value and at least a predefined level of asthma symptoms) incompletely controlled with inhaled beclomethasone, 200 microg twice daily using a spacer device, during the 4-wk run-in period were randomly allocated, in a double-blind, double-dummy manner to one of four treatment groups: (1) montelukast 10 mg plus continuing inhaled beclomethasone; (2) placebo tablet plus continuing inhaled beclomethasone; (3) montelukast 10 mg and inhaled placebo (after blind beclomethasone removal); and (4) placebo tablet and inhaled placebo (after blind beclomethasone removal). The primary endpoints were FEV(1) and daytime asthma symptoms score. Montelukast provided significant (p < 0.05) clinical benefit in addition to inhaled beclomethasone by improving FEV(1), daytime asthma symptom scores, and nocturnal awakenings. Blind removal of beclomethasone in the presence of placebo tablets caused worsening of asthma control, demonstrating that patients received clinical benefit from inhaled corticosteroids. Blind removal of beclomethasone in the presence of montelukast resulted in less asthma control but not to the level of the placebo group. All treatments were well tolerated; clinical and laboratory adverse experiences were generally similar to placebo treatment in this study. In conclusion, montelukast provided additional asthma control to patients benefitting from, but incompletely controlled on, inhaled beclomethasone.", "In a multicenter, randomized, double-blind study, inhaled beclomethasone dipropionate (BDP) 1,500 micrograms/day was compared to placebo in 43 chronic asthmatic patients uncontrolled by inhaled salbutamol and oral theophylline. During the prestudy period, a test of maximal steroid reversibility with oral prednisolone 0.5 mg/kg/day for 14 days was performed. The therapeutic response was measured over an 8-wk period as the ability to maintain the clinical improvement and the optimal pulmonary function induced by prednisolone. During the study, severe asthma exacerbation occurred in one (5%) of the 21 patients who received BDP and in 15 (78%) of the 22 patients who received placebo (p less than 0.001). In patients who received BDP, FEV1 and peak expiratory flow (PEF) remained above the optimal postprednisolone value, with a trend to improvement during the 8-wk study period. In patients who received placebo, FEV1 and PEF decreased and remained below the optimal value. We conclude that, in chronic asthma, inhaled BDP 1,500 micrograms/day maintains the optimal pulmonary function in addition to the clinical benefit induced by a short course of oral corticosteroids.", "nan", "We investigated the effects of long-term treatment with two anti-inflammatory drugs, nedocromil sodium and beclomethasone dipropionate, on airway hyperresponsiveness to methacholine (PC20), on baseline FEV1 and on the bronchodilating effect of a deep breath in 25 nonsteroid-dependent nonatopic asthmatic adults. In all subjects the prestudy PC20 was less than 8 mg/ml, the postbronchodilator FEV1 was greater than 75% predicted, and skin prick tests and RAST to 13 common allergens were negative. After 2 months run-in, the subjects were randomly allocated into 3 parallel treatment groups to inhale double-blind either 4 mg nedocromil (n = 9) or 100 micrograms beclomethasone (n = 8) or placebo (n = 8) 4 times daily for 4 months. PC20 was measured using the 2-min tidal breathing method. The effect of a deep breath was measured during methacholine-induced bronchoconstriction by standardized maximal and partial expiratory flow-volume curves and was expressed as a flow ratio (M/P ratio). Pretreatment values of FEV1, PC20, and M/P ratio were not different between the 3 groups. PC20 did not change in the placebo group, but increased significantly by a factor of 3 after 8 wk of treatment with beclomethasone or nedocromil (p less than 0.001). FEV1 did not change after treatment with placebo or nedocromil (p greater than 0.2), but increased (mean change 0.2 L, SD 0.2) after 4 wk of treatment with beclomethasone (p less than 0.05). Geometric mean M/P ratio increased from 1.98 to 2.66 after 4 wk of beclomethasone (p less than 0.01), but not after nedocromil or placebo.(ABSTRACT TRUNCATED AT 250 WORDS)" ]

[ "3512622", "354331", "4595192", "5030483", "354325", "7172160", "4994687", "504342", "4566123", "4608506" ]

[ "A controlled clinical trial of fluspirilene, a long-acting injectable neuroleptic, in schizophrenic patients with acute exacerbation.", "Double-blind therapeutic evaluation of fluspirilene compared with fluphenazine decanoate in chronic schizophrenics.", "[Results with the sustained-action neuroleptic fluspirilene on chronic schizophrenic patients undergoing occupational therapy].", "Fluspirilene and pipothiazine undecylenate, two long-acting injectable neuroleptics. A double-blind controlled trial in residual schizophrenia.", "A double-blind clinical evaluation of different dose intervals with fluspirilene (IMAP).", "A double-blind comparison of fluspirilene and fluphenazine decanoate in schizophrenia.", "A controlled study of fluspirilene in chronic schizophrenia.", "[A comparative study of the longacting neuroleptics perphenazin-enanthate and fluspirilene (author's transl)].", "A comparison of fluspirilene and trifluoperazine in the treatment of acute schizophrenic psychosis.", "A multicenter controlled trial of fluspirilene and fluphenazine enanthate in chronic schizophrenic syndromes." ]

[ "A 4-week double-blind controlled clinical trial was carried out in which fluspirilene, an injectable diphenylbutylpiperidine neuroleptic given weekly, was compared to chlorpromazine in the treatment of 40 newly admitted schizophrenic patients with acute exacerbation. Similar therapeutic improvement was obtained with both drugs, but men needed a significantly higher mean dose of fluspirilene (23 mg/week) than women (13 mg/week). Fluspirilene induced more parkinsonism than chlorpromazine, but less drowsiness, dizziness, and dry mouth. The difference between the sexes in the potency of fluspirilene and its greater potential to induce parkinsonism may be related to its lesser presynaptic and D1-dopamine receptor blocking properties. The low incidence of autonomic side effects confirms the relative specificity of fluspirilene for dopamine receptors.", "Fifty chronic schizophrenics were randomly assigned to a 16-week treatment either with fluspirilene or with fluphenazine decanoate. The aim of the study was to compare the antipsychotic action and the side effects of the two neuroleptics. Fluphenazine decanoate caused more side effects and the difference between the two groups was statistically significant in the items tremor, severe extrapyramidal effects and parkinsonism. More patients in the fluspirilene group (nine patients) compared with only three in the fluphenazine decanoate group remained free of side effects during the whole trial. Judged from the BPRS fluspirilene proved an equally potent neuroleptic with fluphenazine decanoate although statistically significant improvement has been obtained in more items of the scale in the fluspirilene group. The improvement in the NOSIE-30 was much more clear in the fluspirilene group. Although Clinical Global Impressions of the investigators and the nursing personnel favored fluspirilene, the differences between the two groups were not statistically significant.", "nan", "nan", "The possibility of a biweekly dose of fluspirilene, without deterioration of the clinical picture, was investigated in a group of 34 chronic schizophrenic patients. There were no significant clinical difference between the patients receiving fluspirilene every week and the patients receiving it every two weeks. Therefore it is possible to give fluspirilene in individually adjusted doses with a dose interval of 14 days in stabilized patients.", "A double-blind comparison of fluspirilene and fluphenazine decanoate in 28 schizophrenic patients over six months showed equal improvement and the same incidence of side-effects in each group of patients. It would be expected from the literature that a better ratio of therapeutic to side-effects would appear with fluspirilene than with fluphenazine. The absence of such an effect in this study may be attributable to an initial lack of familiarity by the investigators with the use of fluspirilene, indicating an important potential variable in the comparison of a new drug with an established one.", "nan", "The clinical profile and side-effects of perphenazin-enanthate and fluspirilene were compared in 45 female chronic schizophrenic patients. 100 mg perphenazin-enanthate fortnightly or 8 mg fluspirilene weekly were administered. During the four months' period the psychopathological and somatic symptoms were evaluated by means of the AMP-system and the self-evaluation scale PD-S (v. Zerssen). A covariance analysis was carried out covering 12 AMP syndromes and 6 PD-S factors. The antipsychotic effect of both drugs was similar concerning the paranoid, the hallucinatory-desintegrative and the catatonic syndromes. A significant difference with regard to perphenazin-enanthate was found in the AMP-syndromes of hostility, hypochondria, and autonomic symptoms. Neither drug induced any depression. In the self-rating scale, the factors anxiousness and depressivity were also significantly lower in the perphenazin-enanthate regime. The patients under perphenazin-enanthate required a smaller amount of antiparkinsonian drugs. The more pronounced sedative effect of perphenazin-enanthate can be recommended in hostile and restless schizophrenic patients, whereas fluspirilene should be given to inactive autistic patients.", "nan", "nan" ]

[ "7734010", "15562202", "8708586", "15514192", "7671358", "18997196", "17726081", "12809960", "9613910", "9070554", "17384434", "16801565", "15325833", "9003110" ]

[ "Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group.", "Two-year statin therapy does not alter the progression of intima-media thickness in patients with type 2 diabetes without manifest cardiovascular disease.", "Changes in cardiovascular risk factors by combined pharmacological and nonpharmacological strategies: the main results of the CELL Study.", "Different effects of antihypertensive regimens based on fosinopril or hydrochlorothiazide with or without lipid lowering by pravastatin on progression of asymptomatic carotid atherosclerosis: principal results of PHYLLIS--a randomized double-blind trial.", "Kuopio Atherosclerosis Prevention Study (KAPS). A population-based primary preventive trial of the effect of LDL lowering on atherosclerotic progression in carotid and femoral arteries.", "Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.", "Effects of atorvastatin on bone in postmenopausal women with dyslipidemia: a double-blind, placebo-controlled, dose-ranging trial.", "Randomized, double-blind, placebo-controlled comparison of the action of orlistat, fluvastatin, or both an anthropometric measurements, blood pressure, and lipid profile in obese patients with hypercholesterolemia prescribed a standardized diet.", "Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study.", "Baseline risk factors and their association with outcome in the West of Scotland Coronary Prevention Study. The West of Scotland Coronary Prevention Study Group.", "Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR Trial.", "Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in non-insulin-dependent diabetes mellitus (ASPEN).", "Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial.", "Pravastatin reduces carotid intima-media thickness progression in an asymptomatic hypercholesterolemic mediterranean population: the Carotid Atherosclerosis Italian Ultrasound Study." ]

[ "HMG CoA reductase inhibitors (or statins), a new class of lipid-lowering compounds, have raised expectations for more widespread use than that of the older lipid-lowering drugs. Not only are they more effective in lowering LDL cholesterol, but they are better tolerated as well. No data exist concerning the effect of statins on early carotid atherosclerosis and clinical events in men and women who have moderately elevated LDL cholesterol levels but are free of symptomatic cardiovascular disease.\n Lovastatin (20 to 40 mg/d) or its placebo was evaluated in a double-blind, randomized clinical trial with factorial design along with warfarin (1 mg/d) or its placebo. This report is limited to the lovastatin component of the trial. Daily aspirin (81 mg/d) was recommended for everyone. Enrollment included 919 asymptomatic men and women, 40 to 79 years old, with early carotid atherosclerosis as defined by B-mode ultrasonography and LDL cholesterol between the 60th and 90th percentiles. The 3-year change in mean maximum intimal-medial thickness (IMT) in 12 walls of the carotid arteries was the primary outcome; change in single maximum IMT and incidence of major cardiovascular events were secondary outcomes. LDL cholesterol fell 28%, from 156.6 mg/dL at baseline to 113.1 mg/dL at 6 months (P < .0001), in the lovastatin groups and was largely unchanged in the lovastatin-placebo groups. Among participants not on warfarin, regression of the mean maximum IMT was seen after 12 months in the lovastatin group compared with the placebo group; the 3-year difference was statistically significant (P = .001). A larger favorable effect of lovastatin was observed for the change in single maximum IMT but was not statistically significant (P = .12). Five lovastatin-treated participants suffered major cardiovascular events--coronary heart disease mortality, nonfatal myocardial infarction, or stroke--versus 14 in the lovastatin-placebo groups (P = .04). One lovastatin-treated participant died, compared with eight on lovastatin-placebo (P = .02).\n In men and women with moderately elevated LDL cholesterol, lovastatin reverses progression of IMT in the carotid arteries and appears to reduce the risk of major cardiovascular events and mortality. Results from ongoing large-scale clinical trials may further establish the clinical benefit of statins.", "Cardiovascular disease (CVD) is the most important cause of mortality in patients with type 2 diabetes. We aimed to determine the effect of statin therapy versus placebo on the progression of carotid intima-media thickness (IMT) in type 2 diabetic patients without manifest CVD.\n A randomized, placebo-controlled, double-blind clinical trial was performed in 250 patients with type 2 diabetes. Patients were given either 0.4 mg cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn from the market, 0.4 mg cerivastatin was replaced by 20 mg simvastatin without deblinding the study. The primary end point was the change of mean common carotid IMT, as measured by B-mode ultrasound, over 2 years.\n Common carotid IMT at baseline was 0.780 mm in the placebo group and 0.763 mm in the statin group and did not change significantly after 2 years. There was no significant difference in IMT change in any carotid segment between the groups. LDL cholesterol was reduced by 25% in the statin group and increased by 8% in the placebo group (P <0.001). Cardiovascular events occurred in 12 patients in the placebo group and two patients in the statin group (P=0.006).\n There was no effect of 2 years' statin therapy on carotid IMT in type 2 diabetic subjects. The natural history of IMT in our patients was milder than anticipated. In contrast, we observed a significantly lower cardiovascular event rate on statin therapy. Prognostic tools other than IMT should be explored in this patient group.", "The objectives of the Cost Effectiveness of Lipid Lowering (CELL) study were twofold: (i) to evaluate the effect on overall cardiovascular risk of two types of health care advice (\"usual' and \"intensive') given in primary care, with or without pharmacological medication, with the target being to attain a moderate decrease in cholesterol; (ii) to evaluate the ritual of daily medication on compliance with the health care advice.\n A prospective, double-blind, randomized, controlled trial of 18 months' duration.\n The study was carried out in 32 health centres (out of a total of approximately 850) in Sweden.\n In all, 681 subjects, aged 30-59 years, were randomized. They had at least two cardiovascular risk factors in addition to moderate primary hyperlipidaemia (total cholesterol of at least 6.50 mmol L-1 on three occasions measured by Reflotron triglycerides less than 4.0 mmol L-1 and an LDL:HDL cholesterol ratio of more than 4.0). Most (87%) of the subjects were males; 626 subjects (92%) completed the 18-month follow-up.\n Half the subjects were randomized to 'intensive advice' given in group sessions led by doctors and nurses in primary care. The other half received 'usual advice'. In each of the two advice groups, one-third received an active lipid-lowering drug (pravastatin), one-third placebo, and one-third no drug at all. The tablets were titrated to achieve a 15% reduction in cholesterol.\n Changes in the overall Framingham risk score, and the development of adverse events in each group.\n The change in Framingham risk score was significantly reduced only in subjects taking lipid-lowering medication (together with intensive advice -0.13; 95% CI-0.20, -0.06, and together with usual advice -0.16; 95% CI -0.23, -0.09). The other subjects receiving intensive advice tended to fare better than those on usual advice. Lifestyle was not influenced significantly over the study period. The ritual of daily medication did not affect the outcome.\n As expected, lipid-lowering medication reduced serum cholesterol as well as overall cardiovascular risk in subjects with several risk factors for cardiovascular disease. There was no additive effect of intensive advice to these subjects. However, there was a meagre but significant effect of intensive advice in subjects not receiving active lipid-lowering drugs. One explanation for this difference may be that those on active lipid-lowering medication who had substantial drops in cholesterol might have felt less inclined to change their lifestyle compared with those on other treatment regimens who had less successful drops in cholesterol. There was no benefit from the ritual of taking daily medication.", "The Plaque Hypertension Lipid-Lowering Italian Study (PHYLLIS) tested whether (1) the angiotensin-converting enzyme (ACE) inhibitor fosinopril (20 mg per day) was more effective on carotid atherosclerosis progression than the diuretic hydrochlorothiazide (25 mg per day), (2) pravastatin (40 mg per day) was more effective than placebo when added to either hydrochlorothiazide or fosinopril, and (3) there were additive effects of ACE inhibitor and lipid-lowering therapies.\n A total of 508 hypertensive, hypercholesterolemic patients with asymptomatic carotid atherosclerosis were randomized to: (A) hydrochlorothiazide; (B) fosinopril; (C) hydrochlorothiazide plus pravastatin; and (D) fosinopril plus pravastatin, and followed up blindly for 2.6 years. B-Mode carotid scans were performed yearly by certified sonographers in 13 hospitals and read centrally. Corrections for drift were calculated from readings repeated at study end. Primary outcome was change in mean maximum intima-media thickness of far and near walls of common carotids and bifurcations bilaterally (CBM(max)).\n CBM(max) significantly progressed (0.010+/-0.004 mm per year; P=0.01) in group A (hydrochlorothiazide alone) but not in groups B, C, and D. CBM(max) changes in groups B, C, and D were significantly different from changes in group A. Changes in group A were concentrated at the bifurcations. \"Clinic\" and \"ambulatory\" blood pressure reductions were not significantly different between groups, but total and low-density lipoprotein cholesterol decreased by approximately 1 mmol/L in groups C and D.\n Progression of carotid atherosclerosis occurred with hydrochlorothiazide but not with fosinopril. Progression could also be avoided by associating pravastatin with hydrochlorothiazide.", "The atherosclerotic progression-reducing effect of LDL cholesterol (LDL-C) lowering has been established in subjects with severe atherosclerotic disease but not in persons with elevated LDL cholesterols without severe atherosclerosis. KAPS (Kuopio Atherosclerosis Prevention Study) is the first population-based trial in the primary prevention of carotid and femoral atherosclerosis.\n The eligibility requirements were serum LDL-C > or = 4.0 mmol/L and total cholesterol < 7.5 mmol/L. Out of a geographically defined population, 447 men aged 44 to 65 years (mean, 57) were randomized to pravastatin (40 mg/d) or placebo for 3 years. Less than 10% of the subjects had prior myocardial infarction. Thirty-nine men discontinued study medication; however, efficacy data were available for 424 men. The primary outcome was the rate of carotid atherosclerotic progression, measured as the linear slope over annual ultrasound examinations in the average of the maximum carotid intima-media thickness (IMT) of the far wall of up to four arterial segments (the right and left distal common carotid artery and the right and left carotid bulb). For the carotid arteries, at the overall mean baseline IMT of 1.66 mm, the rate of progression of carotid atherosclerosis was 45% (95% CI, 16 to 69%) less in the pravastatin (0.017 mm/y) than the placebo (0.031 mm/y) group (P = .005). In the common carotid artery there was a treatment effect of 66% (95% CI, 30 to 95%; pravastatin 0.010 mm/y; placebo 0.029 mm/y; P < .002) at the overall mean baseline IMT of 1.35 mm. A treatment effect of 30% (95% CI, -1% to 54%) was found for the carotid bulb (pravastatin, 0.028; placebo, 0.040; P = .056) at the overall mean baseline IMT of 2.0 mm. The treatment effect was larger in subjects with higher baseline IMT values, in smokers and in those with low plasma vitamin E levels. There was no significant treatment effect on atherosclerotic progression in the femoral arteries.\n These data establish the antiatherogenic effect of LDL-C lowering by pravastatin in hypercholesterolemic men in a primary prevention setting and suggest a greater effect in smokers than in nonsmokers.", "Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment.\n We randomly assigned 17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin, 20 mg daily, or placebo and followed them for the occurrence of the combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes.\n The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P<0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P=0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P=0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P=0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes.\n In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events. (ClinicalTrials.gov number, NCT00239681.)\n 2008 Massachusetts Medical Society", "In preclinical models, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase have been shown to positively affect bone remodeling balance. Observational studies and secondary analyses from lipid-lowering trials have yielded inconsistent results regarding the effect of these agents on bone mineral density and fracture risk.\n Our objective was to determine whether clinically significant skeletal benefits result from hydroxymethylglutaryl-coenzyme A reductase inhibition in postmenopausal women.\n We conducted a prospective, randomized, double-blind, placebo-controlled, dose-ranging comparative clinical trial at 62 sites in the United States.\n Participants included 626 postmenopausal women with low-density lipoprotein cholesterol levels of at least 130 mg/dl (3.4 mmol/liter) and less than 190 mg/dl (4.9 mmol/liter), and lumbar (L1-L4) spine bone mineral density T-score between 0.0 and -2.5.\n Once-daily placebo or 10, 20, 40, or 80 mg atorvastatin was administered.\n We assessed percent change from baseline in lumbar (L1-L4) spine bone mineral density with each dose of atorvastatin compared with placebo.\n At 52 wk, there was no significant difference between each atorvastatin and placebo group or change from baseline at any tested dose of atorvastatin or placebo in lumbar (L1-L4) spine bone mineral density. Nor did atorvastatin produce a significant change in bone mineral density at any other site. Changes in biochemical markers of bone turnover did not differ significantly between each atorvastatin and placebo group. All doses of atorvastatin were generally well tolerated, with similar incidences of adverse events across all dose groups and placebo.\n Clinically relevant doses of atorvastatin that lower lipid levels had no effect on bone mineral density or biochemical indices of bone metabolism in this study, suggesting that such oral agents are not useful in the prevention or treatment of osteoporosis.", "The aim of this study was to assess obese patients with hypercholesterolemia whom were prescribed a standardized diet, comparing the action of orlistat, fluvastatin, orlistat with fluvastatin, and placebo on anthropometric measurements, blood pressure (BP), and lipid profile.\n This was a 1-year, randomized, double-blind, placebo-controlled trial. The patients were prescribed a controlled-energy diet and were randomly allocated to receive placebo, orlistat 120 mg TID (O group), fluvastatin 80 mg/d (F group), or olistat 120 mg TID with fluvastatin 80 mg/d (OF group). Clinical measurements (body weight, body mass index [BMI], waist circumference, and BP) and lipid profile assessment (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides [TGs]) were performed at baseline and after 6 months and 1 year of treatment.\n The study included 99 obese patients with hypercholesterolemia (48 men and 51 women; mean [SD] age, 51 [9] years). There were no significant differences between groups in baseline demographic, BP, or plasma lipid values. Three patients dropped out (2 women in the O group and 1 man in the OF group) due to adverse events related to orlistat treatment, including gastrointestinal events (oily spotting and fecal urgency). Ninety-six patients completed the study. There were significant differences from baseline (mean [SD]) in BMI, waist circumference reduction (WCR), and body weight loss (BWL) at 6 months in the OF group (29.9 [1.1] kg/m(2), 2.7 [0.8] cm, and 7.4 [0.9] kg, respectively; all P < 0.05), and BMI, WCR, and BWL at 1 year in the O group (29.0 [1.0] kg/m(2), 3.0 [1.0] cm, and 8.6 [1.0] kg, respectively; all P < 0.02), the F group (29.3 [1.6] kg/m(2), 2.4 [1.0] cm, and 8/0 [1.0] kg, respectively; all P < 0.05), and the OF group (28.4 [0.6] kg/m(2), 4.0 [0.6] cm, and 11.4 [1.0] kg, respectively; all P < 0.01). Significant reductions from baseline in systolic and diastolic BP were observed at 1 year in the O and F groups (all P < 0.05) and the OF group (both P < 0.01). At 6 months, there were significant reductions from baseline in TC and LDL-C in the F group (both P < 0.05) and in TC, LDL-C, and TGs in the OF group (P < 0.02, P < 0.02, and P < 0.05, respectively), as well as a significant increase in HDL-C in the OF group (P < 0.02). At 1 year, there were significant reduction from baseline in TC in the O, F, and OF groups (P < 0.05 and P < 0.01, respectively), LDL-C (P < 0.05, P < 0.02, and P < 0.01, respectively), and TGs (P < 0.02, P < 0.05, and P < 0.02, respectively). Also at 1 year, HDL-C was significantly higher than baseline in the F and OF groups (P < 0.02 and P < 0.01, respectively).\n Improvements in clinical and lipid-profile parameters were found at 1 year with all 3 treatments.", "Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease (CHD), it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol (LDL-C) in patients without CHD extends to individuals with average serum cholesterol levels, women, and older persons.\n To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levels.\n A randomized, double-blind, placebo-controlled trial.\n Outpatient clinics in Texas.\n A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) mmol/L (221 [21] mg/dL) (51 st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women (25th and 16th percentiles, respectively), and median (SD) triglyceride levels were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile).\n Lovastatin (20-40 mg daily) or placebo in addition to a low-saturated fat, low-cholesterol diet.\n First acute major coronary event defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death.\n After an average follow-up of 5.2 years, lovastatin reduced the incidence of first acute major coronary events (1 83 vs 116 first events; relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79; P<.001), myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI, 0.43-0.83; P=.002), unstable angina (87 vs 60 first unstable angina events; RR, 0.68; 95% CI, 0.49-0.95; P=.02), coronary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95% CI, 0.52-0.85; P=.001), coronary events (215 vs 163 coronary events; RR, 0.75; 95% CI, 0.61-0.92; P =.006), and cardiovascular events (255 vs 194 cardiovascular events; RR, 0.75; 95% CI, 0.62-0.91; P = .003). Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL). There were no clinically relevant differences in safety parameters between treatment groups.\n Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assessment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.", "The West of Scotland Coronary Prevention Study recently demonstrated the benefits of pravastatin therapy in the prevention of coronary heart disease events in middle-aged hypercholesterolemic men without prior myocardial infarction. We present an analysis of the influence of baseline risk factors on coronary events and total mortality in the trial, and their interaction with therapy, using the Cox proportional hazards model. The multivariate predictors of fatal or nonfatal coronary events were treatment allocation (pravastatin or placebo), current smoking, diabetes mellitus, nitrate consumption, minor electrocardiographic abnormalities, angina pectoris, family history of premature coronary death, widowhood, blood pressure, and total cholesterol/high density lipoprotein cholesterol ratio. Independent of other risk factors, pravastatin reduced the risk of definite coronary heart disease death or nonfatal myocardial infarction by 32% (95% confidence interval 17 to 44, p = 0.0001), definite or suspected coronary heart disease death by 35% (3 to 56, p = 0.035), cardiovascular death by 33% (4 to 53, p = 0.027), coronary revascularization procedures by 38% (11 to 56, p = 0.009), and all-cause mortality by 24% (2 to 41, p = 0.037). The 5-year risk of fatal or nonfatal myocardial infarction, calculated using the predictors identified in the Cox analysis, ranged from <4.4% in the lowest quartile of risk to >9.6% in the highest quartile. The proportional benefit achieved by pravastatin was independent of other risk factors; hence, the absolute benefit of therapy was greatest in subjects with the highest baseline risk. Such subjects can be identified easily in the population and deserve high priority for treatment.", "Atherosclerosis is often advanced before symptoms appear and it is not clear whether treatment is beneficial in middle-aged individuals with a low Framingham risk score (FRS) and mild to moderate subclinical atherosclerosis.\n To assess whether statin therapy could slow progression and/or cause regression of carotid intima-media thickness (CIMT) over 2 years.\n Randomized, double-blind, placebo-controlled study (Measuring Effects on Intima-Media Thickness: an Evaluation of Rosuvastatin [METEOR]) of 984 individuals, with either age (mean, 57 years) as the only coronary heart disease risk factor or a 10-year FRS of less than 10%, modest CIMT thickening (1.2-<3.5 mm), and elevated LDL cholesterol (mean, 154 mg/dL); conducted at 61 primary care centers in the United States and Europe between August 2002 and May 2006.\n Participants received either a 40-mg dose of rosuvastatin or placebo.\n Rate of change in maximum CIMT (assessed with B-mode ultrasound) for 12 carotid sites; changes in maximum CIMT of the common carotid artery, carotid bulb, and internal carotid artery sites and in mean CIMT of the common carotid artery sites. CIMT regression was assessed in the rosuvastatin group only.\n Among participants in the rosuvastatin group, the mean (SD) baseline LDL cholesterol level of 155 (24.1) mg/dL declined to 78 (27.5) mg/dL, a mean reduction of 49% (P<.001 vs placebo group). The change in maximum CIMT for the 12 carotid sites was -0.0014 (95% CI, -0.0041 to 0.0014) mm/y for the rosuvastatin group vs 0.0131 (95% CI, 0.0087-0.0174) mm/y for the placebo group (P<.001). The change in maximum CIMT for the rosuvastatin group was -0.0038 (95% CI, -0.0064 to -0.0013) mm/y for the common carotid artery sites (P<.001), -0.0040 (95% CI, -0.0090 to 0.0010) mm/y for the carotid bulb sites (P<.001), and 0.0039 (95% CI, -0.0009 to 0.0088) mm/y for the internal carotid artery sites (P = .02). The change in mean CIMT for the rosuvastatin group for the common carotid artery sites was 0.0004 (95% CI, -0.0011 to 0.0019) mm/y (P<.001). All P values are vs placebo group. Overall, rosuvastatin was well tolerated with infrequent serious adverse cardiovascular events (6 participants [0.86%] had 8 events [1.1%] over 2 years).\n In middle-aged adults with an FRS of less than 10% and evidence of subclinical atherosclerosis, rosuvastatin resulted in statistically significant reductions in the rate of progression of maximum CIMT over 2 years vs placebo. Rosuvastatin did not induce disease regression. Larger, longer-term trials are needed to determine the clinical implications of these findings.\n clinicaltrials.gov Identifier: NCT00225589", "Cardiovascular disease (CVD) risk is increased in type 2 diabetes. The purpose of this study was to assess the effect of 10 mg of atorvastatin versus placebo on CVD prevention in subjects with type 2 diabetes and LDL cholesterol levels below contemporary guideline targets.\n Subjects were randomly assigned to receive 10 mg of atorvastatin or placebo in a 4-year, double-blind, parallel-group study. The composite primary end point comprised cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, recanalization, coronary artery bypass surgery, resuscitated cardiac arrest, and worsening or unstable angina requiring hospitalization.\n A total of 2,410 subjects with type 2 diabetes were randomized. Mean LDL cholesterol reduction in the atorvastatin group over 4 years was 29% versus placebo (P < 0.0001). When we compared atorvastatin versus placebo, composite primary end point rates were 13.7 and 15.0%, respectively (hazard ratio 0.90 [95% CI 0.73-1.12]). In the subset of 1,905 subjects without prior myocardial infarction or interventional procedure, 10.4% of atorvastatin- and 10.8% of placebo-treated subjects experienced a primary end point (0.97 [0.74-1.28]). In the 505 subjects with prior myocardial infarction or interventional procedure, 26.2% of atorvastatin- and 30.8% of placebo-treated subjects experienced a primary end point (0.82 [0.59-1.15]). Relative risk reductions in fatal and nonfatal myocardial infarction were 27% overall (P = 0.10) and 19% (P = 0.41) and 36% (P = 0.11) for subjects without and with prior myocardial infarction or interventional procedure, respectively.\n Composite end point reductions were not statistically significant. This result may relate to the overall study design, the types of subjects recruited, the nature of the primary end point, and the protocol changes required because of changing treatment guidelines. For these reasons, the results of the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN) did not confirm the benefit of therapy but do not detract from the imperative that the majority of diabetic patients are at risk of coronary heart disease and deserve LDL cholesterol lowering to the currently recommended targets.", "Type 2 diabetes is associated with a substantially increased risk of cardiovascular disease, but the role of lipid-lowering therapy with statins for the primary prevention of cardiovascular disease in diabetes is inadequately defined. We aimed to assess the effectiveness of atorvastatin 10 mg daily for primary prevention of major cardiovascular events in patients with type 2 diabetes without high concentrations of LDL-cholesterol.\n 2838 patients aged 40-75 years in 132 centres in the UK and Ireland were randomised to placebo (n=1410) or atorvastatin 10 mg daily (n=1428). Study entrants had no documented previous history of cardiovascular disease, an LDL-cholesterol concentration of 4.14 mmol/L or lower, a fasting triglyceride amount of 6.78 mmol/L or less, and at least one of the following: retinopathy, albuminuria, current smoking, or hypertension. The primary endpoint was time to first occurrence of the following: acute coronary heart disease events, coronary revascularisation, or stroke. Analysis was by intention to treat.\n The trial was terminated 2 years earlier than expected because the prespecified early stopping rule for efficacy had been met. Median duration of follow-up was 3.9 years (IQR 3.0-4.7). 127 patients allocated placebo (2.46 per 100 person-years at risk) and 83 allocated atorvastatin (1.54 per 100 person-years at risk) had at least one major cardiovascular event (rate reduction 37% [95% CI -52 to -17], p=0.001). Treatment would be expected to prevent at least 37 major vascular events per 1000 such people treated for 4 years. Assessed separately, acute coronary heart disease events were reduced by 36% (-55 to -9), coronary revascularisations by 31% (-59 to 16), and rate of stroke by 48% (-69 to -11). Atorvastatin reduced the death rate by 27% (-48 to 1, p=0.059). No excess of adverse events was noted in the atorvastatin group.\n Atorvastatin 10 mg daily is safe and efficacious in reducing the risk of first cardiovascular disease events, including stroke, in patients with type 2 diabetes without high LDL-cholesterol. No justification is available for having a particular threshold level of LDL-cholesterol as the sole arbiter of which patients with type 2 diabetes should receive statins. The debate about whether all people with this disorder warrant statin treatment should now focus on whether any patients are at sufficiently low risk for this treatment to be withheld.", "The Carotid Atherosclerosis Italian Ultrasound Study (CAIUS) was performed to test the effects of lipid lowering on the progression of carotid intima-media thickness (IMT) in 305 asymptomatic patients from a Mediterranean country.\n Eligibility included hypercholesterolemia (baseline means: low-density lipoprotein [LDL] = 4.68 mmol/L, high-density lipoprotein [HDL] = 1.37 mmol/L), and at least one 1.3 < IMT < 3.5 mm in the carotid arteries. Patients (mean age 55 years, 53% male) were assigned to pravastatin (40 mg/day, n = 151) or placebo (n not equal to 154). Ultrasound imaging was used to quantify IMT at baseline, and semiannually thereafter for up to 3 years. The mean of the 12 maximum IMTs (MMaxIMT), was calculated for each patient visit, and used to determine each patient's longitudinal progression slope. The intention-to-treat group difference in the MMaxIMT progression was chosen a priori as the primary end point.\n Five serious cardiovascular events (1 fatal myocardial infarction), and 7 drop-outs for cancer were registered. In the pravastatin group, LDL decreased -0.22 after 3 months versus -0.01 in the placebo group, and remained substantially unchanged afterward (-0.23 versus +0.01 at 36 months, respectively). Progression of the MMaxIMT was 0.009 +/- 0.0027 versus -0.0043 +/- 0.0028 mm/year (mean +/- SE, P < 0.0007) in the placebo and pravastatin groups, respectively. IMT progression slopes diverged after 6 months of treatment.\n Pravastatin stops the progression of carotid IMT in asymptomatic, moderately hypercholesterolemic men and women. This finding extends the beneficial effects of cholesterol lowering to the primary prevention of atherosclerosis in a population with relatively low cardiovascular event rates, and suggests that this benefit is mediated by specific morphological effects on early stages of plaque development." ]

[ "17443749", "10955337", "15940775", "9858441" ]

[ "Physical activity for osteoarthritis management: a randomized controlled clinical trial evaluating hydrotherapy or Tai Chi classes.", "The effects of a health educational and exercise program for older adults with osteoarthritis for the hip or knee.", "The effects of an exercise program for older adults with osteoarthritis of the hip.", "The effectiveness of exercise therapy in patients with osteoarthritis of the hip or knee: a randomized clinical trial." ]

[ "To determine whether Tai Chi or hydrotherapy classes for individuals with chronic symptomatic hip or knee osteoarthritis (OA) result in measurable clinical benefits.\n A randomized controlled trial was conducted among 152 older persons with chronic symptomatic hip or knee OA. Participants were randomly allocated for 12 weeks to hydrotherapy classes (n = 55), Tai Chi classes (n = 56), or a waiting list control group (n = 41). Outcomes were assessed 12 and 24 weeks after randomization and included pain and physical function (Western Ontario and McMaster Universities Osteoarthritis Index), general health status (Medical Outcomes Study Short Form 12 Health Survey [SF-12], version 2), psychological well-being, and physical performance (Up and Go test, 50-foot walk time, timed stair climb).\n At 12 weeks, compared with controls, participants allocated to hydrotherapy classes demonstrated mean improvements (95% confidence interval) of 6.5 (0.4, 12.7) and 10.5 (3.6, 14.5) for pain and physical function scores (range 0-100), respectively, whereas participants allocated to Tai Chi classes demonstrated improvements of 5.2 (-0.8, 11.1) and 9.7 (2.8, 16.7), respectively. Both class allocations achieved significant improvements in the SF-12 physical component summary score, but only allocation to hydrotherapy achieved significant improvements in the physical performance measures. All significant improvements were sustained at 24 weeks. In this almost exclusively white sample, class attendance was higher for hydrotherapy, with 81% attending at least half of the available 24 classes, compared with 61% for Tai Chi.\n Access to either hydrotherapy or Tai Chi classes can provide large and sustained improvements in physical function for many older, sedentary individuals with chronic hip or knee OA.", "Evaluation of a self-management program for patients with osteoarthritis (OA) of the hip or knee. The program, which consisted of 6 weekly sessions of 2 hours, included health education by a peer and physical exercises taught by a physical therapist.\n Randomized controlled trial. Inclusion criteria were diagnosis of OA of the hip or knee according to ACR clinical and radiographic criteria and age 55 to 75 years. Exclusion criteria: on waiting list for joint replacement. There were pretest, posttest, and followup (6 months) assessments. The experimental group consisted of 56 patients, the control group 49. Outcome variables were pain, quality of life, activity restrictions, knowledge about OA, self-efficacy, body mass index (BMI), and mobility measures. Attention was also paid to effects on health care utilization and lifestyle behavior.\n Significant MANOVA group x time effects (p < 0.05, one-sided) were found for pain, quality of life, strength of the left M. quadriceps, knowledge, self-efficacy, BMI, physically active lifestyle, and visits to the physical therapist. Most effects were moderate at posttest assessment and smaller at followup. No effects were found for range of motion and functional tasks.\n The program was reasonably effective, but more attention should be paid to proactive followup interventions and to the selection of participants.", ". Evaluation of an 8-week exercise program with strength training and lifestyle advice for older adults with osteoarthritis (OA) of the hip. Outcome measures were pain, hip function, disability, quality of life (QOL), and body mass index (BMI).\n Inclusion criteria for this randomized controlled trial were: age >or=55 years, clinical diagnosis of OA according to American College of Rheumatology criteria, and living independently. Interview and physical data were collected at baseline, post-test, and followup (3 mo) by trained interviewers and physical therapists with validated instruments: Harris Hip Score, Sickness Impact Profile, Groningen Activity Restriction Scale, functional tests (walking, timed Up & Go, ascending and descending stairs, and toe reaching), and visual analog scales (pain and QOL). Data were analyzed on an intention-to-treat basis. Effect sizes were calculated.\n There were 109 participants (55 experimental, 54 controls). The 15 participants who dropped out were characterized by less tolerance to pain and younger age. The program had a positive effect on pain (moderate effect at post-test and small effect at followup), hip function (small effect at post-test), self-reported disability (small effect at followup), and the timed Up & Go test (small effect at followup). It did not affect QOL, other measures of observed disability, or BMI.\n The exercise program had positive effects on pain and hip function, which are important mediators of disability. This study fulfilled a need for older adults with hip OA and provides evidence of the benefit of exercise in the management of hip OA.", "To determine the effectiveness of exercise therapy in patients with osteoarthritis (OA) of the hip or knee.\n A randomized single blind, clinical trial was conducted in a primary care setting. Patients with hip or knee OA by American College of Rheumatology criteria were selected. Two intervention groups were compared. Both groups received treatment from the patients' general practitioner, including patient education and medication if necessary. The experimental group also received exercise therapy from a physiotherapist in primary care. The treatment period was 12 weeks. The main outcome measures were pain, medication use (nonsteroidal antiinflammatory drugs, NSAID) and observed disability.\n A total of 201 patients were randomized. Exercise therapy was associated with a reduction of pain in the past week (difference in change -17.0; 95% CI -23.6, -10.4) and observed disability (-0.19; 95% CI -0.38; -0.01). Effect sizes were medium (0.58) and small (0.28), respectively. No effect of exercise therapy was found for the use of NSAID. Additional beneficial effects (p = 0.05) were found for the use of paracetamol (effect size 0.33), global effect as perceived by the patient (effect size 0.68), and muscle strength of the hip (effect size 0.34).\n After 12 weeks, exercise therapy is effective in reducing pain and disability. The size of the effects is medium and small, respectively." ]

[ "15735462", "17262145", "19893466", "19840635", "16674744", "20102063", "277627", "14977302", "21187618", "6955420", "14600693" ]

[ "Effect of MTAD on postoperative discomfort: a randomized clinical trial.", "Influence of sodium hypochlorite-based irrigants on the susceptibility of intracanal microbiota to biomechanical preparation.", "Effect of sodium hypochlorite with the addition of a proteolytic enzyme on postoperative discomfort: a multicenter randomized clinical trial.", "Antibacterial efficacy of MTAD final rinse and two percent chlorhexidine gel medication in teeth with apical periodontitis: a randomized double-blinded clinical trial.", "In vivo evaluation of microbial reduction after chemo-mechanical preparation of human root canals containing necrotic pulp tissue.", "Antimicrobial effect of 0.2% chlorhexidine in infected root canals.", "Analysis of clinical toxicity of endodontic irrigants.", "Antibacterial activity of 2% chlorhexidine gluconate and 5.25% sodium hypochlorite in infected root canal: in vivo study.", "Comparison of 2% chlorhexidine and 5.25% sodium hypochlorite irrigating solutions on postoperative pain: a randomized clinical trial.", "In vivo evaluation of chlorhexidine gluconate solution and sodium hypochlorite solution as root canal irrigants.", "The effect of chlorhexidine as an endodontic disinfectant." ]

[ "The purpose of this study was to compare levels of postoperative discomfort after cleaning and shaping of root canals using two protocols for removal of smear layer. Seventy-three consecutive patients requiring root canal treatment were included. At random, canals were cleaned and shaped with one of the following protocols. In group 1, 5.25% sodium hypochlorite was used as the root canal irrigant. The smear layer was removed by placing 17% EDTA in the canal(s) for 1 min followed by a 5-ml rinse with 5.25% NaOCl. In group 2, canals were irrigated with 1.3% NaOCl; the smear layer was removed by placing MTAD in the canal(s) for 5 min. Access cavities were closed with a sterile cotton pellet and Cavit. The patients recorded degree of discomfort at various time intervals after cleaning and shaping on a visual analogue scale for 1 wk. No significant statistical difference was found in the degree of discomfort between the two groups (p = 0.58).", "This study evaluated the microbiological conditions of root canals, using smears and culture from anterior teeth and premolars with necrotic pulps associated with chronic periapical pathologies, before and after biomechanical preparation (BMP). During double-flared instrumentation, 1, 2.5 and 5% sodium hypochlorite (NaOCl)-based irrigants were used in 3 groups: GI (n=39), GII (n=36) and GIII (n=36), respectively. Before BMP, all cultures were positive and the smears showed microbiologically diverse morphotypes, including fusiforms, pleomorphic, rods, cocci and filaments. Quantitatively, 20, 20 and 23 morphotypes were identified in GI, GII and GIII, respectively). After BMP, the percentages of negative cultures in GI, GII and GIII were 74.2%, 86.3% and 93.4% (p>0.05) and the number of morphotypes decreased to 14, 15 and 5, respectively. All teeth with 2 root canals and/or associated fistulas were microbiologically negative after BMP, regardless of irrigant concentration. Gram-negative morphotypes were more susceptible to the action of irrigants. After irrigation with 5% NaOCl, only structural arrangements consisting of Gram-positive cocci and bacilli persisted. Thus, BMP plus 5% NaOCl offered the best antiseptic potential because in the few positive cultures a significant reduction in the number of microbiological morphotypes was also shown (p<0.05).", "The purpose of this study was to compare the patient's postoperative discomfort when root canal irrigation was performed either with standard sodium hypochlorite or with sodium hypochlorite with the adjunct of a proteolytic enzyme.\n Two hundred patients were endodontically treated in two clinics. The type of irrigant to be used during root canal instrumentation was randomly assigned. Final irrigation was done using EDTA 17%. The canals were filled by warm vertical condensation with guttha-percha and the coronal seal was made using IRM. Patients were given a questionnaire to assess pain and swelling and the number of analgesics and other drugs taken during the first week after treatment.\n A total of 166 questionnaires could have been evaluated. No significant difference was found between groups for pain, swelling and analgesics taken. Moderate pain and swelling was reported only in the first two days after treatment. No antibiotics use was reported. No guttha-percha excess beyond root apex was found by radiographic assessment.\n The irrigating solution containing a proteolytic enzyme does not produce greater postoperative discomfort as compared to the conventional sodium hypochlorite in patients undergoing endodontic therapy.", "Clinical assessment of the efficacy of novel root canal disinfection protocols is an important focus in endodontic research. This randomized double-blinded study assessed the antibacterial efficacy of a final rinse with BioPure MTAD (MTAD) and intracanal medication with 2% chlorhexidine gel (CHX) in teeth with apical periodontitis.\n Canals in 30 teeth (single-rooted and multi-rooted) were prepared by using 1.3% NaOCl, rinsed with MTAD or saline in random sequence, medicated with CHX for 7 days, irrigated with 1.3% NaOCl, and filled. Bacteriologic root canal samples were obtained by aspiration before (1A) and after (1B) canal preparation, after the final rinse (1C), after CHX was flushed (2A), and after final irrigation (2B). Bacteria were enumerated by epifluorescence-microscopy (EFM) by using 2 staining methods and by colony-forming-unit (CFU) counts after 14 days of incubation.\n Bacterial counts (EFM) in 1B were greater than 95% decreased from 1A. Low bacterial densities in 1B, 1C, 2A, and 2B did not differ significantly from each other. EFM counts were consistently higher than CFU counts.\n The final rinse with MTAD and medication with CHX did not reduce bacterial counts beyond levels achieved by canal preparation with NaOCl.", "To determine in vivo, the degree of microbial reduction after chemo-mechanical preparation of human root canals containing necrotic pulp tissue when using two endodontic irrigating reagents, sodium hypochlorite (NaOCl) or chlorhexidine gel (CHX).\n Thirty-two single rooted teeth with necrotic pulp were divided into two groups. One group (n=16) was irrigated with 2.5% NaOCl, whilst the other group (n=16) was irrigated with 2% CHX gel. Assessment of the bacterial load was accomplished by use of real-time quantitative-polymerase chain reaction (RTQ-PCR) directed against the small subunit ribosomal DNA using the SYBRGreen and TaqMan formats. Statistical analysis was performed using the Mann-Whitney test. For contrast, bacterial load was also determined by traditional culture techniques.\n The bacterial load was reduced substantially in both groups (over 96%). However, using RTQ-PCR the bacterial load before and after chemo-mechanical preparation was greater when compared with evaluation using colony forming units (CFU). Furthermore, as measured by RTQ-PCR, the bacterial reduction in the NaOCl-group (SYBRGreen 99.99%; TaqMan: 99.63%) was significantly greater (P<0.01) than in the CHX-group (SYBRGreen 96.62%; TaqMan: 96.60%). According to culture technique 75% of cases were free of bacteria after chemo-mechanical preparation in the NaOCl-group, whilst 50% of cases were bacteria free in the CHX-group.\n NaOCl has not only a higher capacity to kill microorganisms but is also more able to remove cells from the root canal.", "The aim of this study was to identify bacteria from the infected root canals of teeth with chronic apical periodontitis, and to evaluate the antibacterial effect of 0.2% chlorhexidine (CHX), as an irrigant, in reducing the microbial flora 48h after root canal preparation. A total of 44 subjects were randomly divided in the experimental group and the control group. The first bacterial samples from all root canals were obtained in the beginning, before any treatment. During mechanical instrumentation, root canals were irrigated three times, with 0.2% CHX in the experimental group, and with saline solution in the control group. All canals were dried and temporarily sealed with zinc oxide-sulfate cement. After 48 h the second samples were obtained. Bacterial samples were subjected to microbiologic processing. The study indicates that 0.2% CHX is significantly effective in reducing the microbial flora, and could be used as an irrigant solution.", "nan", "In this study, the antibacterial activity of the different antibacterial solutions using as root canal irrigant was compared in the teeth with pulpal necrosis and with periapical pathosis. Thirty root canals of incisors and premolars of 20 patients were used. Before and after the root canal preparation, two canal samples were obtained by a harvesting method using a sterile paper point in the first appointment. During the biomechanical preparation, both irrigant solutions were used for each tooth which were randomly divided into two groups. Last samples were also obtained before the root filling procedure. Samples obtained from the root canals were subjected to microbiologic processing, including anaerobic incubation on trypticase soy agar for 5 to 7 days. After counting of CFU on the plates, we concluded that both chlorhexidine gluconate and sodium hypochlorite were significantly effective to reduce the microorganisms in the teeth with necrotic pulp, periapical pathologies, or both, and could be used successfully as an irrigant solution.", "To compare the levels of postoperative pain after cleaning and shaping of root canals using two different root canal irrigants for debridement.\n Forty patients with irreversible pulpitis, pulp necrosis and non-vital teeth exhibiting acute apical periodontitis requiring root canal treatment were included. At random, canals were cleaned and shaped with the following protocols. 2% chlorhexidine solution in group I and 5.25% sodium hypochlorite solution in group II were used as an irrigants. Access cavities were closed with a sterile cotton pellet and cavit. The patients recorded degree of pain at various time intervals after cleaning and shaping on a visual analogue scale for 1 week.\n The mean pain score for group I was between 0.65 and 3.35 and for group II was between 0.95 and 4.50. There was significant difference in the pain level between the two groups only at 6 th hour postoperatively (P<0.05) and the pain was more in sodium hypochlorite group.\n More pain was present in teeth irrigated using 5.25% sodium hypochlorite when compared to that in teeth irrigated using 2% chlorhexidine solution. Significant difference in pain level was present only at 6th hour postoperatively, and at all other periods (24 th hour, 4 th and 7 th days) there was no significant difference in pain level between the two groups.", "nan", "The purpose of this study was to establish whether addition of a 2% chlorhexidine rinse to a conventional treatment protocol enhances the rate of the successful disinfection of the root canal system in vivo.\n Twenty-four teeth with infected necrotic pulps and resorbing apical periodontitis were treated with a conventional technique in which 1% NaOCl as irrigant was used. Half of the cases received an additional rinse with 2% chlorhexidine. Prereduced thioglycollate medium was used to take cultures that were incubated for 4 weeks.\n Cultivable bacteria were retrieved at the conclusion of the first visit in 1 out of 12 chlorhexidine cases whereas in the control group 7 out of 12 cases showed growth. This difference was significant (P < .05).\n The findings are clinically important." ]

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[ "Radiotherapy alone for non-small cell lung carcinoma. Five-year disease-free survival and patterns of failure.", "Radiation therapy for stage I-II non-small cell lung cancer in patients aged 75 years and older.", "The curative treatment by radiotherapy alone of stage I non-small cell carcinoma of the lung.", "Radiotherapy alone for medically inoperable stage I non-small-cell lung cancer: the Duke experience.", "High-dose radiation therapy for inoperable non-small cell lung cancer without mediastinal involvement (clinical stage N0, N1).", "Limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer.", "Radical radiotherapy for early nonsmall cell lung cancer.", "Hyperfractionated radiotherapy alone for clinical stage I nonsmall cell lung cancer.", "Results of radical radiation therapy in clinical stage I, technically operable non-small cell lung cancer.", "Prognostic factors in the treatment of node-negative nonsmall cell lung carcinoma with radiotherapy alone.", "Radiation therapy alone for stage I non-small cell lung cancer.", "The influence of tumor size and pre-treatment staging on outcome following radiation therapy alone for stage I non-small cell lung cancer.", "Curative radiotherapy for technically operable stage I nonsmall cell lung cancer.", "High-dose, hyperfractionated, accelerated radiotherapy using a concurrent boost for the treatment of nonsmall cell lung cancer: unusual toxicity and promising early results.", "Limited field irradiation in early stage (T1-2N0) non-small cell lung cancer.", "Curative radiotherapy in non-small cell carcinoma of the lung.", "Radiotherapy in inoperable stage I lung cancer.", "Medically Inoperable Lung Carcinoma: The Role of Radiation Therapy.", "Local control in medically inoperable lung cancer: an analysis of its importance in outcome and factors determining the probability of tumor eradication.", "Radical radiotherapy for medically inoperable non-small cell lung cancer in clinical stage I: a retrospective analysis of 149 patients.", "Radiation therapy a good alternative for unoperable NSCLC.", "Clinical stage II non-small cell lung cancer treated with radiation therapy alone. The significance of clinically staged ipsilateral hilar adenopathy (N1 disease)." ]

[ "One hundred and fifty-three patients with inoperable non-small cell lung cancer (NSCLC) treated with radiotherapy alone have been retrospectively analysed. Normalized Total Dose (NTD) as defined by Macejewski, TN-stage (AJC-system) and histology have been examined with respect to 5-year disease-free survival (DFS) and the patterns of failure so as to identify subgroups of patients that routinely should be treated with radical intent. The 5-year DFS for T1, 2-N0, 1 and T3-N0, 1 staged patients was 30% (7/23) and 25% (4/16) respectively when the tumor NTD (a/b = 10 Gy) was 56-64 Gy vs. 12% (5/41) and 0% (0/10) when the NTD was 48-55 Gy. This difference was statistically significant for the squamous cell histology group. The higher doses significantly altered the patterns of death in N0, 1 staged squamous cell carcinoma and adenocarcinoma patients. Forty-five percent (22/55) and 41% (12/29) of squamous cell and adenocarcinoma patients respectively, died from local relapse without evidence of distant metastases when NTD less tha 55 Gy were given vs. 21% (9/42) and 13% (2/15) when the NTD delivered was 56-64 Gy (p < 0.05). Although for N2, 3 staged patients or patients with direct extension of the tumor into the mediastinum death from local relapse occurred in 38% (10/26) of the high NTD treated patients vs. 51% (19/37) of the low-dose treated ones, the difference was not statistically significant. It is concluded that NSCLC patients should not à priori be considered as non-radiocurable. At least 30% of the patients with early local stages can be long-term disease-free survivors with radiation NTD up to 60 Gy and better results are to be expected with higher doses. Advanced T-stage without mediastinal involvement should be treated with radical intent since a high NTD could give cure rates of over 25%. The disappointing results for patients with mediastinal disease could perhaps be attributed to the low NTD delivered. For patients with good performance status, hyperfractionated regimens delivering high tumor doses should be tested and chemotherapy should be adapted to these radiation treatment schedules.", "Between 1976 and 1992, 32 patients aged 75 and older with stage I-II non-small cell lung cancer (NSCLC) were given definitive radiation therapy. These patients did not undergo surgery because of old age, poor cardiac/pulmonary condition, or refusal to give consent. The mean age was 79 years, and 11 patients were over 80 years old. The histologic type was squamous cell carcinoma in 25 patients and adenocarcinoma in 7. The clinical T and N stage was T1N0 in 4 patients, T2N0 in 9, and T2N1 in 19. The total dose of radiation therapy given to each patient exceeded 60 Gy using 10-MV X-rays. The treatment was completed in all 32 patients without treatment-related complications. The 2- and 5-year overall actuarial survival rates wer 40% and 16%, respectively. Eleven intercurrent deaths occurred, including 7 patients who died of heart disease. The 2- and 5-year cause-specific survival rates were 57% and 36% respectively. None of the patients developed severe pneumonitis requiring hospitalization. All but three patients received radiation therapy on an inpatient basis. The mean duration of the hospital stay for initial treatment was 56 days, and mean ratio to total survival period (mean 739 days) was 8%. Although many elderly patients have concurrent medical complications such as heart disease and chronic pulmonary disease, the present study showed that elderly patients with clinical stage I-II NSCLC can expect a realistic probability of long-term survival with definitive radiation therapy.", "This review was initiated to assess the outcome of treatment with radical radiotherapy with curative intent for patients diagnosed as having stage I non-small cell lung cancer. The study involved a retrospective review of 347 patients with T1 and T2N0M0 tumors treated at the Queensland Radium Institute during the period 1985 to 1992. The main reasons for not proceeding to surgery included poor performance status, old age, or refusal to submit to surgery. The median age for the group was 70 years, with the range being 34 to 90 years. Patients in this group were all treated by a standard technique involving external-beam radiotherapy to 50 Gy, minimum tumor dose, in 20 fractions over 4 weeks. The overall survival rate was 27% at 5 years with a median survival of 27.9 months. The 5-year recurrence-free survival was 23% with the median being 19.5 months. There was a strong correlation of survival to tumor size with 5-year survival rates being 32% and 21% for T1 and T2 tumors, respectively. Multivariate analysis found only T stage to be associated with overall survival (p < 0.01). In addition, the analysis showed that age younger than 70 years was a prognostic factor that approached statistical significance at the p < 0.05 level of significance. We conclude from this large series of patients with stage I non-small cell lung cancer that radical radiotherapy with curative intent may be a viable alternative to surgery in those patients who either refuse surgery or are judged to be unfit for operation.", "To review our experience treating clinical Stage I non-small-cell lung carcinoma with radiotherapy alone using modern techniques and staging. The effect of dose and volume on outcome is to be analyzed.\n Between January 1980 and December 1995, 156 patients with Stage I medically inoperable non-small-cell lung cancer were irradiated at Duke University Medical Center and the Durham Veterans Administration Medical Center. Fifteen patients were excluded from analysis (7 treated with palliative intent, and 8 lost to follow-up immediately following radiation). Characteristics of the 141 evaluable patients were as follows: Median age 70 years (range 46-95); gender: male 83%, female 17%; institution: DUMC 65%, DVAMC 35%; T1N0 54%, T2N0 46%; median size 3 cm (range 0.5 to 8); pathology: squamous cell carcinoma 52%, adenocarcinoma 18%, large cell carcinoma 19%, not otherwise specified 11%; presenting symptoms: weight loss 26%, cough 23%, none (incidental diagnosis) 57%. All patients underwent simulation prior to radiotherapy using linear accelerators of > or = 4 MV. No patients received surgery or chemotherapy as part of their initial treatment. The median dose of radiotherapy (not reflecting lung inhomogeneity corrections) was 64 Gy (50 to 80 Gy) given in 1.2 bid to 3 Gy qid fractionation. The majority of cases included some prophylactic nodal regions (73%).\n Of the 141 patients, 108 have died; 33% of intercurrent death, 35% of cancer, and 7% of unknown causes. At last follow-up, 33 patients were alive (median 24 months, range 7-132 months). The 2- and 5-year overall survival was 39% and 13%, respectively (median 18 months). The corresponding cause-specific survival was 60%, and 32% (median 30 months). On multivariate analysis, significant factors influencing overall and/or cause-specific survival were age, squamous cell histology, incidental diagnosis, and pack-years of smoking. There was a nonsignificant trend towards improved cause-specific survival with higher radiotherapy doses and larger treatment volumes. On patterns of failure analysis, 42% of failures were local-only and 38% were distant-only. Regional-only failure occurred in 4 patients (7%), 3 of whom failed solely in an unirradiated nodal site. Analysis of factors correlating with local failure at 2 years was performed using a multinominal logistic regression analysis. Significant factors associated with a lower local failure included incidental diagnosis and absence of cough with a strong trend toward significance for higher radiotherapy dose (p = 0.07) and larger treatment volume (p = 0.08). Patients who were locally controlled had an improved cause-specific survival at 5 years over those who were not controlled (46% vs. 12%, p = 0.03). Grade III-V complications occurred in 2 patients (1.5%).\n Patients with clinical Stage I medically inoperable non-small-cell lung cancer treated with contemporary radiotherapy alone achieved a 5-year cause-specific survival of 32%. Uncontrolled lung cancer was the primary cause of death in these patients, and local failure alone represented the most common mode of failure (42%). Patients who were locally controlled had a significantly improved cause-specific survival over those who failed locally. Because higher doses of radiotherapy appear to provide improved local control, studies of dose escalation are warranted until dose-limiting toxicity is observed.", "To evaluate the usefulness of radiation therapy alternative to surgery for clinical N0-N1 non-small cell lung cancer (NSCLC).\n From 1976 through 1989, 116 patients with NSCLC without mediastinal involvement were treated with definitive radiation therapy alone at Gunma University Hospital. All patients were treated with once-daily standard fractionation using 10 MV X-rays. The total dose ranged from 60 Gy to 80 Gy.\n The actuarial 2- and 5-year survival rates of the entire group were 43% and 20%, respectively with a median survival time of 19 months. The survival of 76 patients with stage T2 tumors was significantly better than that of 28 patients with T3 tumors (mean survival time 21 versus 15.5 months; p < 0.05). Sixty-two patients with tumors less than 5 cm in diameter had a 2-year progression rate of 20%, in comparison with 39% of 54 patients with tumors greater than 5 cm. The difference of survivals for these 2 groups was statistically significant. Twelve patients given a total dose of 80 Gy or more had only 17% local progression at the time of last follow-up, however, 5 of them developed severe stenosis of proximal bronchus after 6 to 15 months.\n These results should provide support for definitive radiation therapy using 60 to 70 Gy to manage the patients with medically inoperable NSCLC without mediastinal involvement.", "The outcome of limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer (NSCLC) was analyzed to discuss the elective irradiation of regional lymph nodes. From 1976 through 1994, 36 patients with peripheral stage I NSCLC were treated with definitive radiation therapy (RT) alone at Gunma University hospital. The total dose ranged from 60 to 81 Gy with a 2 Gy-daily standard fractionation, although only one patient received 48 Gy. Ten patients received elective irradiation of the regional lymph nodes with a total dose of 40 Gy or more. The overall response rate was 97% with 31% complete responses. The overall survival rates at 3 and 5 years were 42 and 23%, and disease-specific survival rates were 56 and 39% at 3 and 5 years, respectively. In 26 patients without the elective regional irradiation, disease-specific survival rates at 3 and 5 years were 53 and 40%, respectively, whereas they were 64 and 39% in 10 patients with the regional nodal irradiation. The cumulative 5-year local progression rate was 28%, and the overall progression rate was 60% at 5 years. Four patients had a local recurrence as the only site of initial tumor progression. Combined local and regional progression was seen in two patients, and one patient had a local recurrence in combination with distant metastasis. Twelve patients had distant failure without evidence of local or regional progression. Only one patient without regional nodal irradiation developed an isolated regional failure. No patient had serious complications related to RT. High-dose limited field RT is justified for medically inoperable patients with peripheral stage I NSCLC. The regional nodal irradiation can be omitted in these pulmonary compromised patients because of the low regional relapse rate. Dose-escalation by a conformal RT with a small target volume can be expected to provide a better local control rate and better survival.", "To evaluate the results of a departmental treatment policy in a consecutive series of patients with nonsmall cell carcinoma of the lung. A second purpose was to estimate the survival of patients treated with radical intent. A third purpose was to estimate the impact of comorbidity on the selection of patients for treatment and on its outcome.\n The records of 720 consecutive patients referred to a single Department of Radiation Oncology between 1979 and 1985 were reviewed. One hundred fifty patients with early stage (Stage I and II disease) were studied in detail and the results are presented for the outcome of 103 patients treated by radical radiotherapy. All patients were followed for a minimum period of five years or until death.\n Patients referred for radiation therapy were elderly and usually had squamous cell carcinoma of the lung. Comorbidity was significant as was weight loss which occurred in a third of patients. The overall survival of patients treated with radical intent was 13%. In a small subgroup of patients with T1 tumors without weight loss and aged under 70 survival reached 50% at 5 years with no treatment-related mortality and with insignificant treatment-related morbidity.\n Highly selected subsets of patients suitable for treatment with radiotherapy can be defined equally as well as highly selected subsets of patients can be selected for surgery. Treatment outcome can be surprisingly good in these subsets indicating that the treatment of nonsmall cell lung cancer, particularly in older patients without comorbidity should not automatically be by a surgical approach.", "Among patients with Stage I nonsmall cell lung cancer (NSCLC), those treated with conventional radiotherapy show poorer prognosis than those treated by surgery. To improve the prognosis of such patients, we have used hyperfractionated radiation therapy.\n Between 1988 and 1993, 49 patients were treated with hyperfractionated radiotherapy with 1.2 Gy twice daily to a total dose of 69.6 Gy. All patients were technically operable, but 29 had medical problems and 20 refused surgery. The median age and Karnofsky Performance Status was 63 years and 90, respectively. No patient received chemotherapy or immunotherapy. Prophylactic mediastinal irradiation was not given.\n The median survival time was 33 months, and the 5-year survival rate was 30%. The rate at 5 years for freedom from each of relapse, local recurrence, mediastinal lymphnode metastasis, and distant metastasis was 41%, 55%, 89%, and 75%, respectively. Univariate analysis revealed that higher Karnofsky Performance Status score, absence of weight loss before treatment, and T1 stage were associated with better survival, although the T stage became insignificant on multivariate analysis. There were two Grade 3 acute toxicities and three Grade 3 late toxicities, but there was no Grade 4-5 toxicity.\n The results of this study compare favorably with those of most previous studies employing conventional fractionation. Further studies on hyperfractionation seem to be warranted for Stage I NSCLC.", "From 1970 to 1983, 1,646 lung cancer patients were referred for treatment to the Hunter Radiation Therapy Center, Yale-New Haven Hospital. Forty-three patients had clinical Stage I non-small cell lung cancer felt to be surgically resectable but were treated with radical radiation therapy either for medical reasons (37 patients) or because the patient refused surgery (six patients). This group of clinical Stage I lung cancer patients is understaged by modern criteria since the majority of patients did not have thoracic CT scans and staging was based on fairly limited clinical and radiographic studies. The histological diagnosis was squamous cell carcinoma in 53% of the Stage I patients, adenocarcinoma in 25%, and other non-small cell histologies in 22%. All patients were treated with megavoltage irradiation and the mediastinum was treated in 88% of the patients. Eleven patients were treated with a continuous course (CC) and 32 patients received split course (SC) therapy based on physician preference. The CC consisted of a median fraction size of 200 cGy to a total median dose of 5900 cGy in 6-7 weeks. The SC used a median fraction site of 275 cGy to a total median dose of 5400 cGy over a 6-week period with a 2-week rest in the middle of treatment. The actuarial survival rate of the 43 clinical Stage I patients was 36% at 3 years and 21% at 5 years. Intrathoracic failures occurred in 39% of the patients. Despite the fact that the CC group was similar to the SC group in terms of age, histology, and tumor extent, the CC patients had a lower thoracic failure rate (2/11) versus 15/32), a longer median survival (51.6 months versus 27 months), and a better actuarial 5-year survival rate (45% versus 12%) when compared to the SC patients. Using Cox regression analysis to compare survival curves, the CC group had a significantly better survival compared to the SC group (p = .04).", "For patients with early stage nonsmall cell lung carcinoma (NSCLC) but medically inoperable, aggressive radiation therapy might impact on survival.\n Between 1980 and 1990, 71 patients treated at MDACC by radiation therapy alone for NSCLC because of medical contradindications for surgery were analyzed. All patients had histologic or cytologic confirmation of NSCLC. The median total radiation dose was 63.23 Gy with 79% of patients receiving doses exceeding 60 Gy. The radiographic response was documented at completion of radiation therapy and 6 months after completion of radiation therapy. The median follow-up time was 36 months, ranging from 14-61 months.\n Overall survival rates at 3 and 5 years were 19 and 12%, respectively. The disease-specific survival (DSS) rates at 3 and 5 years were 44 and 32%, respectively. The DSS rates at 3 years by T-stage were: 49% for T1, 47% for T2, 26% for T3, and 32% for T4. The local control rates at 3 and 5 years were 66 and 56%, respectively. The local control rates at 3 years by T-stage were: 89% for T1, 61% for T2, 42% for T3, and 55% for T4. Univariately, the significant favorable prognostic factors for DSS were a KPS > or = 70, tumor size < or = 5 cm, no chest-wall invasion, and a radiation dose > or = 50 Gy. The significant favorable prognostic factors for local control were tumor size < or = 4 cm, no chest-wall invasion, a radiation dose > 60 Gy, and a complete response confirmed by chest x-ray at 6 months after radiotherapy (p = 0.04). Coverage of nodal drainage areas did not affect survival or local control. No lethal complications were seen, and documented symptomatic radiation pneumonitis occurred in only 7% of cases. Hence, the significant favorable prognostic factors for DSS were a KPS of > or = 70, tumor size < or = 5 cm, no chest-wall invasion, and a radiation dose > or = 50 Gy. The significant favorable prognostic factors for local control were tumor size of < or = 4 cm, no chest-wall invasion, a radiation dose > 60 Gy, and a complete response confirmed by chest x-ray at 6 months after radiotherapy. Multivariate analysis showed that the most important prognostic factor for DSS was KPS, and the most important prognostic factor for local control was radiation dose.\n Patients with a KPS of > or = 70, a tumor size < 5 cm, and no chest-wall invasion would benefit most from treatment with radiation alone to doses exceeding 60 Gy. This patient group represents the best sample for studying the benefit of conformal radiotherapy.", "This paper is a retrospective analysis of patients with clinical Stage I non-small cell carcinoma of the lung treated with definitive radiation therapy alone. The results of therapy, patterns of failure and the relationship of technical aspects of the delivery of radiotherapy to outcome are presented.\n From 1980 through 1990, 53 patients with Stage I non-small cell lung cancer were treated with definitive radiation therapy alone at the Radiation Oncology Center of the Mallinckrodt Institute of Radiology and its affiliated hospitals. All patients had a pathologic diagnosis of non-small cell lung cancer and were not candidates for surgical resection because of either patient refusal (10 patients), poor performance status (5 patients), or premorbid medical problems (38 patients). The median age was 73 years. Histologic cell type included squamous (32), adenocarcinoma (11), large cell (4), and unclassified non-small cell (6). Initial tumor size was < or = 3 cm in 23 patients, between 3 and 5 cm in 13 patients and > or = 5 cm in 17 patients. Diagnostic staging varied during the study period. All patients had chest X-rays and computed tomography scans of the chest. A majority had liver and bone scans, but only four underwent mediastinoscopy. The radiation therapy was of megavoltage energy in all patients, with a median primary prescription tumor dose of 63.2 Gy. Survival was measured from the date radiation therapy was initiated.\n The actuarial overall survival rate for the entire group was 19% at 3 years and 6% at 5 years, with a median survival time of 20.9 months. Of the 49 deaths, 35 died of lung cancer; 13 died of intercurrent illness, and one died of pancreatic cancer, which made the actuarial cause-specific survival 33% at 3 years and 13% at 5 years. The actuarial 3-year disease-free survival was 33%. Local primary tumor progression occurred in 22 patients, resulting in a 51% 3-year actuarial freedom from local progression. An additional four patients failed in regional lymph nodes that were included in the original treatment portals. Multivariate analysis found only T stage to be associated with overall survival (p = .02). However multivariate analysis showed age as a prognostic factor to be approaching statistical significance (p = .07). Patients under 70 years of age showed an increased survival rate compared to patients over 70 years. Radiation therapy doses > or = 65 Gy appeared to result in a decreased proportion of patients dying of lung cancer with no apparent increase in either acute or long-term complication rates.\n Results of definitive radiation therapy for inoperable Stage I non-small cell lung remain inferior to surgical therapy. Potential methods to improve local control with radiotherapy are discussed.", "From 1970 through 1987, 77 patients with Stage I lung cancer were treated with definitive radiation therapy (RT) alone at the Fox Chase Cancer Center or the Hospital of The University of Pennsylvania. All patients had a pathologic diagnosis of non-small cell lung cancer and were not candidates for surgical resection because of premorbid medical problems or patient refusal. The median age was 72 years, although 10 patients were over 80. The histologic cell type was squamous in 44, adenocarcinoma in 15, large cell in 3, adenosquamous in 1, non-small cell in 11, and bronchioli-alveolar in 3. Tumor size was retrievable in 75 patients and 25 were less than or equal to 3 cm, 41 from 3-6 cm, and 9 greater than 6 cm. Diagnostic staging varied during the study period. Twelve patients, evaluated with a CT scan of the chest, including the liver, and a bone scan were classified as having \"excellent\" staging, 24 patients with conventional tomography, liver-spleen scan and a bone scan had \"good\" staging, and 41 patients were staged less rigorously. The RT was of megavoltage energy in all patients. The median dose was 60 Gy. The mediastinum was treated in all but eight patients who had poor pulmonary function. Survival was measured from the date of pathologic diagnosis. The actuarial 3-year survival rate of the entire group of patients is 17% with a median survival time of 20 months. Of the 61 deaths, 51 were due to disease and 10 were due to intercurrent disease without evidence of tumor recurrence. The actuarial 3-year disease-specific survival (DSS) was 22%. The 3-year disease-specific survival for patients with tumors less than 3 cm and from 3-6 cm was 30% and 17%, respectively. All nine patients with tumors greater than 6 cm were dead of disease. Local progression occurred in 33 patients, resulting in a 44%, 3-year actuarial freedom from local progression. The median time to local failure was 28 months and there were no local failures after 3 years in the 18 patients eligible for observation beyond this point. Of the patients with \"excellent\" staging, only 2 of 12 were dead of disease compared with 22 of 24 with \"good\" staging and 30 of 41 of the remainder. In this large group of Stage I non-small cell lung cancer, thorough pre-treatment staging and smaller tumor size are associated with a more favorable outcome.", "Retrospective study of patients with Stage I nonsmall cell lung cancer (NSCLC) unable to undergo surgery or refusing surgery.\n Between 1984 and 1990, 47 patients with technically operable Stage I NSCLC received hypofractionated radiotherapy. The total dose varied from 32 Gy in six fractions (two fractions/week) or 40 Gy split course in ten fractions (low-dose schedules) to 48 Gy in 12 fractions or 56 Gy in 20 fractions (high-dose schedules). The mean age of the patients was 75 years. Three patients refused surgery and 44 patients were inoperable due to their medical condition. Severe associated disease was present in 34 patients (72.3%).\n The intrathoracic recurrence rate was 25.5%. In a multivariate analysis, tumor size was identified as the only significant factor predictive for intrathoracic failure (p < 0.001). Disease-specific survival was 90, 53, and 32% at 1, 3, and 5 years, respectively. In Cox's proportional hazards analysis, only tumor size was predictive for disease-specific survival. Overall survival (all causes) was 70, 33, and 15% at 1, 3, and 5 years, respectively. In Cox's proportional hazards analysis, only the presence of severe associated disease was predictive for overall survival (p < 0.01), while tumor size did not attain statistical significance (p = 0.08). There were no severe acute or late side-effects.\n Radiotherapy can effectively control small nonsmall cell tumors. The reported results are comparable to those achieved with more fractionated radiation schedules. In patients of age or in poor medical condition, hypofractionated radiotherapy can be given with curative intent, with minimal burden to the patient.", "The treatment of nonsmall cell lung cancer (NSCLC) with conventional radiotherapy (RT) results in inadequate local tumor control and survival. We report results of a Phase II trial designed to treat patients with a significantly increased total dose administered in a reduced overall treatment time using a hyperfractionated, accelerated treatment schedule with a concurrent boost technique.\n A total of 49 patients with unresectable Stage IIIA/IIIB (38 patients) or medically inoperable Stage I/II (11 patients) NSCLC were prospectively enrolled in this protocol. Radiation therapy was administered twice daily, 5 days/week with > 6 h between each treatment. The primary tumor and adjacent enlarged lymph nodes were treated to a total dose of 73.6 Gy in 46 fractions of 1.6 Gy each. Using a concurrent boost technique, electively irradiated nodal regions were simultaneously treated with a dose of 1.25 Gy/fraction for the first 36 fractions to a total dose of 45 Gy.\n Median survival for the entire group of 49 patients is 15.3 months. Actuarial survival at 2 years is 46%: 60% for 11 Stage I/II patients, 55% for 21 Stage IIIA patients, and 26% for 17 Stage IIIB patients. The actuarial rate of freedom from local progression at 2 years is 64% for the entire group of 49 patients: 62% for Stage I/II patients, 70% for Stage IIIA patients, and 55% for Stage IIIB patients. Patients who underwent serial bronchoscopic reevaluation (4 Stage I/II, 8 Stage IIIA, and 6 Stage IIIB) have an actuarial rate of local control of 71% at 2 years. The median total treatment time was 32 days. Nine of 49 patients (18%) experienced Grade III acute esophageal toxicity. The 2-year actuarial risk of Grade III or greater late toxicity is 30%. The 2-year actuarial rate of severe-late pulmonary and skin-subcutaneous toxicity is 20% and 15%, respectively.\n This treatment regimen administers a substantially higher biologically effective dose compared with conventional and pure hyperfractionation treatment schedules. The overall rate of acute and late toxicity was acceptable. Preliminary rates of overall survival and local control and freedom from local progression compare favorably to results reported with pure hyperfractionated radiotherapy and chemoradiotherapy.", "Radiotherapy can effectively control non-small cell lung cancers (NSCLC) of limited size. This study is conducted to investigate whether limited field irradiation, without irradiation of regional lymph nodes, can safely be used in these patients.\n Between 1988 and 1993, 31 patients with operable T1-2N0 NSCLC received radiotherapy (48 Gy in 12 fractions) to a limited ('postage stamp') field. The hilum and mediastinum were not included in the radiation portals.\n Overall survival was 42% at 3 years. Disease-specific survival at 3 years was 76%. One patient developed an isolated regional failure, one had a combined local and distant failure, one had a combined local, regional and distant failure, while three patients failed at distant sites only. Thus, only two patients (6%) recurred regionally.\n This study shows that 'postage stamp' irradiation is an effective alternative to surgery. Radiation of the hilar and mediastinal lymph nodes can be omitted in these pulmonary compromised patients.", "Recent reports suggest radiotherapy administered to the 5000-6000 cGy level can result in significant long-term survival in non-small cell carcinoma of the lung. This is particularly true for many cases that are technically operable but for medical or other reasons thoracotomy cannot be performed. Such patients drawn from Southern Appalachia where the principal industry is coal mining are the subject of this report. In this region coal miners pneumoconiosis (black lung) is common as well as other chronic respiratory disorders resulting in poor tolerance for surgery. Three hundred and eleven cases of non-small cell carcinoma were irradiated during the 4 years of 1980 through 1983. This group consisted of 77 patients with clinical Stage T1, T2, T3 all N0, M0 tumors, the majority of which were technically operable but upon whom no thoracotomy was performed because of medical reasons or patient refusal. All are available for 5-year study. Each of these patients was uniformly irradiated to 6000 cGy target dose in 30 fractions over 6 weeks using standard techniques. Absolute or crude survival in these 77 patients is as follows: 1 year, 57%; 2 year, 36%; 3 year, 21%; 4 year, 17%; and 5 year, 17%. Comparison with reported surgical series treated for cure show little difference in survival up to 2 years. Thereafter, the survival curves diverge with radiotherapy patients dying at a somewhat higher rate although by 4 years both survival curves slope similarly. A possible explanation for this difference is the advantage thoracotomy offers in early case selection allowing exclusion of advance cases from surgical reports whereas radiotherapy must include patients with occult local metastasis not identifiable on clinical grounds. This experience, among other reports include evidence that radiotherapy can result in long-term survival or cure with minimal morbidity in lung cancer patients in whom surgery carries excessive risk.", "In 38 cases of Stage I lung cancer, for which surgery was not indicated because of poor cardiopulmonary function or other reason, radical irradiation yielded excellent results. The five year survival rate was 42.1%, the 10-year survival rate 28.4% and the 15-year survival rate 17.1%. Postradiation complications which can be life-threatening, were acceptably low in incidence, and there was no radiation-related death. The results support the concept of radical irradiation being acceptable as a treatment modality for Stage I lung cancer if the patients concerned cannot have surgery because of poor cardiopulmonary function or some other reason.", "Although surgery has traditionally been the treatment of choice for patients with resectable non-small cell lung cancer, for those with significant medical problems where surgery is contraindicated, radiation therapy (RT) is a reasonable treatment modality. In contrast to the widely held belief that RT confers little benefit to these patients, a review of the literature and our own series of 245 patients shows that RT can provide significant tumor shrinkage, improved symptoms, and in a small but not negligible number of patients, cure. Several prognostic factors have emerged, including patient performance status, prior weight loss, tumor size, and radiation dose. Patients with a good performance status and a small tumor treated to a dose of 65 Gy or more have a real possibility of long-term survival and cure. Larger tumors demand strategies to improve the therapeutic ratio, such as hyperfractionation, conformal RT, brachytherapy boosts, or chemotherapy. Patients with medically inoperable lung cancer should be offered RT with curative intent, rather than the option of no treatment.", "For patients who are medically unable to tolerate a surgical resection for technically resectable non-small-cell lung carcinoma, radiation therapy is an acceptable alternative. We report on the effect of achieving local control of the primary tumor on survival end-points, and analyze factors that may influence local control.\n We reviewed the records of 152 patients with medically inoperable non-small-cell lung carcinoma treated at our institutions. All patients had technically resectable lesions and no evidence of metastatic disease. Treatment was delivered using megavoltage irradiation to doses ranging from 45 to 75 Gy.\n For patients with tumors 3 cm or less, locally controlling the tumor significantly improved survival (p = .0371). Patients with T1 tumors had a higher probability of survival and disease-free-survival than patients with larger tumors if the primary tumor was locally controlled, but this survival advantage disappeared if the tumor was not controlled. Overall, patients with smaller tumors had a lower incidence of distant spread, but this association was maintained only when the primary tumor was controlled (36 month risk of 10%, 23%, and 57% for tumors < 3 cm, 3-4.9 cm, 5 cm or greater, respectively, p = .0027). For patients whose tumors were not controlled, there was no significant difference in the risk of distant dissemination by tumor size. Higher radiation doses influenced local control and metastatic spread. We observed no influence of the initial field size in the risk of local control and in the probability of survival.\n Radical radiation therapy is an effective treatment for small (T1 or < 3 cm) tumors when treated to doses of 65 Gy or more, and should be offered as an alternative to surgery in elderly or infirm patients. New therapeutic strategies to improve the local control rate should be considered for larger tumors, through the use of hyperfractionated treatment, endobronchial \"boost\" irradiation, and sensitizing chemotherapy agents.", "In order to obtain the standard treatment results of medically inoperable non-small cell lung cancer (NSCLC) in Stage I in the post-CT scan era, a retrospective analysis of patients who were treated by radical radiotherapy was performed.\n 149 cases treated between 1980 and 1989 were accumulated from ten large hospitals in Japan. All patients received a total dose of 55-75 Gy (mean 64.7 Gy) with conventional fractionation. For evaluation of treatment results, complete response (CR) rate, median survival period and long-termed survival rates were used.\n The median survival of the all cases was 27.2 months and the actuarial 3- and 5-year survival rates were 34.2% and 22.2%, respectively. CR was obtained in 57 cases (38%). The CR rate was strongly correlated with the long-term survival (5-year survival rate in CR group: 35.1% compared with PR + NC group: 14.1% (P < 0.0001)). The size of tumor was also of prognostic importance. In 116 patients who died within 5 years after treatment, 66 patients (57%) died of local tumor regrowth.\n Although the medically inoperable NSCLC patients in Stage I should be offered curative radiation therapy, development of some new steps to increase the CR rate and local control rate is urgently needed.", "This retrospective analysis of 133 patients with unoperable NSCLC suggests that radiation therapy administered to GE 6000 cGy level can result in significant long term survival in patients with technically resectable but medically unoperable disease.", "The prognosis of patients with clinically staged hilar nodal involvement (Stage N1) or clinical Stage II non-small cell lung cancer (NSCLC, Stage T1-2N1M0) treated with radiation therapy (RT) alone is not well established.\n Records of 758 patients with clinical Stage I-III NSCLC treated with RT were reviewed. Sixty-two patients were identified with clinical Stage II NSCLC, and 126 patients had Stage N1 disease.\n The median survival time (MST) of the 62 patients with clinical Stage II disease was 17.9 months, with 1-year, 2-year, 3-year, and 5-year overall actuarial survival rates of 70%, 33%, 20%, and 12%, respectively. The survival of patients with clinical Stage II disease was significantly better than that of 389 patients with clinical Stage IIIA disease (MST, 11.3 months; P < 0.008) and 267 patients with clinical Stage IIIB disease (MST, 9.8 months; P = 0.0003), but it was similar to that of 40 patients with clinical Stage I lesions (MST, 15.0 months). Patients with performance statuses of 0-1 lived longer than those with a status of 2 or more (MST, 22.8 versus 6.1 months; P < 0.0001). The median survival for patients with N0, N1, N2, and N3 disease was 13.7, 12.6, 10.9, and 9.1 months, respectively. Patients with Stage N0-1 disease (MST, 13.2 months) had significantly improved MST compared with those with Stage N2-3 disease (MST, 10.3 months).\n The survival of patients with clinical Stage II NSCLC treated with RT alone was significantly better than that of those with clinical Stage IIIA or IIIB disease. It was comparable to that of patients with clinical Stage I lesions. The clinical staging of nodal involvement limited to the ipsilateral hilum does not necessarily portend a worse prognosis than that of patients with clinical Stage N0 disease. The absence of clinically evident Stage N2-3 disease is of significant predictive value for patients with NSCLC treated with RT." ]

[ "11511559", "789186", "6343868", "3101804", "395630", "7018048", "4122561" ]

[ "Drug treatments in upper gastrointestinal bleeding: value of endoscopic findings as surrogate end points.", "Tranexamic acid and upper gastrointestinal haemorrhage--a double-blind trial.", "Cimetidine and tranexamic acid in the treatment of acute upper-gastrointestinal-tract bleeding.", "Tranexamic acid as an aid to reducing blood transfusion requirements in gastric and duodenal bleeding.", "Tranexamic acid in massive haemorrhage from the upper gastrointestinal tract: a double-blind study.", "Local inhibition of the fibrinolytic system in patients with massive upper gastrointestinal hemorrhage.", "Tranexamic acid in upper gastrointestinal haemorrhage." ]

[ "Pharmacotherapy for upper gastrointestinal bleeding has been difficult to evaluate because clinical end points are infrequent and affected by other factors.\n To evaluate whether blood in the stomach at endoscopy reflected severity of bleeding, predicted clinical outcomes, and could be altered by therapeutic agents.\n We studied 414 consecutive admissions with suspected upper gastrointestinal bleeding. Patients were randomised to receive lansoprazole 60 mg followed by 30 mg four times daily, tranexamic acid 2 g followed by 1 g four times daily, both drugs, or placebo for four days, until discharge or a clinical end point occurred. Logistic regression analysis was used to determine predictors of endoscopic changes and clinical outcomes, and to investigate the effects of drug treatments on blood in the stomach.\n Of 414 patients with suspected upper gastrointestinal bleeding, 379 were endoscoped. Upper gastrointestinal bleeding was confirmed in 316. Sixteen required surgery within 30 days and 16 died on the index admission. Trial treatments were evaluable on a per protocol basis in 228 patients. The amount of blood in the stomach was found to reflect initial risk, with significant associations with high risk categorisation (odds ratio 3.7 (95% confidence interval 1.5-9.4) for more than a trace v none/trace), age (1.5 (1.1-1.9) per decade), and initial pulse (1.02 (1.00-1.04) per beat), and to predict rebleeding (9.2 (4.6-18.7)) and surgery (8.2 (2.9-22.9)). Other stigmata were less significant in these respects. The amount of blood in the stomach at endoscopy was reduced significantly by both lansoprazole (0.22 (0.07-0.63)) and tranexamic acid (0.27 (0.09-0.81)), although there was no evidence of synergy.\n Blood in the stomach reflects clinical features in patients with acute upper gastrointestinal bleeding and is reduced by treatment with lansoprazole and tranexamic acid.", "The efficacy of antifibrinolytic therapy in the management of acute upper gastrointestinal haemorrhage has been investigated in a double-blind clinical trial. Two-hundred patients were studied using tranexamic acid, a potent antifibrinolytic agent. Of these, 103 were in the treatment group and 97 in the control group. Patients were analysed to determine severity of initial blood loss, transfusion requirements, together with the incidence of recurrent bleeding, surgical intervention, and death. Final diagnosis as to the site of bleeding was arrived at using endoscopy, barium studies, and the findings at operation and necropsy. The groups were well matched as regards severity of initial haemorrhage, age, sex, aetiological diagnosis, and precipitating factors. A significant difference was observed in the requirement for surgical intervention to control continuing or recurrent haemorrhage. Twenty-three of 97 in the control group and seven of 103 in the treatment group required surgery. There appeared to be a reduction in the transfusion rate after the first three days of hospitalization in the treatment group. There were no significant differences in mortality or in side-effects between the two groups.", "We studied the effects of tranexamic acid (an antifibrinolytic agent) and cimetidine on acute upper-gastrointestinal-tract bleeding in a double-blind randomized placebo-controlled trial in 775 patients with hematemesis or melena or both. Mortality was significantly reduced in patients receiving either tranexamic acid (mortality, 6.3 per cent) or cimetidine (7.7 per cent), as compared with patients receiving placebo (13.5 per cent) (P = 0.0092 for tranexamic acid vs. placebo, P = 0.045 for cimetidine vs. placebo). Ninety-nine patients were withdrawn before the code was broken, mainly because their primary illness was considered not to be due to acute upper-gastrointestinal-tract bleeding. Mortality among those withdrawn was high (22 per cent), and their exclusion reduced death rates to 4 per cent in those given tranexamic acid, 8 per cent in those given cimetidine, and 11 per cent in those given placebo (P = 0.0072 for tranexamic acid vs. placebo, P greater than 0.50 for cimetidine vs. placebo). The reduced mortality associated with tranexamic acid was detectable at both participating hospitals and in most of the main subgroups of patients classified according to site of bleeding. However, treatment with this agent was not associated with any decrease in the rate of rebleeding or the need for operation.", "A prospective randomised double blind study examined the effect of the antifibrinolytic drug tranexamic acid compared with placebo in 154 patients bleeding from verified benign lesions in the stomach or duodenum or both. Three out of 72 patients receiving tranexamic acid underwent emergency surgery compared with 15 out of 82 given placebo (p = 0.010). Nineteen patients receiving placebo rebled during their admission as compared with 10 in the active treatment group (p = 0.097). Blood transfusion requirements were significantly reduced by tranexamic acid (p = 0.018). Side effects occurred in six patients, of which an uncomplicated deep venous thrombosis was the most severe. Tranexamic acid reduces the blood transfusion requirement and need for emergency surgery in patients bleeding from a benign gastric or duodenal lesion.", "In a double-blind trial of tranexamic acid in massive upper gastrointestinal haemorrhage, 76 patients were treated with the active drug and 73 patients with placebo. The doses were 1 g intravenously six times daily for a maximum of 3 days, followed by 1.5 g orally four times daily for a maximum of 4 days. The treatment group and the placebo group were comparable with respect to mean age, diagnoses and laboratory tests but differed slightly with respect to sex and alcohol consumption. The transfusion requirement in the treatment group was less than in the placebo group during the first days after admission, the difference being significant on the second day after admission. Ten patients in the treatment group and 18 patients in the placebo group were operated on. Eleven patients in the treatment group and 12 patients in the placebo group died. In the tranexamic-acid-treated group fewer operations were performed and significantly less blood was needed. It therefore seems highly likely that tranexamic acid has a beneficial effect, although small.", "The effect or oral tranexamic acid on massive upper gastrointestinal hemorrhage was evaluated in a randomized double-blind study. Totally 50 patients entered the trial and seven were excluded, leaving 22 placebo treated and 21 tranexamic acid treated for analysis. The groups were comparable regarding sex, age, diagnosis, and initial laboratory data. Transfusions requirements and operation frequency did not differ. Mortality was slightly reduced and death delayed in tranexamic acid treated patients.", "nan" ]

[ "7797786", "15480319", "15142868", "16846450", "15990772", "15100668", "1447641", "12775858", "16815138", "2754147", "8182225", "8738513" ]

[ "The development and prediction of atopy in high-risk children: follow-up at age seven years in a prospective randomized study of combined maternal and infant food allergen avoidance.", "Three-year outcomes of dietary fatty acid modification and house dust mite reduction in the Childhood Asthma Prevention Study.", "Early life environmental control: effect on symptoms, sensitization, and lung function at age 3 years.", "House dust mite allergen reduction and allergy at 4 yr: follow up of the PIAMA-study.", "The Canadian Childhood Asthma Primary Prevention Study: outcomes at 7 years of age.", "The Canadian asthma primary prevention study: outcomes at 2 years of age.", "Long-term prevention of allergic diseases by using protein hydrolysate formula in at-risk infants.", "Primary prevention of asthma and atopy during childhood by allergen avoidance in infancy: a randomised controlled study.", "Prevention of asthma during the first 5 years of life: a randomized controlled trial.", "Effect of combined maternal and infant food-allergen avoidance on development of atopy in early infancy: a randomized study.", "Effect of allergen avoidance in infancy on allergic manifestations at age two years.", "Allergen avoidance in infancy and allergy at 4 years of age." ]

[ "The natural history of allergic disease and its potential for prevention merit close examination because of the explosive worldwide increase in the prevalence and morbidity of atopic disorders. This study examines the development of atopy at age 7 years in 165 children in a high-risk cohort, previously reported from birth to age 4 years.\n In this prospective, randomized, controlled study of food allergen avoidance in infancy, the prophylactic-treated group consisted of infants whose mothers avoided cow's milk, egg, and peanut during the last trimester of pregnancy and lactation and who, themselves, avoided cow's milk until age 1 year (casein hydrolysate supplementation before age 1), egg until age 2 years, and peanut and fish until age 3 years. The control group consisted of maternal/infant pairs who followed standard feeding practices.\n Despite a significant reduction in food allergy and milk sensitization before age 2 years, none of the following differed between the groups at age 7 years: food allergy, atopic dermatitis, allergic rhinitis, asthma, any atopic disease, lung function, food or aeroallergen sensitization, serum IgE level, or presence of nasal eosinophils or nasal basophilic cells. Children with food allergy by 4 years evidenced higher 7-year (current) prevalences of allergic rhinitis and asthma (p < 0.01). Atopic diseases/parameters at age 7 years were shown, by multivariate analysis (p < 0.05), to be associated with several genetic and environmental risk factors (male gender, maternal nonwhite ethnicity and asthma, and household smoking), as well as predictive atopic markers during infancy (elevated serum IgE level; egg, cow's milk, and peanut sensitization; and nasal eosinophils and nasal basophilic cells).\n These findings help to: (1) elucidate the natural history of atopic disease in high-risk children; (2) document the progression of allergy from atopic dermatitis, food allergy, and food sensitization to respiratory allergy and aeroallergen sensitization despite food allergy prevention in infancy; (3) identify allergy predictive markers; and (4) expand our appreciation of the interactions of genetic and environmental factors in the development of atopy.", "Two factors thought to influence the risk of asthma are the promoting effect of sensitization to house dust mites and the preventive effect of increased omega-3 fatty acids. Although house dust mite allergen avoidance has been used as a preventive strategy in several trials, the effect of omega-3 fatty acid supplementation in the primary prevention of asthma and allergic disease is not known.\n To measure the effects of dietary supplementation with omega-3 fatty acids and house dust mite allergen avoidance in children with a family history of asthma.\n A total of 616 children at high risk of asthma were enrolled antenatally in a randomized controlled trial, and 526 children remained in the trial at age 3 years. The outcomes were symptoms of allergic disease and allergen sensitization.\n There was a significant 10.0% (95% CI, 3.7-16.4) reduction in the prevalence of cough in atopic children in the active diet group ( P=.003; number needed to treat, 10) but a negligible 1.1% (95% CI, -7.1 to 9.5) reduction cough among nonatopic children. There was a 7.2% (95% CI, 10.11-14.3) reduction in sensitization to house dust mite in the active allergen avoidance group ( P=.05; number needed to treat, 14). No significant differences in wheeze were found with either intervention.\n These results suggest that our interventions, designed to be used in simple public health campaigns, may have a role in preventing the development of allergic sensitization and airways disease in early childhood. This offers the prospect of reducing allergic disease in later life.", "We investigated whether environmental control during pregnancy and early life affects sensitization and lung function at the age of 3 years. High-risk children (n = 251) were prenatally randomized to stringent environmental control (active) or no intervention (control). Questionnaires, skin testing, IgE, and specific airway resistance (sRaw) measurement were completed at the age of 3 years. Children in the active group were significantly more frequently sensitized compared with control subjects (at least one allergen by skin tests: risk ratio, 1.61; 95% confidence interval [CI], 1.02-2.55; p = 0.04; mite by IgE: risk ratio, 2.85; 95% CI, 1.02-7.97; p = 0.05). However, sRaw was significantly better in the active group (kiloPascal/second, geometric mean [95% CI]: 1.05 [1.01-1.10] vs. 1.19 [1.13-1.25], p < 0.0001, active vs. control). Maximal flow at functional residual capacity was measured using rapid thoracic compression at the age of 4 weeks in a subgroup. Prospective lung function data (at infancy and 3 years) were obtained in 32 children (14 active and 18 control). There was no difference in infant lung function between the groups, but at 3 years, sRaw was significantly lower in the active compared with control children (p = 0.003). Stringent environmental control was associated with increased risk of mite sensitization but better results for some measurements of lung function in high-risk children at the age of 3 years.", "Exposure to high allergen levels in early life is a risk factor for the development of allergy. We previously reported limited effects of mite allergen impermeable mattress covers in the prevention and incidence of asthma and mite allergy (PIAMA) cohort at the age of 1 and 2 yr. We now present the results of follow-up at 4 yr objectives. To examine the effects of early reduction of house dust mite (HDM) allergen exposure by means of mattress covers on the incidence of allergy and asthma symptoms in the PIAMA birth cohort at the age of 4 yr. High-risk children (allergic mother) were prenatally recruited and randomly allocated to three groups; receiving mite allergen impermeable mattress covers (n = 416), placebo covers (n = 394) or no intervention (n = 472). At 4 yr of age, atopy was assessed by questionnaire; specific Immunoglobulin E (IgE) to inhalant and food allergens was measured in serum. Dust samples collected from the children's mattresses were analysed for mite allergens. Dermatophagoides farinae1 allergen (Der f 1) levels in dust were reduced in the active group. However, Dermatophagoides pteronissinus 1 (Der p 1) levels, sensitization and atopic symptoms were similar in all groups. We found no effect of mite allergen impermeable mattress covers on sensitization and atopy at 4 yr. Moreover, the allergen reducing effects of the covers had disappeared for one of the two mite allergens that were measured.", "Avoidance of any one of the individual risk factors associated with childhood asthma has not been successful in preventing its development.\n The purpose of this study is to determine the effectiveness of a multifaceted intervention program for the primary prevention of asthma in high-risk infants at 7 years of age.\n Five hundred forty-five high-risk infants with an immediate family history of asthma and allergies were prospectively randomized into intervention or control groups prenatally. Intervention measures introduced before birth and during the first year of life included avoidance of house dust, pets, and environmental tobacco smoke and encouragement of breast-feeding with delayed introduction of solid foods. Assessment of outcomes at 7 years consisted of examination by pediatric allergists, methacholine inhalation tests, and allergy skin tests.\n At 7 years, 469 of the 545 children were contacted, and 380 returned for further assessment. The prevalence of pediatric allergist-diagnosed asthma was significantly lower in the intervention group than in the control group (14.9% vs 23.0%; adjusted risk ratio, 0.44; 95% CI, 0.25-0.79). The prevalence of allergic rhinitis, atopic dermatitis, atopy (defined as positive skin test reactions to any common allergen), and bronchial hyperresponsiveness (defined as the provocative concentration of methacholine that induced a 20% decrease in FEV 1 from a postsaline value of less than 7.8 mg/mL) were not significantly different between the 2 groups. The prevalence of asthma (defined as wheeze without colds and the presence of bronchial hyperresponsiveness) was also significantly lower in the intervention group compared with the control group (12.9% vs 25.0%; adjusted risk ratio, 0.39; 95% CI, 0.22-0.71).\n The multifaceted intervention program was effective in reducing the prevalence of asthma in high-risk children at 7 years of age.", "Avoidance of individual risk factors have not been successful in preventing the development of asthma.\n We sought to determine the effectiveness of a multifaceted intervention program in primary prevention of asthma in high-risk infants.\n We identified 545 high-risk infants on the basis of an immediate family history of asthma. Families were randomized into intervention or control groups. Intervention measures included avoidance of house dust mite, pet allergen, and environmental tobacco smoke. Breast-feeding was encouraged with formula supplementation if necessary, and introduction of solid foods was delayed.\n At 2 years of age, 19.5% of the children had asthma, and 14.7% had atopy (positive skin test response to one or more common allergens). Significantly fewer children had asthma in the intervention group compared with in the control group (16.3% vs 23.0%), with 60% less persistent asthma at 2 years. There was a 90% reduction for recurrent wheeze in the intervention group compared with that seen in the control group. Exposure to maternal environmental tobacco smoke during pregnancy or the first year was a risk factor for asthma at 2 years of age. A positive skin test response, particularly to food, at 12 months predicted asthma at 2 years. There was no significant difference for atopy between the intervention and control groups, but daycare reduced atopy at 2 years.\n This multifaceted intervention program during a window of opportunity in the first year of life was effective in preventing asthma in high-risk children at 2 years of age. Future studies with this cohort at school age are important.", "This prospective, long-term study assessed the effects of a protein hydrolysate formula on allergy prevention in infants with a family history of allergy. Infants were randomly assigned to receive either the hydrolysate formula (n = 92) or an adapted cow milk formula (n = 85) alone or with breast-feeding for 4 months. The groups did not differ in family allergy history scores or cord blood IgE levels. After 4 months, total IgE levels and allergic reactions did not differ significantly between groups, although the hydrolysate group had a lower prevalence of eczema. At 12 months of age, neither IgE levels nor allergic reactions were significantly different. At 2 years of age, however, 18 allergic reactions had occurred in the hydrolysate group and 31 had occurred in the control group; the differences were significant for eczema (p < 0.001) but not for asthma. At 4 years of age, allergic signs were found in 11 children in the hydrolysate group and in 17 children in the control group; the difference was significant only for eczema (p < 0.01). These results suggest that early feeding of a protein hydrolysate formula to infants at risk for allergies had a long-term preventive effect on the prevalence of eczema but not of asthma.", "Recent increases in the prevalence of asthma and atopy emphasise the need for devising effective methods for primary prevention in children at high risk of atopy.\n A birth cohort of genetically at risk infants was recruited in 1990 to a randomised controlled study. Allergen avoidance measures were instituted from birth in the prophylactic group (n=58). Infants were either breast fed with mother on a low allergen diet or given an extensively hydrolysed formula. Exposure to house dust mite was reduced by the use of an acaricide and mattress covers. The control group (n=62) followed standard advice as normally given by the health visitors. At age 8, all 120 children completed a questionnaire and 110 (92%) had all assessments (skin prick test, spirometry, and bronchial challenges).\n In the prophylactic group eight children (13.8%) had current wheeze compared with 17 (27.4%) in the control group (p=0.08). Respective figures were eight (13.8%) and 20 (32.3%) for nocturnal cough (p=0.02) and 11 of 55 (20.0%) and 29 of 62 (46.8%) for atopy (p=0.003). After adjusting for confounding variables, the prophylactic group was found to be at a significantly reduced risk for current wheeze (odds ratio (OR) 0.26 (95% confidence interval (CI) 0.07 to 0.96)), nocturnal cough (OR 0.22 (95% CI 0.06 to 0.83)), asthma as defined by wheeze and bronchial hyperresponsiveness (OR 0.11 (95% CI 0.01 to 1.02)), and atopy (OR 0.21 (95% CI 0.07 to 0.62)).\n Strict allergen avoidance in infancy in high risk children reduces the development of allergic sensitisation to house dust mite. Our results suggest that this may prevent some cases of childhood asthma.", "Early life exposures may be important in the development of asthma and allergic disease.\n To test house dust mite (HDM) avoidance and dietary fatty acid modification, implemented throughout the first 5 years of life, as interventions to prevent asthma and allergic disease.\n We recruited newborns with a family history of asthma antenatally and randomized them, separately, to HDM avoidance or control and to dietary modification or control. At age 5 years, they were assessed for asthma and eczema and had skin prick tests for atopy.\n Of 616 children randomized, 516 (84%) were evaluated at age 5 years. The HDM avoidance intervention resulted in a 61% reduction in HDM allergen concentrations (microg/g dust) in the child's bed but no difference in the prevalence of asthma, wheeze, or atopy (P > .1). The prevalence of eczema was higher in the active HDM avoidance group (26% vs 19%; P = .06). The ratio of omega-6 to omega-3 fatty acids in plasma was lower in the active diet group (5.8 vs 7.4; P < .0001). However, the prevalence of asthma, wheezing, eczema, or atopy did not differ between the diet groups (P > .1).\n Further research is required to establish whether other interventions can be recommended for the prevention of asthma and allergic disease.\n House dust mite avoidance measures and dietary fatty acid modification, as implemented in this trial during infancy and early childhood, did not prevent the onset of asthma, eczema, or atopy in high-risk children.", "The effect of maternal and infant avoidance of allergenic foods on food allergy was examined in a prenatally randomized, controlled trial of infants of atopic parents. The diet of the prophylactic-treated group (N = 103) included (1) maternal avoidance of cow's milk, egg, and peanut during the third trimester of pregnancy and lactation and (2) infant use of casein hydrolysate (Nutramigen) for supplementation or weaning, and avoidance of solid foods for 6 months; cow's milk, corn, soy, citrus, and wheat, for 12 months; and egg, peanut, and fish, for 24 months. In the control group (N = 185), mothers had unrestricted diets, and infants followed American Academy of Pediatrics feeding guidelines. The cumulative prevalence of atopy was lower at 12 months in the prophylactic-treated (16.2%) compared to the control (27.1%) group (p = 0.039), resulting from reduced food-associated atopic dermatitis, urticaria and/or gastrointestinal disease by 12 months (5.1% versus 16.4%; p = 0.007), and any positive food skin test by 24 months (16.5% versus 29.4%; p = 0.019), caused primarily by fewer positive milk skin tests (1% versus 12.4%; p = 0.001). The prevalences of allergic rhinitis, asthma, and inhalant skin tests were unaffected. Serum IgE levels in the prophylactic-treated group were marginally lower only at 4 months. Thus, reduced exposure of infants to allergenic foods appeared to reduce food sensitization and allergy primarily during the first year of life.", "One hundred twenty children, identified before birth as being at high risk for atopy, were prenatally assigned to prophylactic or control groups.\n The infants in the prophylactic group either received breast milk from mothers on an exclusion diet or an extensively hydrolyzed formula. Their bedrooms and living rooms were treated repeatedly with an acaricide, and they used polyvinyl-covered mattresses with vented head areas. The infants in the control group were fed conventionally, and no environmental control was recommended.\n A significant advantage, first demonstrated at 1 year of age, persists for children in the prophylactic group. They have less of any allergy or eczema, but the reduced prevalence of asthma is no longer significant. Only three children in the prophylactic group had positive skin prick test results compared with 16 in the control group, suggesting a significant reduction in sensitization.\n A dual approach to allergen avoidance, focusing on foods and aeroallergens, appears to be beneficial in selected high-risk infants. Avoidance of potent allergens in early life increases the threshold for sensitization in these high-risk infants. Whether sensitization has been avoided or merely deferred has yet to be proved.", "In an attempt to prevent or reduce the manifestations of atopic disease, a group of infants considered to be genetically at high risk of atopy was entered in a prenatally randomized, controlled study. A prophylactic group (n = 58) was either breast-fed with their mothers excluding foods regarded as highly antigenic from their diets, or given an extensively hydrolysed formula. In addition, strenuous efforts were made to reduce exposure to the house-dust mite by application of acaricide to the bedroom and living room carpets and upholstered furniture. A control group (n = 62) was fed conventionally by breast or on formula, and no specific environmental measures were taken. The results (previously reported) after 1 year showed significantly less total allergy, asthma, and eczema in the prophylactic group. Similar results were obtained at 2 years although the reduction in asthma no longer achieved statistical significance. However, there was significantly less sensitization, as shown by a battery of skin prick tests (SPTs), to both dietary allergens and aeroallergens in the prophylactic group. All the children have now been reviewed at the age of 4 years, and SPTs to a wide range of dietary allergens and aeroallergens have been performed. The control group continues to show more total allergy (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.21-6.13, P < 0.02), definite allergy (allergic symptoms plus positive SPT) (OR 5.6, CI 1.8-17.9, P < 0.005), and eczema (OR 3.4, CI 1.2-10.1, P < 0.05). More control children have positive SPTs (OR 3.7, CI 1.3-10.0, P < 0.02). A dual approach to the prevention of allergic disease, avoiding as far as possible sensitization to food and aeroallergens, significantly reduces the risk of atopic disease. This should be reserved for infants considered at very high risk of atopy, and close medical and dietetic supervision must be available." ]

[ "3056661", "8553306", "15295690", "8697829" ]

[ "Corticosteroids in the treatment of tuberculous pleurisy. A double-blind, placebo-controlled, randomized study.", "Randomised trial of corticosteroids in the treatment of tuberculous pleurisy.", "A randomized, double-blind, placebo-controlled trial of the use of prednisolone as an adjunct to treatment in HIV-1-associated pleural tuberculosis.", "Corticosteroids in the treatment of tuberculous pleurisy. A double-blind, placebo-controlled, randomized study." ]

[ "A prospective, double-blind, randomized study of the role of corticosteroids in the treatment of tuberculous pleurisy was performed in 40 patients. All patients received adequate antituberculosis chemotherapy (isoniazid, 300 mg/day; rifampin, 450 mg/day; ethambutol, 20 mg/kg/day) for more than nine months. They were randomly assigned to take prednisolone 0.75 mg/kg/day orally or placebo for the initial treatment, which was tapered gradually for the next two to three months. Twenty-one were treated with steroids and 19 were given a placebo. The two groups were identical with regard to age, sex, duration from onset of symptoms to diagnosis, and initial amount of pleural effusion. The mean duration from symptoms (fever, chest pain, dyspnea) to relief was 2.4 days in the steroid-treated group, and 9.2 days in the placebo group (p less than 0.05). Complete reabsorption of pleural effusion occurred an average of 54.5 days in the steroid-treated group and 123.2 days in the placebo group (p less than 0.01). The development of residual pleural thickening was not influenced by the administration of corticosteroids. No serious side effects were noted during the treatment in either group. We conclude that the administration of corticosteroids, in conjunction with antituberculosis chemotherapy, will resolve the clinical symptoms more quickly and hasten the absorption of pleural effusion in patients with tuberculous pleurisy.", "Tuberculous pleurisy can result in pleural fibrosis, calcification and thickening. To prevent these complications, corticosteroids are frequently used in addition to antituberculous drugs; however, new therapeutic regimens can control the disease and minimise the sequelae, and there is no convincing evidence of the benefit of the use of corticosteroids as adjuvant therapy.\n Patients received isoniazid 5 mg/kg and rifampicin 10 mg/kg daily for six months. Additionally, they were randomly assigned to a double blind treatment with either prednisone (1 mg/kg/day for 15 days and then tapering off) or placebo during the first month of treatment. Different clinical, radiological, and functional parameters were evaluated to assess the effect of corticosteroids.\n Fifty seven patients received prednisone and 60 placebo. At the end of the treatment the clinical outcome, the rate of reabsorption of the pleural fluid, the pleural sequelae, as well as lung capacity were similar in both groups.\n Corticosteroids do not influence the clinical outcome or the development of long term pleural sequelae in tuberculous pleurisy.", "Active tuberculosis may accelerate progression of human immunodeficiency virus (HIV) infection by promoting viral replication in activated lymphocytes. Glucocorticoids are used in pleural tuberculosis to reduce inflammation-induced pathology, and their use also might reduce progression of HIV by suppressing immune activation. We examined the effect that prednisolone has on survival in HIV-1-associated pleural tuberculosis.\n We conducted a randomized, double-blind, placebo-controlled trial of prednisolone as an adjunct to tuberculosis treatment, in adults with HIV-1-associated pleural tuberculosis. The primary outcome was death. Analysis was by intention to treat.\n Of 197 participants, 99 were assigned to the prednisolone group and 98 to the placebo group. The mortality rate was 21 deaths/100 person-years (pyr) in the prednisolone group and 25 deaths/100 pyr in the placebo group (age-, sex-, and initial CD4+ T cell count-adjusted mortality rate ratio, 0.99 [95% confidence interval, 0.62-1.56] [P =.95]). Resolution of tuberculosis was faster in the prednisolone group, but recurrence rates were slightly (though not significantly) higher, and use of prednisolone was associated with a significantly higher incidence of Kaposi sarcoma (4.2 cases/100 pyr, compared with 0 cases/100 pyr [P =.02]).\n In view of the lack of survival benefit and the increased risk of Kaposi sarcoma, the use of prednisolone in HIV-associated tuberculous pleurisy is not recommended.", "Although several studies on tuberculous (TB) pleurisy suggest that the addition of corticosteroids to anti-TB therapy may have beneficial effects, these agents are not used routinely. To assess the effects of short-term oral prednisone therapy in TB pleurisy, 74 patients were randomly assigned in a double-blind fashion to treatment with either placebo or prednisone at a dose of 0.75 mg/kg/d for up to 4 weeks with gradual reduction over an additional 2 weeks. All subjects received a standard 3-drug anti-TB chemotherapy regimen for 6 months. TB pleurisy was diagnosed by histologic study and/or culture of pleural biopsy specimens obtained at thoracoscopy. Complete drainage of the effusion was performed simultaneously. Outcome measures were assessed periodically for 24 weeks, including indexes of morbidity and pleural thickening. After randomization, four patients were excluded from the final analysis. Of the 70 patients analyzed, 34 received prednisone and 36 received placebo. Demographic and clinical characteristics of the treatment groups were comparable at the time of hospital admission. Although a statistically significant improvement in symptoms occurred earlier in the prednisone group (8 weeks) than in the placebo group (12 weeks), between-group comparison showed no significant differences at any of the follow-up evaluations. The proportion of subjects in the prednisone group (53.1%) with residual pleural thickening at 6 months did not differ significantly from that of the placebo group (60%). Pleural effusions did not recur in any of the patients. Initial complete drainage of the effusion was associated with greater symptomatic improvement than any subsequent therapy. We conclude that standard anti-TB therapy and early complete drainage is adequate for the treatment of TB pleurisy. The addition of short-term oral prednisone therapy neither results in clinically relevant earlier symptom relief nor confers a beneficial effect on residual pleural thickening." ]

[ "8885736", "15617697", "10074976", "9396908", "15842288", "18055730", "7503169", "19701035", "3684126", "19682886", "15592291", "9351763", "2692178", "18922525", "19087079", "8304889", "18669722", "10775722", "8906005", "14586357", "10759280", "20338954" ]

[ "Does the use of a tocolytic agent affect the success rate of external cephalic version?", "Tocolysis in term breech external cephalic version.", "The effect of spinal anesthesia on the success rate of external cephalic version: a randomized trial.", "A randomized trial of epidural anesthesia to improve external cephalic version success.", "Tocolysis for repeat external cephalic version in breech presentation at term: a randomised, double-blinded, placebo-controlled trial.", "External cephalic version for breech presentation with or without spinal analgesia in nulliparous women at term: a randomized controlled trial.", "Fetal acoustic stimulation, an adjunct to external cephalic version: a blinded, randomized crossover study.", "Intravenous nitroglycerin for external cephalic version: a randomized controlled trial.", "External cephalic version at term: is a tocolytic necessary?", "A randomized controlled trial of the effect of combined spinal-epidural analgesia on the success of external cephalic version for breech presentation.", "Randomized comparison of intravenous nitroglycerin and subcutaneous terbutaline for external cephalic version under tocolysis.", "A randomized placebo-controlled evaluation of terbutaline for external cephalic version.", "A prospective randomised controlled trial of external cephalic version comparing two methods of uterine tocolysis with a non-tocolysis group.", "Intravenous salbutamol for external cephalic version.", "Oral nifepidine versus subcutaneous terbutaline tocolysis for external cephalic version: a double-blind randomised trial.", "Randomized, double blind, placebo controlled comparison of ritodrine and hexoprenaline for tocolysis prior to external cephalic version at term.", "Nifedipine as a uterine relaxant for external cephalic version: a randomized controlled trial.", "Epidural analgesia for cephalic version: a randomized trial.", "A randomized, double blind, controlled trial of tocolysis to assist external cephalic version in late pregnancy.", "Sublingual nitroglycerin versus placebo as a tocolytic for external cephalic version: a randomized controlled trial in parous women.", "Double-blind randomised controlled trial of glyceryl trinitrate spray for external cephalic version.", "Randomized controlled trial of external cephalic version in term multiparae with or without spinal analgesia." ]

[ "Our purpose was to study the effect of ritodrine tocolysis on the success rate of external cephalic version at > or = 36 weeks' gestation.\n This was a prospective, double-blinded, randomized study. All patients were > or = 36 weeks' gestation, confirmed by early ultrasonography. External cephalic version assessment included nonstress testing before and after external cephalic version and ultrasonographic evaluation of type of breech, estimated fetal weight, position of placenta and fetal spine, and amniotic fluid index. Patients were excluded if the breech was not mobile or if they had any contraindications to tocolysis or external cephalic version. After randomization 283 patients received either ritodrine (111 micrograms/min) or identical placebo by intravenous infusion for > or = 20 minutes. Up to three attempts at external cephalic version under ultrasonographic surveillance were performed. With an alpha error of 0.05 and a beta of 0.2, 264 patients were required to complete this study.\n There were no differences between study groups in maternal age, body mass index, gestational age, amniotic fluid index, position of fetal spine, and placental location. Statistical analysis controlled for parity because parity had a major influence on success rates. There was a higher success rate in the group receiving ritodrine tocolysis (52% vs 42%, p = 0.028). Ritodrine improved success rates in nulliparous patients (43% vs 25%, p = 0.026) but not in parous subjects (66% vs 58%, p = 0.385).\n Ritodrine tocolysis improves the success rate of external cephalic version performed at > or = 36 weeks in nulliparous patients.", "To study the effect of ritodrine tocolysis on the success of external cephalic version (ECV) and to assess the role of ECV in breech presentation at our centre.\n A prospective randomized double-blind-controlled trial comparing ritodrine and placebo in ECV of singleton term breech pregnancy at a tertiary hospital.\n Among the 60 patients who were recruited, there was a success rate of 36.7%. Ritodrine tocolysis significantly improved the success rate of ECV (50% vs. 23%; P=0.032). There was a marked effect of ritodrine tocolysis on the ECV success in nulliparae (36.4% vs. 13.0%) and multiparae (87.5% vs. 57.1%). External cephalic version has shown to reduce the rate of cesarean section for breech presentation by 33.5% in our unit.\n External cephalic version significantly reduced the rate of cesarean section in breech presentation, and ritodrine tocolysis improved the success of ECV and should be offered to both nulliparous and parous women in the case of term breech presentation.", "To identify the effect of spinal anesthesia on the success rate of external cephalic version after 36 weeks' gestation.\n Women with singleton breech presentations after 36 weeks' gestation were offered enrollment. Those who agreed were randomized to receive spinal anesthesia or no anesthesia. Up to four attempts were made using ultrasound surveillance. External cephalic version was terminated with patient discomfort or fetal heart decelerations. Statistical analysis based on intent-to-treat was performed using chi2, Student t tests, and multivariate analysis. Sample size projection based on 20% difference in success rate from a baseline of 50% indicated a need for 50 women in each group.\n One hundred two women were entered in the study from October 1993 to August 1997. There were no differences between groups in parity, maternal age, amniotic fluid index, gestational age, birth weight, placental location, type of breech presentation, maternal weight, or gestational age at delivery. Forty-four external cephalic versions were successful. Fifty (49%) women received spinal anesthesia, and 52 (51%) did not; there was no difference in the overall success rate between groups (44% spinal versus 42% no spinal). Spontaneous version occurred before external cephalic version was attempted in four patients in the spinal group (after the spinal was given) and one patient in the no-spinal group. These patients were included in the analysis.\n Spinal anesthesia does not increase the external cephalic version success rate in singleton pregnancies with breech presentations after 36 weeks' gestation.", "This study was designed to determine whether epidural anesthesia would improve external cephalic version success in a safe and effective manner.\n All women > 37 weeks' gestation with breech presentation scheduled for external cephalic version at the medical center from Dec. 1, 1993, to July 31, 1996, were randomized to receive an epidural or no epidural anesthesia. Under ultrasonographic guidance up to three version attempts were performed.\n Sixty-nine women were randomized to receive epidural (n = 35) versus no epidural (n = 34) anesthesia for external cephalic version. There were no statistically significant differences in maternal age, parity, maternal weight, gestational age, estimated fetal weight, or station of the presenting part. The success rate was better for the epidural group (relative risk 2.12, 95% confidence interval 1.24 to 3.62). Neither anterior placentation or oligohydramnios affected the success rate.\n Epidural anesthesia increases success of external cephalic version without any apparent detrimental effect on the maternal-fetal unit.", "External cephalic version (ECV) reduces the incidence of breech presentation at term and caesarean section for non-cephalic births. Tocolytics may improve success rates, but are time consuming, may cause side effects and have not been proven to alter caesarean section rates. The aim of this trial was to determine whether tocolysis should be used if ECV is being re-attempted after a failed attempt.\n To determine whether tocolysis should be used if ECV is being re-attempted after a failed attempt.\n Randomised, double-blinded, placebo-controlled trial.\n UK teaching hospital.\n One hundred and twenty-four women with a breech presentation at term who had undergone an unsuccessful attempt at ECV.\n Relative risks with 95% confidence intervals for categorical variables and a t test for continuous variables. Analysis was by intention to treat.\n Incidence of cephalic presentation at delivery. Secondary outcomes were caesarean section and measures of neonatal and maternal morbidity.\n The use of tocolysis for a repeat attempt at ECV significantly increases the incidence of cephalic presentation at delivery (RR 3.21; 95% CI 1.23-8.39) and reduces the incidence of caesarean section (RR 0.33; 95% CI 0.14-0.80). The effects were most marked in multiparous women (RR for cephalic presentation at delivery 9.38; 95% CI 1.64-53.62). Maternal and neonatal morbidity remain unchanged.\n The use of tocolysis increases the success rate of repeat ECV and reduces the incidence of caesarean section. A policy of only using tocolysis where an initial attempt has failed leads to a relatively high success rate with minimum usage of tocolysis.", "To compare the success of external cephalic version using spinal analgesia with no analgesia among nulliparas.\n A prospective randomized controlled trial was performed in a tertiary referral center delivery suite. Nulliparous women at term requesting external cephalic version for breech presentation were randomized to receive spinal analgesia (7.5 mg bupivacaine) or no analgesia before the external cephalic version. An experienced obstetrician performed the external cephalic version. Primary outcome was successful conversion to vertex presentation.\n Seventy-four women were enrolled, and 70 analyzed (36 spinal, 34 no analgesia). Successful external cephalic version occurred among 24 of 36 (66.7%) women randomized to receive spinal analgesia compared with 11 of 34 (32.4%) without, P=.004 (95% confidence interval [CI] of the difference: 0.0954-0.5513). External cephalic version with spinal analgesia resulted in a lower visual analog pain score, 1.76+/-2.74 compared with 6.84+/-3.08 without, P<.001. A secondary analysis logistic regression model demonstrated that the odds of external cephalic version success was 4.0-fold higher when performed with spinal analgesia P=.02 (95% CI, odds ratio [OR] 1.2-12.9). Complete breech presentation before attempting external cephalic version increased the odds of success 8.2-fold, P=.001 (95% CI, OR 2.2-30.3). Placental position, estimated fetal weight, and maternal weight did not contribute to the success rate when spinal analgesia was used. There were no cases of placental abruption or fetal distress.\n Administration of spinal analgesia significantly increases the success rate of external cephalic version among nulliparous women at term, which allows possible normal vaginal delivery.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT00119184\n I.", "Our purpose was to determine whether fetal acoustic stimulation can improve the chance of successful external cephalic version in patients at 36 to 38 weeks' gestation with fetal midline spine position.\n A randomized, blinded crossover trial was performed. In this \"N of 1\" study, the patient served as her own control.\n Twenty-six patients were enrolled in the study, and three were excluded due to engagement of the fetal breech. In the initial trial with fetal acoustic stimulation to the maternal abdomen, 12 of 12 (100%) changed position to spine lateral and 11 of 12 (92%) were successfully verted. In the control group (fetal acoustic stimulation to nurse's arm), none of 11 (0%) changed position to spine lateral and one of 11 (9%) were successfully verted (p < 0.0001). In the crossover trial eight of 10 (80%) of the original placebo (control) patients were successfully verted after fetal acoustic stimulation to the maternal abdomen and none of 1 (0%) from the original treatment group were successfully verted after placebo fetal acoustic stimulation (p < 0.0001). Combined data from the original and crossover trials indicates 19 of 22 (86%) successful versions after fetal acoustic stimulation to maternal abdomen compared with one of 12 (8%) that had successful external cephalic version after placebo fetal acoustic stimulation.\n Fetal acoustic stimulation shifts fetal position to spine lateral, which increases successful version of fetuses with midline fetal spine presentations.", "To estimate whether treatment with intravenous nitroglycerin for uterine relaxation increases the chance of successful external cephalic version.\n Two double-blind, randomized clinical trials were undertaken: one in nulliparous women and a second in multiparous women. Women presenting for external cephalic version at term were eligible to participate. The primary outcome was immediate success of external cephalic version. Other outcomes were presentation at delivery, cesarean delivery rate, and side effects and complications. Sample size calculations were based on a 100% increase in success of external cephalic version with a one-sided analysis and alpha=0.05 (80% power).\n In total, 126 women were recruited-82 in the nulliparous trial and 44 in the multiparous trial. Seven patients did not have external cephalic version before delivery but were included in the analysis of success of external cephalic version. One patient was lost to follow-up. The external cephalic version success rate for nulliparous patients was 24% (10 of 42) in patients who received nitroglycerin compared with 8% (3 of 40) in those who receive placebo (P=.04, one-sided Fisher exact test, odds ratio 3.85, lower bound 1.22). In multiparous patients, the external cephalic version success rate did not differ significantly between groups: 44% (10 of 23) in the nitroglycerin group compared with 43% (9 of 21) in the placebo group (P=.60).\n Treatment with intravenous nitroglycerin increased the rate of successful external cephalic version in nulliparous, but not in multiparous, women. Treatment with intravenous nitroglycerin appeared to be safe, but our numbers were too small to rule out rare serious adverse effects.\n I.", "This prospective investigation evaluates the benefit of a beta-mimetic tocolytic for external cephalic version. From July 1, 1984 to May 15, 1987, 58 patients who had breech presentations between 37-41 weeks' gestation were considered for external cephalic version. The patients were randomly assigned to one of two groups: tocolytic or no tocolytic. An ultrasound examination, serum alpha-fetoprotein (AFP), Kleihauer-Betke test, and nonstress test (NST) were performed before and after the attempt at version. A version was not attempted if there was evidence of intrauterine growth retardation (IUGR), oligohydramnios, or a nonreactive NST. Patients in the tocolytic group received 200 micrograms/minute of ritodrine hydrochloride for 20 minutes via continuous intravenous infusion before a version was attempted. Twenty of the 30 patients (66.7%) in the tocolytic group and 19 of the 28 patients (67.8%) in the no-tocolytic group had successful versions, a nonsignificant difference. The nine patients with unsuccessful version attempts in the group without a tocolytic then received intravenous ritodrine and underwent a second attempt. Only one of these nine attempts was successful. There were no serious maternal or fetal complications associated with the attempts at version. In our patient population, use of a tocolytic did not significantly increase the probability of a successful version.", "Improving the success of external cephalic version (ECV) for breech presentation may help avoid some cesarean deliveries. The results of randomized trials comparing the success of ECV with neuraxial analgesia compared to control are inconsistent. We hypothesized that combined spinal-epidural (CSE) analgesia would increase the success of ECV when compared with systemic opioid analgesia.\n Parturients with singleton breech presentation (n=96) were randomized to receive CSE analgesia with bupivacaine 2.5mg and fentanyl 15 microg (CSE group) or intravenous fentanyl 50 microg (SYS group) before ECV attempt. The primary outcome was ECV success.\n The success rate of ECV was 47% with CSE and 31% in the SYS group (P=0.14). Subsequent vaginal delivery was 36% for CSE and 25% for SYS (P=0.27). Median [IQR] visual analog pain scores (0-100mm scale) were lower with CSE (3 [0-12]) compared to SYS analgesia (36 [16 to 54]) (P<0.005) and patient satisfaction (0-10 scale) was higher (CSE 10 [9 to 10] versus SYS 7 [4 to 9]) (P<0.005). There were no differences in fetal heart rate patterns, but median time to return to fetal heart rate reactivity after analgesia was shorter with CSE (13 [IQR 9-21] min) compared to the SYS group (39 [IQR 23-51] min) (P=0.02).\n There was no difference in the rate of successful ECV or vaginal delivery with CSE compared to intravenous fentanyl analgesia. Pain scores were lower and satisfaction higher with CSE analgesia, and median time to fetal heart rate reactivity was shorter in the CSE group.", "The purpose of this study was to compare the efficacy and safety of intravenous nitroglycerin with that of subcutaneous terbutaline as a tocolytic agent for external cephalic version at term.\n We performed a prospective randomized trial. Patients between 37 and 42 weeks of gestation were assigned randomly to receive either 200 microg of intravenous nitroglycerin therapy or 0.25 mg of subcutaneous terbutaline therapy for tocolysis during external cephalic version. The rate of successful external cephalic version and side effects were compared between groups.\n Of 59 randomly assigned patients, 30 patients received intravenous nitroglycerin, and 29 patients received subcutaneous terbutaline. The overall success rate of external cephalic version in the study was 39%. The rate of successful external cephalic version was significantly higher in the terbutaline group (55% vs 23%; P = .01). The incidence of palpitations was significantly higher in patients who received terbutaline therapy (17.2% vs 0%; P = .02), as was the mean maternal heart rate at multiple time periods.\n Compared with intravenous nitroglycerin, subcutaneous terbutaline was associated with a significantly higher rate of successful external cephalic version at term.", "To evaluate the efficacy of subcutaneous terbutaline therapy on the success rate of external cephalic version in term gestation.\n Women with singleton noncephalic gestations were assigned randomly to receive either terbutaline (0.25 mg) or placebo. Physicians were blinded to the assignment. Fifteen to 30 minutes after the study drug was administered, external cephalic version was attempted. It was discontinued after three attempts, for patient discomfort, for fetal heart rate decelerations, or when successful. Patients were discharged home after the procedure and allowed to enter spontaneous labor. Primary outcomes evaluated included initial success of version, presentation in labor, and route of delivery.\n One hundred three women were enrolled in the study between January 1994 and June 1995, of whom 52 were assigned to terbutaline and 51 to placebo. External cephalic version was successful in 27 of 52 (52%) women receiving terbutaline compared with 14 of 51 (27%) of those receiving placebo (P = .019). This comparison yielded a relative risk (RR) of 1.9 (95% confidence interval [CI] 1.3, 6.5). Four of the 27 (15%) successful versions in the terbutaline group and three of the 14 (21%) successful versions in the placebo group spontaneously reverted to breech presentation. Ultimately, in labor there were 24 (46%) cephalic presentations in the terbutaline group and 13 (25%) in the placebo group (P = .048, RR 1.84, 95% CI 1.1, 5.8). Cesarean delivery rates were 11 of 41 (27%) for women with successful versions and 58 of 62 (94%) among those with failed versions (P < .001).\n Terbutaline (0.25 mg) administered subcutaneously before an attempted version in women at term with noncephalic presentations significantly increased the initial success rate of version and the rate of cephalic presentations in labor while decreasing the rate of cesarean delivery.", "The use of tocolvtic agents to enhance uterine relaxation and facilitate external cephalic version (ECV) has come under recent debate. We studied 90 breech presentations in late pregnancy who did not have contra-indications to ECV. The patients were randomised into 3 groups of 30 patients each: one was administered oral salbutamol 4 mg t.d.s.; another had intravenous salbutamol infused until the maternal heart rate rose above 100 bpm for 30 mins; and the last served as a control group. All patients in each group were matched for parity and gestation, and each had an intravenous line, thereby masking the treatment group from the 2 doctors who performed half the number of ECVs each. There was no significant difference in the success of ECV between the treatment and control groups (46.6% vs 50.0% vs 46.6%). The gestational age, the placental site, the attitude of the breech, the abdominal girth, and the maternal weight and fetal birth weights did not seem to influence results. On the other hand, there was a significant difference in successful ECV between nullipara (26%) and multipara (75%) (p less than 0.001). There were no cases of abruptio placenta or foetal distress, and one patient entered labour one day after the ECV at 39 weeks gestation. There were 2 cases of spontaneous version after failed ECV, and one case of spontaneous reversion to breech after successful ECV. We conclude that the use of salbutamol does not increase the incidence of successful ECV, but multiparity predicts for a successful outcome.", "To evaluate the success of external cephalic version (ECV) using an adjusted bolus dose of intravenous salbutamol compared with no tocolysis.\n An open-label randomized study of 114 women with a term breech fetus randomized to receive either an intravenous bolus dose of 0.1 mg salbutamol with further boluses every 5 minutes, as required, before commencing ECV, or no tocolysis. Primary outcomes were successful ECV and rate of cesarean delivery.\n Salbutamol tocolysis resulted in a higher rate of successful ECV compared with no tocolysis (70.2% [40/57] vs 36.8% [21/57]; RR 1.9, 95% CI 1.3-2.8; P<0.001). Cesarean delivery rate was lower in the salbutamol group compared with the control group (31.6% [18/57] vs 63.2% [36/57]; RR 0.5, 95% CI 0.3-0.8; P=0.001). Salbutamol dose ranged from 0.1-0.4 mg and outcome was not related to dose.\n Adjusted dose intravenous salbutamol tocolysis prior to ECV increases its success rate and reduces the cesarean delivery rate.", "To evaluate oral nifedipine versus subcutaneous terbutaline tocolysis for external cephalic version (ECV).\n A double-blind randomised trial.\n A university hospital in Malaysia.\n Non-labouring women with a term singleton fetus in breech presentation or transverse lie suitable for elective ECV.\n Participants were randomised to either 10 mg oral nifedipine tablet and subcutaneous saline placebo or oral placebo tablet and 250 microgram bolus terbutaline subcutaneously. Participants and providers were blinded. Ultrasound assessment and cardiotocogram were performed prior to ECV. ECV was commenced 20-30 minutes after treatment. A maximum of two ECV attempts were permitted. Elective caesarean delivery or a repeat ECV attempt at a later date was offered to participants following failed ECV. After successful ECV, management was expectant.\n Primary outcomes were successful ECV (cephalic presentation immediately after ECV) and caesarean delivery.\n Ninety women were randomised: 44 to nifedipine and 46 to terbutaline. Initial ECV success rate was 15/44 (34.1%) versus 24/46 (52.2%) (relative risk [RR] 0.7, 95% CI 0.4-1.1; P= 0.094), and caesarean delivery rate was 34/44 (77.3%) versus 26/46 (56.5%) (RR 1.4, 95% CI 1.01-1.85; numbers needed to treat to benefit 5, 95% CI 2.5-55; P= 0.046) for nifedipine and terbutaline groups, respectively. Neonatal outcome was not different.\n Bolus subcutaneous terbutaline tocolysis for ECV compared with oral nifedipine resulted in less caesarean deliveries. ECV success rate was not significantly higher. Larger studies are indicated.", "External cephalic versions in the study period were performed in a double blind design by 2 experienced practitioners. Sixty-three patients were allocated to treatment with either placebo, ritodrine or hexoprenaline. The main outcome measure studied was successful completion of external cephalic version. Hexoprenaline, but not ritodrine, was statistically more likely to be associated with successful version than placebo (p = 0.04 versus p = 0.22).", "To estimate the effectiveness of nifedipine as a uterine relaxant during external cephalic version to correct breech presentation.\n In this randomized, double-blind, placebo-controlled trial, women with a singleton fetus in breech presentation and a gestational age of 36 weeks or more were eligible for enrollment. Participating women received two doses of either nifedipine 10 mg or placebo, 30 and 15 minutes before the external cephalic version attempt. The primary outcome was a cephalic-presenting fetus immediately after the procedure. Secondary outcome measures were cephalic presentation at delivery, mode of delivery, and adverse events. A sample size of 292 was calculated to provide 80% power to detect a 17% improvement of the external cephalic version success rate, assuming a placebo group rate of 40% and alpha of .05.\n Outcome data for 310 of 320 randomly assigned participants revealed no significant difference in external cephalic version success rates between treatment (42%) and control group (37%) (relative risk 1.1, 95%; 95% confidence interval 0.85-1.5). The cesarean delivery rate was 51% in the treatment group and 46% in the control group (relative risk 1.1, 95% confidence interval 0.88-1.4).\n Nifedipine did not significantly improve the success of external cephalic version. Future use of nifedipine to improve the outcome of external cephalic version should be limited to large clinical trials.", "To determine if epidural analgesia improves the success rate of external cephalic version.\n Women with singleton fetuses in breech or transverse presentation of at least 37 weeks' gestation were offered enrollment in a randomized trial. Inclusion criteria included maternal age of 18 years or older, nonvertex presentation confirmed by ultrasound, intact membranes, reactive fetal nonstress test, and estimated fetal weight (EFW) between 2000 and 4000 g. Women in the epidural group had lumbar epidural catheters inserted, through which 2% lidocaine and 100 microg of fentanyl were infused. External cephalic version attempts were done with ultrasound guidance in a standard fashion for both groups. The primary outcome variable was the successful version of the fetus to a cephalic presentation.\n There were no statistically significant differences between groups in gestation at time of procedure, placental location, fetal lie, gravity, parity, EFW, or amniotic fluid index. External cephalic version was successful in 32 of 54 women (59%) with epidural anesthesia compared with 18 of 54 (33%) with no anesthesia (relative risk [RR] 1.8, 95% confidence interval [CI] 1.2, 2.8, P <.05). Vaginal delivery occurred in 29 of 54 women (54%) in the epidural group and 16 of 54 women (30%) in the control group (RR 1.9, 95% CI 1.2, 2.9, P <.05).\n Epidural analgesia increased the success rate of external cephalic version and the likelihood of subsequent vaginal delivery.", "External cephalic version at term is not always successful. This trial was done to ascertain whether tocolysis has any effect on the success rate.\n A randomized, double blind, controlled trial, with continuous paired sequential analysis. Fifty-one consecutive patients with a singleton fetus in a breech presentation between 36 and 38 weeks gestation, external version being attempted on each. Ritodrine infusion or placebo was infused before attempt at external cephalic version.\n A university teaching hospital with 8000 confinements annually.\n Version was successful in 17 of the 25 patients given tocolysis, but in only eight of the 25 given placebo (p < 0.01). A positive benefit for tocolysis was shown after version had been completed in 10 pairs of patients. However the trial was continued until 25 pairs had been analyzed. The benefit deteriorated during analysis of the last 15 pairs suggesting that the initial benefit may reflect a learning curve for the procedure.\n Tocolysis is likely to improve the success rate of external cephalic version in late pregnancy, especially in nulliparous mothers or where doctors are learning the technique.", "The purpose of this study was to evaluate the efficacy of sublingual nitroglycerin as a tocolytic agent for external cephalic version in parous women.\n A double-blinded randomized controlled trial was performed. Patients with parity of >or=1 at 36 to 40 weeks of gestation who were eligible for external cephalic version were included. Patients were randomized to receive either two sublingual sprays of 400 mug of nitroglycerin or two sprays of placebo 3 minutes before the trial of external cephalic version. Rates of successful external cephalic version and side effects were compared between groups.\n Of 99 patients in the study, 50 patients received sublingual nitroglycerin, and 49 patients received placebo. There were no differences in maternal age, gestational age, estimated fetal weight, amniotic fluid index, and placental location between the two groups. The success rate of external cephalic version was 48% in the nitroglycerin group compared with 63% in the placebo group (P=.13). There was a higher incidence of headaches in the nitroglycerin group (42% vs 4%, P<.001).\n Sublingual nitroglycerin was associated with a higher rate of headache and did not improve the rate of successful external cephalic version.", "A placebo controlled trial of glyceryl trinitrate was carried out in women whose first attempt at external cephalic version without tocolysis had been unsuccessful. No significant differences between groups were found and no side effects were noted. It is recommended that a larger, possibly multicentre study, should be undertaken.", "Neuraxial analgesia significantly increases the success rate of external cephalic version (ECV) among nulliparae. The study objective was to compare ECV success among multiparae with and without spinal analgesia.\n Prospective randomized controlled trial performed over a pre-defined 6 yr period in a tertiary referral delivery suite. Healthy multiparae at term requesting ECV for breech presentation, without fetal or uterine anomaly, were enrolled after written informed consent. Women were randomized to receive either spinal analgesia (bupivacaine 7.5 mg) or no analgesia before the ECV. The primary outcome was successful conversion from breech to vertex presentation, confirmed by ultrasound. Visual analogue pain score and adverse outcomes (complications of anaesthesia or ECV) were recorded. Statistical analysis was performed according to intention to treat using two-sided tests.\n Among 265 multiparae who underwent ECV, 65 consented to enrol, one subsequently refused ECV; therefore, data from 64 women were analysed. ECV was successful in 27 of 31 patients (87.1%) receiving spinal analgesia vs 19 of 33 (57.5%) with no analgesia (P=0.009; 95% CI of difference: 0.075-0.48). ECV with spinal analgesia reduced visual analogue pain score, mean (sd) 1.7 (2.4) vs 5.5 (2.9) without (P<0.0001). Maternal hypotension was seen after spinal analgesia in 10 of 31 (32%) (P=0.0003) and easily treated without adverse outcome. No complications were noted after the ECV.\n Administration of spinal analgesia significantly increased the rate of successful ECV among multiparae at term with increased patient comfort. The trial was registered at the National Institute of Health Trials Registry, NCT00119184, www.clinicaltrials.gov." ]

[ "12187178", "12585303", "11760489", "12126319", "6219949", "11944760", "14534526" ]

[ "Health services utilization with reference drug pricing of histamine(2) receptor antagonists in British Columbia elderly.", "Do pharmaceutical prices respond to potential patient out-of-pocket expenses?", "Impact of the Minimum Pricing Policy and introduction of brand (generic) substitution into the Pharmaceutical Benefits Scheme in Australia.", "Impact of reference-based pricing for histamine-2 receptor antagonists and restricted access for proton pump inhibitors in British Columbia.", "Pharmaceutical reimbursement and drug cost control: the MAC experience in Maryland.", "Impact of reference-based pricing for angiotensin-converting enzyme inhibitors on drug utilization.", "Clinical and economic consequences of reference pricing for dihydropyridine calcium channel blockers." ]

[ "In October 1995, British Columbia introduced a reference pricing policy for five therapeutic classes of drugs, including histamine(2) receptor antagonists (H(2)RAs), for beneficiaries of its prescription drug program, Pharmacare.\n To evaluate utilization trends in consumption of health services in a cohort of Pharmacare beneficiaries to determine if a worsening of health outcomes could be detected after implementation of the reference pricing policy.\n Two cohorts, \"control\" (21 months before the reference pricing policy) and \"exposed\" (at risk for policy effects), were followed for 21 months. Using a longitudinal generalized linear model (Poisson), and controlling for age, sex, and prescriptions in unique drug classes, trend lines in each of these time series were compared for 3 periods: 9 months before policy implementation (or corresponding index date in the control cohort), 6 months after policy implementation, and a subsequent 6-month period.\n Two cohorts, each of size 10,000, were constructed by randomly sampling the population of Pharmacare beneficiaries exposed to H(2)RAs and other antisecretory drugs for 1993 through 1996.\n Prescriptions, physician office visits and associated transactions (ie, laboratory tests), emergency room visits, hospitalizations, hospital length of stay, and vital statistics.\n Differences between periods and between cohorts for health services utilization were not significant or decreased after imposition of the reference pricing policy.\n For these measures, there has been no worsening of health outcomes associated with implementing the reference pricing policy.", "Despite the importance of patient insurance in the market for prescription pharmaceuticals, little is known about the impact of patient reimbursement on the pricing behavior of pharmaceutical firms. I examine the link between potential patient out-of-pocket expenses and pharmaceutical pricing using a unique policy experiment from Germany. Starting in 1989, a maximum reimbursement for a given medicine replaced a flat prescription fee. This change in reimbursement exposes the patient to the price of a prescribed product. Using a product-level panel data set covering several therapeutic categories before and after the policy change, I find that producers significantly decrease prices after the change in potential patient out-of-pocket expenses. Price declines are most pronounced for brand-name products. Moreover, branded products that face more generic competitors reduce prices more.", "To describe the effects of introducing the Minimum Pricing Policy (MPP) and generic (brand) substitution in 1990 and 1994 respectively on the dispensing of Pharmaceutical Benefits Scheme (PBS) prescriptions both at the aggregate and individual patient level.\n The relative proportion of prescriptions with a brand premium and those at benchmark was examined 4 years after introduction of the MPP and again 5 years later after generic substitution by pharmacists was permitted. To determine the impact of a price signal at the individual level, case studies involving a patient tracking methodology were conducted on two drugs (fluoxetine and ranitidine) that received a brand premium.\n From a zero base when the MPP was introduced in 1990, there were 5.4 million prescriptions (17%) dispensed for benchmark products 4 years later in 1994. At this stage generic (brand) substitution by pharmacists was then permitted and the market share of benchmark brands increased to 45% (25.2 million) by 1999. In the patient tracking studies, a significantly lower proportion of patients was still taking the premium brand of fluoxetine 3 months after the introduction of a price signal compared with patients taking paroxetine which did not have a generic competitor. This was also the case for the premium brand of ranitidine when compared to famotidine. The size of the price signal also had a marked effect on dispensing behaviour with the drug with the larger premium (fluoxetine) showing a significantly greater switch away from the premium brand to the benchmark product.\n The introduction in 1990 of the Minimum Pricing Policy without allowing generic substitution had a relatively small impact on the selection of medicines within the Pharmaceutical Benefits Scheme. However the effect of generic substitution at the pharmacist level, which was introduced in December 1994, resulted in a marked increase in the percentage of eligible PBS items dispensed at benchmark. Case studies showed a larger premium resulted in a greater shift of patients from drugs with a brand premium to the benchmark alternative.", "Two programs to reduce expenditures for common gastrointestinal drugs were introduced simultaneously by British Columbia (BC) Pharmacare in 1995. Reference-based pricing restricted reimbursement for all histamine-2 receptor antagonists (H2RAs) to the cost of the least expensive H2RA available, generic cimetidine. Special authority restricted reimbursement for proton pump inhibitors (PPIs) to patients who met certain eligibility criteria. We evaluated the effect of reference-based pricing for H2RAs and special authority for PPIs on dispensing and reimbursement for senior citizen beneficiaries of BC Pharmacare.\n Itemized monthly claims data for upper gastrointestinal drugs were obtained from BC Pharmacare for all beneficiaries 65 years of age or older. Periods before and after implementation of reference-based pricing and special authority were compared with respect to defined daily doses dispensed per 100,000 beneficiaries, BC Pharmacare reimbursement per 100,000 beneficiaries, BC Pharmacare reimbursement per defined daily dose and beneficiary contributions per defined daily dose. We used regression models to project forward trends in expenditures observed before implementation of the new policies and hence to estimate accrued cost savings.\n Before reference-based pricing and special authority, the numbers of defined daily doses that were dispensed and total BC Pharmacare reimbursements for H2RAs appeared to be declining gradually, whereas those for PPIs were rising. With reference-based pricing, the monthly defined daily dose of cimetidine dispensed increased more than 4-fold, to 116,257 per 100,000 beneficiaries, while those of other restricted H2RAs decreased by more than half, to 50,927 per 100,000 beneficiaries. Special authority immediately reduced the dispensed volumes of PPIs by one-fourth, but growth in volume then appeared to resume at its previous rate. The estimated annualized cost savings achieved by reference-based pricing and special authority were $1.8 million to $3.2 million for H2RAs (depending on the estimation method used) and $5.5 million for PPIs. However, beneficiary contributions for H2RAs increased from negligible amounts to approximately 16% of total drug expenditures.\n Reference-based pricing and special authority appear to have been successful in altering prescribing habits and reducing provincial expenditures for upper gastrointestinal drugs, but they have increased the financial burden on senior citizen beneficiaries.", "The Maximum Allowable Cost (MAC) program was mandated by the federal government in 1976 in an effort to curb drug expenditures under Medicare and Medicaid by limiting reimbursements for prescription products dispensed to program beneficiaries. MAC performance is usually evaluated in terms of state compliance with federal guidelines. The present study broadens this approach to include other sources of variation in program effectiveness across states. In the case of Maryland, the MAC program offers encouraging signs of at least limited success in curbing Medicaid drug expenditures. The results of the study show a significant, but short-lived, decline in spending levels, suggesting the possibility of program-induced increases in wholesale prices or dispensing fees over time.", "Increasing copayments for higher-priced prescription medications has been suggested as a means to help finance drug coverage for elderly patients, but evaluations of the impact of such policies are rare. The objective of this study was to analyze the effect of reference-based pricing of angiotensin-converting enzyme (ACE) inhibitors on drug utilization, cost savings and potential substitution with other medication classes.\n We analyzed 36 months of claims data from British Columbia for 2 years before and 1 year after implementation of reference-based pricing (in January 1997). The 119,074 patients were community-living Pharmacare beneficiaries 65 years of age or older who used ACE inhibitors during the study period. The main outcomes were changes over time in use of ACE inhibitors, use of antihypertensive drugs and expenditures for antihypertensive drugs, as well as predictors of medication switching related to reference-based pricing.\n We observed a sharp decline (29%) in the use of higher-priced cost-shared ACE inhibitors immediately after implementation of the policy (p < 0.001). After a transition period, the post-implementation utilization rate for all ACE inhibitors was 11% lower than projected from pre-implementation data. However, overall utilization of antihypertensives was unchanged (p = 0.40). The policy saved $6.7 million in pharmaceutical expenditures during its first 12 months. Patients with heart failure or diabetes mellitus who were taking a cost-shared ACE inhibitor were more likely to remain on the same medication after implementation of reference-based pricing (OR 1.12 [95% confidence interval, CI, 1.06-1.19] and 1.28 [95% CI 1.20-1.36] respectively). Patients with low-income status were more likely than those with high-income status to stop all antihypertensive therapy (OR 1.65 [95% CI 1.43-1.89]), which reflects a general trend toward discontinuation of therapy among these patients even before implementation of reference-based pricing.\n Reference-based pricing in British Columbia achieved a sustained reduction in drug expenditures, and no changes in overall use of antihypertensive therapy were observed. Further research is needed on the overall health and economic effects of such policies.", "Reference pricing is a medication cost-sharing policy that fully covers medications which are less expensive than a standard reference price and requires patients to pay the extra cost of higher-priced drugs in a class of therapeutically substitutable drugs. Little information exists on the clinical and economic consequences. We analyzed changes in drug utilization, physician visits, hospitalizations, long-term care admissions, and expenditures after the introduction of reference pricing for dihydropyridine calcium channel blockers (CCBs) among patients aged 65 years or older in British Columbia, Canada.\n This quasiexperimental longitudinal study was performed in the setting of Pharmacare, the state-funded drug benefits plan of all elderly persons in British Columbia. Study patients comprised all elderly residents of British Columbia who were enrolled in the provincial health insurance program and received dihydropyridine CCBs at the time of the policy change (35,886) and a subgroup of high-priced dihydropyridine CCB users (23,116). We studied the implementation of reference drug pricing on Jan 1, 1997, affecting all elderly Pharmacare beneficiaries. The main outcome measures were drug utilization, drug expenditures, physician visits, hospitalizations, long-term care, and net savings.\n The start of reference pricing was followed by a significant reduction in high-priced dihydropyridine CCBs (-150 monthly doses per 10,000 elderly persons), with a corresponding increase in fully covered dihydropyridine CCBs (+116). Overall, antihypertensive use did not decline (P =.46). Low-income status was a risk factor for discontinuing treatment (odds ratio, 1.64; 95% confidence interval [CI], 1.36 to 1.99); however, this was already observed to a similar magnitude 12 months before reference pricing (odds ratio, 1.46). In the overall study cohort, there was no increase in rates of physician visits, hospitalizations, and long-term care admissions. However, the 9% of patients who actually switched medications showed an 18% increase (95% CI, 8% to 28%) in physician visits and an increase of Canadian $13 (95% CI, Canadian $3 to Canadian $24) in costs of physician visits per patient as compared with nonswitchers during the transition but not afterward. This temporary increase may have been a result of additional prescribing and monitoring in switchers. Changes in drug expenditures and physician services resulted in net savings of Canadian $1.6 million in the first 12 months of policy implementation.\n Reference pricing as implemented in British Columbia may be a model for successful pharmaceutical cost-containment without adversely affecting patients or cost-shifting." ]

[ "9013456", "16780548", "11920308", "11003347", "18261177", "9730559", "22094954", "11750538", "8304654", "12937241", "18622294", "11571454", "17973956", "11602864" ]

[ "Control of cytomegalovirus-associated morbidity in renal transplant patients using intensive monitoring and either preemptive or deferred therapy.", "Prophylactic versus preemptive oral valganciclovir for the management of cytomegalovirus infection in adult renal transplant recipients.", "Preemptive use of oral ganciclovir to prevent cytomegalovirus infection in liver transplant patients: a randomized, placebo-controlled trial.", "Cytomegalovirus antigenemia directed pre-emptive prophylaxis with oral versus I.V. ganciclovir for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, controlled trial.", "Improvement in long-term renal graft survival due to CMV prophylaxis with oral ganciclovir: results of a randomized clinical trial.", "Clinical course of cytomegalovirus (CMV) viremia with and without ganciclovir treatment in CMV-seropositive kidney transplant recipients. Longitudinal follow-up of CMV pp65 antigenemia assay.", "Valganciclovir prophylaxis versus preemptive therapy in cytomegalovirus-positive renal allograft recipients: 1-year results of a randomized clinical trial.", "Preemptive oral ganciclovir therapy versus prophylaxis to prevent symptomatic cytomegalovirus infection after kidney transplantation.", "High-dose acyclovir compared with short-course preemptive ganciclovir therapy to prevent cytomegalovirus disease in liver transplant recipients. A randomized trial.", "Pre-emptive therapy of CMVpp65 antigen positive renal transplant recipients with oral ganciclovir: a randomized, comparative study.", "Prophylaxis followed by preemptive therapy versus preemptive therapy for prevention of human cytomegalovirus disease in pediatric patients undergoing liver transplantation.", "Prospective randomized trial to assess the value of preemptive oral therapy for CMV infection following liver transplantation.", "Valacyclovir prophylaxis versus preemptive valganciclovir therapy to prevent cytomegalovirus disease after renal transplantation.", "Cytomegalovirus pp65 antigen-guided preemptive therapy with ganciclovir in solid organ transplant recipients: a prospective, double-blind, placebo-controlled study." ]

[ "The objective of this randomized, prospective study was to compare preemptive to deferred treatment of cytomegalovirus (CMV) infection in high-risk renal transplant recipients. Conducted at a university-affiliated transplant center, the study included 36 renal allograft recipients with donor or recipient CMV-seropositivity who received anti-thymocyte induction therapy. Ganciclovir was administered intravenously for 21 days upon detection of CMV viremia (preemptive, N = 15) or detection of CMV viremia associated with a CMV syndrome (deferred, N = 21). Shell vial culture, conventional culture, and polymerase chain reaction (PCR) were performed upon buffy-coat specimens weekly for 12 to 16 wk. CMV and non-CMV-associated charges were calculated. The comparative sensitivities of PCR, shell vial culture, and conventional culture were 91%, 44%, and 47%, respectively. A delay in specimen processing of > 24 h severely compromised the sensitivity of culture techniques but not that of PCR. Preemptive therapy tended to decrease symptomatic CMV episodes (0.4 versus 0.6 episodes per patient randomized; P = 0.22). One patient in each group had organ involvement, and no patient died. Allograft function and survival were similar. Ganciclovir use was increased in the preemptive group (1.2 versus 0.6 courses per patient randomized; P = 0.02). CMV-associated charges were $10,368 (preemptive) versus $5,752 (deferred); P = 0.13. PCR is superior to conventional monitoring to detect CMV viremia. Culture cannot be considered the \"gold standard\" for detection of CMV viremia, especially when transport of specimens over distances results in processing delays. Preemptive therapy may reduce symptomatic CMV infections in renal transplant recipients. It was associated with higher CMV-related charges but equivalent overall charges versus deferred treatment with intensive monitoring. Either strategy can achieve control of CMV infection after renal transplantation.", "Prophylaxis reduces cytomegalovirus (CMV) disease, but is associated with increased costs and risks for side effects, viral resistance and late onset CMV disease. Preemptive therapy avoids drug costs but requires frequent monitoring and may not prevent complications of asymptomatic CMV replication. Kidney transplant recipients at risk for CMV (D+/R-, D+/R+, D-/R+) were randomized to prophylaxis (valganciclovir 900 mg q.d. for 100 days, n=49) or preemptive therapy (900 mg b.i.d. for 21 days, n=49) for CMV DNAemia (CMV DNA level>2000 copies/mL in >or=1 whole blood specimens by quantitative PCR) assessed weekly for 16 weeks and at 5, 6, 9 and 12 months. More patients in the preemptive group, 29 (59%) than in the prophylaxis group, 14 (29%) developed CMV DNAemia, p=0.004. Late onset of CMV DNAemia (>100 days after transplant) occurred in 11 (24%) randomized to prophylaxis, and none randomized to preemptive therapy. Symptomatic infection occurred in five patients, four (3 D+/R- and 1 D+/R+) in the prophylactic group and one (D+/R-) in the preemptive group. Peak CMV levels were highest in the D+/R- patients. Both strategies were effective in preventing symptomatic CMV. Overall costs were similar and insensitive to wide fluctuations in costs of either monitoring or drug.", "The use of postdetection antiviral treatment of cytomegalovirus (CMV) as a strategy to prevent infection and disease in solid-organ transplant patients has not been evaluated by placebo-controlled trials. We carried out such a study in 69 patients who had received liver transplants and had positive results of CMV polymerase chain reaction within 8 weeks after transplantation but did not have concomitant CMV infection or disease. These patients were randomly assigned to receive placebo or oral ganciclovir for 8 weeks. CMV infection developed in 21% and disease developed in 12% of placebo recipients (P =.022), compared with 3% and 0%, respectively, among ganciclovir recipients (P =.003). Similarly, in the placebo arm, 55% and 36% of CMV-negative patients who received organs from CMV-positive donors developed CMV infection or disease, respectively (P =.02), compared with 11% and 0% of such patients in the ganciclovir arm (P <.01). Oral ganciclovir administered on CMV detection by PCR prevents CMV infection or disease after liver transplantation.", "The efficacy of pre-emptively administered oral ganciclovir in preventing cytomegalovirus (CMV) disease has not been documented in liver transplant recipients. We sought to compare the efficacy of pre-emptive oral ganciclovir with that of i.v. ganciclovir for the prevention of CMV disease after liver transplantation, and to determine whether withholding prophylaxis in the absence of CMV antigenemia, reliably identified patients in whom no prophylaxis was necessary.\n Surveillance cultures for CMV pp65 antigenemia were performed in all patients at weeks 2, 4, 6, 8, 12, and 16. Patients with CMV antigenemia were randomized into two study groups. The experimental group received oral ganciclovir for 6 weeks (2 g t.i.d. for 2 weeks, then 1 g t.i.d. for 4 weeks), and the control group received i.v. ganciclovir (5 mg/kg q 12 hr) for 7 days.\n Of 72 consecutive liver transplant recipients studied, CMV antigenemia occurred in 31% (22 of 72). Twenty-two patients with asymptomatic antigenemia were randomized to two study groups. CMV disease (viral syndrome) occurred in 9% (1 of 11) of the patients in the i.v. ganciclovir group and in 0% (0 of 11) of the patients in the oral ganciclovir group. None of the study patients developed tissue invasive CMV disease. The median reduction in antigenemia level with oral ganciclovir was 55% at week 1, and 100% at week 2. Overall, 64% of the patients by week 1, 93% by week 2, and 100% by week 4 had antigenemia levels below the baseline after oral ganciclovir. Of 50 patients without CMV antigenemia, none developed CMV disease.\n Pre-emptive prophylaxis based on CMV antigenemia can effectively target the patients for CMV prophylaxis; 69% of the patients never received antiviral prophylaxis and did not develop CMV disease. Antiviral therapy instituted upon detection of antigenemia prevented tissue invasive CMV in both ganciclovir groups. Pre-emptively administered oral ganciclovir was effective as prophylaxis for CMV disease after liver transplantation.", "Oral ganciclovir prophylaxis and intravenous preemptive therapy are competitive approaches to prevent cytomegalovirus (CMV) disease after renal transplantation. This trial compared efficacy, safety and long-term graft outcome in 148 renal graft recipients randomized to ganciclovir prophylaxis (N = 74) or preemptive therapy (N = 74). Hierarchical testing revealed (i) patients with CMV infection had more severe periods of impaired graft function (creatinine clearance(max-min) 25.0 +/- 14.2 mL/min vs. 18.1 +/- 12.5 mL/min for patients without CMV infection; p = 0.02),(ii) prophylaxis reduced CMV infection by 65% (13 vs. 33 patients; p < 0.0001) but (iii) creatinine clearance at 12 months was comparable for both regimes (54.0 +/- 24.9 vs. 53.1 +/- 23.7 mL/min; p = 0.92). No major safety issues were observed, and patient survival at 12 months was similar in both groups (5 deaths [6.8%] vs. 4 [5.4%], p = 1.0000). Prophylaxis significantly increased long-term graft survival 4 years posttransplant (92.2% vs. 78.3%; p = 0.0425) with a number needed to treat of 7.19. Patients with donor +/recipient + CMV serostatus had the lowest rate of graft loss following prophylaxis (0.0% vs. 26.8%; p = 0.0035). In conclusion, it appears that routine oral prophylaxis may improve long-term graft survival for most renal transplant patients. Preemptive therapy can be considered in low risk patients in combination with adequate CMV monitoring.", "This study was designed to evaluate the longitudinal history of cytomegalovirus (CMV) infection and to test the capacity of ganciclovir as effective therapy in CMV-seropositive renal transplant recipients. The CMV viremia was detected with CMV pp65 antigenemia assay in 153 renal transplants. The recipients were classified as having low-grade and high-grade CMV infections according to the severity of CMV infection. The recipients with low-grade CMV infections were observed without ganciclovir treatment, and the recipients with high-grade CMV infection were randomly assigned to ganciclovir-treated and untreated groups. The clinical course between low-grade and high-grade CMV infections was evaluated. All recipients with low-grade CMV infection (n = 62) showed spontaneous remission regardless of immunosuppresants. In high-grade CMV infection (n = 31), the ciclosporin A treated group (n = 11) showed no evidence of CMV disease, and the methylprednisolone-treated group (n = 8) showed CMV disease in 1 (25%) of 4 ganciclovir-untreated recipients. In the OKT3 group (n = 12), symptomatic CMV infection was observed in 6 (100%) ganciclovir-untreated recipients contrary to no CMV disease in the ganciclovir-treated group (p < 0.05). In conclusion, the CMV antigenemia assay is effective in monitoring CMV viremia, and ganciclovir treatment should be done during early CMV viremia in OKT3-treated recipients.", "Cytomegalovirus (CMV) prevention can be achieved by prophylaxis or preemptive therapy. We performed a prospective randomized trial to determine whether renal transplant recipients with a positive CMV serostatus (R+) had a higher rate of CMV infection and disease after transplantation when treated preemptively for CMV infection, compared with primary valganciclovir prophylaxis.\n Prophylaxis was 2 × 450 mg oral valganciclovir/day for 100 days; preemptive patients were monitored by CMV-polymerase chain reaction (PCR), and after a positive PCR test received 2 × 900 mg valganciclovir/day for at least 14 days followed by secondary prophylaxis. Valganciclovir dosage was adjusted according to renal function. Patients are followed up for 5 years and initial 12-month data are presented. Two hundred and ninety-six recipients were analyzed (168 donor/recipient seropositive [D+/R+], 128 donor seronegative/recipient seropositive [D-/R+]; 146 receiving prophylaxis and 150 preemptive therapy).\n Overall, CMV infection (asymptomatic CMV viral load ≥ 400 CMV DNA copies/mL proven by CMV-PCR) was significantly higher in recipients under preemptive therapy (38.7% vs. 11.0%, P<0.0001), with the highest incidence in D+/R+ preemptive patients (53.8% vs. 15.6%, P<0.0001). D+/R+ recipients with preemptive therapy also had the highest rate of CMV disease (CMV syndrome and tissue-invasive disease that was clinically diagnosed and biopsy proven) (19.2% vs. 4.4%, P=0.003). Renal function assessed by creatinine clearance was similar for both groups. Graft loss occurred in 7 vs. 4 patients on preemptive versus prophylactic therapy (P>0.05). Tolerability was similar for both treatment groups.\n Oral valganciclovir prophylaxis significantly reduces CMV infection and disease, particularly for D+/R+ patients. Hence, our study supports routine prophylaxis for all D+/R+ recipients.", "nan", "To assess the efficacy of high-dose oral acyclovir therapy compared with preemptive, short-course ganciclovir therapy (administered only if cytomegalovirus [CMV] shedding occurred) to prevent CMV disease in liver transplant recipients.\n A randomized controlled trial.\n Liver transplant center at a university-affiliated Veterans Affairs Medical Center.\n 47 consecutive patients having liver transplantation.\n Patients were stratified by their CMV antibody status and the CMV antibody status of the donor and were randomly assigned to one of two treatment groups. Surveillance cultures for CMV (buffy coat and urine) were done every 2 to 4 weeks for 24 weeks in all patients. One group received high-dose oral acyclovir (800 mg four times daily). The experimental group received no acyclovir, but if surveillance cultures were positive, ganciclovir (5 mg/kg intravenously twice daily) was administered for 7 days.\n Cytomegalovirus shedding and CMV disease were measured in the two groups.\n Cytomegalovirus shedding before the onset of CMV disease occurred in 25% (6 of 24) of patients in the acyclovir group compared with 22% (5 of 23) in the experimental group. Cytomegalovirus disease developed in 29% (7 of 24) of the acyclovir group and in 4% (1 of 23) of the experimental group (P < 0.05). No hematologic toxicity occurred with ganciclovir.\n Oral acyclovir is ineffective prophylaxis against CMV in liver transplant recipients. Preemptive, short-course ganciclovir therapy in patients with CMV shedding was well tolerated and provided effective prophylaxis against subsequent CMV disease; this protocol targets the patients at risk for CMV disease and minimizes toxicity and expense.", "About one-quarter of renal transplant patients will suffer from symptomatic cytomegalovirus (CMV) disease if no preventive therapeutic measures are taken. In this prospective, randomized single-centre study pre-emptive therapy with oral ganciclovir is compared with conventional deferred treatment.\n Renal transplant recipients (n= 455) over 18 years of age were screened weekly for CMV pp65 antigenaemia during the first 12 weeks post-transplantation. If CMV pp65 antigen in leukocytes appeared within 8 weeks post-transplantation patients were randomized and included in the study. Five patients developed CMV disease before positive CMV pp65, and 14 patients with a positive antigen test developed CMV disease before randomization could take place, all these representing a limitation of the applicability of the results in the overall renal transplant population. Altogether 179 patients were not randomized for various reasons. Eighty patients completed the study, 42 were randomized to receive pre-emptive oral ganciclovir therapy and 38 to conventional deferred treatment (control group).\n Time from transplantation to start of ganciclovir capsules was 36 (12-60) days and duration of oral ganciclovir therapy was 49 (27-70) days, median (range). No patient in the pre-emptive treatment group, but nine of 38 patients (23.7%) in the control group, developed CMV disease during the first 12 weeks post-transplantation (P= 0.0009). In the period from 3 months to 1 year post-transplantation, two patients in each group developed CMV disease. There were no significant differences in acute rejection or renal function between treatment groups during the first post-transplant year.\n Pre-emptive oral ganciclovir therapy in renal transplant recipients during the first 12 weeks post-transplantation effectively prevents CMV disease during this time period. The incidence of late CMV disease (3 months to 1 year after transplantation) was similar in the two groups, indicating that pre-emptive therapy does not result in late onset of CMV disease.", "Twenty-one pediatric liver transplant recipients were enrolled in a study comparing prophylaxis followed by preemptive therapy (10 patients) versus preemptive therapy alone (11 patients) for prevention of human cytomegalovirus (HCMV) disease. In the prophylaxis arm, patients were treated with ganciclovir for 30 days, then preemptive therapy was initiated with virologic monitoring for pp65 antigenemia. In the preemptive therapy arm, patients were treated on reaching 100,000 DNA copies/mL whole blood. An interim analysis showed that, although numbers of both infected and treated patients were comparable in the two arms, the median number of total days of antiviral therapy per patient (30 vs. 18, P<0.01) was significantly higher in the prophylaxis arm. No case of HCMV disease occurred in either arm. Therefore, the trial was interrupted and prophylaxis replaced with preemptive therapy alone. In parallel, the development of T-cell-mediated immune response was found to be comparable in both arms.", "With the development of sensitive tests to detect cytomegalovirus (CMV) viremia, preemptive approaches become a reasonable alternative to general CMV prophylaxis. We performed a randomized trial comparing pp65-antigenemia guided preemptive therapy using oral ganciclovir with symptom-triggered intravenous ganciclovir treatment.\n Eighty-eight of 372 liver transplant recipients developed antigenemia early after orthotopic liver transplantation. Twenty-eight symptomatic patients with antigenemia were excluded from randomization and treated with intravenous ganciclovir. Sixty pp65-antigen-positive asymptomatic patients were randomized to receive either oral ganciclovir 3x1 g/day for 14 days (group 1) or no preemptive treatment (group 2). Patients that developed CMV disease were treated with intravenous ganciclovir 2x5 mg/kg body weight for 14 days. The high-risk (Donor+/Recipient-) patients were equally distributed in the two study groups.\n Three of 30 (10%) patients on oral ganciclovir developed mild to moderate CMV disease compared with 6/30 (20%) patients in the control group. In the Donor+/Recipient- patients, the incidence of CMV disease was 1/6 and 3/7. All disease episodes resolved after intravenous treatment. The 1- and 3-year patient and organ survival was the same in the study groups and in the patients with or without CMV infection. No deaths related to CMV occurred.\n The positive predictive value of pp65-antigenemia for the development of CMV disease was very low, and, in 28/88 patients (32%), antigenemia did not precede symptoms. Therefore, pp65-antigenemia is of limited value in deciding on the timing and need for ganciclovir therapy after liver transplantation.", "Both preemptive therapy and universal prophylaxis are used to prevent cytomegalovirus (CMV) disease after transplantation. Randomized trials comparing both strategies are sparse. Renal transplant recipients at risk for CMV (D+/R-, D+/R+, D-/R+) were randomized to 3-month prophylaxis with valacyclovir (2 g q.i.d., n = 34) or preemptive therapy with valganciclovir (900 mg b.i.d. for a minimum of 14 days, n = 36) for significant CMV DNAemia (>/=2000 copies/mL by quantitative PCR in whole blood) assessed weekly for 16 weeks and at 5, 6, 9 and 12 months. The 12-month incidence of CMV DNAemia was higher in the preemptive group (92% vs. 59%, p < 0.001) while the incidence of CMV disease was not different (6% vs. 9%, p = 0.567). The onset of CMV DNAemia was delayed in the valacyclovir group (37 +/- 22 vs. 187 +/- 110 days, p < 0.001). Significantly higher rate of biopsy-proven acute rejection during 12 months was observed in the preemptive group (36% vs. 15%, p = 0.034). The average CMV-associated costs per patient were $5525 and $2629 in preemptive therapy and valacyclovir, respectively (p < 0.001). However, assuming the cost of $60 per PCR test, there was no difference in overall costs. In conclusion, preemptive valganciclovir therapy and valacyclovir prophylaxis are equally effective in the prevention of CMV disease after renal transplantation.", "The aim of this study was to evaluate pp65 antigen-guided antiviral therapy in preventing human cytomegalovirus (HCMV) infection in solid organ transplant recipients.\n Ten kidney and two liver transplant recipients with asymptomatic HCMV infection were randomized either for i.v. ganciclovir or placebo treatment in a prospective, double-blind study. All patients were positive by HCMV pp65 antigen test at levels >5 positive cells/2 x 10(5) investigated cells.\n No cases of HCMV end-organ disease occurred. In contrast to patients on placebo (5/7), none of the patients on ganciclovir (0/5) developed HCMV-associated symptoms (P=0.01). However, because of the small number of patients, all three high-risk patients (donor seropositive, recipient seronegative) were randomized to placebo and all three developed symptoms.\n Preemptive antiviral therapy guided by the pp65 antigen test seems to have a beneficial effect on preventing HCMV-associated symptoms in kidney and liver transplant recipients." ]

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[ "Glycoprotein IIB/IIIA inhibitor to reduce postpercutaneous coronary intervention myonecrosis and improve coronary flow in diabetics: the 'OPTIMIZE-IT' pilot randomized study.", "Randomised placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention: IMPACT-II. Integrilin to Minimise Platelet Aggregation and Coronary Thrombosis-II.", "Prophylactic abciximab in elective coronary stenting: results of a randomized trial.", "Does pre-treatment with aspirin and loading dose clopidogrel obviate the need for glycoprotein IIb/IIIa antagonists during elective coronary stenting? A focus on peri-procedural myonecrosis.", "Platelet membrane receptor glycoprotein IIb/IIIa antagonism in unstable angina. The Canadian Lamifiban Study.", "Randomized, double-blind, placebo-controlled dose-ranging study of tirofiban (MK-383) platelet IIb/IIIa blockade in high risk patients undergoing coronary angioplasty.", "Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization.", "A comparison of dual vs. triple antiplatelet therapy in patients with non-ST-segment elevation acute coronary syndrome: results of the ELISA-2 trial.", "A multicenter study of the tolerability of tirofiban versus placebo in patients undergoing planned intracoronary stent placement.", "Abciximab in patients with acute ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention after clopidogrel loading: a randomized double-blind trial.", "Clinical benefits of adjunctive tirofiban therapy in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.", "The additive value of tirofiban administered with the high-dose bolus in the prevention of ischemic complications during high-risk coronary angioplasty: the ADVANCE Trial.", "Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial.", "A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel.", "Intensifying platelet inhibition with tirofiban in poor responders to aspirin, clopidogrel, or both agents undergoing elective coronary intervention: results from the double-blind, prospective, randomized Tailoring Treatment with Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel study.", "Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial.", "A randomized trial comparing primary infarct artery stenting with or without abciximab in acute myocardial infarction.", "Safety and efficacy of the platelet glycoprotein IIb/IIIa inhibitor abciximab in Chinese patients undergoing high-risk angioplasty.", "Multicenter, randomized, double-blind, placebo-controlled trial of the platelet integrin glycoprotein IIb/IIIa blocker Integrelin in elective coronary intervention. IMPACT Investigators.", "A randomized trial comparing phosphorylcholine-coated stenting with balloon angioplasty as well as abciximab with placebo for restenosis reduction in small coronary arteries.", "Randomized clinical trial of abciximab in diabetic patients undergoing elective percutaneous coronary interventions after treatment with a high loading dose of clopidogrel.", "Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators.", "Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators.", "Effect of tirofiban plus clopidogrel and aspirin on primary percutaneous coronary intervention via transradial approach in patients with acute myocardial infarction.", "Clinical pharmacology of higher dose eptifibatide in percutaneous coronary intervention (the PRIDE study).", "International, randomized, controlled trial of lamifiban (a platelet glycoprotein IIb/IIIa inhibitor), heparin, or both in unstable angina. The PARAGON Investigators. Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network.", "Acute platelet inhibition with abciximab does not reduce in-stent restenosis (ERASER study). The ERASER Investigators.", "Bivalirudin and clopidogrel with and without eptifibatide for elective stenting: effects on platelet function, thrombelastographic indexes, and their relation to periprocedural infarction results of the CLEAR PLATELETS-2 (Clopidogrel with Eptifibatide to Arrest the Reactivity of Platelets) study.", "Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. The PURSUIT Trial Investigators. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy.", "Efficacy of abciximab for patients undergoing balloon angioplasty: data from Japanese evaluation of c7E3 Fab for elective and primary PCI organization in randomized trial (JEPPORT).", "A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators.", "Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE Study.", "Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction.", "Effect of glycoprotein IIb/IIIa receptor blockade with abciximab on clinical and angiographic restenosis rate after the placement of coronary stents following acute myocardial infarction.", "Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. The RESTORE Investigators. Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis.", "Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomised trial.", "Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial.", "Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. The EPIC Investigation.", "Randomized trial of a GPIIb/IIIa platelet receptor blocker in refractory unstable angina. European Cooperative Study Group.", "Glycoprotein IIb/IIIa inhibitors improve outcome after coronary stenting in clopidogrel nonresponders: a prospective, randomized study.", "Effects of integrelin, a platelet glycoprotein IIb/IIIa receptor antagonist, in unstable angina. A randomized multicenter trial.", "Usefulness of platelet glycoprotein IIb/IIIa inhibitors in coronary stenting for reconstruction of complex lesions: procedural and 30 day outcome.", "A randomized, double-blind, placebo-controlled trial of abciximab for prevention of in-stent restenosis in diabetic patients after coronary stenting: results of the ASIAD (Abciximab in Stenting Inhibits restenosis Among Diabetics) Trial.", "Effect of additional temporary glycoprotein IIb/IIIa receptor inhibition on troponin release in elective percutaneous coronary interventions after pretreatment with aspirin and clopidogrel (TOPSTAR trial).", "Randomized, placebo-controlled trial of titrated intravenous lamifiban for acute coronary syndromes." ]

[ "Subgroup analyses of trials enrolling acute coronary syndrome patients suggest that inhibition of glycoprotein IIb/IIIa can improve the outcome of diabetic patients undergoing percutaneous coronary interventions (PCIs), possibly by improving microvascular perfusion. However, the efficacy of small-molecule IIb/IIIa receptor inhibitors to improve microvascular perfusion in stable diabetic patients undergoing elective PCI has not been specifically investigated.\n We randomized consecutive stable diabetic patients, undergoing elective PCI, to tirofiban or placebo groups along with double antiplatelet therapy. High-dose bolus (25 microg/kg per 3 min) of tirofiban was administered immediately before PCI followed by 8 h continuous infusion (0.15 microg/kg per min). Postprocedural myonecrosis was assessed prospectively by measurement of cardiac troponin T (cTnT) at 6 and 24 h after PCI. The primary end-points were post-PCI coronary flow estimated by corrected thrombolysis in myocardial infarction frame count and post-PCI myocardial infarction. Platelet aggregation was measured by platelet function analyser-100 values.\n Forty-six patients entered the study (22 randomized to placebo and 24 randomized to tirofiban). The study drug was associated with a significant increase of platelet function analyser-100 values that peaked immediately after PCI and was maintained at 6 h (pre-PCI: 131 +/- 65 s; post-PCI: 222 +/- 49 s; after 6 h: 219 +/- 55 s).Post-PCI corrected thrombolysis in myocardial infarction frame count was similar in tirofiban and in placebo groups (10.2 +/- 3.6 vs. 12.0 +/- 7.6, P = 0.30, respectively). The prevalence of raised cTnT levels was similar in the two groups (25 vs. 30%, P = 0.56, respectively). At multivariate analysis, direct stenting (associated with reduced myonecrosis) and postdilatation (associated with increased myonecrosis) predicted cTnT elevation.\n A high-dose bolus of tirofiban in stable diabetic patients undergoing elective PCI, along with double antiplatelet therapy, was associated with a significant further inhibition of platelet aggregation which, however, did not translate in a lower incidence of post-PCI distal embolization.", "Platelet-mediated thrombosis has been implicated in the development of ischaemic complications of percutaneous coronary intervention. We investigated whether inhibition of the platelet glycoprotein IIb/IIIa integrin with eptifibatide (Integrilin) could prevent such complications.\n We undertook a double-blind, placebo-controlled trial at 82 centres in the USA, enrolling 4010 patients undergoing elective, urgent, or emergency coronary intervention. Patients were assigned one of three treatments: placebo (n = 1328), a bolus of 135 micrograms/kg eptifibatide followed by an infusion of 0.5 microgram kg-1 min-1 for 20-24 h (n = 1349), or 135 micrograms/kg eptifibatide bolus with a 0.75 microgram kg-1 min-1 infusion (n = 1333). The coronary procedure was started within 10-60 min of the start of study treatment. The primary endpoint was the 30-day composite occurrence of death, myocardial infarction, unplanned surgical or repeat percutaneous revascularisation, or coronary stent implantation for abrupt closure (by intention to treat). The primary safety endpoint was major bleeding.\n By 30 days, the composite endpoint had occurred in 151 (11.4%) patients in the placebo group compared with 124 (9.2%) in the 135/0.5 eptifibatide group (p = 0.063) and 132 (9.9%) in the eptifibatide 135/0.75 group (p = 0.22). By treatment-received analysis, the 135/0.5 regimen produced a significant reduction in the composite endpoint (11.6 vs 9.1%, p = 0.035), but the 135/0.75 regimen produced a less substantial reduction (11.6 vs 10.0%, p = 0.18). Eptifibatide treatment did not increase rates of major bleeding or transfusion.\n In the 135/0.5 group, treatment with eptifibatide during coronary intervention reduced rates of early abrupt closure and ischaemic events at 30 days. Non-significant differences were seen with the 135/0.75 regimen. The doses studied thus appear to be at the low end of the efficacy-response curve. Further investigation to refine eptifibatide dosing during coronary intervention is warranted.", "The use of abciximab (c7E3 Fab; ReoPro , Eli Lilly & Company, Indianapolis, Indiana) during percutaneous coronary intervention (PCI) decreases the incidence of early (30-day) and late (6-month to 1 year) adverse cardiac ischemic events. In a high-risk population, abciximab also reduced the need for target lesion revascularization. PCI of lesions with complex morphology, particularly long lesions, is associated with more complicated outcomes. The use of multiple and/or long intracoronary stents to cover long coronary lesions may lower the incidence of acute or subacute occlusion, but is still limited by a high late restenosis rate. We characterized patients undergoing elective implantation of long or multiple overlapping coronary stents and determined the impact of abciximab administration on clinical and angiographic outcomes.\n In a prospective, single-center randomized trial, a total of 107 patients undergoing elective implantation of long or multiple overlapping coronary stents were randomly assigned to receive either standard-dose heparin (n = 53) or abciximab plus low-dose heparin (n = 54). The use of abciximab was not associated with an increased incidence of bleeding or vascular complications compared to standard heparin regimen (3.7% versus 3.8%, respectively; p = NS). A 68% reduction in composite in-hospital cardiac events (i.e., death, myocardial infarction, urgent revascularization) was observed in the abciximab group (3.7% versus 11.5%, p = 0.1). At 6-month follow-up, a 48% reduction of target lesion revascularization (11% versus 21%; p = 0.1) and a decrease in binary angiographic restenosis were observed for abciximab-treated patients (17% versus 34%; p < 0.05).\n The peri-procedural use of abciximab during implantation of long or multiple overlapping coronary stents is safe and effective, as it does not increase bleeding or vascular complications compared to standard heparin anticoagulation and reduces the incidence of in-hospital adverse cardiac events; moreover, abciximab improves 6-month clinical and angiographic outcomes in such a complex setting.", "Although full platelet inhibition with aspirin and thienopyridines before coronary stenting has significantly reduced the risk of acute stent thrombosis, peri-procedural myonecrosis still occurs frequently and is associated with increased death rate. Whether further inhibition of platelet aggregation by a glycoprotein IIb/IIIa antagonist may provide an additional cardioprotection is unknown.\n A total of 200 patients pre-treated with aspirin and a loading dose of clopidogrel (450 mg) were randomized just before coronary intervention (percutaneous coronary intervention, PCI) to treatment with or without abciximab. Platelet aggregation was assessed in samples collected during the procedure and the degree of platelet aggregation inhibition was correlated with cardiac enzyme release post-PCI. Abciximab treatment achieved a more complete inhibition of aggregation than dual oral antiplatelet therapy alone (median value of 1 vs. 50%, normal 100%). Any pathological increase in creatinine kinase-MB (CK-MB) post-PCI was present in 21% of the abciximab group and in 22% of the no-abciximab group (P = 0.9). Also the occurrence of clinically relevant myonecrosis [myocardial infarction (MI) = CK-MB > 3x upper limit of normal] was not significantly influenced by treatment assignment: 9 vs. 10% (P = 0.9). In a multiple logistic regression model including clinical, angiographic, and procedural characteristics, post-PCI myonecrosis was not correlated with the degree of platelet aggregation inhibition but with procedural features (such as long inflation time) and with the presence of multi-vessel disease. There were no cases of acute or subacute stent thrombosis. At 6 months, major adverse cardiac events, including cardiac death, non-fatal MI, or target lesion revascularization occurred in 13% of abciximab patients and in 16% of the control patients (P = 0.6).\n In the studied patients scheduled for elective coronary stenting and pre-treated with aspirin and a loading dose of clopidogrel, further inhibition of platelet aggregation by abciximab does not afford additional cardioprotection. Our data suggest that distal athero-embolization rather than thrombo-embolization is involved in the phenomenon of myonecrosis post-elective stenting.", "Ligand binding to the platelet membrane receptor glycoprotein (GP) IIb/IIIa, the final and obligatory step to platelet aggregation, can now be inhibited by pharmacological agents. This study was designed to evaluate the potential of lamifiban, a novel nonpeptide antagonist of GP IIb/IIIa, for the management of unstable angina.\n In a prospective, dose-ranging, double-blind study, 365 patients with unstable angina were randomized to an infusion of 1, 2, 4, or 5 micrograms/min of lamifiban or of placebo. Treatment was administered for 72 to 120 hours. Outcome events were measured during the infusion period and after 1 month. Concomitant aspirin was administered to all patients and heparin to 28% of patients. Lamifiban, all doses combined, reduced the risk of death, nonfatal myocardial infarction, or the need for an urgent revascularization during the infusion period from 8.1% to 3.3% (P = .04). The rates were 2.5%, 4.9%, 3.3%, and 2.4% with increasing doses. At 1 month, death or nonfatal infarction occurred in 8.1% of patients with placebo and in 2.5% of patients with the two high doses (P = .03). The highest dose of lamifiban additionally prevented the need for an urgent intervention. Lamifiban dose-dependently inhibited platelet aggregation. Bleeding times were significantly prolonged with platelet inhibition of > 80%. Major (but neither life-threatening nor intracranial) bleedings occurred in 0.8% of patients with placebo and 2.9% with lamifiban.\n The nonpeptide GP IIb/IIIa antagonist lamifiban protected patients with unstable angina from severe ischemic events during a 3- to 5-day infusion and reduced the incidence of death and infarction at 1 month, suggesting considerable promise for this new therapeutic approach.", "The objectives of this double-blind, placebo-controlled, randomized dose-ranging study were 1) to examine the safety and tolerability of tirofiban (MK-383), a new nonpeptide platelet IIb/IIIa receptor antagonist, on a background of intravenous heparin and aspirin therapy; 2) to study the pharmacodynamics and pharmacokinetics of tirofiban; and 3) to evaluate the incidence of adverse cardiac outcomes (urgent repeat revascularization, myocardial infarction and death) with tirofiban versus placebo in a high risk subset of patients undergoing coronary angioplasty.\n Abrupt vessel closure complicates 4% to 8% of angioplasty procedures. Recent data have suggested that agents that antagonize the platelet glycoprotein IIb/IIIa receptor may reduce the incidence of adverse ischemic outcomes after coronary angioplasty.\n Seventy-three patients received tirofiban in three sequential dose panels and 20 patients received placebo. Patients within each panel were randomized to receive either tirofiban or placebo in a 3:1 randomization design. Bolus doses of 5, 10 and 10 microg/kg and continuous infusion (16 to 24 h) doses of 0.05, 0.10 and 0.15 microg/kg per min were administered in panels I, II and III, respectively. Patients received concomitant heparin and aspirin for the angioplasty procedure. Data on patients receiving placebo (heparin and aspirin only) were pooled across panels for comparisons. The pharmacodynamic effect of tirofiban on ex vivo platelet aggregation to 5 micromol/liter adenosine diphosphate (ADP) and bleeding times were measured. Clinical outcomes were assessed in all patients, but the power to detect clinically meaningful differences (a one-third reduction in clinical events) between groups was limited (5%).\n Tirofiban was associated with a dose-dependent inhibition of ex vivo ADP-mediated platelet aggregation that was sustained during intravenous infusion and resolved rapidly after drug cessation. Adverse bleeding events, largely related to vascular access site hemorrhage, were slightly increased at the highest dose. Adverse clinical outcomes were infrequent in all patients and were not different among the small number of patients within each group.\n This study establishes a rational and generally well tolerated dosing regimen for administration of tirofiban as adjunctive therapy in high risk angioplasty patients. The impact of tirofiban on adverse clinical outcomes after angioplasty awaits definition by a larger clinical trial.", "Blockade of the platelet glycoprotein IIb/IIIa receptor with abciximab (a monoclonal-antibody Fab fragment directed against the receptor) has been shown to diminish ischemic complications among patients undergoing high-risk coronary angioplasty or directional atherectomy but increases bleeding complications. The widespread applicability of this treatment is unknown, particularly in view of the observed risk of hemorrhage.\n In a prospective, double-blind trial, we randomly assigned patients undergoing urgent or elective percutaneous coronary revascularization at 69 centers to receive abciximab with standard-dose, weight-adjusted heparin (initial bolus of 100 U per kilogram of body weight); abciximab with low-dose, weight-adjusted heparin (initial bolus of 70 U per kilogram); or placebo with standard-dose, weight-adjusted heparin. The primary efficacy end point was death from any cause, myocardial infarction, or urgent revascularization within 30 days of randomization.\n The trial was terminated at the first interim analysis, with 2792 of the planned 4800 patients enrolled. At 30 days, the composite event rate was 11.7 percent in the group assigned to placebo with standard-dose heparin; 5.2 percent in the group assigned to abciximab with low-dose heparin (hazard ratio, 0.43; 95 percent confidence interval, 0.30 to 0.60; P<0.001); and 5.4 percent in the group assigned to abciximab with standard-dose heparin (hazard ratio, 0.45; 95 percent confidence interval, 0.32 to 0.63; P<0.001). There were no significant differences among the groups in the risk of major bleeding, although minor bleeding was more frequent among patients receiving abciximab with standard-dose heparin.\n Inhibition of the platelet glycoprotein IIb/IIIa receptor with abciximab, together with low-dose, weight-adjusted heparin, markedly reduces the risk of acute ischemic complications in patients undergoing percutaneous coronary revascularization, without increasing the risk of hemorrhage.", "To compare dual vs. triple antiplatelet pre-treatment in patients with non-ST-elevation acute coronary syndrome (NSTE ACS) who were planned for early catheterization.\n A total of 328 consecutive patients with NSTE ACS were included and were randomized to pre-treatment with dual (n = 166, aspirin, clopidogrel 600 mg) or triple antiplatelet therapy (n = 162, aspirin, clopidogrel 300 mg, and Tirofiban). The primary endpoint was enzymatic infarct size, defined as cumulative LDH release (LDHQ(48)). Initial TIMI flow of the culprit vessel was a pre-specified secondary endpoint. Angiography was performed in 98% of patients at a median of 23 h after admission. Enzymatic infarct size (median, 25-75%) was 166 (60-349) IU/L in the triple group compared with 193 (75-466) IU/L in the dual group (P = 0.2). Initial TIMI 3 flow of the culprit vessel was significantly more often observed after triple antiplatelet therapy (67 vs. 47%, P = 0.002). At 30 days follow-up, myocardial infarction (MI) occurred in 46% of patients in the triple antiplatelet group, compared with 57% in the dual antiplatelet group, P = 0.052. No significant difference in bleeding was present.\n This study showed that in patients with NSTE ACS, triple antiplatelet pre-treatment was associated with a non-significant reduction in enzymatic infarct size, a significantly better initial perfusion of the culprit vessel, and a trend towards a better survival without death or MI. Further, large-scale studies should be performed to find whether the beneficial trend in favour of triple antiplatelet pre-treatment can be reproduced.", "The use of intravenous glycoprotein IIb/IIIa-receptor antagonists has been shown to improve outcomes in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Tirofiban has shown benefit in a wide range of patients presenting with acute coronary syndromes. Although this agent has been used in patients undergoing percutaneous coronary intervention, a literature search identified no prospective data comparing tirofiban with placebo in patients undergoing planned intracoronary stent placement.\n This study examined the tolerability of tirofiban in patients undergoing percutaneous intervention with planned intracoronary stent placement.\n This was a multinational, multicenter, prospective, randomized, double-blind, placebo-controlled trial in patients scheduled to undergo PTCA with planned intracoronary stent placement. Patients were randomized in a 3:2 ratio to receive tirofiban as an intravenous bolus (10 microg/kg over 3 minutes) and maintenance infusion (0.10 microg/kg per minute for 36 hours) or a bolus and infusion of placebo. All patients received periprocedural aspirin and heparin and an optional postprocedural thienopyridine (ticlopidine or clopidogrel). Laboratory and safety monitoring were performed throughout the 36 hours after the procedure and at hour 40 or hospital discharge. The primary end point was the proportion of patients with bleeding, defined according to Thrombolysis in Myocardial Infarction (TIMI) trial criteria. The number of patients with cardiac events (death, myo- cardial infarction, urgent revascularization) during the first 30 days after stent placement was also assessed.\n Eight hundred ninety-four patients (536 tirofiban, 358 placebo) were enrolled, all of whom received aspirin and heparin periprocedurally and optional ticlopidine or clopidogrel after the procedure. No significant between-group differences were observed in the incidence of TIMI major bleeding (0.2% tirofiban, 0.6% placebo) or any TIMI bleeding (3.2% and 1.7%, respectively). The incidence of TIMI minor bleeding was higher with tirofiban than with placebo (2.8% vs 0.6%). The 30-day incidence of the composite end point of any cardiac event was 3.9% in both groups.\n On a background of concomitant aspirin, heparin, and a thienopyridine, tirofiban was generally well tolerated in patients undergoing PTCA with planned intracoronary stent placement. Further investigation is needed to ascertain the optimal dosing of tirofiban and heparin to achieve reductions in ischemic complications of intracoronary stenting with an acceptable incidence of bleeding complications.", "The glycoprotein IIb/IIIa receptor inhibitor abciximab has improved the efficacy of primary percutaneous coronary interventions in patients with acute myocardial infarction. However, it is not known whether abciximab remains beneficial after adequate clopidogrel loading in patients with acute ST-segment-elevation myocardial infarction.\n A total of 800 patients with acute ST-segment-elevation myocardial infarction within 24 hours from symptom onset, all treated with 600 mg clopidogrel, were randomly assigned in a double-blind fashion to receive either abciximab (n=401) or placebo (n=399) in the intensive care unit before being sent to the catheterization laboratory. The primary end point, infarct size measured by single-photon emission computed tomography with technetium-99m sestamibi before hospital discharge, was 15.7+/-17.2% (mean+/-SD) of the left ventricle in the abciximab group and 16.6+/-18.6% of the left ventricle in the placebo group (P=0.47). At 30 days, the composite of death, recurrent myocardial infarction, stroke, or urgent revascularization of the infarct-related artery was observed in 20 patients in the abciximab group (5.0%) and 15 patients in the placebo group (3.8%) (relative risk, 1.3; 95% CI, 0.7 to 2.6; P=0.40). Major bleeding complications were observed in 7 patients in each group (1.8%).\n Upstream administration of abciximab is not associated with a reduction in infarct size in patients presenting with acute myocardial infarction within 24 hours of symptom onset and receiving 600 mg clopidogrel.", "There is continued debate as to whether a combined reperfusion regimen with platelet glycoprotein IIb/IIIa inhibitor-tirofiban provides additional benefit in optimal myocardial reperfusion for patients with acute ST-segment elevation myocardial infarction (STEMI). This study was conducted to investigate the clinical benefits of adjunctive tirofiban therapy combined with primary percutaneous coronary intervention (PCI) in patients with STEMI.\n One hundred and seventy-two consecutive patients with STEMI presented within 12 h of symptoms were randomly allocated to primary PCI combined with early (upstream group, n=57) or late administration of tirofiban (downstream group, n=57) or primary PCI treatment alone (control group, n=58). Clinical characteristics, angiographic findings, and in-hospital outcomes were compared between groups, as well as left ventricular ejection fraction (LVEF) and major adverse cardiac events (MACE, including death, reinfarction and target vessel revascularization) at 30-day and 6-month clinical follow-up.\n Despite comparable baseline clinical features among three groups, angiographic and procedural characteristics and outcomes differed significantly between patients receiving tirofiban treatment and controls, with respect to preprocedural (upstream: 28.1%, downstream: 7.0%, control: 5.2%, P<0.001) and postprocedural thrombolysis in myocardial infarction (TIMI) grade 3 flow of infarct-related artery (98.2, 94.7, 86.2%, P=0.03), TIMI myocardial perfusion grade 3 (75.4, 70.2, 53.4%, P=0.03), corrected TIMI frame count (20.4+/-5.0, 23.1+/-5.3, 32.2+/-6.7, P<0.001), resolution of the sum of ST-segment elevation (6.16+/-1.21, 6.02+/-1.09, 4.53+/-2.65 mm, P<0.001), peak value of creatine kinase-MB (218.0+/-72.5, 224.2+/-69.4, 255.3+/-77.0 ng/ml, P=0.02) and troponin I (76.0+/-21.5, 79.8+/-18.7, 86.4+/-11.0 ng/ml, P=0.007), and average hospital stay (10.6+/-5.4, 12.6+/-4.7, 14.5+/-6.5 days, P=0.001). The MACE rate at 30 days (3.5, 5.3, 15.5%, P=0.04) was reduced and LVEF (0.51+/-0.07, 0.50+/-0.07, 0.47+/-0.08, P=0.008) was higher in upstream and downstream groups than in controls. At 6-month follow-up, the MACE rate was not significantly different among groups (7.0, 8.8, 17.2%, P=0.17), but LVEF in upstream and downstream groups was significantly improved (0.59+/-0.06, 0.57+/-0.07, 0.54+/-0.07, P<0.001). Subgroup analysis demonstrated a statistically significant difference between upstream and downstream groups in preprocedural TIMI grade 3 flow (P=0.003) and postprocedural corrected TIMI frame count (P=0.007), which resulted in a shortened hospital stay (P=0.04), reduction of MACE rate at 30-day and 6-month follow-up by 34 and 20%, respectively. Multivariate logistic analysis revealed that age more than 65 years [odds ratio (OR)=3.42, P<0.01], tirofiban therapy (OR=0.56, P<0.05) and LVEF less than 0.5 during hospitalization (OR=2.56, P<0.01) were major independent predictors of MACE at 6-month clinical follow-up. No significant difference in hemorrhagic complications among three groups was noted (upstream: 10.5%, downstream: 12.3%, control: 6.9%, P=0.61).\n This prospective study indicates that adjunctive tirofiban therapy for patients with STEMI who undergo primary PCI can significantly improve reperfusion level in the infarct area, clinical outcomes at 30-day and 6-month follow-up, especially with upstream tirofiban therapy, and is safe.", "We sought to determine the safety and efficacy of high-dose bolus (HDB) tirofiban in high-risk patients undergoing percutaneous coronary intervention (PCI).\n The use of HDB tirofiban in the catheterization laboratory is controversial. In particular, in patients with acute coronary syndromes undergoing PCI, there is no evidence that tirofiban administered in the catheterization laboratory is superior to heparin alone. This finding probably reflects the suboptimal platelet inhibition when tirofiban is employed at RESTORE (Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis) regimen.\n A total of 202 patients (mean age 69 +/- 8 years; 137 males [68%]) undergoing high-risk PCI, pretreated with thienopyridines, were consecutively randomized to HDB tirofiban (25 microg/kg/3 min, and infusion of 0.15 microg/kg/min for 24 to 48 h) or placebo immediately before the procedure and then followed for a median time of 185 days (range 45 to 324 days) for the occurrence of the primary composite end point of death, myocardial infarction, target vessel revascularization (TVR), and bailout use of glycoprotein (GP) IIb/IIIa inhibitors.\n The cumulative incidence of the primary end point was 35% and 20% in placebo and HDB tirofiban groups, respectively (hazard ratio 0.51, 95% confidence interval 0.29 to 0.88; p = 0.01). This difference was mainly due to the reduction of myocardial infarction and bailout use of GP IIb/IIIa inhibitors, with no significant effect on TVR or death. The safety profile did not differ between tirofiban and placebo.\n The use of tirofiban, when administered at HDB, is safe and significantly reduces the incidence of ischemic/thrombotic complications during high-risk PCI.", "No specifically designed studies have addressed the role of the glycoprotein IIb/IIIa inhibitor abciximab in patients with non-ST-segment elevation acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) after pretreatment with 600 mg of clopidogrel.\n To assess whether abciximab is associated with clinical benefit in high-risk patients with ACS undergoing PCI after pretreatment with 600 mg of clopidogrel.\n International, multicenter, randomized, double-blind, placebo-controlled study conducted from March 2003 through December 2005, enrolling 2022 patients (mean age, 66 years) with non-ST-segment elevation ACS undergoing PCI.\n Patients were assigned to receive either abciximab (0.25 mg/kg of body weight bolus, followed by a 0.125-microg/kg per minute [maximum, 10 microg/min] infusion for 12 hours, plus heparin, 70 U/kg of body weight) or placebo (placebo bolus and infusion of 12 hours, plus heparin bolus, 140 U/kg). All patients received clopidogrel, 600 mg, at least 2 hours prior to the procedure, as well as 500 mg of oral or intravenous aspirin.\n The primary end point was a composite of death, myocardial infarction, or urgent target vessel revascularization occurring within 30 days after randomization; secondary end points were rates of in-hospital major and minor bleeding.\n Of 2022 patients enrolled, 1012 were assigned to abciximab and 1010 to placebo. The primary end point was reached in 90 patients (8.9%) assigned to abciximab vs 120 patients (11.9%) assigned to placebo, a 25% reduction in risk with abciximab (relative risk [RR], 0.75; 95% CI, 0.58-0.97; P = .03). Among patients without an elevated troponin level, there was no difference in the incidence of primary end point events between the abciximab group (23/499 patients [4.6%]) and the placebo group (22/474 patients [4.6%]) (RR, 0.99; 95% CI, 0.56-1.76; P = .98), whereas among patients with an elevated troponin level, the incidence of events was significantly lower in the abciximab group (67/513 patients [13.1%]) compared with the placebo group (98/536 patients [18.3%]), which corresponds to an RR of 0.71 (95% CI, 0.54-0.95; P = .02) (P = .07 for interaction). There were no significant differences between the 2 groups regarding the risk of major and minor bleeding as well as need for transfusion.\n Abciximab reduces the risk of adverse events in patients with non-ST-segment elevation ACS undergoing PCI after pretreatment with 600 mg of clopidogrel. The benefits provided by abciximab appear to be confined to patients presenting with an elevated troponin level.\n ClinicalTrials.gov Identifier: NCT00133003.", "Whether the glycoprotein IIb/IIIa inhibitor abciximab is beneficial in patients undergoing elective percutaneous coronary intervention after pretreatment with clopidogrel is unknown.\n We enrolled 2159 patients with coronary artery disease who underwent a percutaneous coronary intervention: 1079 patients were randomly assigned in a double-blind manner to receive abciximab and 1080 patients to receive placebo. All patients were pretreated with a 600-mg dose of clopidogrel at least two hours before the procedure. The primary end point of the trial was the composite of death, myocardial infarction, and urgent target-vessel revascularization within 30 days after randomization.\n The incidence of the primary end point was 4 percent (45 patients) in the abciximab group, as compared with 4 percent (43 patients) in the placebo group (relative risk, 1.05; 95 percent confidence interval, 0.69 to 1.59; P=0.82). Most adverse events were myocardial infarctions: the incidence was 4 percent (40 patients) in the abciximab group and 4 percent (41 patients) in the placebo group (P=0.91). Twelve patients (1 percent) in the abciximab group and eight patients (1 percent) in the placebo group had major bleeding complications (P=0.37). Profound thrombocytopenia occurred in 10 patients (1 percent) in the abciximab group but in none in the placebo group (P=0.002).\n Our data suggest that in patients at low-to-intermediate risk who undergo elective percutaneous coronary intervention after pretreatment with a high loading dose of clopidogrel, abciximab is associated with no clinically measurable benefit within the first 30 days.\n Copyright 2004 Massachusetts Medical Society", "Inhibition of platelet aggregation after aspirin or clopidogrel intake varies greatly among patients, and previous studies have suggested that poor response to oral antiplatelet agents may increase the risk of thrombotic events, especially after coronary angioplasty. Whether this reflects suboptimal platelet inhibition per se, which might benefit from more potent antiplatelet agents such as tirofiban, is unknown.\n We screened 1277 patients to enroll 93 aspirin, 147 clopidogrel, and 23 dual poor responders, based on a point-of-care assay, who underwent elective coronary angioplasty at 10 European sites for stable or low-risk unstable coronary artery disease. Patients were randomly assigned in a double-blind manner to receive either tirofiban (n=132) or placebo (n=131) on top of standard aspirin and clopidogrel therapy. The primary end point, consisting of troponin I/T elevation at least 3 times the upper limit of normal, was attained in 20.4% (n=27) in the tirofiban group compared with 35.1% (n=46) in the placebo group (relative risk, 0.58; 95% confidence interval, 0.39 to 0.88; P=0.009). The rate of major adverse cardiovascular events within 30 days in the tirofiban group also was reduced (3.8% versus 10.7%; P=0.031). The overall incidence of bleeding was low, likely explained by a substantial use of the transradial approach, and did not differ between the 2 groups.\n In low-risk patients according to clinical presentation who had poor responsiveness to standard oral platelet inhibitors via a point-of-care assay, intensified platelet inhibition with tirofiban lowers the incidence of myocardial infarction after elective coronary intervention.", "The most effective magnitude and timing of antiplatelet therapy is important in patients with acute ST-elevation myocardial infarction (STEMI). We investigated whether the results of primary coronary angioplasty (PCI) can be improved by the early administration of the glycoprotein IIb/IIIa blocker tirofiban at first medical contact in the ambulance or referral centre.\n We undertook a double-blind, randomised, placebo-controlled trial in 24 centres in the Netherlands, Germany, and Belgium. Between June 29, 2006, and Nov 13, 2007, 984 patients with STEMI who were candidates to undergo PCI were randomly assigned to either high-bolus dose tirofiban (n=491) or placebo (N=493) in addition to aspirin (500 mg), heparin (5000 IU), and clopidogrel (600 mg). Randomisation was by blinded sealed kits with study drug, in blocks of four. The primary endpoint was the extent of residual ST-segment deviation 1 h after PCI. Analysis was by intention to treat. The trial is registered, number ISRCTN06195297.\n 936 (95%) patients were randomly assigned to treatment after a prehospital diagnosis of myocardial infarction in the ambulance. Median time from onset of symptoms to diagnosis was 76 min (IQR 35-150). Mean residual ST deviation before PCI (10.9 mm [SD 9.2] vs 12.1 mm [9.4], p=0.028) and 1 h after PCI (3.6 mm [4.6] vs 4.8 mm [6.3], p=0.003) was significantly lower in patients pretreated with high-bolus dose tirofiban than in those assigned to placebo. The rate of major bleeding did not differ significantly between the two groups (19 [4%] vs 14 [3%]; p=0.36).\n Our finding that routine prehospital initiation of high-bolus dose tirofiban improved ST-segment resolution and clinical outcome after PCI, emphasises that further platelet aggregation inhibition besides high-dose clopidogrel is mandated in patients with STEMI undergoing PCI.", "We sought to evaluate the efficacy of abciximab as adjunctive therapy to routine infarct-related artery (IRA) stenting.\n The impact of abciximab on the efficacy of myocardial reperfusion and the outcome of patients with acute myocardial infarction (AMI) undergoing IRA stenting have not yet been defined.\n In a randomized trial, we assigned 400 patients with AMI to undergo IRA stenting alone or stenting plus abciximab. The primary end point was a composite of death, reinfarction, target vessel revascularization (TVR), and stroke at one month.\n The incidence of the primary end point was lower in the abciximab group than in the stent only group (4.5% and 10.5%, respectively; p = 0.023), and randomization to abciximab was independently related to the risk of the primary end point (odds ratio 0.41, 95% confidence interval 0.17 to 0.97; p = 0.041). Early ST-segment resolution was more frequent in the abciximab group (85% vs. 68%, p < 0.001). Infarct size, as assessed by one-month technetium-99m sestamibi scintigraphy, revealed smaller infarcts in the abciximab group. At six months, the cumulative difference in mortality between the groups increased (4.5% vs. 8%), and the incidence of the composite of six-month death and reinfarction was lower in the abciximab group than in the stent only group (5.5% and 13.5%, respectively; p = 0.006). Six-month repeat TVR and restenosis rates were similar in the two groups.\n Abciximab plus IRA stenting should be considered the routine reperfusion strategy in patients with AMI undergoing primary percutaneous mechanical revascularization, especially in high-risk patients.", "Platelets are believed to play a role in the ischemic complications of coronary angioplasty, such as abrupt closure of coronary vessels during or soon after the procedure. Accordingly, we evaluated the effect of a chimeric monoclonal antibody abciximab, directed against the platelet glycoprotein IIb/IIIa receptor, in patients undergoing angioplasty who were at high risk for ischemic complications. This receptor is the final common pathway for platelet aggregation.\n In a prospective, double-blind trial, we randomly assigned 42 patients to receive a bolus and an infusion of placebo or a bolus and an infusion of abciximab. Low-dose, weight-adjusted heparin (initial dose of 70 U/kg of body weight) was used in both groups. Patients underwent coronary angioplasty for high-risk clinical situations involving unstable angina or high-risk coronary morphologic characteristics. The primary study end-point consisted of any of the following: death, nonfatal myocardial infarction, unplanned surgical revascularization, unplanned repeat percutaneous procedure, unplanned implantation of a coronary stent, or insertion of an intra-aortic balloon pump for refractory ischemia within 30 days of randomization.\n Compared with placebo, the abciximab resulted in a trend toward reduction in periprocedural myocardial infarction from 15% to 0%, although the differences were not statistically significant (p = 0.099). There were no significant differences between the two groups in the risk of major and minor bleeding and the need for blood transfusion.\n Inhibition of platelet glycoprotein IIb/IIIa receptor with abciximab, together with low-dose, weight-adjusted heparin, had a favorable trend toward the reduction of periprocedural myocardial infarction in patients undergoing high-risk angioplasty, without increasing the risk of hemorrhage.", "Platelet aggregation and thrombosis have been implicated in the pathogenesis of coronary angioplasty complications. Integrelin, a synthetic cyclic heptapeptide with high affinity and marked specificity for platelet integrin glycoprotein IIb/IIIa, effectively blocks ADP-induced platelet aggregation.\n In 150 patients undergoing elective percutaneous coronary intervention, random assignment was made to one of three treatment regimens: placebo; a 90-micrograms/kg bolus of Integrelin before angioplasty followed by a 1.0-micrograms.kg-1.min-1 infusion of Integrelin for 4 hours; or a 90-micrograms/kg bolus followed by a 1.0-microgram.kg-1.min-1 infusion of Integrelin for 12 hours. Patients were followed to 30 days for the composite occurrence of myocardial infarction, stent implantation, repeat urgent or emergency percutaneous intervention or coronary bypass surgery, or death. Pharmacodynamic data were obtained in a subset of 31 patients. Administration of a 90-micrograms/kg bolus of Integrelin achieved an 86% inhibition of platelet aggregation, and this inhibition was maintained by a 1.0-microgram.kg-1.min-1 infusion. There was a trend toward reduction in end-point events from 12.2% (placebo) to 9.6% (4-hour infusion) to 4.1% (12-hour infusion), although these differences were not statistically significant (P = .13 for the 12-hour group compared with placebo). Major bleeding occurred in 8%, 8%, and 2% of patients, while minor bleeding was observed in 14%, 33%, and 47% of patients, respectively. There was no difference in bleeding index among groups (1.5, 1.7, and 1.3, respectively), defined as [(change in hematocrit/3)+red blood cell units transfused].\n This first clinical investigation of Integrelin during routine, elective, low- and high-risk coronary intervention supports the potential efficacy of Integrelin in routine coronary interventions. Pharmacodynamic analyses demonstrate that profound and sustained inhibition of platelet function is achieved, although a higher bolus dose may be required. Definitive assessment of efficacy and safety will need to await a large-scale study powered to achieve statistical significance.", "The objective of this randomized trial was to assess the antirestenotic effects of phosphorylcholine (PC)-coated stents as well as of abciximab in small coronary arteries when compared with percutaneous transluminal coronary angioplasty (PTCA) and placebo respectively.\n Stent coating with PC has been shown to reduce protein absorption and platelet activation which may reduce the risk of restenosis. Furthermore, on the basis of nondedicated studies abciximab is believed to reduce the risk of restenosis after coronary interventions.\n A total of 502 patients with lesions situated in small coronary arteries (vessel diameter </=2.5 mm) were randomly assigned to be treated with either PC-coated stents (n = 253) or PTCA (n = 249) and with either abciximab (n = 251) or placebo (n = 251) with the use of a 2 x 2 factorial design. All patients were pretreated with 600 mg clopidogrel. The primary end-point was the incidence of angiographic restenosis (>/=50% diameter stenosis) at follow-up; death or myocardial infarction, and target vessel revascularization (TVR), were assessed as secondary end-points.\n Angiographic restenosis did not differ between patients treated with PC-coated stents or with PTCA (39.0% vs. 34.2%; P = 0.30) and between patients receiving abciximab or placebo (39.3% vs. 34.3%; P = 0.29). Similarly, the need for TVR at 1-year follow-up did not differ between patients receiving PC-coated stents or PTCA (20.2% vs. 20.5%; P = 0.98) as well as between patients treated with abciximab or placebo (18.7% vs. 21.9%; P = 0.44).\n PC-coated stents and abciximab failed to reduce the incidence of angiographic restenosis after percutaneous coronary intervention of small coronary arteries. These data strengthen the belief that future studies on prevention of restenosis in small coronary arteries should focus on drug-eluting stents.", "Diabetic patients are at increased risk of adverse outcomes after percutaneous coronary interventions. Although subset analyses suggest particular benefit from the administration of abciximab in diabetic patients, no dedicated large randomized trials have been performed in diabetic patients undergoing percutaneous coronary intervention, and certainly not after pretreatment with a high loading dose of clopidogrel.\n This study (Intracoronary Stenting and Antithrombotic Regimen: Is Abciximab a Superior Way to Eliminate Elevated Thrombotic Risk in Diabetics [ISAR-SWEET] Study) enrolled 701 diabetic patients with coronary artery disease who underwent an elective percutaneous coronary intervention after pretreatment with a 600-mg dose of clopidogrel >2 hours before the procedure: 351 patients were randomly assigned to abciximab and 350 patients to placebo. The primary end point of the trial was the composite incidence of death and myocardial infarction at 1 year. The frequency of angiographic restenosis (diameter stenosis > or =50%) was the secondary end point. The incidence of death or myocardial infarction was 8.3% in the abciximab group and 8.6% in the placebo group (P=0.91), with a relative risk of 0.97 (95% CI, 0.58 to 1.62). The incidence of angiographic restenosis was 28.9% in the abciximab group and 37.8% in the placebo group (P=0.01), with a relative risk of 0.76 (95% CI, 0.62 to 0.94). The incidence of target lesion revascularization was 23.2% in the abciximab group and 30.4% in the placebo group (P=0.03).\n The findings of this study do not support a significant impact of abciximab on the risk of death and myocardial infarction in diabetic patients undergoing percutaneous coronary interventions after pretreatment with a 600-mg loading dose of clopidogrel at least 2 hours before the procedure. The present findings suggest, however, that abciximab reduces the risk of restenosis in diabetic patients receiving coronary bare metal stents.", "The benefit of catheter-based reperfusion for acute myocardial infarction (MI) is limited by a 5% to 15% incidence of in-hospital major ischemic events, usually caused by infarct artery reocclusion, and a 20% to 40% need for repeat percutaneous or surgical revascularization. Platelets play a key role in the process of early infarct artery reocclusion, but inhibition of aggregation via the glycoprotein IIb/IIIa receptor has not been prospectively evaluated in the setting of acute MI.\n Patients with acute MI of <12 hours' duration were randomized, on a double-blind basis, to placebo or abciximab if they were deemed candidates for primary PTCA. The primary efficacy end point was death, reinfarction, or any (urgent or elective) target vessel revascularization (TVR) at 6 months by intention-to-treat (ITT) analysis. Other key prespecified end points were early (7 and 30 days) death, reinfarction, or urgent TVR. The baseline clinical and angiographic variables of the 483 (242 placebo and 241 abciximab) patients were balanced. There was no difference in the incidence of the primary 6-month end point (ITT analysis) in the 2 groups (28.1% and 28.2%, P=0.97, of the placebo and abciximab patients, respectively). However, abciximab significantly reduced the incidence of death, reinfarction, or urgent TVR at all time points assessed (9.9% versus 3.3%, P=0.003, at 7 days; 11.2% versus 5.8%, P=0.03, at 30 days; and 17.8% versus 11.6%, P=0.05, at 6 months). Analysis by actual treatment with PTCA and study drug demonstrated a considerable effect of abciximab with respect to death or reinfarction: 4.7% versus 1.4%, P=0.047, at 7 days; 5.8% versus 3.2%, P=0.20, at 30 days; and 12.0% versus 6.9%, P=0.07, at 6 months. The need for unplanned, \"bail-out\" stenting was reduced by 42% in the abciximab group (20.4% versus 11.9%, P=0.008). Major bleeding occurred significantly more frequently in the abciximab group (16.6% versus 9.5%, P=0.02), mostly at the arterial access site. There was no intracranial hemorrhage in either group.\n Aggressive platelet inhibition with abciximab during primary PTCA for acute MI yielded a substantial reduction in the acute (30-day) phase for death, reinfarction, and urgent target vessel revascularization. However, the bleeding rates were excessive, and the 6-month primary end point, which included elective revascularization, was not favorably affected.", "Antithrombotic therapy improves the prognosis of patients with acute coronary syndromes, yet the syndromes remain a therapeutic challenge. We evaluated tirofiban, a specific inhibitor of the platelet glycoprotein IIb/IIIa receptor, in the treatment of unstable angina and non-Q-wave myocardial infarction.\n A total of 1915 patients were randomly assigned in a double-blind manner to receive tirofiban, heparin, or tirofiban plus heparin. Patients received aspirin if its use was not contraindicated. The study drugs were infused for a mean (+/-SD) of 71.3+/-20 hours, during which time coronary angiography and angioplasty were performed when indicated after 48 hours. The composite primary end point consisted of death, myocardial infarction, or refractory ischemia within seven days after randomization.\n The study was stopped prematurely for the group receiving tirofiban alone because of excess mortality at seven days (4.6 percent, as compared with 1.1 percent for the patients treated with heparin alone. The frequency of the composite primary end point at seven days was lower among the patients who received tirofiban plus heparin than among those who received heparin alone (12.9 percent vs. 17.9 percent; risk ratio, 0.68; 95 percent confidence interval, 0.53 to 0.88; P=0.004). The rates of the composite end point in the tirofiban-plus-heparin group were also lower than those in the heparin-only group at 30 days (18.5 percent vs. 22.3 percent, P=0.03) and at 6 months (27.7 percent vs. 32.1 percent, P=0.02). At seven days, the frequency of death or myocardial infarction was 4.9 percent in the tirofiban-plus-heparin group, as compared with 8.3 percent in the heparin-only group (P=0.006). The comparable figures at 30 days were 8.7 percent and 11.9 percent (P=0.03), respectively, and those at 6 months were 12.3 percent and 15.3 percent (P=0.06). The benefit was consistent in the various subgroups of patients and in those treated medically as well as those treated with angioplasty. Major bleeding occurred in 3.0 percent of the patients receiving heparin alone and 4.0 percent of the patients receiving combination therapy (P=0.34).\n When administered with heparin and aspirin, the platelet glycoprotein IIb/IIIa receptor inhibitor tirofiban was associated with a lower incidence of ischemic events in patients with acute coronary syndromes than in patients who received only heparin and aspirin.", "Aspirin and clopidogrel can improve myocardial reperfusion and alleviate myocardial injury during percutaneous coronary intervention (PCI). Whether the addition of intravenous tirofiban during this procedure produces further benefit has not been clarified in ST segment elevation myocardial infarction (STEMI) patients. We evaluated this on STEMI patients who underwent primary PCI (p-PCI) via transradial artery approach.\n Consecutive patients were randomized into tirofiban group (n=72) or placebo group (n=78). Angiographic analysis included initial and final thrombolysis in myocardial infarction (TIMI) flow grade (TFG), corrected TIMI frame count (CTFC) and TIMI myocardial perfusion grade (TMPG) of the thrombotic vessel. Platelet aggregation rate (PAR), creatine phosphokinase (CPK), CPK isoenzyme MB (CPK-MB) and troponin I levels were measured and TIMI definitions were used to assess bleeding complications. Left ventricular performance parameters were investigated with equilibrium radionuclide ventriculography. Major adverse cardiac events (MACE) were followed up for 6 months.\n The cases of TFG 0 and 1 before PCI, TFG 0 when first crossing of guide wire were less, and the cases of TFG 3 after PCI was more in tirofiban group than those in placebo group. The final CTFC was fewer and the incidence of no reflow phenomenon was lower, as well the percentage of final TFG 3 was higher in tirofiban group than those in placebo group (all P<0.05). Mean peak CPK-MB was significantly lower, while the left ventricular performance parameters 1 week after PCI were much more improved in tirofiban group than those in the placebo group. PAR was significantly decreased shortly after tirofiban infusion. The incidence of 6-month MACE in tirofiban group was obviously lower than that in the placebo group. No statistical difference was noted between the two groups with regard to bleeding complications.\n Intravenous tirofiban infusion, in addition to aspirin and clopidogrel in STEMI patients with p-PCI via transradial artery access, can quickly inhibit platelet aggregation, loosen occlusive thrombus, improve myocardial reperfusion and reduce incidence of MACE with few complications of vessel access and bleeding.", "This study describes the dose-exploration phase of the PRIDE trial, an investigation of the clinical pharmacology of higher dose eptifibatide in patients who underwent elective percutaneous coronary intervention (PCI). Outcomes of treatment with the platelet glycoprotein IIb/IIIa inhibitors were dependent upon proper dosing selection. In this multicenter, placebo-controlled clinical study, 127 patients were randomized 1:1:2:2 into 1 of the following treatment groups: placebo; eptifibatide as a 135 microg/kg bolus followed by a 0.75 microg/kg/min infusion; eptifibatide as a 180 microg/kg bolus with a 2.0 microg/kg/min infusion; or eptifibatide as a 250 microg/kg bolus with a 3.0 microg/kg/min infusion. Light transmission aggregometry was used to determine platelet aggregation in response to 20 microM adenosine diphosphate, and platelet receptor occupancy was also determined. Eptifibatide exhibited linear pharmacokinetics over the dose range studied. Inhibition of platelet aggregation was greater in samples collected in sodium citrate compared with those collected in D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone. The 180/2.0 dosing regimen achieved 90% inhibition of platelet aggregation immediately (5 minutes) and at steady state (8 to 24 hours). At 1 hour, mean inhibition of platelet aggregation was 80%. Eptifibatide exhibited dose-dependent pharmacodynamics that were dependent upon choice of anticoagulant. A 180 microg/kg bolus followed by a 2.0 microg/kg/min infusion at steady state achieved >80% inhibition of platelet aggregation. With the single-bolus regimen, however, there was an early loss of the inhibition of platelet aggregation before steady state was reached. Additional dose-exploration studies may further optimize eptifibatide dosing.", "Unstable angina and non-Q-wave myocardial infarction involve coronary arterial plaque rupture, platelet activation, and thrombus formation. This study tested the benefit of different doses of lamifiban (a platelet IIb/IIIa antagonist) alone and in combination with heparin in patients with these conditions to select the most promising lamifiban regimen for subsequent evaluation.\n At 273 hospitals in 20 countries, 2282 patients were randomly assigned to lamifiban (2x2 factorial design: low-dose [1 microg/min] with and without heparin versus high-dose [5 microg/min] with and without heparin) or to standard therapy (placebo and heparin). All patients received aspirin. The composite primary end point of death or nonfatal myocardial infarction at 30 days occurred in 11.7% of those receiving standard therapy, 10.6% receiving low-dose lamifiban, and 12.0% receiving high-dose lamifiban (P=0.668). By 6 months, this composite was lowest for those assigned to low-dose lamifiban (P=0.027) and intermediate for those assigned to high-dose lamifiban (P=0.450) compared with control (13.7%, 16.4%, and 17.9%, respectively). Compared with control, the combination of high-dose lamifiban and heparin resulted in more intermediate or major bleeding (12.1% versus 5.5%; P=0.002) and a similar rate of ischemic events. Conversely, low-dose lamifiban and heparin yielded similar bleeding rates as in the control group but fewer ischemic events at 6 months (12.6% versus 17.9%; P=0.025).\n In unstable angina and non-Q-wave infarction, platelet IIb/IIIa antagonism with lamifiban reduces adverse ischemic events at 6 months beyond that of aspirin and heparin therapy. The role of conjunctive heparin remains uncertain but appears more favorable with low-dose IIb/IIIa antagonism. Larger-scale study is needed to more reliably estimate these effects.", "Although stents reduce restenosis compared with balloon angioplasty, their long-term efficacy is limited by neointimal hyperplasia. Platelet and alpha(v)beta(3) integrin receptor inhibition limits neointimal proliferation in animal models of arterial injury.\n We tested whether the dual beta(3) integrin blocking agent abciximab, administered for 12 or 24 hours at the same intravenous dose as that shown to reduce adverse clinical events (death, infarction, and revascularization) after angioplasty, would reduce restenotic tissue volume, as measured by intravascular ultrasound at 6 months. Two hundred twenty-five patients were randomly allocated to placebo or abciximab before coronary intervention. Of the 215 patients who received stents and study drug, 191 (88.8%) returned for late (>/=4 months) coronary evaluation. Tissue volume, expressed as a percentage of stent volume, did not differ: 25+/-15%, 27+/-15%, and 29+/-14% for the patients in the placebo and the 12- and 24-hour abciximab groups, respectively. Lack of abciximab benefit was confirmed by quantitative coronary angiography (dichotomous restenosis: 11.6%, 18. 9%, and 19.4%; loss index: 0.33, 0.52, and 0.47, respectively, P=NS).\n Potent platelet inhibition with abciximab, as administered in this study, does not reduce in-stent restenosis. The interrelationship between stents, platelets, and neointimal proliferation requires further study.", "The primary objective of this study was to compare the effect of therapy with bivalirudin alone versus bivalirudin plus eptifibatide on platelet reactivity measured by turbidometric aggregometry and thrombin-induced platelet-fibrin clot strength (TIP-FCS) measured by thrombelastography in percutaneous coronary intervention (PCI) patients. The secondary aim was to study the relation of platelet aggregation and TIP-FCS to the occurrence of periprocedural infarction.\n Bivalirudin is commonly administered alone to clopidogrel naïve (CN) patients and to patients on maintenance clopidogrel therapy (MT) undergoing elective stenting. The effect of adding eptifibatide to bivalirudin on platelet reactivity (PR) and TIP-FCS, and their relation to periprocedural infarction in these patients are unknown.\n Patients (n = 200) stratified to clopidogrel treatment status were randomly treated with bivalirudin (n = 102) or bivalirudin plus eptifibatide (n = 98). One hundred twenty-eight CN patients were loaded with 600 mg clopidogrel immediately after stenting, and 72 MT patients were not loaded. The PR, TIP-FCS, and myonecrosis markers were serially determined.\n In CN and MT patients, bivalirudin plus eptifibatide was associated with markedly lower PR at all times (5- and 20-microM adenosine diphosphate-induced, and 15- and 25-microM thrombin receptor activator peptide-induced aggregation; p < 0.001 for all) and reduced mean TIP-FCS (p < 0.05). Patients who had a periprocedural infarction had higher mean 18-h PR (p < 0.0001) and TIP-FCS (p = 0.002).\n For elective stenting, the addition of eptifibatide to bivalirudin lowered PR to multiple agonists and the tensile strength of the TIP-FCS, 2 measurements strongly associated with periprocedural myonecrosis. Future studies of PR and TIP-FCS for elective stenting may facilitate personalized antiplatelet therapy and enhance the selection of patients for glycoprotein IIb/IIIa blockade. (Peri-Procedural Myocardial Infarction, Platelet Reactivity, Thrombin Generation, and Clot Strength: Differential Effects of Eptifibatide + Bivalirudin Versus Bivalirudin [CLEAR PLATELETS-2]; NCT00370045.", "Aggregation of platelets is the pathophysiologic basis of the acute coronary syndromes. Eptifibatide, a synthetic cyclic heptapeptide, is a selective high-affinity inhibitor of the platelet glycoprotein IIb/IIIa receptor, which is involved in platelet aggregation. We tested the hypothesis that inhibition of platelet aggregation with eptifibatide would have an incremental benefit beyond that of heparin and aspirin in reducing the frequency of adverse outcomes in patients with acute coronary syndromes who did not have persistent ST-segment elevation.\n Patients who had presented with ischemic chest pain within the previous 24 hours and who had either electrocardiographic changes indicative of ischemia (but not persistent ST-segment elevation) or high serum concentrations of creatine kinase MB isoenzymes were enrolled in the study. They were randomly assigned, in a double-blind manner, to receive a bolus and infusion of either eptifibatide or placebo, in addition to standard therapy, for up to 72 hours (or up to 96 hours, if coronary intervention was performed near the end of the 72-hour period). The primary end point was a composite of death and nonfatal myocardial infarction occurring up to 30 days after the index event.\n A total of 10,948 patients were enrolled between November 1995 and January 1997. As compared with the placebo group, the eptifibatide group had a 1.5 percent absolute reduction in the incidence of the primary end point (14.2 percent, vs. 15.7 percent in the placebo group; P=0.04). The benefit was apparent by 96 hours and persisted through 30 days. The effect was consistent in most major subgroups except for women (odds ratios for death or nonfatal myocardial infarction, 0.8 [95 percent confidence interval, 0.7 to 0.9] in men, and 1.1 [0.9 to 1.31 in women). Bleeding was more common in the eptifibatide group, although there was no increase in the incidence of hemorrhagic stroke.\n Inhibition of platelet aggregation with eptifibatide reduced the incidence of the composite end point of death or nonfatal myocardial infarction in patients with acute coronary syndromes who did not have persistent ST-segment elevation.", "The efficacy and safety of abciximab were investigated in Japanese patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) or unstable angina.\n The 973 patients were randomized into 3 groups: the low-dose group (L group) received bolus injection of 0.20 mg/kg followed by 12-h infusion; the high-dose group (H group) received bolus injection of 0.25 mg/kg followed by 12-h infusion; the placebo group (P group) received bolus and infusion of placebo. The incidence of the primary endpoint (30-day post-PCI coronary events: death, MI or urgent revascularization) was 3.6%, 1.6%, and 4.1% in the P, L, and H groups, respectively, with no significant difference between the P and L groups (P=0.104) or between the P and H groups (P=0.772). The incidence of bleeding tended to increase in a dose-dependent manner.\n No significant difference in the incidence of coronary events was found between the placebo and abciximab groups, so the efficacy of abciximab in preventing post-PCI coronary events in Japanese patients was not confirmed.", "Activation of platelets is central to the pathophysiology of unstable angina. We studied whether inhibition of the final common pathway for platelet aggregation with tirofiban, a nonpeptide glycoprotein IIb/IIIa receptor antagonist, would improve clinical outcome in this condition.\n In a double-blind study, we randomly assigned 3232 patients who were already receiving aspirin to additional treatment with intravenous tirofiban for 48 hours. The primary end point was a composite of death, myocardial infarction, or refractory ischemia at 48 hours.\n The incidence of the composite end point was 32 percent lower at 48 hours in the group that received tirofiban (3.8 percent, vs. 5.6 percent with heparin; risk ratio, 0.67; 95 percent confidence interval, 0.48 to 0.92; P=0.01). Percutaneous revascularization was performed in 1.9 percent of the patients during the first 48 hours. At 30 days, the frequency of the composite end point (with the addition of readmission for unstable angina) was similar in the two groups (15.9 percent in the tirofiban group vs. 17.1 percent in the heparin group, P=0.34). There was a trend toward a reduction in the rate of death or myocardial infarction with tirofiban (a rate of 5.8 percent, as compared with 7.1 percent in the heparin group; risk ratio, 0.80; 95 percent confidence interval, 0.61 to 1.05; P=0.11), and mortality was 2.3 percent, as compared with 3.6 percent in the heparin group (P=0.02). Major bleeding occurred in 0.4 percent of the patients in both groups. Reversible thrombocytopenia occurred more frequently with tirofiban than with heparin (1.1 percent vs. 0.4 percent, P=0.04).\n Tirofiban was generally well tolerated and, as compared with heparin, reduced ischemic events during the 48-hour infusion period, during which revascularization procedures were not performed. The incidence of refractory ischemia and myocardial infarction was not reduced at 30 days, but mortality was lower among the patients given tirofiban. Platelet inhibition with aspirin plus tirofiban may have a role in the management of unstable angina.", "Platelet aggregation is a dominant feature in the pathophysiology of unstable angina. Percutaneous transluminal coronary angioplasty (PTCA) in patients with this disorder carries an increased risk of thrombotic complications. Abciximab (c7E3) blocks the platelet glycoprotein IIb/IIIa receptor, thus preventing platelet adhesion and aggregation. The CAPTURE study was a randomised placebo-controlled multicentre trial to assess whether abciximab can improve outcome in patients with refractory unstable angina who are undergoing PTCA.\n The study recruited patients with refractory unstable angina, defined as recurrent myocardial ischaemia under medical treatment including heparin and nitrates. Predefined stopping rules were met at a planned interim analysis of data for 1050 patients, and recruitment was stopped. Data for 1265 patients (of 1400 scheduled) are presented here. After angiography, patients received a randomly assigned infusion of abciximab or placebo for 18-24 h before PTCA, continuing until 1 h afterwards. The primary endpoint was the occurrence within 30 days after PTCA of death (any cause), myocardial infarction, or urgent intervention for recurrent ischaemia. Analyses were by intention to treat.\n By 30 days, the primary endpoint had occurred in 71 (11.3%) of 630 patients who received abciximab compared with 101 (15.9%) of 635 placebo recipients (p = 0.012). The rate of myocardial infarction was lower in the abciximab than in the placebo group before PTCA (four [0.6%] vs 13 [2.1%], p = 0.029) and during PTCA (16 [2.6%] vs 34 [5.5%], p = 0.009). Major bleeding was infrequent, but occurred more often with abciximab than with placebo (24 [3.8%] vs 12 [1.9%], p = 0.043). At 6-month follow-up, death, myocardial infarction, or repeat intervention had occurred in 193 patients in each group.\n In patients with refractory unstable angina, treatment with abciximab substantially reduces the rate of thrombotic complications, in particular myocardial infarction, before, during, and after PTCA. There was no evidence that this regimen influenced the rate of myocardial infarction after the first few days, or the need for subsequent reintervention.", "When administered in conjunction with primary coronary stenting for the treatment of acute myocardial infarction, a platelet glycoprotein IIb/IIIa inhibitor may provide additional clinical benefit, but data on this combination therapy are limited.\n We randomly assigned 300 patients with acute myocardial infarction in a double-blind fashion either to abciximab plus stenting (149 patients) or placebo plus stenting (151 patients) before they underwent coronary angiography. Clinical outcomes were evaluated 30 days and 6 months after the procedure. The angiographic patency of the infarct-related vessel and the left ventricular ejection fraction were evaluated at 24 hours and 6 months.\n At 30 days, the primary end point--a composite of death, reinfarction, or urgent revascularization of the target vessel--had occurred in 6.0 percent of the patients in the abciximab group, as compared with 14.6 percent of those in the placebo group (P=0.01); at 6 months, the corresponding figures were 7.4 percent and 15.9 percent (P=0.02). The better clinical outcomes in the abciximab group were related to the greater frequency of grade 3 coronary flow (according to the classification of the Thrombolysis in Myocardial Infarction trial) in this group than in the placebo group before the procedure (16.8 percent vs. 5.4 percent, P=0.01), immediately afterward (95.1 percent vs. 86.7 percent, P=0.04), and six months afterward (94.3 percent vs. 82.8 percent, P=0.04). One major bleeding event occurred in the abciximab group (0.7 percent); none occurred in the placebo group.\n As compared with placebo, early administration of abciximab in patients with acute myocardial infarction improves coronary patency before stenting, the success rate of the stenting procedure, the rate of coronary patency at six months, left ventricular function, and clinical outcomes.", "In the Intracoronary Stenting and Antithrombotic Regimen-2 trial (ISAR-2), we sought to investigate the effect of abciximab on angiographic and clinical restenosis after stenting following acute myocardial infarction (AMI). We also intended to assess the impact of abciximab on clinical outcome in this setting.\n It is unclear whether abciximab reduces neointima formation after stenting. Such an effect may be particularly prominent in thrombus-containing lesions.\n Patients undergoing stenting within 48 h after onset of AMI were randomly assigned to receive either standard-dose heparin or abciximab plus reduced-dose heparin. Of 401 patients randomized, 366 without 30-day adverse events were eligible for six-month angiographic follow-up. Scheduled angiography was performed in 80% of these patients.\n By 30 days, the composite clinical end point of death, reinfarction, and target lesion revascularization (TLR) was reached in 5.0% of the abciximab group and in 10.5% of the control group (p = 0.038). At one year, absolute reduction in the composite clinical end point by abciximab was still 5.7% but had lost its statistical significance. Our primary end point, late lumen loss, was 1.26+/-0.85 mm with abciximab and 1.21+/-0.74 mm with standard heparin (p = 0.61), and binary angiographic restenosis rates were 31.1% and 30.6%, respectively (p = 0.92).\n In patients undergoing stenting following AMI, abciximab exerted beneficial effects by substantially reducing the 30-day rate of major adverse cardiac events. During one-year follow-up, there was no additional benefit from a reduction in TLR nor did abciximab reduce angiographic restenosis.", "Adverse cardiovascular events associated with thrombotic occlusion occur in 4% to 12.8% of patients after coronary angioplasty. Recently, potent antiplatelet agents have been used to reduce those thrombotic complications. Tirofiban is a highly selective, short-acting inhibitor of fibrinogen binding to platelet glycoprotein (GP) IIb/IIIa that inhibits ex vivo platelet aggregation in response to a variety of agonists.\n The RESTORE trial (Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis) was a randomized, double-blind, placebo-controlled trial of tirofiban in patients undergoing coronary interventions (balloon angioplasty or directional atherectomy) within 72 hours of presentation with an acute coronary syndrome (unstable angina pcctoris or acute myocardial infarction). The end points of the study were death from any cause, myocardial infarction, coronary bypass surgery due to angioplasty failure or recurrent ischemia, repeat target-vessel angioplasty for recurrent ischemia, and insertion of a stent due to actual or threatened abrupt closure of the dilated artery, and the primary end point was a composite representing the occurrence of any of these events. The prespecified primary hypothesis of the study was that tirofiban, administered as a bolus of 10 microg/kg over a 3-minute period and followed by a 36-hour infusion of 0.15 microg x kg(-1) x min(-1), would result in a reduction in the 30-day composite end point compared with placebo. Patients (n=2139) who were already receiving treatment with aspirin and heparin were randomized to receive tirofiban or placebo. The primary composite end point at 30 days was reduced from 12.2% in the placebo group to 10.3% in the tirofiban group, a 16% relative reduction (P=.160). However, 2 days after angioplasty, the tirofiban group had a 38% relative reduction in the composite end point (P< or =.005), and at 7 days there was a 27% relative reduction (P=.022), largely because of a reduction in nonfatal myocardial infarction and the need for repeat angioplasty. When repeat angioplasty or coronary artery bypass surgery procedures were included in the composite only if performed on an urgent or emergency basis, the composite 30-day event rates were 10.5% for the placebo group and 8.0% for the tirofiban group, a relative reduction of 24% (P=.052). Major bleeding, including transfusion, was not significantly different between the two groups (3.7% in the placebo group and 5.3% in the tirofiban group; P=.096). When the Thrombolysis In Myocardial Infarction (TIMI) criteria for major bleeding were used, the incidence was 2.1% in the placebo group compared with 2.4% in the tirofiban group (P=.662). Thrombocytopenia was similar in the placebo and tirofiban groups (0.9% for the placebo group versus 1.1% for the tirofiban group; P=.709).\n In patients undergoing coronary angioplasty for acute coronary syndromes, tirofiban protects against early adverse cardiac events related to thrombotic closure. At 30 days, however, the reduction in adverse cardiac events was no longer statistically significant. The bleeding observed with tirofiban was not statistically different from that observed with placebo.", "Glycoprotein IIb/IIIa blockers reduce procedure-related thrombotic complications of percutaneous coronary intervention, and the risk of death and myocardial infarction in patients with acute coronary syndromes. The effect on risk of death and myocardial infarction is particularly apparent in patients undergoing early percutaneous coronary interventions. We did a randomised, multicentre trial to study the effect of the glycoprotein IIb/IIIa blocker abciximab on patients with acute coronary syndromes who were not undergoing early revascularisation.\n We enrolled 7800 patients who were admitted to hospital with chest pain and either ST-segment depression or raised troponin T or I concentrations. 2598 were randomly assigned placebo, 2590 an abciximab bolus and 24 h infusion, and 2612 an abciximab bolus and 48 h infusion; all patients received aspirin and either unfractionated or low-molecular-weight heparin. The primary endpoint was death or myocardial infarction at 30 days after randomisation. Analysis was by intention to treat.\n There were no drop-outs. 209 (8.0%) patients on placebo, 212 (8.2%) on 24 h abciximab, and 238 (9.1%) on 48 h abciximab died or had a myocardial infarction before day 30 (odds ratio 1.0 [95% CI 0.83-1.24], for difference between placebo and 24 h abciximab, and 1.1 [0.94-1.39] for difference between placebo and 48 h abciximab). The lack of benefit from treatment with abciximab was consistent in most subgroups investigated; in particular, no benefit was seen in patients with raised cardiac troponin T or I concentrations at enrolment, although these patients did have a strongly increased risk of subsequent events. Bleeding rates were low, but increased with abciximab, particularly when continued for 48 h. Additionally, thrombocytopenia was more frequent with abciximab than with placebo.\n Although the explanations for our findings are unclear, this study indicates that abciximab is not beneficial as first-line medical treatment in patients admitted with acute coronary syndromes.", "The platelet glycoprotein IIb/IIIa inhibitors, although effective in reducing ischaemic complications of percutaneous coronary intervention, are used in few coronary stent implantation procedures. ESPRIT (Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy) is a randomised, placebo-controlled trial to assess whether a novel, double-bolus dose of eptifibatide could improve outcomes of patients undergoing coronary stenting.\n We recruited 2064 patients undergoing stent implantation in a native coronary artery. Immediately before percutaneous coronary intervention, patients were randomly allocated to receive eptifibatide, given as two 180 microg/kg boluses 10 min apart and a continuous infusion of 2.0 microg/kg/min for 18-24 h, or placebo, in addition to aspirin, heparin, and a thienopyridine. The primary endpoint was the composite of death, myocardial infarction, urgent target vessel revascularisation, and thrombotic bailout glycoprotein IIb/IIIa inhibitor therapy within 48 h after randomisation. The key secondary endpoint was the composite of death, myocardial infarction, or urgent target vessel revascularisation at 30 days.\n The trial was terminated early for efficacy. The primary endpoint was reduced from 10.5% (108 of 1024 patients on placebo [95% CI 8.7-12.4%]) to 6.6% (69 of 1040 [5.1-8.1%]) with treatment (p=0.0015). The key 30 day secondary endpoint was also reduced, from 10.5% (107 of 1024 patients on placebo [8.6-12.3%]) to 6.8% (71 of 1040 [5.3-8.4%]; p=0.0034). There was consistency in reduction of events across all components of the composite endpoint and among the major subgroups. Major bleeding was infrequent but arose more often with eptifibatide than placebo (1.3%, 13 of 1040 [0.7-2.1%]) vs 0.4%, 4 of 1024 [0.1-1.0%]; p=0.027).\n Routine glycoprotein IIb/IIIa inhibitor pretreatment with eptifibatide substantially reduces ischaemic complications in coronary stent intervention and is better than a strategy of reserving treatment to the bailout situation.", "Platelets are believed to play a part in the ischemic complications of coronary angioplasty, such as abrupt closure of the coronary vessel during or soon after the procedure. Accordingly, we evaluated the effect of a chimeric monoclonal-antibody Fab fragment (c7E3 Fab) directed against the platelet glycoprotein IIb/IIIa receptor, in patients undergoing angioplasty who were at high risk for ischemic complications. This receptor is the final common pathway for platelet aggregation.\n In a prospective, randomized, double-blind trial, 2099 patients treated at 56 centers received a bolus and an infusion of placebo, a bolus of c7E3 Fab and an infusion of placebo, or a bolus and an infusion of c7E3 Fab. They were scheduled to undergo coronary angioplasty or atherectomy in high-risk clinical situations involving severe unstable angina, evolving acute myocardial infarction, or high-risk coronary morphologic characteristics. The primary study end point consisted of any of the following: death, nonfatal myocardial infarction, unplanned surgical revascularization, unplanned repeat percutaneous procedure, unplanned implantation of a coronary stent, or insertion of an intraaortic balloon pump for refractory ischemia. The numbers of end-point events were tabulated for 30 days after randomization.\n As compared with placebo, the c7E3 Fab bolus and infusion resulted in a 35 percent reduction in the rate of the primary end point (12.8 vs. 8.3 percent, P = 0.008), whereas a 10 percent reduction was observed with the c7E3 Fab bolus alone (12.8 vs. 11.5 percent, P = 0.43). The reduction in the number of events with the c7E3 Fab bolus and infusion was consistent across the end points of unplanned revascularization procedures and nonfatal myocardial infarction. Bleeding episodes and transfusions were more frequent in the group given the c7E3 Fab bolus and infusion than in the other two groups.\n Ischemic complications of coronary angioplasty and atherectomy were reduced with a monoclonal antibody directed against the platelet IIb/IIIa glycoprotein receptor, although the risk of bleeding was increased.", "Patients with unstable angina despite intensive medical therapy, ie, refractory angina, are at high risk for developing thrombotic complications: myocardial infarction or coronary occlusion during percutaneous transluminal coronary angioplasty (PTCA). Chimeric 7E3 (c7E3) Fab is an antibody fragment that blocks the platelet glycoprotein (GP) IIb/IIIa receptor and potently inhibits platelet aggregation.\n To evaluate whether potent platelet inhibition could reduce these complications, 60 patients with dynamic ST-T changes and recurrent pain despite intensive medical therapy were randomized to c7E3 Fab or placebo. After initial angiography had demonstrated a culprit lesion suitable for PTCA, placebo or c7E3 Fab was administered as 0.25 mg/kg bolus injection followed by 10 micrograms/min for 18 to 24 hours until 1 hour after completion of second angiography and PTCA. During study drug infusion, ischemia occurred in 9 c7E3 Fab and 16 placebo patients (P = .06). During hospital stay, 12 major events occurred in 7 placebo patients (23%), including 1 death, 4 infarcts, and 7 urgent interventions. In the c7E3 Fab group, only 1 event (an infarct) occurred (3%, P = .03). Angiography showed improved TIMI flow in 4 placebo and 6 c7E3 Fab patients and worsening of flow in 3 placebo patients but in none of the c7E3 Fab patients. Quantitative analysis showed significant improvement of the lesion in the patients treated with c7E3 Fab, which was not observed in the placebo group, although the difference between the two treatment groups was not significant. Measurement of platelet function and bleeding time demonstrated > 90% blockade of GPIIb/IIIa receptors, > 90% reduction of ex vivo platelet aggregation to ADP, and a significantly prolonged bleeding time during c7E3 Fab infusion, without excess bleeding.\n Combined therapy with c7E3 Fab, heparin, and aspirin appears safe. These pilot study results support the concept that effective blockade of the platelet GPIIb/IIIa receptors can reduce myocardial infarction and facilitate PTCA in patients with refractory unstable angina.", "The aim of this study was to assess, in clopidogrel nonresponders undergoing elective percutaneous coronary intervention (PCI), the benefit of adjusted antiplatelet therapy with glycoprotein (GP) IIb/IIIa antagonist administration during PCI for 1-month clinical outcome.\n Numerous biological studies have reported interindividual variability in platelet response to clopidogrel with clinical relevance, and high post-treatment platelet reactivity (adenosine diphosphate-induced aggregation >70%) has been proposed to define nonresponse to clopidogrel. These nonresponders might benefit from tailored antiplatelet therapy.\n One hundred forty-nine clopidogrel nonresponders referred for elective PCI were prospectively included and randomized to \"conventional group\" (n = 75) or \"active group\" with GP IIb/IIIa antagonist (n = 74). All patients received 250-mg aspirin and 600-mg clopidogrel before PCI and platelet testing.\n The rate of cardiovascular events at 1 month was significantly lower in the \"active group\" than in the \"conventional group\": 19% (n = 14) versus 40% (n = 30), p = 0.006, odds ratio: 2.8; 95% confidence interval: 1.4 to 6.0. No patient in either group had post-procedural Thrombolysis In Myocardial Infarction major bleeding or required transfusions.\n The present study suggested benefit of tailored antiplatelet therapy during elective PCI with GP IIb/IIIa antagonist for clopidogrel nonresponders without increased bleeding risk.", "Although aspirin is beneficial in patients with unstable angina, it is a relatively weak inhibitor of platelet aggregation. The effect of Integrelin, which inhibits the platelet fibrinogen receptor glycoprotein (GP) IIb/IIIa, on the frequency and duration of Holter ischemia was evaluated in 227 patients with unstable angina.\n Patients received intravenous heparin and standard ischemic therapy and were randomized to receive oral aspirin and placebo Integrelin; placebo aspirin and low-dose Integrelin. 45 micrograms/kg bolus followed by a 0.5 microgram.kg-1. min-1 continuous infusion; or placebo aspirin and high-dose Integrelin, 90 micrograms/kg bolus followed by a 1.0-microgram.kg-1, min-1 constant infusion. Study drug was continued for 24 to 72 hours, and Holter monitoring was performed. Patients randomized to high-dose Integrelin experienced 0.24 +/- 0.11 ischemic episodes (mean +/- SEM) on Holter lasting 8.41 +/- 5.29 minutes over 24 hours of study drug infusion. Patients randomized to aspirin experienced a greater number (1.0 +/- 0.33, P < .05) and longer duration (26.2 +/- 9.8 minutes, P = .01) of ischemic episodes than the high-dose Integrelin group. There was no evidence of rebound ischemia after withdrawal of study drug. In 46 patients, platelet aggregation was rapidly inhibited by Integrelin in a dose-dependent fashion. The number of clinical events was small, and there were no bleeding differences in the three treatment arms.\n Intravenous Integrelin is well tolerated, is a potent reversible inhibitor of platelet aggregation, and added to full-dose heparin reduces the number and duration of Holter ischemic events in patients with unstable angina compared with aspirin.", "Intracoronary stent implantation during percutaneous transluminal coronary angioplasty (PTCA) has shown favorable results, reducing acute complications associated with PTCA, such as coronary artery dissection and abrupt or threatened vessel closure. However, treatment of lesions with a complex morphology and diffuse disease, requiring long or multiple coronary stents, is still associated with a poorer outcome. We investigated the hypothesis that abciximab might lead to a different outcome in patients with complex coronary lesions, which require long or multiple stent implantation.\n One hundred and six patients were randomized to receive either a combination of abciximab (bolus and 12 hour infusion) and weight-adjusted low-dose heparin or weight-adjusted heparin alone and followed up to 30 days.\n The procedural success rate was 100% in both groups of patients. In the control group a composite rate of major adverse events such as any death irrespective of cause, Q wave or non-Q wave myocardial infarction, acute or subacute stent thrombosis and urgent revascularization of 15.3% was shown at 30-day follow-up. The use of abciximab reduced the composite adverse event rate to 3.7% (76% absolute reduction, p < 0.05).\n The use of abciximab during high risk stenting is safe and reduces the risk of cardiac events at 30-day follow-up as compared to standard treatment with heparin. A longer follow-up period is warranted to confirm the beneficial effects observed at 30 days with abciximab in this setting.", "Coronary stenting is associated with a high incidence of restenosis in patients with diabetes mellitus. Recent data suggest that diabetic patients treated with abciximab have a lower rate of target vessel revascularization (TVR). We sought to investigate whether abciximab can reduce in-stent restenosis after coronary stenting in diabetic patients.\n In this prospective double-blind trial, we randomly assigned 254 patients with type 2 diabetes mellitus undergoing nonurgent coronary stenting to receive abciximab with an initial heparin bolus of 50 U/kg (n = 128) or placebo with an initial heparin bolus of 70 U/kg (n = 126). All patients received aspirin and clopidogrel before the procedure. The primary endpoint was angiographic restenosis by quantitative coronary angiography at 6 months. The secondary endpoint was death, myocardial infarction (MI), or target lesion revascularization (TLR) at 6 months.\n The clinical, angiographic, and procedural characteristics were matched between the 2 groups. Angiographic follow-up was completed in 226 patients (90%). Angiographic restenosis occurred in 29.1% of the abciximab group, and 24% of the placebo group (p = 0.30). The rates of the secondary endpoint were similar between the 2 groups (23.4% in the abciximab group versus 22.2% in the placebo group; p = 0.88). TLR was performed on 36 (18.4%) lesions in 29 (23.4%) patients of the abciximab group, and 26 (13.6%) lesions in 23 (18.3%) patients of the placebo groups, respectively (p = 0.21 and 0.35, respectively).\n Abciximab does not reduce angiographic restenosis or TLR in type 2 diabetic patients undergoing nonurgent coronary stenting.", "The Troponin in Planned PTCA/Stent Implantation With or Without Administration of the Glycoprotein IIb/IIIa Receptor Antagonist Tirofiban (TOPSTAR) trial investigated: 1) the amount of troponin T (TnT) release after nonacute, elective percutaneous coronary intervention (PCI) in patients pretreated with aspirin and clopidogrel; and 2) the effect of additional glycoprotein (GP) IIb/IIIa receptor inhibiton on postinterventional TnT release.\n No data are available yet as to whether additional administration of a GP IIb/IIIa receptor antagonist might be beneficial in patients undergoing elective PCI already pretreated with aspirin and clopidogrel.\n After bolus application of the study medication (tirofiban [T] or placebo [P]), PCI was performed followed by an 18-h continuous infusion of T/P. Primary end point of the study was incidence and amount of TnT release after elective PCI after 24 h.\n A total of 12 h after PCI troponin release was detected in 63% of the patients receiving P and in 40% of the patients receiving T (p < 0.05), after 24 h in 69% (P) and 48% (T) (p < 0.05) and after 48 h in 74% (P) versus 58% (T) (p < 0.08) of the patients. No differences were observed regarding major bleeding, intracranial bleeding or nonhemorrhagic strokes. After nine months a reduction of combined death/myocardial infarction/target vessel revascularization could be observed in the tirofiban group ([T] 2.3% vs. [P] 13.04%, p < 0.05).\n Troponin T release occurs after successful intervention in 74% of the patients undergoing elective PCI after 48 h even after pretreatment with aspirin and clopidogrel. The GP IIb/IIIa receptor antagonist tirofiban is able to decrease the incidence of troponin release significantly in this patient population.", "Platelet glycoprotein IIb/IIIa inhibitors reduce the rate of death or myocardial infarction among patients with acute coronary syndromes without persistent ST-segment elevation, but their effects may depend on plasma concentrations. We tested whether the addition of lamifiban, titrated to achieve target plasma concentrations, to standard care would improve clinical outcomes.\n We randomized 5225 patients at 389 centers in 29 countries to receive a bolus and </=72-hour infusion of lamifiban or placebo, adjusted for renal function, with aspirin and heparin. The primary end point was the composite of death, myocardial infarction, or severe, recurrent ischemia at 30 days. Baseline characteristics did not differ significantly by treatment. The primary end point occurred in 11.8% of lamifiban-treated patients and in 12.8% of placebo-treated patients (OR, 0.914; 95% CI, 0.769 to 1.087; P=0.329). Bleeding was more common in lamifiban-treated patients, but intracranial hemorrhage was not increased. Among the subgroup who had plasma lamifiban concentrations measured, 91% had a concentration >18 ng/mL at steady state, but their outcomes did not differ from those with lower concentrations.\n Lamifiban showed no significant effects on clinical outcomes in patients with non-ST-elevation acute coronary syndromes, despite achievement of adequate plasma concentrations." ]

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[ "Efficacy and tolerability of citalopram in comparison with fluvoxamine in depressed outpatients: a double-blind, multicentre study. The LUCIFER Group.", "Noradrenergic function and clinical outcome in antidepressant pharmacotherapy.", "Interest of a loading dose of milnacipran in endogenous depressive inpatients. Comparison with the standard regimen and with fluvoxamine.", "A comparative study of the efficacy and safety profiles between fluvoxamine and nortriptyline in Japanese patients with major depression.", "A double-blind, placebo-controlled trial of fluvoxamine versus imipramine in outpatients with major depression.", "Fluvoxamine maleate in the treatment of depression: a single-center, double-blind, placebo-controlled comparison with imipramine in outpatients.", "Antidepressant efficacy and tolerability of milnacipran, a dual serotonin and noradrenaline reuptake inhibitor: a comparison with fluvoxamine.", "Fluvoxamine versus imipramine and placebo: a double-blind comparison in depressed patients.", "Pituitary-adrenocortical hyperfunction and intolerance to fluvoxamine, a selective serotonin uptake inhibitor.", "Clinical trials of fluvoxamine vs chlorimipramine with single and three times daily dosing.", "A double-blind, randomized comparison of fluvoxamine with mianserin in depressive illness.", "[Maprotiline versus fluvoxamine: comparison of their effects on the hypothalamo-hypophyseal-thyroid axis].", "A comparison of fluvoxamine and fluoxetine in the treatment of major depression.", "The effects of psychomotor performance of fluvoxamine versus mianserin in depressed patients in general practice.", "Neuroendocrine (HPA axis) and clinical correlates during fluvoxamine and amitriptyline treatment.", "[Multicenter study comparing efficacy and tolerance of moclobemide and fluvoxamine in hospitalized and ambulatory patients with severe depressive episodes].", "Fluvoxamine maleate, a serotonergic antidepressant; a comparison with chlorimipramine.", "Prolactin response to d-fenfluramine in major depression before and after treatment with serotonin reuptake inhibitors.", "Effects of the serotonin type 2A, 3A and 3B receptor and the serotonin transporter genes on paroxetine and fluvoxamine efficacy and adverse drug reactions in depressed Japanese patients.", "A double-blind comparison of fluvoxamine and paroxetine in the treatment of depressed outpatients.", "Changes in daily life experience associated with clinical improvement in depression.", "A double-blind comparison of fluvoxamine and dothiepin in the treatment of major affective disorder.", "A double-blind placebo-controlled study of fluvoxamine and imipramine in out-patients with primary depression.", "A double-blind, randomised comparison of fluvoxamine with dothiepin in the treatment of depression in elderly patients.", "Use of a standardized documentation system (BLIPS/BDP) in the conduct of a multicenter international trial comparing fluvoxamine, imipramine, and placebo.", "Fluvoxamine versus fluoxetine in major depressive episode: a double-blind randomised comparison.", "Sertraline versus fluvoxamine in the treatment of elderly patients with major depression: a double-blind, randomized trial.", "Plasma levels of catecholamine metabolites predict the response to sulpiride or fluvoxamine in major depression.", "The role of neuropharmacologic selectivity in antidepressant action: fluvoxamine versus desipramine.", "A double-blind comparative study of the clinical efficacy of fluvoxamine and chlorimipramine.", "Fluvoxamine as effective as clomipramine against symptoms of severe depression: results from a multicentre, double-blind study.", "[Comparative efficacy and tolerance of fluvoxamine and amitriptyline in the treatment of moderate and severe depression in mental hospital].", "CPT performance in major depressive disorder before and after treatment with imipramine or fluvoxamine.", "Fluvoxamine and clomipramine in depressed hospitalised patients: results from a randomised, double-blind study.", "The effect of amitriptyline, doxepin, fluvoxamine, and paroxetine treatment on heart rate variability.", "Response to total sleep deprivation before and during treatment with fluvoxamine or maprotiline in patients with major depression--results of a double-blind study.", "Fluvoxamine, imipramine, and placebo in the treatment of depressed outpatients: effects on depression.", "Efficacy and tolerability of moclobemide compared with fluvoxamine in depressive disorder (DSM III). A French/Swiss double-blind trial.", "A placebo-controlled inpatient comparison of fluvoxamine maleate and imipramine in major depression.", "A double-blind clinical trial of fluvoxamine and imipramine in patients with primary depression." ]

[ "In 16 depression clinics in hospitals and outpatient facilities in the Netherlands, a study was performed to evaluate and compare the efficacy and tolerability of citalopram and fluvoxamine and to determine the difference in the incidence of gastrointestinal side-effects. A total of 217 patients with a depressive disorder (DSM-III-R criteria) and a score of at least 16 on the Hamilton rating scale for depression were randomized to treatment. The results of this study indicate that the two drugs are equally effective. The adverse events occurring during treatment show a similar pattern between the two drugs, but citalopram is better tolerated than fluvoxamine. Citalopram induces fewer gastrointestinal adverse events compared with fluvoxamine. However, this did not affect the drop-out rates.", "Controversy remains regarding the role of noradrenergic systems in determining clinical response to antidepressant pharmacotherapy. Pineal gland production of melatonin can serve as a physiologic index of noradrenergic function. The aim of this study was to examine the effects of antidepressant treatment on 24-hour urinary excretion of the principle metabolite of melatonin, 6-sulfatoxymelatonin in treatment responders and nonresponders. Twenty-four outpatients meeting DSM-III-R criteria for Major Depression received treatment with either fluvoxamine or imipramine for 6 weeks while participating in a placebo-controlled double-blind clinical trial. Twenty-four hour excretion of 6-sulfatoxymelatonin was measured at baseline and at the conclusion of the treatment trial. Changes in urinary excretion of 6-sulfatoxymelatonin distinguished antidepressant responders from nonresponders, with a significant increase observed in the former group and a significant decrease in the latter. The degree of clinical response was correlated with the change in 6-sulfatoxymelatonin excretion. These results suggest that enhanced noradrenergic function may play an important role in determining clinical response to antidepressant pharmacotherapy.", "A multicenter controlled study was designed to test the hypothesis that a loading dose of an antidepressant could shorten the latency of its clinical efficacy. Three parallel groups of about 40 endogenous depressive inpatients received either a loading dose of milnacipran (300 mg daily for 2 weeks and 150 mg daily during the 2 following weeks), the standard regimen of milnacipran in severe depression (200 mg daily for 4 weeks), or fluvoxamine (200 mg daily for 4 weeks). The duration of the study was 4 weeks, with assessments at baseline and after 4, 9, 14, 21, and 28 days of therapy by means of Montgomery and Asberg depression scale (MADS), the Hamilton depression scale, the Clinical Global Impressions (CGI), and a checklist of symptoms and side-effects. Results showed very similar evolution in the 3 treatment groups. In addition, the level of side-effects did not exhibit significant differences among the treatment groups, except for excitement-nervousness and akathisia which were more frequently reported with fluvoxamine. These results do not support the usefulness of a loading dose of an antidepressant such as milnacipran. They demonstrate however that milnacipran can be given at a 300 mg daily dose from the very first day of treatment with an excellent tolerance.", "The aim of this study was to compare the efficacy and safety profiles between fluvoxamine and nortriptyline in Japanese patients with major depression.\n The efficacy and safety profiles of fluvoxamine, a selective serotonin-reuptake inhibitor, and nortriptyline were compared under a single-blind fashion in 74 Japanese patients with major depression. The efficacy was assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D), Clinical Global Impression Scale (CGI) severity and improvement scores, while the safety profiles were assessed using the UKU Side Effect Rating Scale at baseline, and on days 7, 14, 28 and 56. Moreover, with the aim of determining the distinct efficacy profiles of each drug, the effects on each of the factor scores extracted by the principal component analysis performed for HAM-D scores were compared between drugs.\n Both drug groups showed significant amelioration of depressive symptomatology over the trial period lasting for 8 weeks. Statistical analyses revealed no significant between-group differences regarding the efficacy assessed by either HAM-D or CGI scores; however, the efficacy of nortriptyline tended to appear earlier than that of fluvoxamine. Moreover, no significant differences were obtained for the factor scores, representing 'depressed mood', 'physical symptoms' or 'sleep disturbances', although 'sleep disturbances' appeared to improve earlier in the nortriptyline group than in the fluvoxamine group. As for the safety profiles, the nortriptyline group scored a significantly higher incidence of adverse events such as dysarthria or orthostatic dizziness, as well as increased heart rate.\n These findings suggest that fluvoxamine is generally comparable to nortriptyline in its efficacy and superior in its safety profile, in accordance with findings obtained in previous comparative clinical trials conducted in Caucasian populations.", "The authors employed a double-blind, placebo-controlled design to investigate the effectiveness of fluvoxamine versus imipramine in 54 outpatients with moderate major depression. Fluvoxamine proved superior to placebo but not to imipramine on the Hamilton Rating Scale for Depression and the Montgomery and Asberg Depression Rating Scale. Nausea and hyperarousal were the most common side effects in the fluvoxamine-treated patients.", "The efficacy and safety of fluvoxamine maleate, a selective serotonin reuptake inhibitor, was compared with placebo and imipramine in patients with major depressive disorder. Previous literature has cited a dose range of 100 to 300 mg/day of fluvoxamine maleate for the treatment of major depression; however, this study demonstrates that a dose range of 50 to 150 mg/day is as effective as imipramine (80-240 mg/day). After a 1- to 2-week, single-blind, placebo washout phase, 150 depressed outpatients were randomized to double-blind treatment with fluvoxamine maleate (50-150 mg/day), imipramine (80-240 mg/day), or placebo for 6 weeks. Fluvoxamine produced a significant therapeutic benefit over placebo (p < or = 0.05) as assessed by the total score on the Hamilton Rating Scale for Depression; imipramine (80-240 mg/day) produced similar results. The secondary outcome variables (i.e., Clinical Global Impression severity of illness item and 56-Item Hopkins Symptom Checklist depression factor) also showed significant differences between fluvoxamine maleate and placebo during three of the four final weeks of the study. Both fluvoxamine maleate and imipramine appeared to be safe and well tolerated by the majority of patients. As expected from the pharmacology of these agents, the imipramine groups reported more anticholinergic effects (dry mouth, dizziness, and urinary retention) and electrocardiographic effects, whereas the fluvoxamine group reported more nausea, somnolence, and abnormal ejaculation. The majority of these adverse events were mild to moderate and, with the exception of dry mouth (imipramine) and abnormal ejaculation (fluvoxamine), were transient. The data clearly demonstrate the antidepressant activity and tolerability of fluvoxamine maleate (50-150 mg/day) as compared with placebo; it is also as effective as the tricyclic antidepressant imipramine (80-240 mg/day) in patients with major depressive disorder.", "The antidepressant efficacy and tolerability of milnacipran, a dual action serotonin-noradrenaline reuptake inhibitor, were compared with those of the selective serotonin reuptake inhibitor, fluvoxamine, in 113 patients with moderate to severe major depression. Treatment with milnacipran, 50 mg b.d. for 6 weeks, produced a significantly greater reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores than fluvoxamine, 100 mg b.d. (P = 0.007; 65.4% versus 49.9%, respectively); significantly greater decreases were also seen on days 7 (P = 0.04) and 28 (P = 0.03). The response rate (the proportion of patients showing a decrease in MADRS scores of at least 50%) was 78.9% in patients receiving milnacipran, compared with 60.7% in fluvoxamine-treated patients (P = 0.04). Milnacipran also produced greater improvements in 24-item Hamilton Depression Rating Scale scores (P = 0.05). On the Clinical Global Impression Improvement scale, 77.2% of milnacipran-treated patients were rated as considerably or markedly improved, compared with 60.7% of patients receiving fluvoxamine (P = 0.06 chi-squared). Both treatments were well tolerated; the only significant difference between the two groups was a higher incidence of tremor and drowsiness in patients treated with fluvoxamine. It is concluded that milnacipran may offer some advantages over selective serotonin reuptake inhibitors, such as fluvoxamine, in the treatment of moderate to severe major depression.", "Approximately 20 million patients suffer from major depressive disorder each year, indicating a need for antidepressant agents that are synonymous with effectiveness, tolerability and patient compliance. The authors examined the effects of fluvoxamine, a selective serotonin reuptake inhibitor, in the treatment of outpatients meeting DSM-III-R criteria for major depressive disorder. A randomized, double-blind, parallel group, placebo- and imipramine-controlled single center study was conducted in 150 outpatients. Patients were randomized to receive up to 150 mg/day of fluvoxamine as a single bedtime dose, 240 mg/day of imipramine on a twice-daily (BID) schedule, or placebo for six weeks. Efficacy measurements included HAM-D, MADRS, CGI, Raskin-Covi and SCL-56 scales. The HAM-D total score indicated that both active treatment groups showed significantly (p < or = 0.05) greater therapeutic benefit than did placebo. Severely depressed patients (HAM-D > or = 30) responded better to fluvoxamine in five of six measures. Side-effects from fluvoxamine were similar to those reported for other selective serotonin reuptake inhibitors (nausea, somnolence) and were well tolerated. Imipramine was associated with anticholinergic effects such as dry mouth and dizziness. The pharmacokinetic properties of fluvoxamine which allow the drug to be administered as a single daily dose should aid in the maintenance of patient compliance, while offering significant clinical benefit in the improvement of depressive symptoms.", "Of nine nonsuppressors on the dexamethasone suppression test (DST), five (56%) developed intolerable side effects during treatment with fluvoxamine, a new serotonin uptake inhibiting antidepressant, compared with three of 24 suppressors (13%).", "1 Two double-blind, randomised studies were performed to compare the efficacy of fluvoxamine and chlorimipramine in depressed patients. In the first study the effects of a single daily dosage of between 100 and 300 mg of fluvoxamine were compared with those of chlorimipramine at a dosage of 50-150 mg daily in 43 out-patients with endogenous depression. 2 In a second study using three times daily dosing with a daily dosage of 150-300 mg for both fluvoxamine and chlorimipramine, 30 in-patients with unipolar depression were assessed. 3 Four weeks of treatment with single daily dosing resulted in a mean improvement of 61.4% (+/- s.d. 31.7) on the Hamilton Rating Scale for Depression (HAMD) for fluvoxamine and of 65.3% (+/- s.d. 25.8) for chlorimipramine. In the study with three times daily dosing the mean results were 72.9% (+/- s.d. 22.3) improvement for fluvoxamine and 62.1% (+/- s.d. 28.5) for chlorimipramine. 4 At similar dosages, fluvoxamine had significantly less untoward effects on blood pressure than chlorimipramine. Anticholinergic effects were also fewer in the fluvoxamine group, as were nervous system symptoms, with the latter difference reaching statistical significance (P = 0.02). 5 We conclude that fluvoxamine, given in a single daily dose of 150-250 mg, provides antidepressant efficacy similar to chlorimipramine. At this dosage it may be expected to produce less anticholinergic effects and have less influence on blood pressure than chlorimipramine.", "The efficacy and CNS effects of the selective 5-HT re-uptake inhibitor fluvoxamine were compared with mianserin in depressed hospital out-patients in a double-blind randomized trial. Patients had to meet DSM-III criteria for Major Depressive Episode and achieve a score of at least 30 on the Montgomery-Asberg Depression Rating Scale (MADRS) after a 1-week placebo baseline period. Active treatment was for 6 weeks with an initial dose of either 100 mg fluvoxamine or 60 mg mianserin; after 1 week the dosage could be increased to 300 mg or 180 mg, respectively. Data from 63 patients (30 received fluvoxamine) were analyzed. The treatment groups were comparable with regard to age and history and severity of depression. Efficacy assessments showed similar improvements with each drug; MADRS scores improved by 65.6% with fluvoxamine and by 60.8% with mianserin. There were no significant differences between treatments at any assessment. Sedative effects were assessed using the Leeds Sleep Evaluation Questionnaire and the Digit Symbol Substitution Test. Mianserin caused a shift towards sedation in the first week in all visual analogue scales; getting to sleep and sleep quality were improved but waking was more difficult than with fluvoxamine. Similarly, the mianserin group performed less well on the Digit Symbol Substitution Test. The study confirmed that both drugs are effective treatments for depressive illness but that mianserin gives rise to sedation during the first week.", "The TRH test has been used in psychiatry these last 20 years. One of the most promising results is that concerning the possibility to use it to identify the best moment to stop a treatment after clinical recovery of the depressive episode. For that it is necessary to demonstrate an absence of intrinsic action of antidepressants on the HPT axis physiology. This overt, randomized study has compared the actions on T3, T4, basal TSH and its response to the TRH test after 75 mg/day of maprotiline and 100 mg/day of fluvoxamine, both administrated in depressed patients during 28 days. Forty patients (20 men and 20 women) were studied, 20 patients per treatment. The inclusion criteria were those of DSM III-R for major depression and dysthymia as well a minimum score of 25 at MADRS scale. Blood samples for T3, T4 and basal TSH dosages were made before TRH intranasal administration (2 mg) at days 1 and 28 of the treatment. We haven't observed any difference before treatment between the 2 groups for clinical and biological studied parameters. After treatment both antidepressants produced equivalent improvement of depression evaluated by MADRS (fluvoxamine:dMADRS = 16.95 +/- 7.11; maprotiline: dMADRS = 17.10 +/- 6.84. t = 0.07, NS). T3 and T4 variations between the beginning and the end of the study weren't also significantly different between the 2 groups. Basal TSH was increased in the maprotiline group but decreased in the fluvoxamine group resulting in a significant difference (fluvoxamine: dTSH = 0.31 +/- 0.76 mUI/l. Maprotiline : dTSH = -0.23 +/- 0.66 mUI/l. t = 2.40, p < 0.02). The TSH response to TRH was decreased in the fluvoxamine group (ddTSH = 0.24 +/- 6.65 mUI/l. dAUC = 103.98 +/- 596.84 mUI/l) while it was increased in the maprotiline group (ddTSH = -3.59 +/- 5.88 mUI/l. dAUC = -355.80 +/- 505.67 mUI.min/l). The difference between the 2 treatments was not significant when evaluated by ddTSH (t = 1.53, NS) but it became significant if evaluated by dAUC (t = 2.63, p < 0.01). As we could demonstrate an absence of influence of the clinical evolution between both groups in the hormonal variations observed, we concluded to a intrinsic difference action on HPT axis between fluvoxamine and maprotiline. This difference could be linked to the different aminergic action of these 2 antidepressants.", "This randomized, double-blind, parallel-group design study of 100 outpatients with major depressive disorder is the first study in the United States to compare the efficacy and tolerability of fluvoxamine (100-150 mg/day) and fluoxetine (20-80 mg/day). After a variable, single-blind, washout period, patients were randomized to receive either fluvoxamine (51 patients) of fluoxetine (49 patients) for 7 weeks. Efficacy was assessed with the 21-item Hamilton Rating Scale for Depression (HAM-D), and Clinical Global Impressions scale for severity and improvement. Eighty-four percent of each treatment group completed the study with each group having a mean score at end point of less than 10. Both groups demonstrated a 60% improvement in HAM-D scores over the 7-week trial. There were no statistically significant differences observed between the two groups on any efficacy parameter. The medications were well tolerated, with only two patients in each group who were terminated because of side effects. There were differences in the side-effect profiles, with fluvoxamine being associated with less nausea than fluoxetine. In summary, fluvoxamine and fluoxetine were equally effective in reducing depressive symptoms, but the two drugs displayed slightly different side-effect profiles.", "This study examined the psychomotor and antidepressant effects of fluvoxamine in a depressed, GP patient population, compared to those of mianserin. It was a single centre, double-blind, six-week study, preceded by a one-week pre-treatment placebo washout, in 59 patients suffering from major depressive episode (DSM III) and scoring over 24 on MADRS. The starting dose was 100 mg fluvoxamine or 60 mg mianserin daily for one week, rising to 300 mg fluvoxamine or 180 mg mianserin. Both treatment groups showed significant improvement over time with no differences between drugs in terms of efficacy. Fluvoxamine and mianserin were both shown to be effective in the treatment of depressive illness. Some psychomotor impairment in the first few days and weight gain over a longer period could affect compliance with mianserin. Fluvoxamine does not reduce psychomotor performance or cause weight gain.", "The effect of amitriptyline on hypothalamic-pituitary-adrenocortical (HPA) axis activity was compared with that of fluvoxamine in 38 patients suffering from DMS-IV major depressive disorder. Basal plasma adrenocorticotropic hormone and cortisol levels were determined in the so-called \"observation window\" of an hour (08:00-09:00 h), and cortisol levels were determined again at 20:00 h. Clinical and biochemical assessments were performed before therapy (T0), at day 14 (T14), and at day 42 (T42) of the course of antidepressant treatment. At T0, neuroendocrine parameters did not differ in patients from those in controls, except for the ratio between cortisol levels at 20:00 h and the mean level of the \"window\" (ratio F20/F8), which was significantly higher, suggesting a dysregulation of the circadian pattern of cortisol. Although a decrease in the ratio F20/F8 was already apparent at T14 of both treatments, the repeated measures analysis of variance failed to demonstrate a significant variation with time (T0, T14, and T42) and with treatment (amitriptyline and fluvoxamine) for any hormonal measure. At T42, both treated groups showed a similar level of clinical improvement. Our results did not demonstrate any effect of antidepressant therapy on the cortisol circadian rhythm abnormality.", "In a double blind study performed in psychiatric clinics the efficacy and tolerability of the new antidepressant Moclobemide was compared. Moclobemide belongs to a new class of substances called RIMA (Reversible Inhibitor of the monoamine oxidase type A). 61 patients with major depression (according to DSM-III) were either treated with Moclobemide or Fluvoxamine, a selective reuptake-inhibitor of 5-HT. The latter belongs to a class of antidepressants known for their better tolerability compared to tricyclic antidepressants. Moclobemide was as effective as Fluvoxamine but much better tolerated as shown by a lower incidence of side effects such as gastrointestinal problems or headache.", "1. Fluvoxamine is a potent serotonin re-uptake inhibitor, with little or no noradrenergic or anticholinergic activity. 2. The results of three studies using an almost identical protocol with a prospectively randomized, double-blind design comparing fluvoxamine and chlorimipramine are presented. 3. In a population of 98 subjects suffering from a variety of depressive conditions, there was a marked improvement over four weeks in both groups. dosage was maintained between 150 and 300 mg per day. 4. There were no changes of clinical importance in vital signs, hematology or biochemistry, but pulse rates increased in the chlorimipramine group. 5. There were fewer concurrent signs and symptoms in the fluvoxamine group, especially those attributable to anticholinergic activity.", "Central serotonin dysfunction is thought to be involved in the etiology of major depression. Serotonergic challenge studies before and after treatment of depressed patients have yielded conflicting results; however, these studies have not focused on the effect of antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs) on serotonergic challenge studies.\n The authors studied 19 outpatients with major depressive disorder using prolactin response to d-fenfluramine as a measure of central serotonergic functioning. Testing of patients was conducted just before and right after 8 weeks of treatment with either fluoxetine (n = 10) or fluvoxamine (n = 9) as part of a randomized, double-blind treatment trial. Blood samples for prolactin were collected prior to administration of d-fenfluramine (0.5 mg/kg) and then over the next 5 hours.\n Unlike previous studies in which antidepressant treatment produced an enhanced prolactin response to fenfluramine, in this study there was no increase in prolactin response to d-fenfluramine following SSRI treatment. In fact, prolactin response to d-fenfluramine was significantly diminished after treatment with fluvoxamine but not fluoxetine.\n The implications of these findings are discussed with regard to possible mechanisms of action of SSRI treatment.", "In this study, we tested the influence of the serotonin type 2A, 3A and 3B receptor genes (HTR2A, HTR3A, HTR3B) in addition to a polymorphism in the promoter region of the serotonin transporter (SERTPR), and investigated the different characteristics of clinical responses to paroxetine and fluvoxamine. A total of 100 Japanese patients affected by major recurrent depression were enrolled in a randomized 6-week study. The clinical response was evaluated using the Hamilton Rating Scale for Depression (HAM-D), and adverse drug reactions were assessed at each visit. Patients with the l allele of SERTPR showed a better response to SSRIs than s/s genotype carriers (p = 0.015-0.042), more significantly to fluvoxamine. The -1438G/G genotype of HTR2A was associated with a good response to SSRIs (p = 0.010-0.039), especially to fluvoxamine, and significantly with severe nausea in paroxetine-treated patients (p = 0.013). The 178C/C genotype of the HTR3A was associated with an antidepressant response (p = 0.022-0.042), and more significantly in paroxetine-treated patients (p = 0.002-0.042). These effects were independent of one another. We replicated the finding that the SERPTR polymorphism was associated with a response to SSRIs. We additionally found that HTR2A and HTR3A polymorphisms are associated with the efficacy, and the HTR2A polymorphism is also associated with adverse drug reactions. Furthermore, the effects of these polymorphisms varied from one SSRI to another and thus may depend on the characteristics of each SSRI.", "Fluvoxamine and paroxetine, both serotonin selective reuptake inhibitors (SSRIs), were compared at two centers in a 7-week double-blind study in outpatients with major depression, diagnosed by DSM-III-R criteria.\n Sixty patients were randomly assigned to receive dosage titrated upward to between 50-150 mg/day of fluvoxamine (N = 30) or 20-50 mg/day of paroxetine (N = 30). The mean +/- SD daily dose administered at the last assessment was 102 +/- 44 mg/day for fluvoxamine and 36 +/- 13 mg/day for paroxetine. Sixteen (53%) fluvoxamine-treated patients and 10 (33%) paroxetine-treated patients were titrated to the maximum permissible dosage of either drug. Sample size was calculated to provide at least 85% power at 5% level of significance to detect at least a 1.00-point difference in mean severity of adverse events, assuming a standard deviation of 1.0.\n Fluvoxamine and paroxetine were similarly effective in ameliorating depression as demonstrated by mean total scores of 10.9 +/- 7.3 (p < .00) and 11.5 +/- 7.4 (p < .00), respectively, in the Hamilton Rating Scale for Depression (HAM-D). Adverse events were mostly mild to moderate in severity. The most common events were headache (N = 17, 57%), nausea (N = 14, 47%), sweating (N = 10, 33%), somnolence (N = 9, 30%), diarrhea (N = 9, 30%), dry mouth (N = 8, 27%), dizziness (N = 8, 27%), and, among males, impotence (N = 3, 21%) and ejaculatory abnormality (N = 3, 21%) in the paroxetine group, and headache (N = 12, 40%), somnolence (N = 12, 40%), nausea (N = 11, 37%), dry mouth (N = 11, 37%), insomnia (N = 9, 30%), asthenia (N = 7, 23%), and dyspepsia (N = 7, 23%) in the fluvoxamine group. The only statistically significant difference between treatment groups was for sweating (33% paroxetine vs. 10% fluvoxamine, p = .028).\n Observed differences in some side effects, although not statistically significant, indicate that when a patient has difficulty tolerating one SSRI, the clinician may choose to change to a different agent within the same class.", "Changes in depressed outpatients' experience of daily activities after 6 weeks of antidepressant treatment were assessed with the experience sampling method (ESM). On the sickness impact profile, treatment responders (HAM-D < or = 7, n = 12) improved more than nonresponders (n = 9) in the domains of household chores, leisure and social activities. On ESM measures completed 10 x each day for 6 days pre- and posttreatment, responders showed greater increases in time spent in chores and greater decreases in passive leisure time than nonresponders. Responders showed greater increases in positive affect and greater decreases in negative affect during all activities. Thus, ESM provides quantitative evidence of changes in real life time use and subjective experience accompanying clinical improvement.", "nan", "1 A double-blind placebo-controlled study of fluvoxamine and imipramine was performed in a group of depressed patients. Twenty-two patients received fluvoxamine (mean dose 101 mg/day), 25 received imipramine (mean dose 127 mg/day) and 22 received placebo. 2 Apart from an increase in the SGOT and SGPT values of four imipramine patients, no statistically significant changes in haematology or urinalysis were judged to be medically relevant. Fluvoxamine exhibited fewer anticholinergic side effects than imipramine. 3 Both fluvoxamine treated patients and imipramine-treated patients exhibited a statistically significant improvement at the end of the 28-day treatment period with respect to the placebo patients, as measured using the Hamilton Rating Scale for Depression, and the Clinical Global Impression Scale. Evaluations of the results of the Beck Depression Inventory and the Profile of Mood States revealed a statistically significant improvement for imipramine patients with respect to placebo at week 4, but not for fluvoxamine patients. It is postulated on the basis of quantitative pharmaco-EEG findings, that the slight superiority of imipramine over fluvoxamine was due to underdosing of the latter.", "The efficacy and tolerability of the selective 5-HT reuptake inhibitor fluvoxamine were compared with the tricyclic dothiepin in 52 elderly (age greater than 64 years) hospital patients in a multi-centre double-blind randomised trial. Patients met DSM-III criteria for 'major depressive episode' and scored greater than 29 on the Montgomery Asberg Depression Rating Scale (MADRS) after a one-week placebo baseline. Active treatment was for six weeks. The dosage of both drugs was 50 mg nocte for three days, 100 mg nocte for the remainder of the first week, thereafter increasing to a maximum of 200 mg/day according to response/tolerance. MADRS scores improved by 63.5% with fluvoxamine and 60.0% with dothiepin; there were no significant differences between treatments at any assessment. Nausea, dizziness, headache, somnolence and constipation in both groups, plus dry mouth and asthenia in the dothiepin group were more frequent than single reports. Two patients in each group discontinued treatment owing to unwanted effects. There were no clinically significant changes in haematological, biochemical or cardiovascular parameters.", "nan", "A double-blind, multinational study was conducted to compare the efficacy and safety of fluvoxamine and fluoxetine in outpatients with major depressive episode; 184 patients were randomised to fluvoxamine (100 mg/day) or fluoxetine (20 mg/day) for 6 weeks. Both drugs were effective and there were no statistically significant differences between them in the area under the curve of change from baseline in the Hamilton depression rating scale (HAMD) total score. However, the percentage of HAMD responders (>or= 50% decrease in HAMD total score) at week 2, the clinical global improvement severity of illness score at week 2 and the depression subscale of the irritability, depression and anxiety scale at weeks 1, 2 and 4, all showed significant advantages for fluvoxamine. During the last 2 weeks, fluvoxamine was significantly more effective in improving the HAMD sleep disturbance scale. Both drugs were well tolerated and there were no marked differences in their side effect profiles which were typical of SSRIs. Fluvoxamine and fluoxetine have similar efficacy and safety profiles in the treatment of major depressive episode; the findings of this study indicate that fluvoxamine may have a faster onset of action with respect to resolution of depressive symptoms and result in a better improvement in sleep quality.\n Copyright 2003 John Wiley & Sons, Ltd.", "Major depression is a common psychiatric disorder in the elderly population. The efficacy of tricyclic antidepressants is well established, and selective serotonin reuptake inhibitors appear to have a similar effectiveness along with advantages in terms of tolerability and safety. Given the lack of literature data regarding fluvoxamine in the treatment of depressed elderly patients, the aim of the present study was to compare its efficacy and tolerability with those of sertraline in a sample of elderly patients.\n Under double-blind conditions, 93 hospitalized patients older than 59 years, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for a major depressive episode, were randomly assigned to receive sertraline (150 mg daily) or fluvoxamine (200 mg daily) for 7 weeks. The clinical response was defined as a reduction on the Hamilton Rating Scale for Depression score to 8 or below.\n At study completion, the response rates were 55.6% (25/45) and 71.8% (28/39) for sertraline and fluvoxamine, respectively. No significant difference in final response rates was found between the 2 treatment groups (P = 0.12). A repeated-measures analysis of variance on Hamilton Rating Scale for Depression scores revealed a significantly different decrease of depressive symptoms between the 2 treatment groups, favoring fluvoxamine (P = 0.007). The overall safety profile of sertraline and fluvoxamine was favorable with no differences between the 2 drugs.\n The results of this double-blind trial show that sertraline and fluvoxamine may be effective compounds in the treatment of elderly depression with the latter showing some advantage in terms of speed of response. These findings warrant further replication in placebo-controlled studies.", "We investigated the relationships between the changes in plasma catecholamine metabolites obtained from depressed patients before and after administration of sulpiride, a benzamide compound, or fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), and between clinical responses to treatment with each of these drugs. Responders to sulpiride had significantly lower plasma homovanillic acid (pHVA) levels before administration of sulpiride than did non-responders or controls (responders: 4.5 +/- 3.1 ng/ml, non-responders: 11.1 +/- 5.9 ng/ml, controls: 10.9 +/- 5.3 ng/ml). Positive relationships were observed between changes in pHVA levels and improvement rates in the 17-item Hamilton Depression Rating Scale (Ham-D). In contrast, responders to fluvoxamine had significantly higher plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels before administration of fluvoxamine than did non-responders or controls (responders: 8.5 +/- 1.8 ng/ml, non-responders: 5.9 +/- 2.I ng/ml, controls: 5.2 +/- 2.9 ng/ml). Negative relationships were observed between changes in pMHPG levels and improvement rates in Ham-D. These results suggest that lower pretreatment pHVA levels and higher pretreatment levels of pMHPG might be predictors of response to sulpiride and fluvoxamine, respectively, and that sulpiride might produce a functional increase in the dopaminergic system, resulting in improvement in some depressive symptoms; fluvoxamine, on the other hand, might produce a functional decrease in the noradrenergic system via serotonergic neurons, resulting in improvement of those symptoms.", "Forty patients with a diagnosis of major depressive disorder were entered in a double-blind study to assess comparative clinical response and pharmacologic parameters of fluvoxamine, a highly selective blocker of serotonin reuptake, and desipramine, a noradrenergic agent. Eighteen patients receiving desipramine and 17 patients receiving fluvoxamine completed the study. Fluvoxamine was comparable to desipramine in its antidepressant efficacy and was better tolerated and caused minimal side effects. There was a direct linear relationship between plasma fluvoxamine levels and clinical response and a nonlinear relationship between plasma desipramine levels and clinical response. The pharmacologic specificity of the two drugs was assessed by determining uptake inhibition of serotonin and norepinephrine. The authors found a positive relationship between Hamilton Rating Scale for Depression scores and norepinephrine uptake inhibition for desipramine but found no such relationship between fluvoxamine and serotonin uptake inhibition. Although there was a clear-cut difference in the quality of pharmacologic specificity and a partial relationship to clinical response, the authors were unable to identify neuropharmacologic factors that would predict either treatment response or selective amelioration of symptomatologies in this patient population.", "1 We report the results of a comparative clinical trial of a new antidepressant drug fluvoxamine (a specific re-uptake inhibitor of 5-hydroxytryptamine (5-HT)) with chlorimipramine. Thirty-two patients with mixed depression received one or the other drug at the same daily dosage of 150 mg. 2 In both drug groups there was an overall clinically significant improvement for all items on the Hamilton Rating Scale for Depression (67% improvement in both groups). 3 In the chlorimipramine group there were more digestive symptoms and anticholinergic effects; the difference with the fluvoxamine group approached statistical significance. 4 No clinically important effects of either treatment were observed on heart-rate or blood pressure.", "Although selective serotonin reuptake inhibitors (SSRIs) are better tolerated than tricyclic antidepressants, their efficacy in severe depression remains to be further elucidated.\n A double-blind, multicentre study was conducted in 86 severely depressed inpatients (>or= 25 on the 17-item Hamilton depression rating scale [HAMD] total score) to compare the efficacy and safety of fluvoxamine with that of clomipramine. Following placebo run-in, 86 patients were randomised to receive fluvoxamine or clomipramine (100-250 mg/day) for 8 weeks.\n Fluvoxamine and clomipramine both resulted in marked improvements; there were no statistically significant differences between them on the 17-item HAMD total score, the clinical global impression severity of illness or global improvement items or the Montgomery-Asberg depression rating scale, at any visit. At the end of the study, 71% in the fluvoxamine group and 69% in the clomipramine group were responders (>or= 50% decrease in 17-item HAMD total score). However, fluvoxamine was better tolerated than clomipramine. Clomipramine was associated with a higher incidence of overall and treatment-related adverse events. In addition, the percentage of patients discontinued prematurely due to adverse events was more than twice as high with clomipramine than with fluvoxamine (24% vs 11%).\n Fluvoxamine and clomipramine are equally effective in severe depression, but fluvoxamine has a better safety and tolerability profile.\n Copyright 2003 John Wiley & Sons, Ltd.", "The aim of the study was to compare the efficacy and tolerance of fluvoxamine (FL) and amitriptyline (AM) in the treatment of patients hospitalized for moderate and severe depression and to evaluate the spectrum of antidepressive activity in FL. The study was open, randomized and comparative. Sixty patients (mean age 41 +/- 2.9 years) diagnosed as having recurrent depressive disorder, a moderate or severe depressive episode (ICD-10 F33.1, F33.2) were divided into two equal groups treated with FL or AM. The efficacies of FL and AM were comparable, with AM exhibiting an earlier clinical effect and FL having a better tolerance. FL was defined as an antidepressant with the predominantly sedative effect comparable to that of AM, but being better tolerated.", "Numerous neuropsychological studies have reported deficits in cognitive and attentional functioning in depressed patients. However, there are limited data available about unmedicated depressed patients and the effects of antidepressant treatment on attentional performance. In this study, a Continuous Performance Test (CPT) was employed to evaluate the attentional performance of depressed inpatients during a drugfree period (n = 52) in comparison to healthy control subjects (n = 73). After 4 weeks of double-blind treatment with imipramine (TCA) or fluvoxamine (SSRI) at adequate plasma levels the CPT performance was studied again. We found that the unmedicated patients had a significantly impaired performance on all CPT parameters (reaction time, omission errors and commission errors) in comparison to the controls. None of the CPT parameters correlated with the severity of the depression or the level of psychomotor retardation. However, the CPT performance in the patient group was significantly related to subjective mood state (depression, tension). Double-blind treatment with imipramine or fluvoxamine resulted in an improvement of the CPT performance. In the imipramine treatment group the mean reaction time decreased significantly, and after treatment with fluvoxamine a significant decrease of the mean reaction time and the number of omission errors was detected. Both antidepressants induced a significant improvement of clinical state, but we did not find a relationship between the altered CPT performance and the changes on the clinical scales. Future studies should investigate other mechanisms underlying the improved attentional performance after treatment.\n Copyright 2002 Elsevier Science Ltd.", "The efficacy of the selective serotonin reuptake inhibitors (SSRIs) and the tricyclic antidepressants is well established, although data on the efficacy of SSRIs in severe depression is limited. Several studies have demonstrated that fluvoxamine is as effective as clomipramine in the treatment of severe depression. The aim of this four-week study was to compare the efficacy and tolerability of fluvoxamine and clomipramine in hospitalised depressed patients. Patients were eligible for entry into the study if they had an established diagnosis of depression, and an overall score of more than 17 on the first 17-items of the Hamilton Rating Scale for Depression (HAMD). Twenty patients received fluvoxamine 100-300 mg in divided daily doses (mean daily dose 204 mg), and 20 received clomipramine 50-150 mg in divided daily doses (mean daily dose 106 mg) for four weeks. Efficacy was assessed using the HAMD and Clinical Global Impression (CGI) scales, at baseline and weekly intervals thereafter. The investigator's overall rating of efficacy and tolerability was also noted. At the end of the study, both fluvoxamine and clomipramine produced a marked to moderate therapeutic effect. Compared with baseline both fluvoxamine and clomipramine produced similar improvements in the HAMD total, HAMD item and CGI scores. More patients in the clomipramine group experienced anticholinergic side-effects and orthostatic hypotension. Furthermore, a significant difference in favour of fluvoxamine was found with regard to the investigator's overall assessment of undesirable signs and symptoms (p = 0.023; Wilcoxon's test). In conclusion, fluvoxamine is as effective as clomipramine in hospitalised depressed patients, and is better tolerated.", "A total of 32 unmedicated patients with episodes of major depression (DSM-III-R) and 32 normal control subjects matched for age and sex were tested for heart rate variability (R-R variation) while resting and during deep breathing. Compared with the group of healthy subjects, the depressed patients showed no abnormalities before therapy. The patients were randomly allocated for treatment with 150 mg of amitriptyline per day (N = 8), 150 mg of doxepin per day (N = 8), 150 mg of fluvoxamine per day (N = 8), and 20 mg of paroxetine per day (N = 8). During treatment with either amitriptyline or doxepin, the coefficients of variation at rest and during deep breathing, which are largely independent of heart rate, had significantly decreased after 14 days (p = 0.012), whereas patients treated with fluvoxamine or paroxetine showed no significant changes of heart rate variability parameters after 14 days. The implications of these findings are discussed.", "To test the hypothesis that the antidepressant effects of total sleep deprivation (TSD) are linked to the serotonergic and/or noradrenergic system the authors carried out a double-blind study (fluvoxamine versus maprotiline) in 42 inpatients with endogenous depression (ICD). Patients were randomized to a four-week treatment with either fluvoxamine (100-300 mg/day) or maprotiline (100-300 mg/day). In addition, patients underwent a TSD procedure before and after one week of antidepressant medication. There was a statistically significant reduction of depression ratings (HDRS) in both the fluvoxamine and maprotiline group. The day-1 response to TSD before antidepressive medication was not associated with a clear relationship to the outcome after four weeks of treatment with either fluvoxamine or maprotiline. On the other hand, the day-2 response to TSD was significantly correlated with a good outcome to subchronic treatment with maprotiline. Furthermore, the results of the authors' data suggest that a favorable short-term outcome of TSD may be connected to antidepressants enhancing the serotonergic neurotransmission. The global comparison between fluvoxamine and maprotiline revealed that the group of patients treated with fluvoxamine had a significantly higher efficiency index (CGI) than the maprotiline group; fluvoxamine was rated to be tolerated excellently in 70% of the patients whereas this percentage was only 43% in the maprotiline group. There was also significantly more vertigo and dry mouth in the maprotiline group whereas the fluvoxamine group was rated to have significantly more sleep disturbances during the trial.", "nan", "The efficacy and tolerability of moclobemide and fluvoxamine, two new types of antidepressant agents, were compared in a multicentre, double-blind prospective study of patients with a diagnosis of major depressive episode (DSM III). Patients were randomized to receive either moclobemide (150 mg) or fluvoxamine (50 mg) twice daily for 7 days, immediately following a washout period of at least 1 week. Dosages were increased where necessary on day 8, to a maximum of moclobemide 450 mg or fluvoxamine 200 mg and in most cases were maintained at these levels for the remainder of the study period (4-6 weeks). Both treatment groups showed a marked antidepressant effect. While both treatments were well tolerated, moclobemide showed a more favourable side-effect profile than fluvoxamine. Of the 126 patients eligible for evaluation, 34 withdrew from therapy, 22% in the moclobemide group and 30% in the fluvoxamine group. Adverse events were reported in 41.8% of patients treated with moclobemide compared to 60.3% of patients in the fluvoxamine group. Reports of dry mouth and other anticholinergic effects were more frequent among those treated with fluvoxamine. A greater number of gastrointestinal complaints, especially nausea, also occurred in the fluvoxamine-treated patients.", "Fluvoxamine, a selective serotonin reuptake inhibitor, was investigated in a 6-week double-blind study among severely ill inpatients with DSM-III major depression. All but 1 patient also fulfilled criteria for melancholia. Following a 3-day placebo wash-out patients were randomly assigned to fluvoxamine, imipramine or placebo. Sixty of 81 patients completed at least 2 weeks following wash-out and were evaluated for efficacy. Analysis of covariance (controlling for baseline scores) showed significant (p less than 0.05) differences on CGI severity and BPRS total and a similar trend (p = 0.08) on the Hamilton Depression Scale. Fluvoxamine was superior (p less than or equal to 0.02) to both placebo and imipramine on these measures. Fluvoxamine's most common adverse effects were nausea and agitation. The number of fluvoxamine patients withdrawn for side-effects was less than imipramine and not significantly different than placebo. Fluvoxamine was not associated with significant changes in vital signs, ECG or laboratory tests. The results therefore indicate that fluvoxamine is a safe and highly effective treatment for hospitalized patients with major depression.", "nan" ]

[ "3531953", "3288258" ]

[ "Analgetic activity of calcitonin in patients with painful osteolytic metastases of breast cancer. Results of a controlled randomized study.", "Evaluation of salmon calcitonin treatment in bone metastases from breast cancer--a controlled trial." ]

[ "The analgesic effect of salmon calcitonin was tested by a double-blind clinical randomized controlled trial in 40 female patients with painful osteolytic metastases. Twenty patients were administered (daily) 100 IU of salmon calcitonin subcutaneously over 28 days, while the other 20 were administered identical ampoules containing 2 ml of physiological solution over the same period of time. The basic treatment (chemotherapy, hormone therapy) was not changed during the trial, and had to be stabilized for a minimum of 3 months prior to the trial. The effect of calcitonin was monitored with respect to daily analgesic consumption, duration of pain, patient's functional capacity, patient's own assessment of pain, and assessment of efficacy by the investigator. Statistically significant differences were established in terms of reduced analgesic consumption, shorter duration of pain and the patient's subjective assessment of pain duration and intensity; the difference was not statistically significant with regard to patient's functional capacity. The objective assessment of the analgesic effect of calcitonin by the investigator showed the drug to be extremely useful in 3 patients and moderately useful in 11 patients; 3 instances of 'moderately useful' were observed in the placebo group. No changes were observed in serum calcium levels; there were likewise no skeleton changes as established by X-rays and bone scintiscans before and at the end of treatment. The trial has shown calcitonin to produce a pronounced analgesic effect in breast cancer patients with painful osteolytic metastases.", "Salmon calcitonin 100 MRCU/day or a saline placebo were given in daily injections for at least three months to 49 patients with bone metastases from breast cancer in a randomized double-blind trial. All patients were normocalcemic, and most patients had stable or regressing disease at start of trial. No improvement in general performance or bone pain was detected as measured by a visual analogue scale, the daily duration of pain or consumption of analgetic drugs. Calcitonin had no effect on disease progression as judged by bone scans and radiographs. Calcitonin therapy did not affect serum calcium, alkaline phosphatase, bone gla-protein, or the urinary excretion of calcium and hydroxyproline. Serum phosphate and magnesium decreased significantly during calcitonin treatment (p = 0.01, and 0.00005, respectively). It was concluded that salmon calcitonin in this dosage has no discernible effect on skeletal pain, general performance, bone metabolism or disease progression in patients with breast cancer metastatic to bone. A significant decrease in serum phosphate and magnesium probably indicated an effect of calcitonin on the renal excretion of these ions." ]

[ "18381542", "21402642" ]

[ "Growth and nutrient intakes of human milk-fed preterm infants provided with extra energy and nutrients after hospital discharge.", "Nutrient enrichment of mother's milk and growth of very preterm infants after hospital discharge." ]

[ "The purpose of this pilot study was to determine whether mixing a multinutrient fortifier to approximately one half of the human milk fed each day for a finite period after discharge improves the nutrient intake and growth of predominantly human milk-fed low birth weight infants. We also assessed the impact of this intervention on the exclusivity of human milk feeding.\n Human milk-fed (> or = 80% feeding per day) low birth weight (750-1800 g) infants (n = 39) were randomly assigned at hospital discharge to either a control or an intervention group. Infants in the control group were discharged from the hospital on unfortified human milk. Nutrient enrichment of human milk in the intervention group was achieved by mixing approximately one half of the human milk provided each day with a powdered multinutrient human milk fortifier for 12 weeks after discharge. Milk with added nutrients was estimated to contain approximately 80 kcal (336 kJ) and 2.2 g protein/100 mL plus other nutrients. Intensive lactation support was provided to both groups.\n Infants in the intervention group were longer during the study period, and those born < or = 1250 g had larger head circumferences than infants in the control group. There was a trend toward infants in the intervention group to be heavier at the end of the intervention compared with those in the control group. Mean protein, zinc, calcium, phosphorus, and vitamins A and D intakes were higher in the intervention group.\n Results from this study suggest that adding a multinutrient fortifier to approximately one half of the milk provided to predominantly human milk-fed infants for 12 weeks after hospital discharge may be an effective strategy in addressing early discharge nutrient deficits and poor growth without unduly influencing human milk feeding when intensive lactation support is provided.", "To determine if the addition of a multinutrient human milk fortifier to mother's milk while breastfeeding very preterm infants after hospital discharge is possible and whether it influences first-year growth.\n Of a cohort of 320 infants (gestational age: 24-32 weeks; birth weight: 535-2255 g), breastfed infants (65% [n = 207]) were randomly assigned shortly before hospital discharge to receive either unfortified (n = 102, group A) or fortified (n = 105, group B) mother's milk until 4 months' corrected age (CA). The remaining infants were bottle-fed with a preterm formula (group C). Follow-up was performed at term and at 2, 4, 6, and 12 months' CA.\n Mean duration of breastfeeding after term was not significantly different between groups A and B (11.8 and 10.6 weeks, respectively). Weight, length, and head circumference were not significantly different between groups A and B at 12 months' CA. Compared with groups A and B, infants in group C had a higher increase in weight z score until term and in length z score until 6 months' CA. At 12 months' CA, boys in group C were significantly longer and heavier compared with those in groups A and B, whereas girls in group C were longer and heavier compared with those in group A only. A higher protein intake was related to a higher serum urea nitrogen level and growth.\n Fortification of mother's milk after hospital discharge while breastfeeding very preterm infants was possible without influencing breastfeeding duration but did not significantly influence growth parameters at 1 year of age compared with unfortified mother's milk." ]

[ "18378519", "2046107", "2873015", "14654762", "4862069", "9732338", "3475430", "10639539", "2911834", "8575241" ]

[ "Treatment of hypertension in patients 80 years of age or older.", "Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group.", "Oslo Hypertension Study.", "Results of the pilot study for the Hypertension in the Very Elderly Trial.", "Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg.", "Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group.", "Influence of antihypertensive drug treatment on morbidity and mortality in patients over the age of 60 years. European Working Party on High blood pressure in the Elderly (EWPHE) results: sub-group analysis on entry stratification.", "Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators.", "Morbidity and mortality in the Systolic Hypertension in the Elderly Program (SHEP) pilot study.", "Post-stroke antihypertensive treatment study. A preliminary result." ]

[ "Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear. It has been suggested that antihypertensive therapy may reduce the risk of stroke, despite possibly increasing the risk of death.\n We randomly assigned 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting-enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke.\n The active-treatment group (1933 patients) and the placebo group (1912 patients) were well matched (mean age, 83.6 years; mean blood pressure while sitting, 173.0/90.8 mm Hg); 11.8% had a history of cardiovascular disease. Median follow-up was 1.8 years. At 2 years, the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group. In an intention-to-treat analysis, active treatment was associated with a 30% reduction in the rate of fatal or nonfatal stroke (95% confidence interval [CI], -1 to 51; P=0.06), a 39% reduction in the rate of death from stroke (95% CI, 1 to 62; P=0.05), a 21% reduction in the rate of death from any cause (95% CI, 4 to 35; P=0.02), a 23% reduction in the rate of death from cardiovascular causes (95% CI, -1 to 40; P=0.06), and a 64% reduction in the rate of heart failure (95% CI, 42 to 78; P<0.001). Fewer serious adverse events were reported in the active-treatment group (358, vs. 448 in the placebo group; P=0.001).\n The results provide evidence that antihypertensive treatment with indapamide (sustained release), with or without perindopril, in persons 80 years of age or older is beneficial. (ClinicalTrials.gov number, NCT00122811 [ClinicalTrials.gov].).\n Copyright 2008 Massachusetts Medical Society.", "To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal (total) stroke in isolated systolic hypertension.\n Multicenter, randomized, double-blind, placebo-controlled.\n Community-based ambulatory population in tertiary care centers.\n 4736 persons (1.06%) from 447,921 screenees aged 60 years and above were randomized (2365 to active treatment, 2371 to placebo). Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg. Of the participants, 3161 were not receiving antihypertensive medication at initial contact, and 1575 were. The average systolic blood pressure was 170 mm Hg; average diastolic blood pressure, 77 mm Hg. The mean age was 72 years, 57% were women, and 14% were black.\n --Participants were stratified by clinical center and by antihypertensive medication status at initial contact. For step 1 of the trial, dose 1 was chlorthalidone, 12.5 mg/d, or matching placebo; dose 2 was 25 mg/d. For step 2, dose 1 was atenolol, 25 mg/d, or matching placebo; dose 2 was 50 mg/d.\n Primary. Nonfatal and fatal (total) stroke. Secondary. Cardiovascular and coronary morbidity and mortality, all-cause mortality, and quality of life measures.\n Average follow-up was 4.5 years. The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group, and the 5-year average diastolic blood pressure was 72 and 68 mm Hg, respectively. The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo. The relative risk by proportional hazards regression analysis was 0.64 (P = .0003). For the secondary end point of clinical nonfatal myocardial infarction plus coronary death, the relative risk was 0.73. Major cardiovascular events were reduced (relative risk, 0.68). For deaths from all causes, the relative risk was 0.87.\n In persons aged 60 years and over with isolated systolic hypertension, antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36%, with 5-year absolute benefit of 30 events per 1000 participants. Major cardiovascular events were reduced, with 5-year absolute benefit of 55 events per 1000.", "The Oslo Hypertension Study started in 1972 and lasted for 66 (range 60-78) months. A total of 785 healthy men, aged 40 to 49 years, with mild hypertension were randomised to a drug-treated group and to an untreated, control group. The drugs used for treatment were hydrochlorothiazide alone in 36%, hydrochlorothiazide and propranolol in 26%, hydrochlorothiazide and methyldopa in 20%, and other drugs in 18%. A total of 95% in the drug-treated group received hydrochlorothiazide. Pressure complications, such as stroke and aneurysms, only occurred in the control group. Coronary events were more numerous in the drug-treated group, so that the total incidence of cardiovascular complications did not significantly differ between the treated and untreated groups. After 5 and 10 years, total mortality was found to be the same in both groups. However, the 10-year coronary heart disease mortality was significantly higher in the drug-treated group than in the untreated controls (14 v 3, p less than 0.01). Possible reasons for the failing effect of drug treatment of hypertension on coronary heart disease is discussed, and attention is drawn to the adverse effect of diuretics and beta-adrenergic blockers, both on lipid and carbohydrate metabolism. This is in contrast to the alpha-adrenergic blocker, prazosin, which has been shown to improve the blood lipid profile.", "The risks and benefits of treating hypertension in individuals older than 80 years are uncertain. A meta-analysis has suggested that a reduction in stroke events of 36% may have to be balanced against a 14% increase in total mortality.\n To report the results of the pilot study of the Hypertension in the Very Elderly Trial (HYVET), which is in progress to address these issues.\n The HYVET-Pilot was a multicentre international open pilot trial. In 10 European countries, 1283 patients older than 80 years and with a sustained blood pressure of 160-219/90-109 mmHg were allocated randomly to one of three treatments: a diuretic-based regimen (usually bendroflumethiazide; n = 426), an angiotensin-converting enzyme inhibitor regimen (usually lisinopril; n = 431) or no treatment (n = 426). The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment. Target blood pressure was < 150/80 mmHg and mean follow-up was 13 months.\n In the combined actively treated groups, the reduction in stroke events relative hazard rate (RHR) was 0.47 [95% confidence interval (CI) 0.24 to 0.93] and the reduction in stroke mortality RHR was 0.57 (95% CI 0.25 to 1.32). However, the estimate of total mortality supported the possibility of excess deaths with active treatment (RHR 1.23, 95% CI 0.75 to 2.01).\n The preliminary results support the need for the continuing main HYVET trial. It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 (nine non-fatal), but may be associated with 20 extra non-stroke deaths.", "nan", "To determine whether tight control of blood pressure with either a beta blocker or an angiotensin converting enzyme inhibitor has a specific advantage or disadvantage in preventing the macrovascular and microvascular complications of type 2 diabetes.\n Randomised controlled trial comparing an angiotensin converting enzyme inhibitor (captopril) with a beta blocker (atenolol) in patients with type 2 diabetes aiming at a blood pressure of <150/<85 mm Hg.\n 20 hospital based clinics in England, Scotland, and Northern Ireland.\n 1148 hypertensive patients with type 2 diabetes (mean age 56 years, mean blood pressure 160/94 mm Hg). Of the 758 patients allocated to tight control of blood pressure, 400 were allocated to captopril and 358 to atenolol. 390 patients were allocated to less tight control of blood pressure.\n Predefined clinical end points, fatal and non-fatal, related to diabetes, death related to diabetes, and all cause mortality. Surrogate measures of microvascular and macrovascular disease included urinary albumin excretion and retinopathy assessed by retinal photography.\n Captopril and atenolol were equally effective in reducing blood pressure to a mean of 144/83 mm Hg and 143/81 mm Hg respectively, with a similar proportion of patients (27% and 31%) requiring three or more antihypertensive treatments. More patients in the captopril group than the atenolol group took the allocated treatment: at their last clinic visit, 78% of those allocated captopril and 65% of those allocated atenolol were taking the drug (P<0.0001). Captopril and atenolol were equally effective in reducing the risk of macrovascular end points. Similar proportions of patients in the two groups showed deterioration in retinopathy by two grades after nine years (31% in the captopril group and 37% in the atenolol group) and developed clinical grade albuminuria >=300 mg/l (5% and 9%). The proportion of patients with hypoglycaemic attacks was not different between groups, but mean weight gain in the atenolol group was greater (3.4 kg v 1.6 kg).\n Blood pressure lowering with captopril or atenolol was similarly effective in reducing the incidence of diabetic complications. This study provided no evidence that either drug has any specific beneficial or deleterious effect, suggesting that blood pressure reduction in itself may be more important than the treatment used.", "The European Working Party on High blood pressure in the Elderly (EWPHE) trial was a double-blind randomized placebo-controlled trial of antihypertensive treatment in patients over the age of 60 years. Entry criteria included both a sitting diastolic blood pressure on placebo treatment in the range of 90-119 mmHg and a systolic blood pressure in the range of 160-239 mmHg. Eight-hundred and forty patients were randomly assigned either to active treatment (hydrochlorothiazide + triamterene) or a matching placebo. If blood pressure remained elevated methyldopa was added to the active regimen and matching placebo to the placebo regimen. Before randomization, the patients were stratified in eight strata according to sex, age groups between 60 and 69 years or 70 years and over, and the presence or absence of cardiovascular complications of hypertension. Both the intention-to-treat and 'on randomized treatment' analyses suggested a benefit from active treatment in men and women. Formal statistical significance was achieved for male cardiovascular mortality (intention-to-treat analyses) and for cardiovascular events in females. Although the event rates were greater for patients with previous cardiovascular events and patients over the age of 70 years, the percentage reduction in cardiovascular events was similar in these groups to those without complications and in patients between 60 and 69 years of age. However, little benefit from treatment could be demonstrated in patients over the age of 80 years. The presence or absence of smoking had no influence on response to treatment in these elderly patients.", "Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction, whether or not they have heart failure. We assessed the role of an angiotensin-converting-enzyme inhibitor, ramipril, in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure.\n A total of 9297 high-risk patients (55 years of age or older) who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were randomly assigned to receive ramipril (10 mg once per day orally) or matching placebo for a mean of five years. The primary outcome was a composite of myocardial infarction, stroke, or death from cardiovascular causes. The trial was a two-by-two factorial study evaluating both ramipril and vitamin E. The effects of vitamin E are reported in a companion paper.\n A total of 651 patients who were assigned to receive ramipril (14.0 percent) reached the primary end point, as compared with 826 patients who were assigned to receive placebo (17.8 percent) (relative risk, 0.78; 95 percent confidence interval, 0.70 to 0.86; P<0.001). Treatment with ramipril reduced the rates of death from cardiovascular causes (6.1 percent, as compared with 8.1 percent in the placebo group; relative risk, 0.74; P<0.001), myocardial infarction (9.9 percent vs. 12.3 percent; relative risk, 0.80; P<0.001), stroke (3.4 percent vs. 4.9 percent; relative risk, 0.68; P<0.001), death from any cause (10.4 percent vs. 12.2 percent; relative risk, 0.84; P=0.005), revascularization procedures (16.3 percent vs. 18.8 percent; relative risk, 0.85; P<0.001), cardiac arrest (0.8 percent vs. 1.3 percent; relative risk, 0.62; P=0.02), [corrected] heart failure (9.1 percent vs. 11.6 percent; relative risk, 0.77; P<0.001), and complications related to diabetes (6.4 percent vs. 7.6 percent; relative risk, 0.84; P=0.03).\n Ramipril significantly reduces the rates of death, myocardial infarction, and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure.", "The pilot study of the Systolic Hypertension in the Elderly Program was a randomized, double-blind, placebo-controlled trial of drug therapy for isolated systolic hypertension. It followed 551 elderly participants with untreated blood pressures of greater than 160/less than 90 mm Hg for an average of 34 months. Mean age of the participants was 72 years; 63% were women, and 82% were white. Pretreatment blood pressures averaged 172/75 mm Hg. Participants were randomly assigned to treatment with chlorthalidone or placebo as Step I medication. Blood pressures at annual visits averaged 141/68 and 157/73 mm Hg for the drug-treated and placebo-treated groups, respectively, with 60% and 33% of the survivors on blinded medication having systolic blood pressures of less than 160 mm Hg at their last annual visit. All-cause mortality rates for the drug-treated and placebo-treated groups were 25.4 and 22.7 deaths per 1,000 participant-years of risk, and rates for definite \"first stroke\" were 8.3 and 12.8 per 1,000 years of risk. Differences between groups were significant for systolic and diastolic blood pressure but not for death or stroke rates. A full-scale study has begun to determine the effects of drug therapy for isolated systolic hypertension on stroke and mortality rates.", "Post-stroke Antihypertensive Treatment Study (PATS) was a randomized, double-blind and placebo-controlled trial, which aimed at determining whether antihypertensive treatment could reduce the risk of fatal and nonfatal stroke incidence in patients with a history of stroke or transient ischemic attack (TIA). 5,665 patients were randomized by a sealed envelope system. Systolic blood pressure (SBP) ranged from 80 to 280 mm Hg and diastolic (DBP) from 50 to 150 mmHg. The average SBP was 154 mmHg and average DBP 93 mmHg. The mean age was 60 years. Among the patients, women accounted for 28%. In 71% the latest stroke was ischemic. Average follow-up approximated to 2 years. The three-year average SBP was 149 mmHg for the placebo group and 144 mmHg for the indapamide treatment group, and the three-year DBP was 89 mmHg and 87 mmHg respectively. The three-year first incidence of fatal and nonfatal stroke was 12.3 per 100 patients placebo treatment and 9.4 per 100 with indapamide. The relative risk by proportional hazards regression analysis was 0.71 (P = 0.0009). For deaths from all causes, the relative risk was 0.91. (P > 0.05). The findings of this trial indicate that in patients with a history of stroke or TIA, blood pressure reduction of 5/2 mmHg with 2.5 mg indapamide reduced the first incidence of fatal and nonfatal stroke by 29%, with three-year absolute benefit of 29 events per 1000 participants." ]

[ "1762975", "12244905", "8097215", "8792352" ]

[ "A comparison of transparent adherent and dry sterile gauze dressings for long-term central catheters in patients undergoing bone marrow transplant.", "What really affects the incidence of central venous catheter-related infections for short-term catheterization?", "A comparison of two transparent film-type dressings in central venous therapy.", "Comparison of central venous catheter dressings in bone marrow transplant recipients." ]

[ "Patients undergoing bone marrow transplant (BMT) are at great risk of infection and sepsis. Long-term central catheters (LTCCs), required for IV therapy, can be a portal of entry for infectious agents. This randomized, prospective study compared two types of catheter dressings in 98 patients undergoing BMT: a dry sterile gauze dressing (DSGD) changed daily and a transparent adherent dressing (TAD) changed every four days. Study outcomes included incidence and severity of local and systemic complications, patient assessment of comfort, and calculation of nursing time. One case of catheter-related infection occurred during the study. No significant differences existed between the two dressings in the incidence of positive skin cultures or local complications with the exception of skin irritation. The TAD caused less skin irritation, was preferred by patients, cost less, and required less nursing time. The findings indicate that TADs provide a safe, comfortable, and cost-effective alternative to DSGDs for patients undergoing BMT and receiving antibiotic support during aplasia.", "Central venous catheterization is one of the important sepsis reasons in surgical patients. In this randomized controlled study, the effect of the frequency and type of catheter site care, as well as age, coexisting malignancy or diabetes mellitus, total parenteral nutrition administration and antibiotics use, on central venous catheter infection was investigated. Seventy-two single-lumen polyurethane catheters were included. In group I (n: 33), a transparent occlusive dressing was applied to the insertion site and not removed for 7 days unless there were signs of local infection. In group II (n: 39), daily site care was done with povidone-iodine 10% solution and a new sterile gauze was applied. Chi-square, linear correlation and multiple regression tests were used for statistical analysis. Mean duration of catheters was 8 +/- 4 days. There was no catheter-related sepsis. Ten (13.9%) patients had positive catheter tip cultures of whom three had site infection as well. The incidence of site and tip infections were not significantly different in group I and II (p > 0.05). Site infection and age younger than 60 years significantly increased the rate of tip infection (p: 0.004 and p: 0.02 respectively). Total parenteral nutrition administration was associated with higher rate of tip infection (p: 0.06). Coexisting malignancy or diabetes mellitus, duration of catheter and antibiotics use did not have any significant effect on the rate of central venous catheter infections (p > 0.05). In conclusion, we observed that the frequency of insertion site care and the type of dressing applied to the site had no significant effect on the rate of CVC infection. Insertion site infection was the most significant factor increasing the incidence of catheter tip infection. The use of the CVC for total parenteral nutrition facilitated tip infection as well.", "A prospective randomized clinical trial has been conducted to compare the clinical performance, with prolonged use, of two film-type transparent dressings used over subclavian and jugular single-lumen venous catheters. 'OpSite', a traditional dressing with a moderate moisture vapour permeability was compared with a new dressing of high moisture vapour permeability, 'OpSite IV3000'. Information was collected daily to assess the nature and incidence of complications, dressing durability and the ease of application and removal. One hundred and one patients provided two well-matched populations receiving a total of 153 dressings for a total of 780 catheter-days. No differences between the two dressings were noted with respect to the incidence of complications, such as moisture accumulation or lifting, and dressing durability. The low incidence of catheter-related sepsis ('OpSite' group three episodes and 'OpSite IV3000' group one episode) suggests that transparent dressings do not increase this risk. This clinical study demonstrated the new 'OpSite IV3000' to be easier to handle, leading to better application, improved catheter fixation and easy removal.", "To determine the effect of two central venous catheter (CVC) dressing protocols on catheter-related infections in hospitalized patients with long-term tunneled catheters undergoing an autologous bone marrow transplant (BMT), to determine the prevalence of long-term CVC-related infections in this population, and to identify other factors in the study sample related to long-term CVC infection.\n Experimental.\n BMT unit of a regional oncology center in a tertiary care hospital.\n The sample consisted of 101 adult patients with cancer with long-term, tunneled CVCs inserted in the operating room on admission for autologous BMT.\n Patients randomly were assigned to one of two dressing-change procedure groups. The control group received the current standard of care for patients receiving BMT--a dry, sterile gauze dressing (DSGD) changed every 24 hours. The experimental group received Opsite 3000TM (Smith + Nephew Ltd., Massilon, OH) transparent moisture vapor permeable dressings (MVPD) changed weekly.\n CVC infection rates, frequency of IV tubing changes, immune status, duration of catheter use, occurrence and outcome of catheter occlusion, and use of a catheter for total parenteral nutrition.\n Researchers determined the difference in CVC-related infections between the two groups and the impact of select variables on CVC-related infection. When all categories of CVC-related infection (i.e., suspected, sepsis, tunnel) were considered, no statistical difference was found in the likelihood of the groups remaining infection-free (p = 0.76) over time. CVC sepsis occurred in one patient in the DSGD group and five patients in the MVPD group; however, this difference was not statistically significant over time (p = 0.067).\n Development of CVC sepsis or tunnel infection in close proximity to the time of CVC surgical placement suggests that factors other than the assigned dressing were associated with the occurrence of CVC-related infection in three cases. Although the MVPD group required dressing changes more frequently than every seven days (as specified by the protocol) because of exit-site drainage and nonocclusiveness, transparent dressings were more cost-effective than daily gauze dressings in this population.\n For adults undergoing autologous BMT, either DSGD or transparent CVC dressing can be used safely based on patient preference and skin tolerance to the dressing material." ]

[ "1901083", "3714523", "3195529", "8160279", "21962214", "10745332" ]

[ "Effect on neutrophil kinetics and serum opsonic capacity of intravenous administration of immune globulin to neonates with clinical signs of early-onset sepsis.", "Immunoglobulin supplementation in prevention or treatment of neonatal sepsis.", "IgM-enriched intravenous immunoglobulin therapy in neonatal sepsis.", "The use of IgM-enriched intravenous immunoglobulin for the treatment of neonatal sepsis in preterm infants.", "Treatment of neonatal sepsis with intravenous immune globulin.", "Multicenter randomized placebo controlled trial of therapy with intravenous immunoglobulin in decreasing mortality due to neonatal sepsis." ]

[ "This study was designed to test the hypothesis that administration of immune globulin to human neonates with early-onset bacterial sepsis would (1) facilitate neutrophil egress from the marrow, (2) improve serum opsonic capacity, and (3) facilitate recovery from the infectious illness. Twenty-two newborn infants with clinical signs of early-onset sepsis were given an intravenous infusion of either 750 mg of immune globulin (IVIG) per kilogram of body weight or the same volume of a vehicle control (albumin). All 22 infants survived, but significant hematologic, immunologic, and respiratory differences were observed after the IVIG and not after the control infusion. Eleven of the patients had neutropenia; 24 hours after the infusions, the neutropenia had resolved in all six IVIG recipients but persisted in all five control recipients (p less than 0.001). Ten patients had I/T neutrophil ratios (a measure of immature neutrophils to total neutrophils on the leukocyte differential count) of less than 0.2. One hour after completion of the infusions, all five IVIG recipients had elevated I/T ratios (mean +/- SEM:0.10 +/- 0.05 before vs 0.43 +/- 0.03 after infusion; p less than 0.001), suggesting a prompt release of neutrophils from the marrow neutrophil storage pool into the circulation; no increase in the I/T ratio was observed in the control recipients. Six hours after the IVIG infusions, the ratio of arterial oxygen tension to fraction of inspired oxygen increased; no increase was observed after control infusions. Serum concentrations of IgG, IgG1, IgG2, IgG3, IgG4, and total hemolytic complement and the capacity of serum to support opsonophagocytosis of type II and type III group B streptococci increased markedly in the IVIG recipients but not in the control subjects. We conclude that administration of 750 mg IVIG per kilogram to neonates with clinical signs of early-onset sepsis was associated with immunologic, hematologic, and physiologic improvement.", "nan", "Despite the development of newer generation of antibiotics, mortality from neonatal sepsis remains high. In a prospective, randomized study, we investigated the use of IgM-enriched immunoglobulin therapy in neonatal sepsis. Two groups of 30 infants each (matched for gestational age, sex, weight, and other variables) were randomly allocated to receive either antibiotics alone (control group) or antibiotics plus 5 mL/kg/d for four days of IgM-enriched immunoglobulin intravenously (immunotherapy group). Mortality from sepsis in the control group was 20% (6/30), while in the immunotherapy group it was 3.3% (1/30). We conclude that IgM-enriched immunoglobulin therapy in conjunction with antibiotic therapy significantly reduces mortality from neonatal sepsis.", "The value of IgM-enriched immunoglobulin therapy in 44 preterm infants with neonatal sepsis was evaluated in a prospective randomized study. All infants received antibiotic therapy and fresh plasma and/or whole blood transfusions. Twenty randomly-chosen infants were allocated to receive 5 ml/kg/d of IgM-enriched immunoglobulin intravenously for three days. Although the mortality rate in preterm infants whose gestational ages were 31-34 weeks in the immunotherapy group was slightly lower than in the control group, the general mortality rate from sepsis in the control group (9/24) and in the immunotherapy group (6/20) showed no statistically significant difference (37.5% vs 30.0%, p < 0.05).", "Neonatal sepsis is a major cause of death and complications despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in endogenous immunoglobulin. Meta-analyses of trials of intravenous immune globulin for suspected or proven neonatal sepsis suggest a reduced rate of death from any cause, but the trials have been small and have varied in quality.\n At 113 hospitals in nine countries, we enrolled 3493 infants receiving antibiotics for suspected or proven serious infection and randomly assigned them to receive two infusions of either polyvalent IgG immune globulin (at a dose of 500 mg per kilogram of body weight) or matching placebo 48 hours apart. The primary outcome was death or major disability at the age of 2 years.\n There was no significant between-group difference in the rates of the primary outcome, which occurred in 686 of 1759 infants (39.0%) who received intravenous immune globulin and in 677 of 1734 infants (39.0%) who received placebo (relative risk, 1.00; 95% confidence interval, 0.92 to 1.08). Similarly, there were no significant differences in the rates of secondary outcomes, including the incidence of subsequent sepsis episodes. In follow-up of 2-year-old infants, there were no significant differences in the rates of major or nonmajor disability or of adverse events.\n Therapy with intravenous immune globulin had no effect on the outcomes of suspected or proven neonatal sepsis.", "To determine whether therapy with intravenous immunoglobulin G (IVIG) would decrease mortality in neonatal sepsis.\n Three tertiary care neonatal intensive care units in the city of Bangalore.\n All neonates admitted to the Neonatal Intensive Care Units with the clinical diagnosis of sepsis and having at least C-reactive protein and one other rapid diagnostic criteria positive were enrolled. Neonates with a birth weight of less than 1000 g and those with any major congenital malformation were excluded. The neonates were randomized to receive 1 g/kg of IVIG on three consecutive days or an equivalent amount of placebo. The rest of the treatment including antibiotics and supportive care was as per the treating physician's decision. The main outcome variable was survival.\n The trial was carried out over a period of 8 months and recruited 58 neonates. Seven neonates who qualified but did not receive either IVIG or placebo were taken into a separate control group, and one baby who received only one dose of IVIG was excluded from the analysis. Twenty-five neonates were enrolled into the IVIG arm and 25 in the placebo arm. The neonates in the therapy and placebo groups were comparable in terms of birth weight (2144+/-675 g vs. 2072+/-682 g), gestation (37.0+/-3.56 vs. 35.8+/-3.52 weeks), sex distribution, duration of stay, and number requiring ventilation. The placebo group had a significantly higher number of babies with positive blood culture. Seven babies in each group died (p>0.05). There was no significant benefit in using IVIG (OR 1.0; 95% CI 0.25-4.07) (p = 0.74).\n In the sample studied therapy with IVIG did not reduce mortality in neonatal sepsis" ]

[ "9339095", "12193911", "10453828", "11814498", "17187804", "14562597", "15491565", "16001749", "9170825", "17629164", "15738009", "9170463", "12854927", "9184950", "15925045", "8290188", "9396885", "11194687", "17028904", "12475576", "17877293", "11938791", "18399337", "16780844", "14687051", "10688506", "12557801", "15036709", "9322632", "9491868", "18715414", "12841697", "15913628", "7778637", "8369246", "16101609", "7675376", "12592272", "12830602", "11392598", "15625147", "8960988", "17219155", "10368502", "9083316", "9396895", "10338065", "7659811", "11453262", "15145271", "12648174", "10838340", "18569471", "12648175", "9175387", "8697339", "16624192", "11444788", "11966483", "16162347", "17326881", "11075969", "9704771", "15295374", "8841210", "11843388", "11818106", "7485307", "11814497", "10486474", "8694043", "12920470", "9397101", "15339772", "15777441", "9502664", "15954870", "11042301", "12767565", "11803223", "9290452", "11561740", "16406221", "15603033", "11641678", "17077234", "7778636", "10659896", "15450119", "9803069", "9572178", "12554247", "16232176", "16753768", "15294364", "16129547" ]

[ "A randomised double-blind study of vaginal misoprostol vs dinoprostone for cervical ripening and labour induction in prolonged pregnancy.", "Misoprostol versus low-dose oxytocin for cervical ripening: a prospective, randomized, double-masked trial.", "Misoprostol for induction of labour at term: a more effective agent than dinoprostone vaginal gel.", "Prostaglandin E2 gel versus misoprostol for cervical ripening in patients with premature rupture of membranes after 34 weeks.", "Induction of labor with misoprostol or oxytocin in Tanzania.", "Vaginal misoprostol for induction of labour: a more effective agent than prostaglandin F2 alpha gel and prostaglandin E2 pessary.", "Induction of labor with misoprostol in grand multiparous patients.", "[Comparative study of the effect of intravaginal misoprostol at 50 and 100 micrograms in cervical ripening and labor induction].", "Randomized comparison of misoprostol and dinoprostone for preinduction cervical ripening and labor induction.", "Labor induction at term: a comparison of the effects of 50 microg and 25 microg vaginal misoprostol.", "Outpatient misoprostol compared with dinoprostone gel for preinduction cervical ripening: a randomized controlled trial.", "Labor induction with intravaginal misoprostol in term premature rupture of membranes: a randomized study.", "Randomized controlled trial of vaginal misoprostol versus dinoprostone vaginal insert for labor induction.", "A comparative trial of labor induction with misoprostol versus oxytocin.", "Induction of labor with three different techniques at 41 weeks of gestation or spontaneous follow-up until 42 weeks in women with definitely unfavorable cervical scores.", "Intravaginal misoprostol versus dinoprostone as cervical ripening and labor-inducing agents.", "A double-blind comparison of the safety and efficacy of intravaginal misoprostol and prostaglandin E2 to induce labor.", "Comparison between vaginal misoprostol and cervical dinoprostone for cervical ripening and labor induction.", "A randomized comparison between intravaginal misoprostol and prostaglandin E2 for labor induction.", "Misoprostol and dinoprostone therapy for labor induction: a Doppler comparison of uterine and fetal hemodynamic effects.", "Comparative study of misoprostol vs dinoprostone for induction of labour.", "[Clinical observation of misoprostol on induction in late pregnancy].", "Efficacy and safety of misoprostol in induction of labour in a Nigerian tertiary hospital.", "Intravaginal misoprostol in preterm premature rupture of membranes with low Bishop scores.", "A randomised trial comparing low dose vaginal misoprostol and dinoprostone for labour induction.", "Labour characteristics and uterine activity: misoprostol compared with oxytocin in women at term with prelabour rupture of the membranes.", "[Misoprostol and oxytocin for induction of cervical ripening and labor in patients with term pregnancy and premature membrane rupture].", "Induction of labor with 50 and 100 microg of misoprostol: comparison of maternal and fetal outcomes.", "A comparison of intermittent vaginal administration of misoprostol with continuous dinoprostone for cervical ripening and labor induction.", "Labor induction with prostaglandin E1 misoprostol compared with dinoprostone vaginal insert: a randomized trial.", "Induction of labour in nulliparous and multiparous women: a UK, multicentre, open-label study of intravaginal misoprostol in comparison with dinoprostone.", "Six hourly vaginal misoprostol versus intracervical dinoprostone for cervical ripening and labor induction.", "Cervical ripening and labor induction with 25 microg vs. 50 microg of intravaginal misoprostol.", "Misoprostol: an effective agent for cervical ripening and labor induction.", "Intravaginal misoprostol as a cervical ripening agent.", "Misoprostol versus expectant management in premature rupture of membranes at term.", "Randomized controlled trial of vaginal misoprostol and intracervical prostaglandin E2 gel for induction of labor at term.", "Comparative efficacy and cost of the prostaglandin analogs dinoprostone and misoprostol as labor preinduction agents.", "Misoprostol for cervical ripening at and near term--a comparative study.", "Is high-dose misoprostol able to lower the incidence of cesarean section? A randomized controlled trial.", "Cardiotocographic abnormalities associated with dinoprostone and misoprostol cervical ripening.", "Comparison of labor induction with misoprostol vs. oxytocin/prostaglandin E2 in term pregnancy.", "Efficacy and safety of six hourly vaginal misoprostol versus intracervical dinoprostone: a randomized controlled trial.", "Misoprostol is more efficacious for labor induction than prostaglandin E2, but is it associated with more risk?", "A randomized comparison between misoprostol and dinoprostone for cervical ripening and labor induction in patients with unfavorable cervices.", "A randomized clinical trial comparing misoprostol with prostaglandin E2 gel for preinduction cervical ripening.", "A double-blind randomized trial of two dose regimens of misoprostol for cervical ripening and labor induction.", "[Misoprostol--a PGE1 analog for induction of labor at term: comparative and randomized study with oxytocin].", "Misoprostol versus dinoprostone for cervical priming prior to induction of labour in term pregnancy: a randomised controlled trial.", "Intravaginal misoprostol vs. dinoprostone as cervical ripening and labor-inducing agents.", "Dinoprostone versus misoprostol: a randomized study of nulliparous women undergoing induction of labor.", "Comparative cost analysis of prostaglandin analogues dinoprostone and misoprostol as labor preinduction agents.", "Prospective randomised controlled trial to compare safety and efficacy of intravaginal Misoprostol with intracervical Cerviprime for induction of labour with unfavourable cervix.", "Randomized trial in multiparous patients: investigating a single vs. two-dose regimen of intravaginal misoprostol for induction of labor.", "Comparison of intracervical and intravaginal misoprostol for cervical ripening and labour induction in patients with an unfavourable cervix.", "Preinduction cervical ripening with intravaginal prostaglandin E1 methyl analogue misoprostol: a randomized controlled trial.", "Efficacy of dinoprostone, intracervical foleys and misoprostol in labor induction.", "A comparison of intermittent vaginal administration of two different doses of misoprostol suppositories with continuous dinoprostone for cervical ripening and labor induction.", "Induction of labor in toxemia with misoprostol.", "Misoprostol vs. oxytocin for induction of labor.", "Induction of labour with intravaginal misoprostol and prostaglandin E2 gel: a comparative study.", "A randomized comparison of one single dose of vaginal 50 microg misoprostol with 3 mg dinoprostone in pre-induction cervical ripening.", "Induction of labor with misoprostol for premature rupture of membranes beyond thirty-six weeks' gestation.", "A randomized trial that compared intravaginal misoprostol and dinoprostone vaginal insert in pregnancies at high risk of fetal distress.", "Vaginal misoprostol for induction of labor: a randomized controlled trial.", "Induction of labour with a viable infant: a randomised clinical trial comparing intravaginal misoprostol and intravaginal dinoprostone.", "Labor induction with vaginal misoprostol and extra-amniotic prostaglandin F2alpha gel.", "Labor induction with intravaginal misoprostol versus intracervical prostaglandin E2 gel (Prepidil gel): randomized comparison.", "Oral and vaginal misoprostol compared with dinoprostone for induction of labor: a randomized controlled trial.", "Randomized comparison between intravaginal misoprostol and dinoprostone for cervical ripening and induction of labor.", "A comparison of differing dosing regimens of vaginally administered misoprostol for preinduction cervical ripening and labor induction.", "Misoprostol versus oxytocin for labor induction in term and post-term pregnancy: randomized controlled trial.", "Extemporaneous preparation of misoprostol gel for cervical ripening: a randomized trial.", "Misoprostol outpatient cervical ripening without subsequent induction of labor: a randomized trial.", "A randomised controlled trial comparing low dose vaginal misoprostol and dinoprostone vaginal gel for inducing labour at term.", "Misoprostol as a labor induction agent.", "Outpatient misoprostol cervical ripening without subsequent induction of labor to prevent post-term pregnancy.", "Outpatient cervical ripening with intravaginal misoprostol.", "Labor induction post-term with 25 micrograms vs. 50 micrograms of intravaginal misoprostol.", "Comparison of 25 and 50 microg vaginally administered misoprostol for preinduction of cervical ripening and labor induction.", "Randomized trial of two doses of the prostaglandin E1 analog misoprostol for labor induction.", "Randomized controlled trial of 50 and 100 mcg of misoprostol for induction of labor at term.", "Induction of labor with misoprostol in pregnancies with advanced maternal age.", "Vaginal misoprostol in managing premature rupture of membranes.", "Vaginally administered misoprostol for outpatient cervical ripening in pregnancies complicated by diabetes mellitus.", "Controlled-release misoprostol vaginal insert in parous women for labor induction: a randomized controlled trial.", "A comparison of misoprostol and prostaglandin E2 gel for preinduction cervical ripening and labor induction.", "Uterine and fetal Doppler flow changes after misoprostol and oxytocin therapy for induction of labor in post-term pregnancies.", "Comparison of misoprostol and dinoprostone for elective induction of labour in nulliparous women at full term: a randomized prospective study.", "A comparison between 25 micrograms and 50 micrograms of intravaginal misoprostol for labor induction.", "Disruption of prior uterine incision following misoprostol for labor induction in women with previous cesarean delivery.", "No benefit, but increased harm from high dose (100 microg) misoprostol for induction of labour: a randomised trial of high vs. low (50 microg) dose misoprostol.", "Urinary cyclic guanosine 3',5'-monophosphate and cyclic adenosine 3',5'-monophosphate changes in spontaneous and induced onset active labor.", "A prospective randomized study comparing misoprostol and oxytocin for premature rupture of membranes at term.", "Influence of misoprostol or prostaglandin E(2) for induction of labor on the incidence of pathological CTG tracing: a randomized trial.", "Induction of labor in great grandmultipara with misoprostol." ]

[ "Dinoprostone, is presently used in our standard protocol for cervical ripening and labour induction. In search for a cheaper alternative, misoprostol has been found to be a good substitute. In view of the potential saving it might offer, we set out to test its efficacy against the standard dinoprostone.\n A randomised double-blind study involving 50 pregnant women with prolonged pregnancy, treated at a government hospital in Malaysia, was carried out. Two hundred micrograms of intravaginal misoprostol were compared with 3 mg of dinoprostone in each treatment arm.\n In the misoprostol group, labour was successfully established in 92% of cases compared to 64% in the dinoprostone group (p = 0.04). The induction-delivery interval was shorter with more women delivering within 12 hours (72% vs 28%, p = 0.047). Maternal and neonatal complications, mode of delivery, the need for oxytocin and pethidine were quite similar statistically. Polysystole was more frequent (28% vs 12%, p = 0.28) in the misoprostol group but it was not associated with fetal distress.\n The study showed that misoprostol was a more effective drug in labour induction.", "A variety of cervical ripening agents exist, yet none is ideal. We performed a prospective, randomized, double-masked comparison of low-dose minimal-escalation oxytocin to misoprostol in a predominantly high-risk population.\n Patients were allocated prospectively in a double-masked, randomized, stratified basis by an investigational pharmacist between December 1996 and December 2000 to receive either active intravenous oxytocin and placebo intravaginal misoprostol or intravenous placebo oxytocin and 50 microg of active intravaginal misoprostol. The infusion rate of oxytocin was increased from 1 to 4 mU/min; misoprostol (25 microg) was repeated at 4 hourly intervals if there were <3 uterine contractions per 10-minute interval.\n Demographic characteristics did not differ between study groups nor did the indications for induction. Overall, the interval to delivery was less in the misoprostol group; however, vaginal delivery occurred in 61% versus 66% (not significant) of patients in the misoprostol versus oxytocin group. Indication for cesarean delivery in the misoprostol group was fetal intolerance to labor in 27% compared with 8% in the oxytocin groups (P <.05), whereas labor abnormalities were more commonly the cause in the oxytocin group versus misoprostol (26% vs 10%, P <.05). The proportion of patients was similar in each group overall and when evaluated on the basis of parity and when delivery was compared at 12, 24, and 36 hours after the initiation of cervical priming.\n Our data indicate that misoprostol and low-dose minimal-escalation oxytocin appear to be equally effective for cervical priming. Low-dose oxytocin may have a preferential role in the high-risk parturient whose fetus is at increased risk for fetal intolerance to labor", "To compare the efficacy of vaginal misoprostol and dinoprostone vaginal gel for induction of labour at term.\n A single-blind randomised comparative trial.\n Induction and labour wards of a UK teaching hospital.\n Two hundred and eleven pregnant women at term in whom induction of labour was indicated, and with no contra-indication to the use of prostaglandins for the induction of labour.\n The women were randomly assigned to receive vaginal administration of either misoprostol 50 microg four hourly (to a maximum of four doses) or dinoprostone gel 1 mg six hourly (to a maximum of three doses).\n Time from induction to delivery, oxytocin requirement in labour, analgesic requirement, mode of delivery, neonatal outcome.\n The misoprostol group had a highly significant reduction in median induction-delivery interval compared with the dinoprostone group (14.4 hours vs 22.9 hours; P < 0.00001). In addition, more women delivered after only one dose (77% vs 49%; P < 0.0001, OR 3.51, 95% CI 1.94-6.35), and within 12 and 24 hours. There was a reduced need for oxytocin augmentation in labour (21% vs 47%; P < 0.0001, OR 0.30, 95% CI 0.16-0.54). There was no difference in analgesia requirement in labour, or in mode of delivery. There were no adverse neonatal outcomes associated with the use of misoprostol. Women in the misoprostol group experienced more pain in the interval between induction and being given analgesia in labour, but this did not reach statistical significance.\n Misoprostol 50 microg vaginally is a more effective induction agent than 1 mg dinoprostone vaginal gel, with no apparent adverse effects on mode of delivery, or on the fetus. The higher pain scores in the misoprostol group must be balanced against the reduction in time spent having labour induced, and the reduction in need for intravenous oxytocin augmentation. Further randomised studies must continue to exclude the possibility of rare adverse side effects.", "To compare intravaginal misoprostol to prostaglandin (PG) E2 for cervical ripening in women with premature rupture of the membranes (PROM) after 34 weeks of gestation.\n Women with PROM after 34 weeks of gestation and an unripe cervix were randomized to receive PGE2 (2.5 mg) or misoprostol (50 microg). Both agents were placed intravaginally immediately after randomization, and the dose was repeated 6 hours later if necessary. After another 6 hours from the second insertion, oxytocin treatment was started if labor had not begun. Forty patients in each group were required to show a 30% improvement in delivery within 12 hours in the misoprostol group.\n One hundred nine patients were randomized; 54 were assigned to misoprostol and 55 to PGE2. Important demographic and clinical characteristics were similar between the groups. The mean time from first insertion to delivery was 16.4 hours in the misoprostol group and 22.0 hours in the PGE2 group. A second dose was required less frequently in the misoprostol group (22% vs 62% in the PGE2 group), and the percentage of patients delivered within 12 hours was higher in the misoprostol group (41% vs 16%). Tachysystole occurred in 20% and 6% of women in the misoprostol and PGE2 groups, respectively. Hyperstimulation occurred in 9% and 0%, and cesarean delivery in 19% and 26% of women in the misoprostol and PGE2 groups, respectively. Neonatal outcome was similar between groups.\n Intravaginal misoprostol is more effective than local PGE2 application to treat PROM after 34 weeks of gestation, but tachysystole occurs more commonly with misoprostol.", "nan", "To compare labour outcome in women who had labour induced with PGF2 alpha gel, PGE2 vaginal pessary or misoprostol administered intravaginally or orally.\n Unmasked randomised controlled trial.\n Department of Obstetrics and Gynaecology, University of Zimbabwe, Harare.\n Women with a singleton foetus in cephalic presentation after 37 weeks gestation admitted for induction of labour who were randomised to prostaglandin F2 alpha gel (n = 76), prostaglandin E2 pessary (n = 75) and misoprostol administered either intra-vaginally (n = 128) or orally (n = 127).\n Primary outcome was induction to delivery interval. Secondary outcomes included use of oxytocin during labour, mode of delivery, duration of labour, neonatal condition at delivery and maternal complications.\n Four hundred and six women admitted for induction of labour with a singleton foetus in cephalic presentation after 37 weeks gestation were enrolled. To estimate the risk with induction using other agents the odds ratio and 95% confidence interval was calculated using the group that received prostaglandin F2 alpha gel as referents.\n The women were comparable for baseline characteristics. Compared to prostaglandin F2 alpha gel, the need for augmentation with oxytocin in labour was significantly reduced in women induced with prostaglandin E2 pessary (OR 0.46; 95%CI 0.23 to 0.93), vaginal misoprostol (OR 0.34; 95%CI 0.18 to 0.63) and oral misoprostol (OR 0.42; 95%CI 0.22 to 0.78). There was no difference in mode of delivery. There was a significantly reduced risk (OR 0.20; 95%CI 0.04 to 0.86) of Caesarean section (CS) for failure to progress in the vaginal misoprostol group. Labour induced with misoprostol and prostaglandin E2 pessary was significantly shorter than in prostaglandin F2 alpha gel. Vaginal misoprostol significantly shortened the induction to delivery interval. There were more admissions to the neonatal unit in the misoprostol groups.\n Compared to prostaglandin F2 alpha gel, misoprostol and prostaglandin E2 pessary had reduced need for oxytocin and a shorter duration of labour. Effects of misoprostol on the foetus need further investigation before it is used as a routine agent for induction of labour.", "nan", "The objective of this work was to compare the efficacy of 50 and 100 microg of misoprostol administered intravaginally for cervical ripening and labor induction. Ninety-five patients were randomly assigned to receive 50 microg (n=48) or 100 microg (n=47) of misoprostol. The primary measures in this study were cesarean section rate, time from induction to delivery, need for oxytocin use, rate of uterine hyperstimulation and tachysystoles, proportion of fetal distress and neonatal Apgar score. The interval from first dose of prostaglandin to delivery was significantly shorter in the 100 ,g-group (p < 0.05). The use of oxytocin augmentation was significantly higher in the 50 microg-group (64.6% vs. 31.9%). There were 9 cases (18.8%) of tachysystole in the 50-microg group and 12 cases (25.5%) in the 100 microg-group (p NS). The cesarean section rate was double in the 100 microg-group and the difference was statically significant (p < 0.05). There was no report of uterine rupture. It can be concluded that 50 microg of misoprostol applied in the posterior vaginal fornix every 4 hours is an effective dosage for labor induction and has less adverse effects and complications than the 100 microg dose.", "This study attempts to evaluate the clinical effects of prostaglandin (PG) E analogues in preinduction cervical ripening and labor induction and to compare the perinatal outcomes of these medications. Sixty women with term singleton pregnancies were randomized to receive dinoprostone vaginal tablets (group I) or misoprostol vaginal tablets (group II). The Bishop scores were evaluated before drug insertion and every 4 hours during induction. Clinical data and perinatal outcomes were also recorded. There were no significant differences in the preinduction conditions on mean initial Bishop scores between these two groups. Twelve hours after drug insertion, the mean Bishop scores were significantly better in group II (9.7 +/- 3.1 vs 7.3 +/- 2.5, p < 0.05). The mean time from insertion to delivery was shorter in group II (16.5 +/- 2.7 h vs 25.7 +/- 3.8 h, p < 0.001). There were no significant differences in spontaneous labor rate, need for oxytocin augmentation, type of delivery, and Doppler flow velocity waveforms of the umbilical artery. The average number of doses given per patient was 1.8 +/- 1.4 in group II vs 2.7 +/- 0.3 in group I (p < 0.05). The perinatal outcome was similar in the two groups. In conclusion, misoprostol not only appears to be a safe and effective agent for cervical ripening and labor induction but is also more efficient than dinoprostone.", "To compare the effects of 50 microg of vaginal misoprostol with 25 microg for labor induction at term.\n One hundred and forty-seven pregnant women with indications for labor induction and cervical Bishop's score of < or = 6 were randomly assigned to receive either 50 microg (n = 74) or 25 microg (n = 73) of vaginal misoprostol every four hours until either a Bishop's score of > or = 8 or adequate uterine contraction frequency had been achieved. Induction-to-vaginal-delivery time was considered the primary outcome measure.\n Mean induction-to-vaginal-delivery time was significantly shorter in the 50-microg group than in the 25-microg group (526 +/- 141 min vs 745 +/- 218 min, respectively); oxytocin was administered to 65.8% of the patients in the 25-microg group and to 35.1% in the 50-microg group (p < .05). The incidence of tachysystole was significantly higher in the 50-microg group than in the 25-microg group (12% vs 2.7%, p < .05). We found no statistically significant difference between the two groups with respect to the rate of primary cesarean section, incidence of hyperstimulation syndrome, or neonatal outcome (p > .05).\n Fifty micrograms of vaginally administered misoprostol is an effective and inexpensive means of inducing labor at term. Uterine tachysystole may be associated more frequently with a 50-microg dose of vaginal misoprostol than with a 25-microg dose. Clinicians must accurately document the frequency and intensity of uterine contractions before every 50-microg dose of misoprostol is administered.", "To determine whether a single outpatient dose of intravaginal misoprostol (versus intracervical dinoprostone gel) reduces the oxytocin use for induction. Despite the numerous trials examining misoprostol for induction, the efficacy of a single outpatient dose of misoprostol followed by oxytocin induction is unknown.\n Patients with a term, vertex, singleton pregnancy and a Bishop score of 6 or less were randomly assigned to receive misoprostol (n = 42, 0.25 microg intravaginally) or dinoprostone gel (n = 42, 0.5 mg intracervically) the evening before oxytocin induction. Patients were monitored for 3 hours after administration and discharged to home if fetal assessment was reassuring, for readmission the next morning for oxytocin. Primary outcomes were oxytocin dose, time, and dose intensity (dose divided by duration). Secondary outcomes were incidence of labor, uterine hyperstimulation, cesarean delivery, Apgar score. Statistics used were chi(2), Student t test, Mann-Whitney rank sum test, and Fisher exact test. P < .05 was accepted as statistically significant.\n A single dose of misoprostol significantly decreased the cumulative dose of oxytocin, the cumulative time of oxytocin administration, and the dose intensity of oxytocin (dose divided by time). Data are as follows (mean +/- standard error of the mean): oxytocin dose-dinoprostone 10,929 +/- 219 mU, misoprostol 6,081 +/- 170 mU, P = .008; oxytocin time-dinoprostone 798 +/- 11 minutes, misoprostol 531 +/- 11 minutes, P = .009; dose intensity-dinoprostone 11.3 +/- 0.1 mU/min, misoprostol 7.4 +/- 0.2 mU/min, P = .003. Misoprostol induced labor during the ripening period in 19 of 41 of patients, compared with 6 of 42 after dinoprostone (P = .002). There was no difference in cesarean delivery (dinoprostone, 8/42; misoprostol, 9/42; P = 1.00). There was no difference in short-term neonatal outcome. No patient had hyperstimulation or required cesarean delivery for nonreassuring fetal assessment during the ripening period.\n A single dose of misoprostol administered in the outpatient setting significantly decreases oxytocin use, largely due to labor within the ripening period.", "To evaluate the safety and clinical effectiveness of intravaginal misoprostol, a synthetic prostaglandin E1 analogue, for labor induction in gravidas with premature rupture of membranes (PROM) at term.\n One hundred forty-one pregnant women with term PROM were assigned randomly to one of two induction groups: 1) intravaginal misoprostol or 2) intravenous oxytocin by continuous infusion.\n Seventy subjects were allocated to the misoprostol group and 71 to the oxytocin group. The mean (+/- standard deviation) interval from induction to delivery was significantly shorter in the misoprostol group (416 +/- 276 compared with 539 +/- 372 minutes; P = .04). In 85.7% of patients in the misoprostol group, only one dose was required. Intrapartum complication rates, mode of delivery, and neonatal or maternal adverse event rates were similar in the two treatment groups. Uterine tachysystole occurred more frequently with misoprostol than with oxytocin (28.6% compared with 14.0%; P < .04).\n Intravaginal administration of misoprostol induces labor safely and effectively in patients with PROM at term.", "To compare the safety and efficacy of vaginal misoprostol versus dinoprostone vaginal inserts for cervical ripening and labor induction.\n Two hundred singleton gestations with an indication for cervical ripening and induction of labor were randomized to receive either 50 microg of misoprostol intravaginally every 3 h or a 10-mg dinoprostone vaginal insert every 12 h for a maximum of 24 h. Statistical analysis included Student's t test, the Mann-Whitney U test, chi2 analysis and Fisher's exact test.\n Ninety-seven women received vaginal misoprostol while 89 women received the dinoprostone vaginal insert. Fourteen women were removed from the study after randomization. The interval from start of induction to vaginal delivery (794.5 +/-408 min vs. 1005.3 +/- 523 min; p < 0.02) was significantly shorter in the misoprostol group. Women receiving misoprostol were more likely to deliver vaginally both in < 12 h (44% vs. 12%; p < 0.0001) and < 24 h (68% vs. 38%; p < 0.001). A non-reassuring fetal heart rate tracing was the indication for 71.4% (20/28) of Cesarean deliveries in the misoprostol group compared to 40% (14/35) in the dinoprostone group (p = 0.03). There were no significant differences in neonatal outcomes.\n Intravaginal misoprostol and dinoprostone are safe and effective medications for use in cervical ripening before labor induction. Misoprostol results in a shorter interval from induction to delivery. However, Cesarean delivery for a non-reassuring fetal heart rate tracing was more common with misoprostol.", "To determine the efficacy and safety of intravaginal misoprostol compared with intravenous oxytocin in cervical ripening and labor induction.\n The study was carried out at the Department of Obstetrics and Gynecology at the Hospital Loayza, Lima, Peru. The sample included 123 pregnant women with any indication for labor induction. The study was prospective and randomized. We compared the effect of 50 micrograms of intravaginal misoprostol administered every 4 h up to 600 micrograms with that observed using the standard protocol of oxytocin by continuous infusion.\n 57 patients with misoprostol (group 1) and 63 with oxytocin (group 2) were enrolled. Delivery occurred in 45 patients (78.9%) in group 1 and in 37 (58.7%) in group 2 (P < 0.017). Complications including tachysystole, uterine hypertony and hyperstimulation were higher in group 1, 21.1% than in group 2, 7.9% (P < 0.04). The incidence of cesarean section in both groups was similar to the overall incidence in our center. No differences were observed between groups in perinatal and postpartum adverse outcomes. The interval from start of induction to vaginal delivery was significantly shorter in the oxytocin group (8.4 +/- 4.1 vs. 11.3 +/- 6.9 h, P < 0.005).\n Intravaginal administration of misoprostol is a safe and effective alternative for cervical ripening and labor induction. Maternal and neonatal complications did not increase significantly.", "To compare the obstetric outcome of induction of labor at 41 weeks and of follow-up until 42 weeks and induction if the patient has still not given birth at 42 weeks.\n Six hundred women at 287+/-1 days of gestation with definitely unfavorable cervical scores were randomized to labor induction (N=300) or spontaneous follow-up (N=300) with twice-weekly nonstress testing and amniotic fluid measurement and once-weekly biophysical scoring. The treatments used in the induction group were (1) vaginal administration of 50 microg misoprostol (n=100), (2) oxytocin induction (n=100), and (3) transcervical insertion of a Foley balloon (n=100). The primary outcome measures were the cesarean delivery rate, whether or not the normal hospital stay had to be extended, and the neonatal outcomes. Secondary outcome measure included number of emergency cesarean deliveries performed for abnormalities of the fetal heart rate (FHR).\n The abdominal delivery rate was 19.3% in the induction group and 22% in the follow-up group (p=0.4). The mean length of hospital stay in the two main groups was 1.4+/-0.8 days and 1.3+/-1 days, respectively (p=0.1). Significantly higher rates of macrosomia and shoulder dystocia were seen in the follow-up group (24.6 and 2.3%) than in the induction group (7.6%, p<0.001; 0.3%, p=0.03). Meconium-stained amniotic fluid and meconium aspiration syndrome were observed significantly less frequently in the induction group (9.3 and 1.3%) than in the follow-up group (20.3%, p<0.001; 4%, p=0.03). Rates of emergency abdominal delivery in response to worrying FHR traces, neonatal intensive care unit admission, and low umblical artery pH were similar in the two groups. There was one intrauterine fetal death in the follow-up group.\n Induction of labor at 41 weeks of gestation does not increase the cesarean delivery rate or cause a longer stay in hospital than follow-up until 42 weeks, and neonatal morbidity is also lower after induction.", "To compare dinoprostone (prostaglandin E2) and misoprostol (prostaglandin E1) for ripening the cervix and inducing labor at term.\n Sixty-three women were randomized to receive 100 micrograms misoprostol or 3 mg dinoprostone, both as intravaginal tablets.\n There was no statistical difference between the groups for pre-induction status. The mean Bishop scores before drug insertion were almost identical. Twelve hours after insertion, the mean change in the Bishop score was significantly higher in those receiving misoprostol (5.0 versus 3.3) (P = .008). However, there were no significant differences in induction-to-delivery interval, spontaneous labor rates, type of delivery, fetal outcome, or maternal complications.\n Misoprostol is as effective as dinoprostone for inducing labor at term.", "Our purpose was to compare the safety and efficacy of intravaginally administered misoprostol versus prostaglandin E2 for labor induction in a double-blind, randomized trial.\n One hundred three patients with indications for labor induction (including prelabor rupture of membranes) were randomized and received either misoprostol 50 micrograms or prostaglandin E2 (dinoprostone) 3 mg intravaginally. The dose was repeated 6, 24, and 30 hours after the first dose until active labor was achieved. For proper blinding, the drugs were prepared as identical-looking vaginal tablets.\n With use of a random number-generated table 52 patients were allocated to the misoprostol group and 51 to the prostaglandin E2 group. After exclusion of 3 patients, 50 in each group were evaluated. Delivery within 24 hours after administration occurred more often in the misoprostol group (70% vs 46% in the prostaglandin E2 group, p = 0.009), and fewer patients in this group needed more than two doses (12% vs 30%, p = 0.027). No difference in cesarean section rate (12% vs 14%, p = 0.67), fetal heart rate anomalies (33% vs 34%, p = 0.89), tachysystole (8% vs 14%, p = 0.37), hyperstimulation syndrome (0% vs 2%, not significant), meconium passage (28% vs 18%, p = 0.22), and fetal outcome (Apgar score at 1 and 5 minutes, arterial and venous umbilical cord blood pH, transfer to neonatal intensive care unit) was noted between the two groups.\n Intravaginal misoprostol is a safe drug for labor induction with superior effectiveness compared with intravaginal prostaglandin E2.", "To compare the efficacy of intravaginal misoprostol (Cytotec) to intracervical dinoprostone (Prepidil) for pre-induction cervical ripening.\n Sixty-one patients admitted for induction of labor, whose cervices were unfavorable (Bishop score: 4), were randomly assigned to either intravaginal placement of a 50 micrograms misoprostol tablet or intracervical administration of dinoprostone gel.\n Eighteen women (56%) in the misoprostol group and five (17%) in the dinoprostone group achieved cervical ripening within 12 hours (P = 0.007). Fewer doses of misoprostol were required to achieve cervical ripening, and the interval from induction of labor to delivery was shorter in the misoprostol group. Sixteen patients (50%) in the misoprostol group required oxytocin, whereas 26 (90%) in the dinoprostone group required oxytocin augmentation (P = 0.008). There was no significant difference in mode of delivery or neonatal outcome between the two groups.\n Vaginal misoprostol appears to be a more effective cervical ripening agent than cervical dinoprostone.", "The aim of this randomized study was to compare the effectiveness, safety, and side effects of 6 h vaginal misoprostol versus vaginal prostaglandin E(2) (PGE(2)) for labor induction.\n Fifty microgram of misoprostol was given intravaginally in the misoprostol group (204 women), and 3 mg PGE(2) was given intravaginally in the PGE(2) group (211 women). In both groups, the dose was repeated every 6 h for a maximum of three doses, until active labor was achieved. Artificial rupture of membranes and oxytocin infusion was used during labor in both groups where it was indicated.\n The mean interval from the institution of labor induction to delivery was 11.3 +/- 8.6 h for the misoprostol group, and 15.7 +/- 9.3 h for PGE(2 )group (P < 0.05). In the misoprostol group, oxytocin was used less frequently, but there was a higher prevalence of tachysystole. No statistically significant differences were observed between the two groups as regard abnormal patterns of fetal heart rate, the mode of delivery, and the need for neonatal intervention.\n In conclusion, the intravaginal administration of 50 mug misoprostol at 6 h interval (maximum three doses) is comparable in safety, but more effective for induction of labor than 3 mg intravaginal PGE(2).", "To compare the effect of misoprostol (PGE(1)) versus dinoprostone (PGE(2)) on blood flow in uteroplacental circulation during labor induction.\n Eighty-four women with indications for induction of labor were assigned to receive either misoprostol 50 microg per vagina every 4 h as needed or 0.5 mg doses of dinoprostone given intra-cervically every 6 h by means of a randomization table generated by computer. Doppler velocimetry of umbilical, uterine and arcuate arteries was performed immediately before and 2-3 h after the administration of misoprostol or dinoprostone. The SAS system was used to perform statistical analysis.\n There were no significant changes of pulsatility index (PI), resistance index (RI) and systolic/diastolic (S/D) ratio in umbilical arteries after both prostaglandin compounds. Vaginal application of misoprostol significantly increased all ratios in arcuate artery and S/D ratio in uterine artery. Intra-cervically dinoprostone significantly increased PI, RI and S/D ratio in arcuate and uterine arteries.\n Our results indicate that vaginal misoprostol and cervical dinoprostone administration increases uteroplacental resistance but does not affect umbilical blood flow. Misoprostol would be as safe and effective agent as dinoprostone for cervical ripening and labor induction.", "Various methods of induction of labour may be associated with risk and complications. Therefore, this study has been undertaken to compare the safety and efficacy of intra-vaginal misoprostol (PGE1 analogue) with intra-cervical dinoprostone (PGE2) in progress and induction of labour, the maternal side effects and the foetal outcome. 40 pregnant women aged between 16-35 years with indication of induction of labour participated in the study. Twenty patients (control) were administered 0.5 mg dinoprostone intra-cervically, 12 hourly while 20 patients (study group) were given misoprostol 100 microg, 4 hourly, intravaginally. The mean induction of labour initiation interval was 2.08 +/- 1.46 hours in study group and 2.21 +/- 1.20 hours in dinoprostone group. The Induction delivery interval was 6.92 +/- 4.01 hours in misoprostol group and 12.54 +/- 7.73 in dinoprostone group, whereas vaginal route of delivery was 95% in misoprostol group and 85% in dinoprostone group. Average dosages required were 1.55 +/- 1.02 in misoprostol group and 1.30 +/- 0.46 in dinoprostone group. All these result were statistically significant. Very few maternal side effects were reported in study group. There was no significant difference in foetal out come in either group. Therefore, it can be concluded that misoprostol is easy to administer and is cheap, effective, safe and convenient drug for induction of labour.", "Eighty late pregnancy women were randomized into two groups. Misoprostol group and oxytocin group. We observed the different effects of misoprostol and oxytocin on induction, the different effects of misoprostol on induction which was given through rectum or through vagina. The results indicate that the rate of successful induction in misoprostol group is higher than that of oxytocin group, the rate of caesarean section in misoprostol group is lower than that of oxytocin group. There was no significant difference in the durations of misoprostol which was given through rectum or through vagina on induction. It is suggested that misoprostol is more effective on induction than that of oxytocin. We can choose misoprostol given through rectum to prompt delivery in conditions such as premature rupture of membranes and vaginitis.", "Misoprostol - a stable prostaglandin E1 analogue- is effective and safe in the induction of labour. There is paucity of information about the use of misoprostol for labour induction in Nigeria.\n To evaluate the efficacy of misoprostol in the induction of labour in the third trimester. METHODS. Consecutive patients for induction of labour were randomized into misoprostol or oxytocin study groups. The misoprostol group received intravaginal 50 microg 6- hourly to a maximum of four doses. Those in the oxytocin group received a maximum of 48 iu/min. Outcome measures included induction-delivery interval, mode of delivery, Apgar score, perinatal death and maternal complications.\n Sixty-two patients were recruited into the study-34 received misoprostol while 28 received oxytocin. The modal gestational age and Bishop score prior at induction were >36 weeks and 5-7 respectively. Hypertension in pregnancy was the commonest indication for induction of labour followed by prolonged pregnancy. The overall induction-delivery interval was 12.2 +/- 5.2 hours; Misoprostol v oxytocin, mean(range): 12.1(7-27) vs 12.3(4-27) hours, p = 0.88). There were no significant differences in the mean Apgar score and perinatal mortality rate in the two study groups. There were two cases of primary postpartum haemorrhage in the oxytocin group but none in the misoprostol group. One case of ruptured uterus was encountered in the misoprostol group. No case of maternal mortality was recorded. Four patients in the misoprostol group had minor side effects mainly nausea and vomiting.\n The efficacy of misoprostol in the induction of third trimester labour is comparable to oxytocin. The risk of ruptured uterus associated with misoprostol appears higher than that of oxytocin in the induction of labour. Further studies are needed to verify this observation in our setting.", "nan", "To compare vaginal misoprostol with dinoprostone for induction of labour.\n Randomised multicentre trial.\n Labour wards of one university hospital and two teaching hospitals.\n Six hundred and eighty-one women with indication for labour induction at >or=36 weeks of gestation, singleton pregnancy and no previous ceasarean section.\n Misoprostol (25 mcg, hospital-prepared capsule) in the posterior vaginal fornix, every four hours, maximum three times daily or dinoprostone gel (1 mg) every four hours. Oxytocin was administered if necessary.\n Primary: 'adverse neonatal outcome' (5-minute Apgar score <7 and/or umbilical cord pH <7.15). Secondary: labour duration, mode of delivery and patient satisfaction.\n Three hundred and forty-one women received misoprostol and 340 dinoprostone. The median induction-delivery interval was longer in the misoprostol group compared with the dinoprostone group (25 versus 19 hours, P= 0.008). The caesarean section rate was lower in the misoprostol group: 16.1%versus 21%, but this difference was not statistically significant RR = 0.8 (95% CI 0.6-1.04). 'Adverse neonatal outcome' was found to be similar in both groups: 21% in the misoprostol and 23% in the dinoprostone groups. Significantly fewer neonates were admitted to NICU in the misoprostol group compared with dinoprostone 19%versus 26% (RR = 0.7, 95% CI 0.5-0.98).\n Misoprostol in this dosing regimen is a safe method of labour induction. NICU admission rates were lower in the misoprostol group. No difference could be detected in patient satisfaction between groups.", "To compare the labour pattern and uterine activity of oral misoprostol with oxytocin for labour induction in women presenting with prelabour rupture of membranes at term.\n Prospective randomised study.\n Department of Obstetrics and Gynaecology, Queen Mary Hospital, Hong Kong.\n Eighty women presenting with prelabour rupture of membranes at term.\n The women were randomised to receive either 100 microg misoprostol orally every 4 hours to a maximum of three doses, or intravenous oxytocin infusion according to the hospital protocol. Intrauterine pressure transducers were inserted one hour before induction of labour in both groups of women. We compared the pattern of uterine activity, the induction-to-delivery interval, duration of labour, mode of delivery and neonatal outcome between the two groups.\n Both oxytocin and oral misoprostol caused an increase in uterine activity within one hour of labour induction. Peak uterine activity was reached 6-8 h after oral misoprostol, with persistent effects, and 8-10 h after oxytocin, requiring continuous titration of medication. The duration of labour was significantly reduced in nulliparous women, but not in those who were multiparous in the misoprostol group. The induction-to-delivery interval, the mode of delivery and the perinatal outcome were similar for the two groups.\n Oral misoprostol caused earlier peak uterine activity, compared with oxytocin (6-8 h vs 8-10 h). Oral misoprostol was not only as effective as oxytocin in inducing labour in women at term with prelabour rupture of the membranes, but it reduced significantly the duration of labour in nulliparous women.", "To evaluate the effect of the concurrent administration of intravaginal misoprostol and oxytocin for cervical ripening and labor induction on length labor, mode of delivery and perinatal outcomes.\n One hundred seven patients with singleton pregnancy at term, vertex presentations, premature rupture of membranes and Bishop scores of < or = 4 were randomly assigned to receive one of three treatments: Group I: Intravenous oxytocin plus intravaginal misoprostol (n = 36); Group II: Intravenous oxytocin plus placebo intravaginal (n = 34); Group III: Intravaginal misoprostol plus intravenous placebo. The time interval from induction to beginning of the labor, from induction to delivery, mode of delivery and perinatal outcomes were measured.\n The mean time from induction to beginning of labor was different between the groups: Group I: 48.75 minutes, Group II: 107.50 minutes, Group III: 95.94 minutes (p = 0.0024). The mean time in minutes from induction to delivery was different between the groups: Group I: 359.83; Group II: 537.05; Group III: 474.54 (p < 0.05). The frequency of tachysystole, mode of delivery and perinatal outcomes were similar among the three groups.\n Oxytocin that is administered simultaneously with intravaginal misoprostol for cervical ripening and labor induction in patients with pregnancies at term, premature rupture of membranes and Bishop scores < 4 make the labor beginning quickly, significantly shortens induction to delivery times without affecting the mode of delivery and with no apparent adverse maternal and perinatal effects.", "The aim of this randomized controlled study was to compare the efficacy and the safety of different regimens of misoprostol for labor induction. MATERIALS AND METHODS Eligible women received intravaginal 100 microg, every 6 h or 50 microg every 4 h. Treatment continued until: (1) dilatation >3 cm; (2) rupture of membranes (artificial); (3) signs of uterine hyperstimulation; (4) adequate contraction pattern (three contraction/10 min). Managing clinician might use oxytocin during labor. Cesarean section rate was the main outcome that was considered variably. Other outcome measures were neonatal outcome (Apgar scores, meconium staining, and umbilical artery pH) and induction to delivery interval.\n A total number of 72 women received either misoprostol 100 microg (n=37), or 50 microg (n=35) randomly. The two groups had similar mean Bishops scores at induction (4.10+/-2.4 versus 4.2+/-2.1; P=0.85), rates of nulliparity, use of epidural anesthesia, and oxytocin augmentation. In two groups the number of doses of misoprostol used was similar (1.6+/-0.5 versus 1.7+/-0.3)\n There was not any difference between the two groups in the mean+/-S.D. time to delivery (h) and cesarean rate. Likewise, there was not a significance between two groups in the rates of 5 min Apgar score, and of meconium passage.", "Our purpose was to compare the effect of vaginal administration of misoprostol (Cytotec) with that of dinoprostone (Cervidil) on cervical ripening and labor induction.\n Two hundred patients with indications for induction of labor and unfavorable cervical examinations were randomly assigned to receive vaginally administered misoprostol (prostaglandin E1) or the dinoprostone (prostaglandin E2) vaginal insert. Twenty-five microgram tablets of misoprostol were placed in the posterior vaginal fornix every 4 hours for a maximum of six doses. Additional misoprostol was not given after either spontaneous rupture of membranes, adequate cervical ripening (Bishop score of > or = 8 or cervical dilatation of > or = 3 cm), or beginning of active labor. The vaginal insert, Cervidil, containing 10 mg of dinoprostone in a timed-release preparation was placed in the posterior vaginal formix for a maximum period of 24 hours. The vaginal insert was removed for spontaneous rupture of membranes, entry into active labor, adequate cervical ripening, or abnormality of uterine contractile pattern or fetal cardiac activity.\n Of the 200 patients enrolled, 99 were randomized to misoprostol and 101 to dinoprostone. The average interval from start of induction to vaginal delivery was 1 hour shorter in the misoprostol group (1296.7 +/- 722.1 minutes) than in the dinoprostone group (1360.0 +/- 792.0 minutes), but this difference was not statistically significant (p = 0.97). Oxytocin augmentation of labor was used in 50 (50.5%) misoprostol-treated patients and 43 (43.5%) dinoprostone-treated patients (relative risk 1.14, 95% confidence interval 0.86 to 1.51, p = 0.35). There were no significant differences between routes of delivery with misoprostol or dinoprostone. Overall, 38 patients (19.3%) had cesarean deliveries. There was a significantly lower prevalence of tachysystole (six or more uterine contractions in a 10-minute window for two consecutive 10-minute periods) in the misoprostol group (7.1%) than in the dinoprostone group (18.4%) (relative risk 0.52, 95% confidence interval 0.31 to 0.89, p = 0.02). There were no significant differences in frequency of uterine hyperstimulation or hypertonus. Abnormal fetal heart rate tracings were found in 23 (23.2%) of misoprostol-treated patients and 35 (35.7%) of dinoprostone-treated patients (relative risk 0.73, 95% confidence interval 0.52 to 1.01, p = 0.0546). No significant differences were found in meconium passage, 1- or 5-minute Apgar scores < 7, neonatal resuscitations, or admissions to the neonatal intensive care unit between the two groups.\n Vaginally administered misoprostol is as effective as dinoprostone for cervical ripening and the induction of labor. Mean time intervals to delivery, need for oxytocin augmentation, and routes of delivery were similar between the two groups. Incidence of uterine tachysystole with misoprostol every 4 hours was significantly less than with dinoprostone.", "To compare the safety, efficacy, and costs of intravaginal misoprostol versus dinoprostone vaginal inserts for cervical ripening and labor induction.\n Two hundred twenty-three labor induction patients were assigned randomly to one of two treatment groups: 1) intravaginal misoprostol or 2) dinoprostone vaginal inserts. Fifty micrograms of misoprostol were placed in the posterior vaginal fornix every 3 hours for a maximum period of 24 hours. Ten milligrams of dinoprostone was administered in a single application as a vaginal insert for 12 hours.\n Among 223 patients evaluated, 108 were allocated to the misoprostol group and 115 to the dinoprostone group. The median interval from induction to vaginal delivery was significantly shorter in the misoprostol group: 698 (range 395-1053) versus 1041 (range 792-1531) minutes (P < .001). Vaginal delivery within 12 hours of ripening occurred in 40.7% of patients who received misoprostol compared with 19.1% for those receiving dinoprostone (P < .001); no significant difference between the groups was noted for vaginal delivery within 24 hours. Uterine tachysystole occurred more frequently in patients in the misoprostol group (21.3%) than in the dinoprostone group (7.0%) (P = .004). Nevertheless, no statistically significant differences were noted between the groups with respect to intrapartum complications, including uterine hyperstimulation, mode of delivery, and neonatal or maternal adverse outcomes. The average cost per patient for misoprostol treatment was $85 compared with $606 for treatment with the vaginal insert.\n Intravaginal misoprostol and the dinoprostone vaginal insert appear to be safe agents for cervical ripening and labor induction. However, misoprostol is less expensive and more effective than the dinoprostone vaginal insert.", "To compare the efficacy and safety of a 25-microgram vaginal tablet of misoprostol (APL202) with dinoprostone (3-mg vaginal tablet) in cervical ripening and labour induction.\n A randomised, open-label, noninferiority, comparative study in two maternal populations.\n Eighteen NHS study centres across the UK.\n Nulliparous or multiparous women with a singleton pregnancy eligible for induction of labour.\n Women were randomised to receive either misoprostol, initially 25 micrograms (50 micrograms in nulliparous women with Bishop score < or =4) followed by 25 micrograms after 4 and 8 hours, or dinoprostone, initially 3 mg followed by 3 mg after 6 hours. Clinical noninferiority of misoprostol was defined as an absolute difference between treatments of no more than 10% for the primary outcome.\n The number of vaginal deliveries achieved within 24 hours of labour induction. Maternal and fetal safety outcomes.\n A total of 626 women were randomised to misoprostol (n = 318) or dinoprostone (n = 308) treatment. The rate of vaginal deliveries achieved within 24 hours of induction did not significantly differ between the misoprostol and dinoprostone (43 versus 47%; 3.74% difference, 95% CI -3.58 to 11.05, respectively) treatment groups. The treatments were generally comparable for other secondary efficacy measures. Maternal and fetal adverse events were similarly distributed across the misoprostol and dinoprostone groups.\n Low-dose misoprostol is efficacious in cervical ripening and labour induction and demonstrates a similar fetal and maternal safety profile to dinoprostone.", "Prospective clinical trials were conducted to assess the safety and efficacy of 6-hourly vaginal misoprostol versus intracervical dinoprostone for induction of labor.\n A total of 120 pregnant women requiring induction of labor were recruited. Cases were randomized to receive either 50 microg vaginal misoprostol 6 hourly (group 1, n = 60) or 0.5 mg intracervical dinoprostone 6 hourly (group II, n = 60). Outcome measures, such as change in Bishop's score, need of oxytocin, induction delivery interval; complications like tachysystoly, hyperstimulation, abnormal fetal heart rate, and meconium passage were compared between two groups. Statistical analysis was performed by Wilcoxan's Rank sum and Student's t-test.\n Bishop score rise, after 6 h of initiation of therapy was significantly higher in the misoprostol group than dinoprostone, 2.98 +/- 2.57 versus 2.05 +/- 1.83 (P = 0.04). The need of oxytocin augmentation was reduced in misoprostol versus dinoprostone group, 16.6% versus 78.3% (P = <0.001). Induction delivery interval was shorter in misoprostol; 12.8 +/- 6.4 h versus 18.53 +/- 8.5 h in dinoprostone group (P = <0.01). One case (1.6%) in misoprostol group, but none in dinoprostone had tachystole (P = 1.00). Abnormal heart rate pattern was found more in misoprostol than dinoprostone 16.6% versus 4.9% (P = 0.14) and so was the incidence of cesarean section, 26.6 versus 15%, respectively (P = 0.47). Meconium passage was the same in both groups, 10% in each group.\n Vaginal misoprostol 50 microg 6-hourly is safe and effective for induction of labor with lesser need of oxytocin augmentation and shorter induction delivery interval.", "nan", "Our purpose was to compare the safety and efficacy of intravaginal misoprostol versus intracervical prostaglandin E2 gel (dinoprostone) for preinduction cervical ripening and induction of labor.\n Two hundred seventy-six patients with indications for induction of labor and unfavorable cervices were randomly assigned to receive either intravaginal misoprostol or intracervical dinoprostone. Twenty-five micrograms of misoprostol were placed in the posterior vaginal fornix every 3 hours, with a potential maximum of eight doses. Prostaglandin E2 in gel form, 0.5 mg, was placed in the endocervix every 6 hours, with a maximum of three doses. Further medication was withheld with the occurrence of spontaneous rupture of membranes, entry into active phase of labor, or a \"prolonged contraction response.\"\n Among those evaluated, 138 received misoprostol and 137 received dinoprostone. The average interval from start of induction to vaginal delivery was shorter in the misoprostol group (1323.0 +/- 844.4 minutes) than in the dinoprostone group (1532.4 +/- 706.5 minutes) (p < 0.05). Need for oxytocin augmentation of labor occurred more commonly in the dinoprostone group (72.6%) than in the misoprostol group (45.7%) (p < 0.0001). There were no significant differences in the routes of delivery. Twenty-eight of the misoprostol-treated patients (20.3%) and thirty-eight of the dinoprostone-treated patients (27.7%) required abdominal delivery. Complications such as uterine tachysystole and thick meconium passage occurred with similar frequency in the two treatment groups.\n Intravaginal administration of misoprostol appears to be as effective as intracervical dinoprostone for cervical ripening and labor induction. Complications associated with prostaglandin administration were not statistically different between the two treatment groups. The cost of misoprostol ($0.36/100 micrograms) is much less than that of dinoprostone ($75/0.5 mg).", "To determine if misoprostol (exogenous prostaglandin E1 PGE1) used vaginally was of value in improving the Bishop score, leading to an early safe vaginal delivery in women in whom the cervix is unripe and delivery is indicated.\n A double-blind clinical trial.\n Antenatal and labour wards of the University Hospital of the West Indies, Jamaica.\n Forty-five women in the third trimester with various obstetric indications for induction of labour and with no contra-indications to prostaglandins.\n The women were randomly assigned to receive treatment or a placebo. The treated group had 100 micrograms misoprostol inserted vaginally while the placebo was similarly inserted.\n Efficacy of the misoprostol was measured by the increase in the Bishop score 12 h after giving the treatment, the time between insertion and delivery, the need for oxytocin, and the outcome of the pregnancy.\n The prostaglandin was superior to the placebo in ripening the cervix and inducing labour. The change in Bishop score was 5.3 in the misoprostol group compared with 1.5 in the placebo group (P < 0.001). The mean time from insertion to delivery was 15.6 h in the former while it was 43.2 h in the placebo group (P < or = 0.001). The need for oxytocin was also significantly less in the women receiving the prostaglandin compared with those who received the placebo (29% vs 62%, P < 0.02). There was no difference in the two groups in the delivery outcome in terms of complications, Apgar scores and mode of delivery.\n Intravaginal misoprostol is an effective and cheap method of inducing labour in the third trimester.", "To compare the effectiveness of immediate induction of labour with vaginal misoprostol versus expectant management for 24 hours followed by oxytocin induction in women with premature rupture of membranes at term (term PROM).\n An open, randomised, controlled trial.\n Public university hospital in Campinas City, Brazil.\n One hundred and fifty pregnancies, half of them allocated to each group.\n Statistical analysis used Student's t test, the chi2 test, Fisher's exact test, survival analysis and risk ratio estimates with 95% CI.\n Latency period, recruitment to delivery period, period of hospitalisation, mode of delivery, contractility pattern, fetal wellbeing, labour and delivery complications, neonatal and maternal morbidity.\n Both groups had similar general characteristics, but the misoprostol group had a significantly shorter latency period (9.4 vs 15.8 hours), a shorter time interval from recruitment to delivery (18.9 vs 27.5 hours), a shorter period of maternal hospitalisation and a slightly higher proportion of alterations of contractility when compared with the expectant group. Caesarean section rates were 20% in the misoprostol group and 30.7% in the other. There were no differences between them regarding fetal wellbeing, complications during labour and delivery and neonatal or postpartum maternal morbidity. Within 24 hours, 44% of women had delivered in the expectant group against 73.3% in the misoprostol group.\n Immediate labour induction with misoprostol in cases of term PROM shortens the latency period, the total time between recruitment to delivery and the time of maternal hospitalisation, increasing the occurrence of alterations of contractility without any maternal and perinatal outcomes disadvantages.", "To compare misoprostol 25 micrograms administered at 2-hour intervals with intracervical prostaglandin (PG) E2 in women with Bishop scores of 5 or less.\n Subjects were randomly assigned to receive either misoprostol 25 micrograms every 2 hours or a commercially available intracervical preparation containing 0.5 mg of PGE2 gel administered at 6-hour intervals for a maximum of two doses.\n Women who received misoprostol experienced a significantly reduced mean time (+/- standard deviation) from drug administration to onset of three contractions in 10 minutes, 6.7 +/- 5.8 versus 12.4 +/- 9.6 hours (P = .007). Mean time to rupture of membranes was also shorter in the misoprostol group, 9.7 +/- 5.5 versus 13.6 +/- 6.8 hours (P = .01), as was the mean time to delivery, 16.0 +/- 7.7 versus 22.4 +/- 10.9 hours (P = .006). Three patients in the misoprostol group experienced uterine hypertonus but not related fetal morbidity.\n Misoprostol is more effective than intracervical PGE2 in bringing about labor and delivery, but further work is needed to determine the ideal dosing regimen.", "The purpose of this study was to compare the relative efficacy and cost of three commercially available prostaglandin analogs, misoprostol (Cytotec), dinoprostone gel (Prepidil), and dinoprostone insert (Cervidil), as labor preinduction agents.\n One-hundred eleven women with an unfavorable cervix who underwent labor induction were assigned randomly to receive either misoprostol 50 microg every 6 hours for two doses, dinoprostone gel 0.5 mg every 6 hours for two doses, or dinoprostone insert 10 mg for one dose intravaginally. Twelve hours later, oxytocin induction was initiated per standardized protocol. Efficacy and cost of the labor preinduction/induction with the study treatments were compared.\n Mean Bishop score change (+/-SD) over the initial 12-hour interval was significantly greater in the misoprostol group (5.2 +/- 3.1) compared with the dinoprostone insert (3.2 +/- 2.3) or the dinoprostone gel groups (2.2 +/- 1.3, P <.0001). The proportion of women who reached complete dilation (68.4%, 50.0%, 51.4%, respectively; P =.14) and who were delivered (60.5%, 47.4%, 40.0%, respectively; P =.10) within 24 hours of the initiation of induction were not significantly different between the misoprostol, dinoprostone insert, and dinoprostone gel groups. Induction-to-delivery intervals, however, were significantly shorter among women who treated with misoprostol (24.0 +/- 10.8 hours) compared with either the dinoprostone gel (31.6 +/- 13.4 hours) or the dinoprostone insert (32.2 +/- 14.7 hours, P <.05). Overall mean cost per patient that was incurred by labor induction was significantly less for the misoprostol group ($1036.13) compared with the dinoprostone insert group ($1565.72) or the dinoprostone gel group ($1572.92, P <.0001). No significant differences were noted with respect to the mode of delivery or to the adverse maternal/neonatal outcome.\n Misoprostol is more cost-effective than the comparable commercial dinoprostone prostaglandin preparations as an adjuvant to labor induction in women with an unfavorable cervix.", "To compare the safety and efficacy of misoprostol with that of dinoprostone for the induction of labour at term, or near term.\n Three hundred and ninety-six women with term pregnancies were randomised to receive either oral or vaginal misoprostol, or dinoprostone. Women who had had a previous caesarean section (CS) or those with a malpresentation or who were parity > or = 5, were excluded. The control group received dinoprostone 1 mg inserted in the posterior fornix and repeated 6-hourly to a maximum of three doses. The study group received either oral misoprostol 20 micrograms 2-hourly to a maximum of four doses (80 micrograms), or vaginal misoprostol 25 micrograms in the posterior fornix with a switch to the oral misoprostol regimen if there was no change in the Bishop's score or no palpable uterine contractions.\n There was no significant difference in vaginal delivery rate within 24 hours between the groups (58.1% v. 58%, p = 0.633). There were no significant differences in CS rates between the groups; however, more CSs were performed for fetal distress in the misoprostol group than in the dinoprostone group (28% v. 25%). There was a significantly higher incidence of hyperstimulation in the vaginal misoprostol group (21.4%) than in the other two groups (oral misoprostol 16.5%, dinoprostone 8.9%) (p = 0.004). The incidence of meconium staining of liquor was comparable between the groups.\n In selected women, the efficacy of misoprostol for the induction of labour at term is similar to that of dinoprostone but misoprostol is associated with a higher incidence of hyperstimulation.", "To determine whether high-dose (100 microg) misoprostol was able to increase the rate of successful labor induction and lower the incidence of Cesarean section without adverse fetal effects.\n A total of 360 women were randomized to receive either oxytocin (n = 192) by intravenous infusion, or misoprostol (n = 168) 100 microg intravaginally every 4 h. The Cesarean section rate was the primary end-point. Incidences of uterine and fetal heart rate abnormalities during labor and adverse neonatal outcomes were assessed as secondary end-points.\n Compared with those women receiving oxytocin, patients given misoprostol had a significantly shortened labor (10.7+/-6.0 vs. 15.4+/-10.4 h, p < 0.001). The Cesarean section rate did not differ between patients receiving misoprostol or oxytocin (36 (21.4%) vs. 38 (19.8%), p = 0.79) despite a sample size adequate to detect a 13 percentage point difference in this outcome. Patients receiving misoprostol had a higher incidence of the hyperstimulation syndrome (27 (16.1%) vs. 9 (4.7%), p < 0.001), and of fetal intolerance of labor as an indication for Cesarean delivery (23 (63.9%) vs. 15 (39.5%), p = 0.06), and had a greater number of umbilical artery cord blood pH findings of< 7.20 (20 (43.5%) vs. 6 (17.1%), p = 0.02). These worrisome trends on interim analysis resulted in our prematurely terminating the study.\n High-dose intravaginal misoprostol did not reduce the Cesarean section rate and was associated with a greater hazard of fetal intolerance of labor.", "To characterize the frequency and timing of cardiotocographic abnormalities associated with the use of 3 commercially available prostaglandin analogues, misoprostol, dinoprostone gel, and dinoprostone pessary, as labor preinduction agents.\n One-hundred and eleven women undergoing induction of labor with an unfavorable cervix were randomized to receive either misoprostol 50 microg every 6 hours x 2 doses, dinoprostone gel 0.5 mg every 6 hours x 2 doses, or dinoprostone pessary 10 mg x 1 dose for 12 hours intravaginally. Oxytocin induction was initiated per standardized protocol. Cardiotocographic tracings were blindly reviewed, with abnormalities coded using established definitions.\n Fifty-five percent of women treated with misoprostol demonstrated an abnormal tracing event within the initial 24 hours of induction, compared with 21.1% with dinoprostone pessary and 31.4% with the dinoprostone gel. The mean (+/- standard deviation) number of abnormal events was significantly greater in women treated with misoprostol (5.0 +/- 5.9) versus the dinoprostone pessary (1.6 +/- 2.5) and gel (2.2 +/- 3.1) (P < .05). In addition, these events occurred earlier after initial misoprostol dosing (5.0 +/- 4.0 hours), compared with the dinoprostone pessary (9.4 +/- 5.6 hours) and gel (7.7 +/- 6.6). Thirty-nine percent of the misoprostol-treated women had abnormal patterns within 6 hours of initial dosing, compared with those treated with the dinoprostone pessary (7.9%) and gel (17.1%).\n Cardiotocographic abnormalities are more frequent after misoprostol administration compared with the dinoprostone analogues. The early onset and frequent nature of the tracing abnormalities associated with misoprostol raises concern for the potential use of misoprostol for outpatient cervical ripening.", "To compare the efficacy and safety of intravaginal and oral misoprostol vs. oxytocin/prostaglandin E2 (PGE2) gel for third trimester labor induction.\n Two hundred twenty-four pregnant women were randomized to induction of labor either with misoprostol or oxytocin and PGE2 gel. Patients in the misoprostol group (n = 112) received 100 micrograms intravaginal misoprostol followed by 100 micrograms p.o. every 2 h. The oxytocin/PGE2 group consisted of 112 patients who underwent PGE2 cervical instillation 6 h before continuous oxytocin infusion. The perinatal, intrapartum and neonatal characteristics of both groups were determined.\n Induction to active phase of labor was successfully achieved in 96 women (85.7%) in the misoprostol group vs. 86 women (76.8%) in the oxytocin/PGE2 group, but the drug initiation-delivery interval was significantly shorter in the misoprostol group (9.2 +/- 2.4 h) than in the oxytocin/PGE2 group (15.2 +/- 3.2 h, P < 0.001). The incidence of adverse intrapartum outcomes was similar for both methods. Intravaginal misoprostol 100 micrograms followed by a single oral dose of 100 micrograms misoprostol safely produced labor and a vaginal delivery in 70% of patients. More than three tablets were required in only 10% of patients. There was a higher prevalence of cesarean section for failed induction in the oxytocin/PGE2 group than in the misoprostol group (13.4 vs. 6.3%, P < 0.001). The neonatal outcomes of both groups were also similar.\n Misoprostol is significantly more effective for labor induction than oxytocin/PGE2 gel. The maternal intrapartum and neonatal outcomes were the same for both induction regimens. From a clinical and perinatal perspective, misoprostol is an acceptable choice for labor induction.", "To compare the efficacy and safety of intravaginal misoprostol versus dinoprostone cervical gel for cervical ripening and labour induction.\n We carried out an experimental clinical trial in which we enrolled 130 cervical consecutive patients with cervical ripening, randomly assigned to one of the following two treatment groups: (1) intravaginal misoprostol and (2) intracervical dinoprostone gel. A total of 50 microm of misoprostol was placed in the posterior vaginal fornix every 6 h for a maximum period of 24 h and 0.5 mg of dinoprostone was administrated in the uterine cervix every 6 h, for a maximum period of 24 h. The primary outcome measure was the number (rate) of women who went to vaginally deliver within 24 h of the protocol initiation.\n Among 130 patients evaluated, 65 were allocated to the misoprostol group and 65 to the dinoprostone group. The proportion of vaginal delivery within 24 h was significantly higher in the misoprostol group (75%) than in the dinoprostone group (53.8%) (RR = 1.40, 95% CI [1.07-1.45], P = 0.02). There was no significant difference between the mean time interval of delivery in the misoprostol group and the dinoprostone group (14.9 vs.15.8 h) (P = 0.51). The Bishop score was significantly higher in the misoprostol group, 6 h after the onset of the study (1.38; relative risk, 95% CI [1.02-1.85], P = 0.03). The Caesarean delivery rate for fetal distress was higher in the dinoprostone group (21 vs. 10.8%, P = 0.15). The tachysystole (Misoprostol 6.1% vs. dinoprostone 4.6%, relative risk 1.15, 95% CI [0.6-2.24]) and hyperstimulation syndrome rates (Misoprostol 7.6% vs. dinoprostone 4.6%, relative risk 1.26, 95% CI [0.72-2.24]) were slightly increased in the misoprostol group than in the dinoprostone group without reaching the level of statistical signification.\n Misoprostol as used in this protocol is more effective than cervical dinoprostone gel application in the cervical ripening and labour induction. There is a tendency for an increase in the rate of tachysystole and hyperstimulation syndrome.", "Our purpose was to compare the efficacy and safety of misoprostol with dinoprostone (Prepidil) for labor induction.\n In a randomized, controlled trial of labor induction, patients were randomly assigned to receive either 50 microgram of intravaginal misoprostol every 4 hours or 0.5 mg of intracervical prostaglandin E2 every 6 hours. Eligibility criteria included gestation of >/=31 weeks, Bishop score <6, and fewer than 12 contractions per hour. Primary outcomes were cesarean section, induction to delivery time, oxytocin use, and fetal distress requiring delivery.\n One hundred fifty-nine women were randomly assigned to receive misoprostol (n = 81) or Prepidil (n = 78). There were no differences in the indication for induction, preinduction Bishop score, epidural use, or cesarean section rate. Mean time to delivery was significantly shorter in the misoprostol group (19 hours 50 minutes) than in the Prepidil group (28 hours 52 minutes) (P =.005). Only 58% of women in the misoprostol group required oxytocin augmentation, in comparison with 88% of women receiving Prepidil (P =.00002). However, 41% of women receiving misoprostol and 17% receiving Prepidil had late decelerations or bradycardias (P =.001), and 20% of the misoprostol group and 5% of the Prepidil group had deliveries for fetal distress (P =.05).\n Misoprostol is more efficacious than Prepidil for labor induction. However, the significantly increased incidence of abnormal fetal heart rate tracings and the trend in increased deliveries for fetal distress with misoprostol dosing of 50 microgram every 4 hours are of concern. These data suggest that either a lower dose of misoprostol or less frequent dosing of misoprostol should be considered.", "To compare the efficacy and safety of two prostaglandin derivatives, misoprostol and dinoprostone, for ripening the cervix and inducing labor in women with an unfavorable cervix.\n One hundred fifty-five women admitted for induction of labor to St. John's Mercy Medical Center, a teaching community hospital, were randomized to one of two methods: intravaginal misoprostol, 50 microg every 4 hours up to three doses (n = 76); and intracervical dinoprostone gel, 0.5 mg every 6 hours up to three doses (n = 79).\n Misoprostol was more effective than dinoprostone in causing cervical ripening (P = .01), inducing labor (P < .001), shortening the duration of labor (P < .001), and decreasing the need for oxytocin augmentation (P < .001). Nonreassuring fetal heart monitoring patterns associated with hyperstimulation were significantly more frequent (P < .001), and the incidence of cesarean deliveries because of this indication was significantly higher (P = .002) in patients receiving misoprostol.\n Misoprostol is an effective agent for cervical ripening and labor induction, but it causes an increase in cesarean deliveries associated with uterine hyperstimulation.", "Our purpose was to perform a randomized trial comparing intravaginal misoprostol to intravaginal prostaglandin E2 gel for preinduction cervical ripening evaluating efficacy and side effects.\n Seventy-five women seen for induction of labor were randomized to receive 100 micrograms of intravaginal misoprostol or 5 mg of pharmacy-prepared intravaginal prostaglandin E2 gel for cervical ripening before oxytocin induction. Six hours after placement of the study agent, patients were given oxytocin if they were not in labor. The primary outcome measure was induction-to-delivery time; secondary measures were change in Bishop score, delivery mode, and side effects. Results were analyzed by the Student t test and Fisher's exact test, with p < 0.05 considered significant.\n There was no difference in the incidence of primiparity or the median initial Bishop score between the two study groups. The mean time to delivery and the need for oxytocin was significantly less for subjects receiving misoprostol. There was no difference in the incidence of uterine hyperstimulation syndrome or cesarean delivery between the groups.\n This randomized clinical trial indicates that misoprostol is efficacious for preinduction cervical ripening. Misoprostol use resulted in a significantly shorter induction-to-delivery time compared with prostaglandin E2 gel use. The side effects associated with misoprostol may be dose related, and further studies to identify the optimum dosage and interval are needed.", "The objective of this study was to compare the efficacy and safety of two dosing regimens of misoprostol for cervical ripening and labor induction.\n Patients who fulfilled the study criteria were randomized to received misoprostol 25 microg or 50 microg intravaginally every 3 h for a total of eight doses for cervical ripening or until labor was established. Endpoints for successful cervical ripening was achievement of Bishop score of nine or greater, and for labor induction reaching the active phase of labor in the first 24 h. The rates of success, duration of first and second stages of labor, type of delivery, significant side effects, and neonatal outcome were measured and compared between the two study groups. Two hundred and fifty-one patients were randomized in two groups--126 received 50 microg and 125 received 25 microg misoprostol. Demographics of the two study groups were similar.\n Patients in the 50 microg group had a shorter first stage (848 min vs. 1,122 min, P < 0.007), shorter induction-to-vaginal delivery interval (933 min vs. 1,194 min, P < 0.013), decreased incidence of oxytocin augmentation (53.9% vs. 68%, P < 0.015), and decreased total units of oxytocin (2,763 mU vs. 5,236 mU, P < 0.023), but there was a higher hyperstimulation rate (19% vs. 7.2%, P < 0.005).\n Successful induction rate, delivery types, and fetal outcome were similar in both groups. Although the rate of vaginal delivery and neonatal outcome were similar in both groups, the 50 microg regimen had shorter first and second stages of labor, and a higher hyperstimulation rate that was easily manageable, allowing for flexibility in using the higher dose in low-risk pregnancies.", "The efficacy of misoprostol (a PGE1 analog) for induction of labor at term was compared with oxytocin by means of an open and randomized study in 153 pregnant women. A vaginal tablet containing 50 mcg of misoprostol was placed intravaginally in 78 women, the remaining 75 patients received i.v. oxytocin (2-32 mU/min). Bishop's score at the entry of the trial was similar in both groups. Delivery within 24 hours was achieved in 85.7% of the patients induced with misoprostol and in 64% of the patients infused with oxytocin (p < 0.05). Mean induction to delivery interval was significantly shorter in the misoprostol group (552 +/- 211 min; mean =SD) in comparison with that of the oxytocin group (745 +/- 292 min; mean +/- SD) (p < 0.05). The probability of still being pregnant at 24 hours (Life table analysis) was 14% (misoprostol group) and 26% (oxitocyn group). The difference was also statistically significant (p < 0.01). No undesirable side effects were observed in any of the patients, however, polisystoly (> 5 contractions in 10 min) was more frequently observed in the patients induced with misoprostol (24.6% vs 13.3%; p = NS). Cesarean section rate was higher in the oxytocin-induced patients (25.3%) than in the misoprostol-induced women (3.8%) (p < 0.05). The main cause of cesarean section was failure to progress in labor in both groups of patients. Neonatal outcome was good in both groups and there were no differences with respect to birthweight or to Apgar scores.(ABSTRACT TRUNCATED AT 250 WORDS)", "A prospective randomised controlled trial was performed to compare the efficacy and safety of intravaginal misoprostol to that of intravaginal dinoprostone when used for cervical priming prior to the induction of labour; 126 women were recruited to the study and randomised to receive either intravaginal dinoprostone (n = 63) or misoprostol (n = 63) for cervical priming prior to induction of labour. The mean time from insertion of the priming agent to vaginal delivery was significantly shorter in the misoprostol group (925.8 versus 1577.6 minutes), the mean duration of the active length of labour was significantly shorter in the misoprostol group (353.7 versus 496.8 minutes) and more women in the misoprostol group delivered in less than 12 hours (92% versus 76.5%). Women in the misoprostol group were less likely to require a repeated dose of prostaglandin for cervical priming and less likely to require oxytocin for augmentation of labour. There was no difference in the number of women who were delivered vaginally or by Ceasarean section between the two groups. More women developed hyperstimulation during labour in the misoprostol group; however there was no difference between the groups in neonatal outcome in respect to low cord pH or Apgar score at delivery or admission to the neonatal special care nursery.", "nan", "The objectives of the study were to compare the efficacy and safety of intravaginal misoprostol and intravaginal dinoprostone for induction of labor and to quantify the clinical response to suspicious cardiotocographic (CTG) readings.\n One hundred and ninety-one patients were randomized to receive either 50 micro g misoprostol initially then a further identical dose 6 h later or 2 mg dinoprostone initially followed by 1 mg 6 h later, over a period of 24 h. If not in labor after 24 h, then both arms of the study would thereafter receive dinoprostone alone as per hospital protocol.\n The induction to delivery interval (1047 vs. 1355 min, p = 0.01), delivery within 12 h (35.4% vs. 18.9%, p = 0.02) and delivery within 24 h (83.3% vs. 63.3%, p = 0.01) were all shorter in the misoprostol arm. There were no differences in rates of oxytocin augmentation (p = 0.47), tachysystole (p = 0.32) and hyperstimulation syndrome (p = 0.82). There was an increase in the median number of times a doctor was called to advise on a suspicious CTG in the misoprostol group (1 vs. 2 occasions, p = 0.052), but there was no difference in neonatal outcome.\n Intravaginal misoprostol led to a shorter, more efficient labor, and although there was more anxiety related to the CTG, there was no increase in neonatal adverse effects.", "Objective: To compare the relative cost efficacy of three commercially available prostaglandin analogues, misoprostol (Cytotec(R), PGE(1)), dinoprostone gel (Prepidil(R), PGE(2)), and dinoprostone pessary (Cervidil(R), PGE(2)), as labor preinduction agents.Methods: The investigation was conducted as a prospective randomized, blinded phase III clinical trial. One hundred twelve gravid females undergoing induction of labor with an unfavorable cervix (Bishop score </=5) were enrolled and randomized to receive either Cytotec(R) 50 µg q6 hours x 2 doses, Prepidil(R) 0.5 mg q6 hours x 2 doses, or Cervidil(R) 10 mg x 1 intravaginally. Twelve hours after initial treatment, cervical Bishop score was reassigned by the same blinded initial examiner and oxytocin induction initiated per standardized protocol. Therapeutic efficacy and cost of the labor preinduction/induction with the study treatments were compared. Statistical comparisons between groups were made using ANOVA with Bonferroni post test, Wilcoxon rank sum test, and chi(2) test.Results: The three study groups did not differ significantly with respect to parity, gestational age, indication for induction, or initial cervical Bishop score. A significantly greater proportion of patients had a favorable cervix (Bishop score >/=6) after the initial preinduction interval in the Cytotec(R) (79.0%) and Cervidil(R) groups (60.5%) as compared to Prepidil(R) (40.0%) (P <.05). The average relative cost per patient for prostaglandin preinduction was significantly less with Cytotec(R) ($0.42) as compared to both Cervidil(R) ($168.00) and Prepidil(R) ($184.17) (P <.0001). A greater percentage of patients treated with Cytotec(R) (42.1%) achieved active labor and delivered without the use of oxytocin when compared to Cervidil(R) (15.8%) or Prepidil(R) treatment groups (2.9%) (P <.05). Additionally, time to delivery (+/-SD) was significantly shorter in the Cytotec(R) group (24.0 +/- 10.8 h) as compared to the Cervidil(R) (32.2 +/- 14.7 h) or Prepidil(R) groups (33.9 +/- 16.2 h) (P <.05). This reduction in time resulted in a significantly lower overall mean cost per patient incurred by labor induction in the Cytotec(R) group ($723.66) as compared to the Cervidil(R) ($1058.90) or Prepidil(R) treatment ($1124.84) (P <.01). No significant differences were noted with respect to rate of cesarean delivery.Conclusion: Misoprostol is more cost-effective than the comparable commercial dinoprostone prostaglandin preparations as an adjuvant to labor induction in patients with an unfavorable cervix.", "A randomised prospective trial was carried out to compare the efficacy and safety of intravaginal Misoprostol with intracervical dinoprostone gel for induction of labour in cases of unfavourable cervix. One hundred women with an unfavourable cervix requiring induction of labour were randomised to receive either 25 microm vaginal Misoprostol 4-hourly or 0.5 mg of intracervical dinoprostone 12 hourly. The outcome measured was change in Bishop's score, percentage of women going into labour, induction to delivery interval, need for oxytocin, mode of delivery and complications. The parity, mean period of gestation and Bishop's score were similar in both the groups. The improvement in Bishop's score at 12 h was significantly better in the Misoprostol group. Induction to delivery interval was shorter in the Misoprostol group, 16.59 +/- 5.13 h vs 27.77 +/- 12.71 h. The rate of complications was comparable. Vaginal Misoprostol 25 microg 4-hourly is safe and effective for induction of labour with shorter induction to delivery interval.", "Multiparous patients have a higher risk of hyperstimulation and uterine rupture than nulliparous patients. The minimum possible dose of uterotonic drug should be used in induction of labor for multiparous patients to avoid excessive uterine activity, which could increase both maternal and fetal risks.\n One hundred and four women were randomized to either a single dose of 50 micro g of intravaginal misoprostol in 24 h, or two consecutive doses of intravaginal 50 micro g misoprostol 6 h apart.\n The mean induction to delivery interval (789 min [95% CI: 637-941] vs. 576 min [95% CI: 484-667], p = 0.018) and delivery rate within 12 h (63% vs. 83%, p = 0.035) were higher in the two-dose group. The oxytocin augmentation rate (14% vs. 2%, p = 0.03) was higher in the single-dose group. There was a higher rate of clinician input related to suspicious cardiotocographic readings in the single-dose arm (p = 0.04). There was no statistical difference (p > 0.05) between the one- and two-dose regimens with respect to the rates of tachysystole (21% vs. 15%), hyperstimulation (3.9% vs. 0%), and meconium staining at delivery (9.8% vs. 13.2%).\n The two-dose regimen was most efficient, but both regimens were well tolerated by the fetuses.", "To compare the efficacy of intracervical versus intravaginal misoprostol for cervical ripening and labour induction at term in patients with an unfavourable cervix.\n A total of 100 pregnant women with indications for induction of labour and unfavourable cervix (Bishop score < or = 4) were randomly assigned to receive either 100 ug misoprostol administered intracervically (50 cases) or intravaginally (50 cases).\n No significant differences were noted between intracervical and intravaginal misoprostol in terms of Bishop score change, (score 7.2 vs score 7.5), interval from gel insertion to vaginal delivery (17.0 hours vs 16.4 hours), meperidine as analgesic requirement (80% vs 76%), route of delivery and perinatal outcome. Uterine tachysystole occurred in 24 per cent and 32 per cent in the intracervical and intravaginal groups respectively which did not significantly differ, however, all could be rapidly resolved by terbutaline injection. No evidence of fetal distress was noted in these events. Spillage of gel out of the cervix was observed in 70 per cent of patients receiving intracervical misoprostol. Fever was observed in one patient of each group. No other serious side effects were found in both groups. One patient in the intravaginal group had postpartum hemorrhage due to delayed placental separation and uterine atony.\n The two routes of misoprostol gel application appear to be safe and equally effective in ripening cervix and inducing labour, however, the intravaginal application is more convenient to administer practically compared with the intracervical.", "To evaluate the efficacy of intravaginal prostaglandin E1 methyl analogue misoprostol in cervical ripening in patients with unfavorable cervix (Bishop score < 4) requiring labor induction.\n A randomized controlled clinical trial of 62 women in the third trimester with various indications for induction of labor were randomly allocated to receive either 100 micrograms misoprostol inserted vaginally (32) or placebo similarly applied (30). Transvaginal sonography was performed to measure the cervical length before and 12 hrs after insertion.\n The mean change in cervical length and Bishop score was significantly greater in the misoprostol group (24 mm and score 8) compared with in the placebo group (2.2 mm and score 1) (p = 0.001). All but one patients receiving misoprostol went into labor while only one in the placebo group did so. The interval from insertion to vaginal delivery was significantly shorter in the misoprostol group (12.0 vs 25.5 hrs, p < 0.001). Delivery occurred within 24 hrs in 75% and 30% of patients in the misoprostol and placebo groups respectively. Uterine tachsystole occurred more frequently in the misoprostol group (38%) than in the placebo group (0%) (p < 0.001). All could be rapidly reversed by tocolytics without apparent untoward intrapartum effects. No significant differences were noted in the 2 groups in terms of perinatal outcomes and mode of delivery.\n Intravaginal misoprostol is an effective, cheap and safe method for cervical ripening. The higher frequency of uterine tachysystole in the misoprostol group did not increase the risk of adverse intrapartum and neonatal outcomes.", "To compare the efficacy for Dinoprostone, intracervical foleys and misoprostol in labor trial regarding effects on cervical ripening, mode of delivery, induction to delivery interval and maternal complications i.e. tachysystole and postpartum haemorrhage.\n Randomized clinical trial. Place and Duration of Study: Hamdard University Hospital and Patel Hospital between July 2004-June 2005.\n Randomized trial was conducted such that group-A received Dinoprostone at 6 hourly intervals upto two doses. Group-B was induced with intracervical foley catheter. Group-C received 50 micro g oral misoprostol 4 hourly to a maximum of four doses. Cervical ripening, induction to delivery time interval, mode of delivery and maternal morbidity were main outcome measures. Test of proportions was used to compare the significance between the managements.\n In 226 cases, 219 (97%) were successfully induced while 7(3%) did not respond the labour induction. The rates of caesarean section in dinoprostone, intracervical foley and misoprostol were 14.7%, 14.1% and 12.3%, respectively, however, this difference was insignificant among three groups (p=0.911). Rate of earlier response (< or = 12 hours) to labor induction among three groups was insignificant (3.8% vs 4% and 13.7% respectively, p=0.125). Marginal significance of higher rate of complications was observed in those patients who were given misoprostol (p=0.08).\n In this series, all three agents were equally effective in terms of cervical ripening, induction-delivery interval, mode of delivery and maternal complications.", "To compare the efficacy of a vaginal insert administering continuous dinoprostone with vaginal suppositories containing two different doses of misoprostol for cervical ripening and induction of labor.\n In this prospective, randomized, double-blinded study, 118 patients with indications for induction of labor and an unfavorable Bishop score were randomly assigned to receive either continuous dinoprostone, misoprostol 35-microg suppositories, or misoprostol 50-microg suppositories.\n No significant differences were noted among the three groups in the change of Bishop score, induction of active labor or the time from initial treatment to delivery. Active labor occurred in roughly two-thirds of the patients in an average of about 5.7-6.7 h regardless of treatment assignment. When the two misoprostol groups were combined, a shorter interval from insertion to vaginal delivery was observed in the nulliparous women receiving misoprostol than those receiving continuous dinoprostone (21.3 vs. 27.2 h, p = 0.019). Except for the significantly lower incidence of tachysystole observed in the combined misoprostol group (3.8% vs. 15.4%, p = 0.036), there were no other significant differences between the groups in mode of delivery or in adverse maternal, fetal, or neonatal effects.\n Misoprostol suppositories appeared to be as effective and safe as continuous dinoprostone in inducing cervical ripening in this sample.", "To compare the efficacy and complications of intravaginal misoprostol application with oxytocin infusion for induction of labor in toxemia of pregnancy with a modified Bishop score of < or =4.\n A hundred preeclamptic women with a modified Bishop score of < or =4 were randomized into two groups of 50 patients one group receiving 50 microg intravaginal misoprostol 4 times at 4 hour intervals, the second group receiving oxytocin infusion for induction of labor starting from 1 mIU/per minute, increasing it every 30 minutes with 2 mIU/per minute increments up to maximum of 30 mIU/per minute. Modified Bishop scores 12 hours after induction, the time from induction to delivery, the route of delivery, fetal outcome and maternal complications were recorded. Statistical analyses were performed using Mann Whitney-U, Chi-Square and hypothesis tests about differences for two proportions (t test) to determine differences between the two groups. p< or =0.05 was considered significant.\n Misoprostol was significantly superior for induction of labor in toxemia of pregnancy with modified Bishop score of < or =4. After 12 hours median modified Bishop scores of misoprostol administered group and oxytocin administered group were 7 and 4 respectively. Misoprostol administered group 1 was significantly better than oxytocin administered group 2 (p=0.027). The rate of patients who were in labor after 12 hours were 94% and 80% in group 1 and 2 respectively and the difference showed significant difference (p<0.05). The median time from induction to delivery was 14 hours and 16 hours in the misoprostol and oxytocin administered group respectively with significant difference between the groups (p=0.003). The rate of vaginal delivery was significantly higher in the misoprostol administered group 1 (82%) when compared with the oxytocin administered group 2 (66%) (p<0.05). The 1 and 5 minutes median Apgar scores were 5-7 and 6-7.5 in group 1 and 2, respectively with no significant differences between the groups (p=0.96, p=0.64). The rate of admission to neonatal intensive care unit was similar in both groups. The complication rates were similar in all groups and no significant detrimental effects were noted.\n Intravaginal misoprostol is an efficacious, cheap and safe method of induction of labor in toxemia of pregnancy with modified Bishop score of < or =4.", "nan", "A prospective study was carried out at a tertiary care hospital on 100 pregnant women admitted for induction of labour to compare the effect of misoprostol and dinoprostone on the induction of labour. The patients were divided randomly into two groups of 50 each. Group I received 25 microg misoprostol intravaginally every 3 h (maximum dose 200 microg), and Group II received 0.5 mg PGE(2) gel (dinoprostonev) intracervically every 6 h (maximum three doses in 24 h) until good uterine contractions started. The primary outcome measure was vaginal delivery occurring within 24 h of administration of the first dose of either study drug (successful induction). Statistical analysis were conducted using chi(2) test, Fisher exact test, Student's t-test and relative risk (RR) with 95% confidence interval (CI). In the misoprostol group, more patients achieved successful inductions as compared with the dinoprostone group, 80% vs. 62% (P = 0.0473, RR 1.63, 95% CI 0.95-2.81). The mean induction to delivery interval (IDI) was shorter in the misoprostol group, 13.30+/-8.74 (3-40.15) hours, as compared with the dinoprostone group, 18.53+/-11.33 (2-48.07) hours (P = 0.011). Misoprostol was associated with significantly less oxytocin use (18% vs. 50%) as compared with dinoprostone (P = 0.001 RR 0.36, 95% CI 0.19-0.69). In conclusion, although both misoprostol and dinoprostone appear to be effective agents for labour induction, misoprostol is cheaper, stable at room temperature, has shorter IDI and requires less oxytocin. These results make misoprostol superior to dinoprostone for induction of labour especially in developing and tropical countries.", "To compare the efficacy and safety of one single dose of 50 pg misoprostol to one single dose of 3 mg dinoprostone administered vaginally for pre-induction cervical ripening in term-pregnant women, who had indications for induction of labor with unripe cervices.\n A randomized double-blind controlled trial.\n Bangkok Metropolitan Administration Medical College and Vajira Hospital, Bangkok, Thailand.\n One hundred and forty-three singleton pregnant women of > or = 37 weeks of gestation, who had indications for termination of pregnancy. All patients had a Bishop score of 0-6, without contraindications for labor induction.\n The subjects were stratified by parity to nullipara and multipara group. The subjects in each stratum were allocated by randomization to receive a single dose of 50 microg misoprostol or 3 mg dinoprostone, administered vaginally. Twenty-four hours after medication, oxytocin augmentation was given to both groups. Main outcome measure: The Bishop score of cervix at 24 hours after insertion of the studied drugs, the occurrence of abnormal uterine contraction, and the number of vaginal deliveries within 24, 48 hours.\n The demographic data and the initial Bishop score (median score 3.5 versus 4.0) were comparable in both groups. The change of score at 24 hours was one unit higher in misoprostol-treated patients compared with dinoprostone-treated patients (mean change score 6.5 versus 5.5, with 95 per cent CI 0.04 to 2.1, p=0.042) but was not of clinical importance. There was a higher frequency of hyperstimulation syndrome in the misoprostol group (6.9% vs 0%) during 8 hours of cervical ripening. Although the difference was not statistically significant (p=0.058), it was clinically important. Comparing vaginal deliveries between the misoprostol and dinoprostone groups, the frequencies of delivery within 24 hours were 46.3 per cent versus 35.7 per cent (p=0.350), and within 48 hours were 88.9 per cent versus 89.3 per cent (p>0.05), non-significantly different. No significant differences were noted between misoprostol and dinoprostone in terms of interval from start of medication to vaginal delivery and neonatal outcomes.\n The efficacy of a single 50 microg dose of vaginally administered misoprostol, is not clinically different to 3 mg dinoprostone in cervical ripening. Although the study was not sufficiently large to detect the differences in abnormal uterine contractions between the two groups, there was a higher frequency of hyperstimulation syndrome in the misoprostol group compared to the dinoprostone group. Close utero-fetal monitoring in misoprostol-treated patients is needed.", "Our purpose was to compare vaginally administered misoprostol (Cytotec) with intravenous oxytocin for labor induction in women with premature rupture of membranes beyond 36 weeks' gestation.\n Two hundred subjects with rupture of membranes without labor were randomly assigned to receive vaginally administered misoprostol or intravenous oxytocin. Twenty-five micrograms of misoprostol (Cytotec) was placed in the posterior vaginal fornix. If cervical ripening (Bishop score of > or = 8 or cervical dilatation of > or = 3 cm) or active labor did not occur, a single repeat dose of misoprostol was given 6 hours later. Oxytocin was administered intravenously by a standardized incremental infusion protocol to a maximum dose of 22 mU per minute.\n Of the 197 subjects evaluated, 98 received misoprostol and 99 oxytocin. The average interval from start of induction to vaginal delivery was about 1 hour longer in the misoprostol group (811.5 +/- 511.4 minutes) than in the oxytocin group (747.0 +/- 448.0 minutes) (P = .65, log transformed data). Oxytocin administration was necessary in 37 of 98 (37.8%) of misoprostol-treated subjects. Vaginal delivery occurred in 85 misoprostol-treated subjects (86.7%) and 82 (85.9%) oxytocin-treated subjects (relative risk 1.17, 95% confidence interval 0.78 to 1.78, P = .45) with the remainder undergoing cesarean birth. There was no difference in the incidence of tachysystole (six or more uterine contractions in a 10-minute window for two consecutive 10-minute periods) or hypertonus between the two groups. There was no significant difference in frequency of abnormal fetal heart rate tracings between the two groups (29.6% in the misoprostol group and 28.9% in the oxytocin group, P = .91). Chorioamnionitis was diagnosed in 28 (28.6%) misoprostol-treated subjects and 26 (26.3%) oxytocin-treated subjects (P = .72, relative risk 1.06, 95% confidence interval 0.78 to 1.45). No significant differences were found in the incidence of fetal meconium (8.1% and 9.1%), 1- or 5-minute Apgar scores < 7 (11.0% and 10.2% of 1-minute Apgar scores, and 2.0% and 2.0% of 5-minute Apgar scores), neonatal resuscitation (24.5% and 27.6%), or admission to the neonatal intensive care unit (25.5% and 32.3%) between the two groups.\n Vaginal administration of misoprostol (Cytotec) is an effective alternative to oxytocin infusion for labor induction in women with premature rupture of the membranes near term. The incidence of untoward effects is similar with use of the two agents.", "The purpose of this study was to compare the safety and efficacy of misoprostol and dinoprostone in pregnancies at high risk of fetal distress.\n Medical indications for the induction of labor with postdate pregnancy or intrauterine growth restriction were randomized. A sequential design that was based on the triangular test was used.\n At the fourth interim analysis, which included 140 patients, the trial was stopped because no significant difference was found in neonatal safety between misoprostol and dinoprostone, which was assessed on arterial cord pH <7.20 (14.3% vs 10.0%, respectively; P=.60). Neonatal tolerance was similar in the 2 groups, with no difference in the cesarean delivery rate for fetal distress or in the incidence of meconium-stained amniotic fluid. Time to vaginal delivery was shortened by misoprostol (P=.03).\n Misoprostol and dinoprostone are equally safe for the induction of labor in pregnancies that are at high risk of fetal distress; however, misoprostol allowed the earlier induction of labor than did dinoprostone.", "To evaluate the effectiveness and safety of the vaginal application of misoprostol for induction of labor at term, with the interval duration from labor induction to vaginal birth as the primary outcome measure.\n Two hundred twenty-two women with indications for induction of labor at term were randomized to receive either misoprostol 50 micrograms per vagina every 4 hours as needed or our standard approach (physician-chosen combinations of intracervical or vaginal dinoprostone every 6 hours, artificial rupture of membranes, and oxytocin infusion).\n Mean (+/-standard deviation) time to vaginal delivery was 753 +/- 588 minutes for misoprostol versus 941 +/- 506 minutes for the physician-chosen combination (P = .018). Oxytocin infusion was used less frequently (relative risk [RR] 0.48, 95% confidence interval [CI] 0.31-0.74). There was no significant difference in cesarean rate or maternal morbidity. Neonatal outcomes, including cord-blood acid-base analysis, were not significantly different. The estimated cost per patient in Canadian dollars for prostaglandins was $0.22 with misoprostol and $70.00 with standard therapy.\n Vaginal misoprostol is a cost-effective alternative to current labor-induction protocols. We found no evidence of harm to mother or newborn in substantive outcomes.", "To compare the efficacy and safety of vaginal misoprostol (50 microg) with vaginal dinoprostone.\n Double-blind randomised trial.\n Obstetrics Department, Poissy Hospital, France.\n 370 patients with medical indications for induction of labour.\n Vaginal deliveries within 24 hours, as well as time to vaginal deliveries, caesarean rates, costs, and fetal, neonatal and maternal condition.\n Compared with vaginal dinoprostone, vaginal misoprostol resulted in greater efficacy in several areas: vaginal delivery within 24 hours; time to vaginal delivery; and vaginal delivery within 12 hours. There was a non-significant increase in the caesarean section rate for fetal distress in the misoprostol group, but fewer caesarean sections for failed induction. Fetal tolerance was similar in the two groups, although significantly more neonates had a cord pH <7.20 and (non-significantly) none had meconium stained amniotic fluid in the misoprostol group. The incidence of poor neonatal outcome was similar in both groups. Subgroup analysis by indication for induction showed that the higher rates of arterial cord pH <7.20 and of meconium-stained amniotic fluid with misoprostol persisted only in possible fetal compromise. Poor neonatal outcome was less frequent in the misoprostol group in cases of induction for non-fetal indications.\n Vaginal misoprostol resulted in successful and earlier induction of labour more often than dinoprostone, but the safety of misoprostol raises some concern in potentially compromised infants. Misoprostol should be preferred to dinoprostone in cases of induction for non-fetal indications.", "To compare the effectiveness of vaginally administered misoprostol with extra-amniotic prostaglandin F2alpha (PGF2alpha) gel for induction of labor.\n A randomized controlled trial, with women allocated to receive either misoprostol 50 microg intra-vaginally or extra-amniotic PGF2alpha gel 5 mg, was conducted in Harare Maternity Hospital. A total of 152 women were admitted for induction of labor with a term singleton, pregnancy and cephalic presentation were recruited. The main outcome was duration of induction.\n There were no differences in the characteristics of women in the two groups at recruitment. In the misoprostol group there was a significantly reduced need for augmentation of labor with oxytocin (OR=0.36; 95% C.I. 0.17-0.73) and delivery by cesarean section for failure to progress (OR=0.11; 95% C.I. 0.00-0.88). The risk for duration of induction to vaginal delivery exceeding 12, 18 or 24 h was reduced by 18%, 38% and 68%, respectively, but only the risk for duration >24 h was significantly reduced (OR=0.32; 95%C.I. 0.11-0.91). The mean duration of induction was shorter in the misoprostol group, 15.2 vs. 23.6 h (P=0.02). There were no differences in fetal outcome.\n Misoprostol 50 microg was associated with less use of oxytocin in labor, a shorter induction to delivery interval and fewer cesarean sections for failure to progress when compared with extra-amniotic PGF2alpha gel.", "Our purpose was to compare the safety and efficacy of intravaginal prostaglandin E1, misoprostol, with that of intracervical prostaglandin E2 (Prepidil gel) for labor induction.\n One hundred three patients with an indication for induction of labor were randomly assigned to induction with prostaglandin E1, 50 micrograms intravaginally, or with Prepidil gel, 0.5 mg intracervically, every 4 hours until active labor.\n Four patients were excluded, leaving 49 patients who received prostaglandin E1 and 50 who received prostaglandin E2. The time from start of induction to vaginal delivery was significantly shorter in the prostaglandin E1 group (11.4 vs 18.9 hours, p < 0.001), and fewer patients in the prostaglandin E1 group required oxytocin augmentation (23% vs 55%, p < 0.005). No significant differences were noted in mode of delivery or in adverse maternal, fetal, or neonatal effects.\n Intravaginal prostaglandin E1 is a more effective, lower-cost agent for induction of labor than is intracervical prostaglandin E2 gel and is comparable in safety.", "To evaluate the efficacy of oral and vaginal misoprostol compared with the standard regimen using dinoprostone for induction of labor.\n We conducted a multicenter, randomized controlled trial in Cape Town, South Africa. A total of 573 women admitted for induction of labor were randomized to receive oral misoprostol, vaginal misoprostol, or the control, dinoprostone. Misoprostol was given orally or vaginally as a 50-microg dose at 6-hour intervals to a maximum of four doses. The dinoprostone gel was given as a 1-mg dose in the posterior fornix every 6 hours (maximum two doses).\n There was no significant difference in vaginal delivery rate in 24 hours between the vaginal misoprostol and dinoprostone groups. However, significantly fewer women delivered vaginally in the oral misoprostol group compared with those in the dinoprostone group (relative risk 0.71, 99% confidence interval 0.51, 0.99). The median induction to vaginal delivery time in the vaginal misoprostol, oral misoprostol, and dinoprostone groups was 12 hours, 23 hours, and 14 hours, respectively. The cesarean rate was approximately 33% in all the groups. There were more cesareans performed for fetal distress in the vaginal misoprostol group compared with the dinoprostone group (relative risk 2.86, 99% confidence interval 1.49, 5.46). There was a higher incidence of tachysystole in the vaginal misoprostol group (5.8%) compared with the other two groups: oral misoprostol (0.8%) and dinoprostone (0.8%), but this difference was not statistically significant. There were no differences in maternal or fetal complications.\n Vaginal misoprostol is as effective as dinoprostone in induction of labor, but it is associated with more tachysystole and cesarean sections for fetal distress compared with dinoprostone. Oral misoprostol results in fewer vaginal deliveries in 24 hours, but it is not associated with increased tachysystole or fetal distress.", "We sought to evaluate the efficacy and safety of intravaginal misoprostol and dinoprostone for labor induction.\n One hundred eighty-nine women with singleton term pregnancies and unfavorable cervices were randomly assigned to receive intravaginal misoprostol or dinoprostone. The outcome variables were change in Bishop score, time from application to active phase of labor and delivery, fetal and maternal morbidity, and the incidence of cesarean deliveries.\n The interval from application of the initial dose to the beginning of the active phase of labor was 9.8 +/- 5.8 and 14.2 +/- 10.2 hours (P <.01), and the interval from initial dose to delivery was 15.3 +/- 9.8 and 19.1 +/- 13.2 hours (P =.027) for the misoprostol and dinoprostone groups, respectively. There were no significant differences in Bishop score change, cesarean delivery rate, and the incidence of tachysystole, hypersystole, and hyperstimulation. No maternal and neonatal adverse effects were noted.\n Intravaginal misoprostol is more effective than intravaginal dinoprostone for labor induction in low-risk patients at term with unfavorable cervices.", "Our purpose was to compare two dosing regimens of vaginally administered misoprostol for preinduction cervical ripening and induction of labor.\n Five hundred twenty-two patients with indications for induction of labor and unfavorable cervices were randomly assigned to one of two dosing regimens of vaginally administered misoprostol. Twenty-five microgram tablets of misoprostol were placed in the posterior vaginal fornix either every 3 hours to a maximum of eight doses or every 6 hours to a maximum of four doses. The maximal period of cervical ripening was 24 hours regardless of the number of misoprostol doses administered. Medication was not given after either spontaneous rupture of membranes or the beginning of active labor.\n Among 522 patients enrolled, 261 were randomized to receive misoprostol every 3 hours and 261 to receive misoprostol every 6 hours. The average interval from start of induction to vaginal delivery was shorter in the 3-hour dosing group (1311.74 +/- 785.14 minutes) than in the 6-hour dosing group (1476.96 +/- 805.30 minutes) (p < 0.05). Oxytocin augmentation of labor occurred more commonly in the 6-hour dosing group (51.4%) than in the 3-hour dosing group (41.8%) (p < 0.05) [corrected]. There were no significant differences between routes of delivery. Overall, 108 patients (20.8%) were delivered by cesarean section. There was a slightly higher prevalence of tachysystole (six or more uterine contractions in a 10-minute window for two consecutive 10-minute periods) in the 3-hour group (14.6%) than in the 6-hour group (11.2%), but this difference was not statistically different. There were no significant differences in the frequency of uterine hyperstimulation or hypertonus. There was no significant difference between groups in the frequency of abnormal fetal heart rate tracings, meconium passage, 1- or 5-minute Apgar scores < 7, neonatal resuscitations, or admissions to the neonatal intensive care unit.\n Vaginally administered misoprostol is an effective agent for cervical ripening and induction of labor. Patients with the 6-hour dosing schedule had longer intervals to delivery, more frequently required oxytocin augmentation, and had more failed inductions than did patients with 3-hour dosing. Further investigation to characterize the safety of misoprostol is needed.", "Misoprostol, a synthetic E1 methyl analog prostaglandin, is at present receiving attention as a cervical modifier and labor induction agent. However, there is still a need for better determination of its safety and effectiveness.\n To compare intravaginal misoprostol versus intravenous oxytocin for cervical ripening and labor induction in pregnant women with unripe cervices.\n Randomized controlled trial.\n The study was performed at the Leonor Mendes de Barros Maternity Hospital between November 1998 and December 2000.\n 210 pregnant women with intact membranes and indication for labor induction were selected.\n The women randomly received 25 g of vaginal misoprostol every 4 hours, not exceeding 8 doses (105 women), or oxytocin in a continuous infusion (105 women).\n The main parameters measured were: latent period, time from induction to vaginal delivery, delivery route, occurrence of vaginal delivery with time, occurrence of uterine tonus alterations, hypoxia and neonatal morbidity. To verify the statistical significance of the differences between the groups, the chi-squared, Student t and log-rank tests were used.\n There were no significant differences between the groups concerning conditions for labor induction, age, parity, race, marital status, family income, initial Bishop Index and number of prenatal visits. The cesarean section rate, latent period and period from induction to vaginal delivery were significantly lower for the misoprostol group. With regard to uterine tonus alterations, tachysystole was significantly more common in the misoprostol group. However, there was no difference in hypoxia and neonatal morbidity between the groups.\n 25 g of misoprostol used vaginally every 4 hours is safer and more efficient for cervical ripening and labor induction than oxytocin.", "To compare the safety and efficacy of intravaginal misoprostol gel with that of tablets for ripening the cervix and inducing labor in women with unfavorable cervices.\n Four hundred sixty-seven gravidas were randomized to receive misoprostol tablets (n = 234) or misoprostol gel (n = 233). The gel was prepared in the antepartum unit immediately before use by dissolving the tablet in 1 mL normal saline and mixing with 4 mL hydroxyethylcellulose gel. In both groups, a 50-microgram dose was applied intravaginally every 8 hours for two doses, then increased to 100-microgram for a total of six applications or 500 micrograms.\n The mean interval in hours from drug administration to start induction or labor (13.8 versus 18.2) and delivery (22.4 versus 29.0) was significantly less in the tablet group than in the gel group (P < .01 for both). Oxytocin and epidural use and the mean number of misoprostol insertions (1.4 versus 1.9) were lower in the tablet group than in the gel group (P < .05 for all). The incidences of tachysystole (13.7 versus 7.3%) and hyperstimulation (15.8 versus 7.7%) were significantly higher in the tablet group than in the gel group. Cesarean delivery rates and neonatal outcomes were similar between the groups.\n Intravaginal misoprostol gel is associated with fewer uterine contractile abnormalities than the tablet form of the drug but results in a slower time to labor or delivery.", "To estimate the effect of outpatient administration of a single dose of vaginal misoprostol at term on the interval to delivery in women with unfavorable cervices.\n Randomized, double blind, placebo-controlled trial comparing a single 25-microg outpatient intravaginal dose of misoprostol to placebo in pregnant women with Bishop scores less than 9 at 40 weeks or greater. After placement of the study medication, subjects were permitted to go into spontaneous labor unless an indication for induction developed. Analysis was by intent to treat. The interval to delivery, defined as the time from medication placement to delivery, was compared by Student t test and by survival analysis with the log-rank test.\n Thirty-three women were randomly assigned to receive misoprostol, and 35 were assigned to receive placebo. The mean interval to delivery was significantly less in the misoprostol group, 4.2 +/- 4.1 compared with 6.1 +/- 3.6 days, P =.04. The interval to delivery for only the nulliparous patients was significantly less in the misoprostol group, 4.2 +/- 4.0 compared with 7.2 +/- 3.7 days, P =.02. The survival curves for the interval to delivery were significantly different (P =.04 by log-rank test) with 4.1 days median interval to delivery for misoprostol compared with 9.2 days for placebo. There were no adverse outcomes in either group.\n A single 25-microg outpatient intravaginal dose of misoprostol is effective in decreasing the interval to delivery in women with unfavorable cervices at term.", "To compare the efficacy of low dose vaginal misoprostol and dinoprostone vaginal gel for induction of labour at term.\n A single-blind randomised controlled trial.\n Antenatal and labour ward of a UK district general hospital.\n Two hundred and sixty-eight women requiring induction of labour at term (>37 weeks of gestation) with no significant fetal or medical condition, no previous uterine surgery and no contraindication to prostaglandin.\n Misoprostol 25 microg (one-quarter of a 100 microg tablet) was inserted into the posterior vaginal fornix every 4 hours (to a maximum of six doses) or dinoprostone vaginal gel 1-2 mg 6 hourly (maximum of 3 mg in 24 hours).\n Induction-to-vaginal delivery interval.\n Requirements for oxytocin, mode of delivery, number of women delivering < 24 hours, incidence of uterine contraction abnormalities, incidence of abnormal cardiotocograph (CTG) recordings, 5-minute Apgar scores, umbilical cord pH recordings, analgesia requirements, admission to NICU and blood loss at delivery.\n There were no significant differences between the two groups in induction-to-vaginal delivery interval, mode of delivery, number of women delivering within 24 hours and neonatal outcomes. The incidence of uterine contraction abnormalities (tachysystole and hyperstimulation) and the incidence of abnormal CTG recordings were also similar for both groups.\n Low dose vaginal misoprostol is as effective as dinoprostone gel for inducing labour at term. There would be substantial cost savings, estimated at around 3.9 million UK pounds per annum, for maternity services if low dose misoprostol became the agent of choice for inducing labour in the UK.", "The objective of this investigation was to compare the efficacy, safety, and cost of intravaginal misoprostol as a labor induction agent to a standard protocol using prostaglandin E2 (Prepidil) and intravenous oxytocin. Thirty-eight patients requiring induction of labor with an unfavorable cervix (Bishop score < or = 5) were prospectively randomized to receive either 50 mcg misoprostol every 4 hours until delivery, or a single dose of PGE2 gel (0.5 mg) followed by intravenous oxytocin infusion. Changes in Bishop scores were recorded in a blinded fashion. Clinical outcomes were compared in the two groups, including induction-to-delivery times and cesarean section rates. Seventeen women were treated with misoprostol, 19 patients received PGE2/oxytocin, and two patients dropped out of the study. The groups did not differ significantly with respect to age, parity, gestational age, weight, height, reason for induction, or initial Bishop score. There was a significant difference in the median change of the Bishop score among those treated with misoprostol (4) and those of the control group (1) (P < 0.001). Fifteen (88%) receiving misoprostol delivered within 36 hours compared with 9 (47%) of controls (P = 0.01). Significantly more women in the misoprostol arm (8) experienced tachysystole when compared with the control group (0) (P < 0.01). There were no perinatal morbidities in either group. These data support misoprostol as an effective and economical cervical-ripening and labor-inducing agent.", "Interventions that may help shorten the duration of pregnancy in an African setting where facilities for fetal monitoring in post-term pregnancy are limited, and induction is not without its hazards, are needed.\n To determine whether outpatient administration of intravaginal misoprostol safely decreases the interval to delivery in postdate pregnancies.\n Open randomized controlled trial.\n Zonal district hospitals, Kwale, Southern Nigeria (August 2000 to October 2001).\n Seventy-seven women were randomized at 40 weeks gestation to receive either 25 microg misoprostol intravaginally (38) or gentle cervical assessment only (39) on an outpatient basis. Subjects were then allowed to go into spontaneous labor unless an indication for induction developed.\n Interval to delivery, duration of labor, and incidence of side-effects.\n Misoprostol was associated with significant decrease in mean time to delivery (4.5 +/- 4.1 versus 7.4 +/- 5.2 days; P = 0.008), earlier gestational age at delivery (40.6 +/- 0.6 versus 41.4 +/- 0.05 weeks; P < 0.001) and shorter duration of active labor (6.1 +/- 4.0 versus 8.2 +/- 5.3 h; P = 0.028), without any significant increase in fetal distress, low Apgar score at delivery or other side-effects.\n Outpatient administration of low-dose misoprostol can safely shorten the length of gestation in postdate pregnancies.", "To determine if outpatient cervical ripening using misoprostol can initiate labor within 48 hours of medication administration and to determine if time from medication administration to time of delivery is decreased using outpatient cervical ripening.\n Uncomplicated singleton, vertex pregnancies at 41 weeks' gestation or later with Bishop score of 4 or less were eligible for enrollment. Other inclusion criteria included intact membranes, less than eight uterine contractions per hour, a reactive nonstress test, and amniotic fluid index (AFI) over 5 cm. After randomization, 25 micro(cg) of misoprostol or placebo was placed within the posterior vaginal fornix. Patients were continuously monitored for 4 hours, then discharged if not in active labor. Patients returned in 24 hours for a repeat administration of the respective medication. Patients not delivered within 48 hours were admitted for inpatient induction of labor. Statistical analysis was performed with the Fisher, Student t, chi(2), and Mann-Whitney U tests, with P <.05 considered statistically significant.\n Among the 60 patients enrolled, 27 (45%) received misoprostol and 33 (55%) received placebo. The majority (24 of 27, 88.9%) of study group patients entered active labor within 48 hours after dosing, compared with 16.7% (five of 33) of placebo group patients (P <.001). The time from initial dose to delivery was significantly shorter in the misoprostol group (36.9 +/- 3.8 compared with 61.3 +/- 3.8 hours, P <.001).\n Intravaginal misoprostol is effective for outpatient cervical ripening. No adverse effects were encountered, although further study is required to determine the safety of this treatment regimen.", "To compare the effectiveness of 25 microg vs. 50 microg of intravaginal misoprostol for cervical ripening and labor induction beyond 41 weeks' gestation.\n The study population consisted of 120 women not in active labor with a gestational age >41 weeks, singleton pregnancy with vertex presentation, reactive fetal heart rate tracing, amniotic fluid index >/=5, and Bishop score <5. Women were randomized to receive either 25 microg (n=60) or 50 microg (n=60) of intravaginal misoprostol. The dose was repeated every 4 h (maximum number of doses limited to six) until the patient exhibited three contractions in 10 min. The main outcome measure was the induction-vaginal delivery interval.\n There was no significant difference between the two groups with regard to the induction-vaginal delivery interval (685+/-201 min in the 25 microg group vs. 627+/-177 min in the 50 microg group, P=0.09). The proportion of women delivering vaginally with one dose of vaginal misoprostol was significantly greater in the 50 microg group (0/49 vs. 41/47, P<0.001). There were no differences in the rates of cesarean and operative vaginal delivery rates, or in the incidences of tachysystole and hyperstimulation syndrome in the two treatment groups. Neonatal outcomes were also similar.\n Intravaginal administration of 25 microg of misoprostol appears to be as effective as 50 microg for cervical ripening and labor induction beyond 41 weeks' gestation.", "Our purpose was to compare the efficacy of 25 microg and 50 microg intravaginally administered misoprostol tablets for cervical ripening and labor induction. Either 25-microg (n: 58) or 50-microg (n: 56) misoprostol tablets were randomly administered intravaginally to 114 subjects with an unripe cervix for labor induction. The physician was blinded to the medication. Intravaginal misoprostol was given every 4 h until the onset of labor. The mean Bishop score before misoprostol administration was 2.1 +/- 1.6 in the 25-microg group and 2.0 +/- 1.4 in the 50-microg group (p > 0.05). With the 25-microg dose the time until delivery was significantly longer (991.2 +/- 514.4 min vs. 703.12 +/- 432.6 min in the 50-microg group). The use of oxytocin augmentation was significantly higher in the 25-microg group (63.8%) than the 50-microg group (32.1%; p < 0.05). The proportions of patients with tachysystoles and hypersystoles were not significantly different between the two groups (19 and 6.9%, respectively, in the 25-microg group and 25 and 17.8%, respectively, in 50-microg group; p > 0.05). Overall, in the 25-microg group more women achieved vaginal delivery (79.3 vs. 60.7%; p < 0.05). The rate of cesarean sections due to non-reassuring fetal status was higher in the 50-microg misoprostol group (28.6 vs. 10.3%; p < 0.05). The number of neonates with a low 1-min Apgar score (<7) was significantly higher in the 50-microg misoprostol group (26.8 vs. 8.6%; p < 0.05), but 5-min Apgar scores and umbilical artery blood gas values at the time of delivery were not significantly different between the groups (p > 0.05). One patient in the 25-microg group suffered a ruptured uterus. Intravaginal administration of 25 microg of misoprostol is a clinically effective labor induction regimen and has the least adverse effects and complications.\n Copyright 2002 S. Karger AG, Basel", "Our purpose was to compare the safety and effectiveness of intravaginally administered misoprostol at doses of 25 micrograms and 50 micrograms for indicated labor induction in patients with an unfavorable cervix.\n Three hundred ninety-nine patients received either 25 micrograms or 50 micrograms of misoprostol, placed intravaginally in the posterior fornix, in this randomized double-blind trial. The dose was repeated every 3 hours until adequate labor was achieved (at least three contractions in 10 minutes).\n Among 399 patients evaluated, 192 patients were allocated to the 25 micrograms group and 207 patients to the 50 micrograms group. The start-to-delivery interval was shorter in the 50 micrograms group (826 minutes vs 970 minutes, p = 0.02). The incidence of vaginal delivery after one dose was higher in the 50 micrograms group (38.2% vs 25.0%, p = 0.007). Patients receiving 25 micrograms required oxytocin augmentation more frequently than did those receiving 50 micrograms (27.1% vs 16.9%, p = 0.02). No differences were noted in the cesarean or other operative delivery rates among patients in the two treatment groups. The incidence of newborns with a cord pH < 7.16 was greater in the 50 micrograms group (13.0% vs 6.8%, p = 0.04). Although the incidence of hyperstimulation was similar between the groups, the incidence of tachysystole was higher in the 50 micrograms group (32.8% vs 15.6%, p = 0.0001).\n Although a dose of 50 micrograms is associated with a shorter start-to-delivery interval and a higher incidence of vaginal delivery after one dose, 25 micrograms of intravaginal misoprostol is effective and associated with a lower incidence of tachysystole and cord pH values < 7.16.", "To compare the safety and efficacy of two different regimens of misoprostol for labor induction at term, we conducted a randomized controlled trial on women presenting for induction of labor at > or =37 weeks' gestation. Eligible women were randomized to receive intravaginal misoprostol 50 microg every 4 h or 100 microg every 6 h until any of the following: 1) adequate contraction pattern (3 contractions/10 min); 2) dilatation >3 cm; 3) artificial rupture of membranes; or 4) signs of uterine hyperstimulation. Use of oxytocin during labor was at the discretion of the managing clinician. The main outcome variable considered for analysis was cesarean section rate. Secondary outcome measures were induction to delivery interval and neonatal outcome (Apgar scores, meconium staining, and umbilical artery pH). A total of 58 women were randomized to receive either misoprostol 100 microg (n=26) or 50 microg (n=32). The 100 and 50 microg groups had similar mean Bishop's scores at induction (4.0+/-2.3 vs 4.1+/-2.2, p=0.87), rates of nulliparity, use of epidural anesthesia, and oxytocin augmentation. The number of doses of misoprostol used was similar in the two groups (1.4+/-0.6 vs 1.8+/-1.2). The mean+/-standard deviation time to delivery (hours) (11.9+/-7.3 vs 14.3+/-9.6 h, p=0.30) and cesarean section rate (35% vs 19%, p=0.30, relative risk: 1.8, 95% confidence interval 0.7-5.4) were not different in the 100 vs 50 microg group. Power analysis demonstrated that 132 women would be required in each group to achieve statistical significance in the primary outcome measure (alpha=0.05, beta=0.80). Similarly, rates of 5-minute Apgar scores <7 (4% vs 3%, p=1.0), and of meconium passage (17% vs 25%, p=0.73) were not significantly different between the two groups.", "The objective was to compare the efficacy and complications of intravaginal misoprostol application with oxytocin infusion for induction of labor in advanced aged pregnancies with a Bishop score of < 6.\n A hundred advanced aged (> or = 35 years) pregnant patients with a Bishop score of < 6 were randomized into two groups. The first group (50 patients) received 50 microg intravaginal misoprostol four times with 4 h intervals and the second group received oxytocin infusion for induction of labor starting from 2 mIU/min and was increased every 30 min with 2 mIU/min increments up to a maximum of 40 mIU/min. The time from induction to delivery, the route of delivery, fetal outcome, and maternal complications were recorded. Statistical analyses were performed using the Mann-Whitney U, Chi-squared and t tests to determine differences between the two groups. A p value < or = 0.05 was considered significant.\n Misoprostol was superior for induction of labor in advanced aged pregnancies with Bishop score of < 6, as the mean time from induction to delivery was 9.61 +/- 4.12 h and 11.46 +/- 4.86 h in the misoprostol and oxytocin groups respectively, with a significant difference between the groups (p = 0.04). The rate of vaginal delivery was higher in the misoprostol group (84.0%) than in the oxytocin group (80.0%), but the difference did not reach significance (p = 0.60). The rates of placental abruption and postpartum hemorrhage were similar in both groups and no cases of uterine rupture occurred. The 1- and 5-min mean Apgar scores were 6.98 +/- 1.17 to 9.08 +/- 0.99 and 6.88 +/- 1.81 to 9.00 +/- 1.35 in the misoprostol and oxytocin groups respectively, with no significant differences between the groups (p = 0.74, p = 0.83). No cases of asphyxia were present. The rate of admission to the neonatal intensive care unit was similar in both groups.\n Intravaginal misoprostol seems to be an alternative method to oxytocin in the induction of labor in advanced aged pregnant women with low Bishop scores, as it is efficacious, cheap, and easy to use. But large studies are necessary to clarify safety with regard to the rare complications such as uterine rupture.", "We compared the efficacy of misoprostol with that of prostaglandin E2 in cervical ripening and labour induction. Thus 238 women with rupture of membranes beyond 36 weeks gestation without labour were randomized to receive 50 microg misoprostol vaginal gel or 5 mg of prostaglandin E2 gel. Bishop score was evaluated before drug application and 6 hours later. Clinical data and perinatal outcome were recorded. Mean time from induction to delivery and the need for oxytocin were significantly less in the misoprostol group. There were no significant differences in spontaneous labour rate, type of delivery and perinatal outcome. It is concluded that intravaginal misoprostol is safe and more effective than prostaglandin E2 for preinduction cervical ripening in premature rupture of membranes beyond 36 weeks gestation.", "To compare the use of vaginally administered misoprostol to placebo for outpatient labor induction in patients with diabetes.\n In this double-masked, controlled clinical trial, pregnant women with diabetes and gestational age of >38(1/2) weeks were randomized to receive 25 microg misoprostol or placebo vaginally on days 1 and 4 of a 7-day outpatient cervical ripening period. If necessary, inpatient labor induction was managed by using a standard protocol.\n Of 120 women included in the study, 57 received misoprostol and 63 received placebo. Most of the women had been diagnosed with gestational (Class A) diabetes. Similar numbers of misoprostol and placebo-treated women delivered within 7 days of the first dose (31/57 [54%] vs 36/63 [57%], P =.63). The mean (+/-SEM) interval from induction to delivery was similar (8530.5 minutes +/-1439.7 minutes vs 6712.5 minutes +/-606.4 minutes, P =.23).\n Vaginally administered misoprostol was no more effective than placebo in reducing the need for inpatient labor induction or the induction-delivery interval. Outpatient cervical ripening with use of vaginally administered misoprostol was well tolerated.", "To assess the ability of a controlled-release misoprostol vaginal insert to induce labor using dose reservoirs of 25, 50, 100, and 200 microg.\n This double-blind, dose ranging, randomized study was carried out in parous women requiring induction of labor at term. Each woman was randomly assigned to receive a single misoprostol vaginal insert that could remain in place for up to 24 hours and was removed for onset of active labor, an adverse event, or having reached 24 hours in situ. The primary outcome measure was time from insertion of the misoprostol vaginal insert to vaginal delivery of the neonate.\n A total of 124 women participated in the study. The median time to vaginal delivery was 27.5, 19.1, 13.1, and 10.6 hours for the 25-, 50-, 100-, and 200-microg doses, respectively. The percentage of women who delivered vaginally within 12 hours was 9%, 14%, 47%, and 53% (P<.001 using the 25-microg group as the comparator) and within 24 hours was 42%, 79%, 81%, and 70% (P=.003). Uterine hyperstimulation syndrome occurred in one woman who received the 25-mug, two women who received the 100-microg, and three women who received the 200-microg dose reservoirs.\n Misoprostol vaginal inserts effectively induced labor in pregnant parous women at term.\n I.", "Our purpose was to compare the safety and efficacy of intravaginal misoprostol versus intracervical prostaglandin E2 (dinoprostone) gel for preinduction cervical ripening and induction of labor.\n One hundred thirty-five patients with indications for induction of labor and unfavorable cervices were randomly assigned to receive either intravaginal misoprostol or intracervical dinoprostone. Fifty microgram tablets of misoprostol were placed in the posterior vaginal fornix every 3 hours for a maximum of six doses. Prostaglandin E2 in gel form, 0.5 mg, was placed into the endocervix every 6 hours for a maximum of three doses. Medication was not given after either spontaneous rupture of membranes or beginning of active labor.\n Among 135 patients enrolled, 68 received misoprostol and 67 received dinoprostone. The average interval from start of induction to vaginal delivery was shorter in the misoprostol group (903.3 +/- 482.1 minutes) than in the dinoprostone group (1410.9 +/- 869.1 minutes) (p < 0.001). Oxytocin augmentation of labor occurred more often in the dinoprostone group (65.7%) than in the misoprostol group (33.8%) (p < 0.001). There were no significant differences between routes of delivery. Ten of the misoprostol-treated patients (14.7%) and 13 of the dinoprostone-treated patients (19.4%) had cesarean deliveries. There was a higher prevalence of tachysystole (six or more uterine contractions in a 10-minute window for two consecutive 10-minute periods) in the misoprostol group (36.7%) than in the dinoprostone group (11.9%) (p < 0.001). However, there were no significant differences in frequency of uterine hyperstimulation or hypertonus. There was a higher prevalence of meconium passage in the misoprostol group (27.9%) than in the dinoprostone group (10.5%) (p < 0.05). There was no significant difference in frequency of abnormal fetal heart rate tracings, 1- or 5-minute Apgar scores < 7, neonatal resuscitations, or admissions to the neonatal intensive care unit between the two groups.\n Vaginally administered misoprostol is an effective agent for cervical ripening and induction of labor; however when given at this dosage, it is associated with a higher prevalence of tachysystole and meconium passage than is dinoprostone. Further studies to compare the safety of misoprostol to that of dinoprostone and to delineate an optimal dosing regimen for misoprostol are needed.", "To compare the effect of misoprostol vs. oxytocin on blood flow in uteroplacental circulation during labor induction.\n Ninety-one women with indications for induction of labor were assigned to receive either misoprostol 50 microg per vagina every 4 h as needed or intravenous oxytocin by means of a randomization table generated by computer. Doppler velocimetry of umbilical, uterine and arcuate arteries was performed immediately before and 2-3 h after administration of misoprostol or oxytocin. Pulsatility index (PI), resistance index (RI) and systolic/diastolic (S/D) ratios were measured for these arteries. The SAS system was used to perform statistical analysis.\n There were no significant changes of PI, RI and S/D ratios in umbilical arteries during misoprostol and oxytocin inductions. Vaginal application of misoprostol significantly increased PI, RI and S/D ratios in arcuate arteries and S/D ratio in uterine arteries.\n Our results indicate that intravaginal misoprostol administration increases uteroplacental resistance but probably does not substantially affect placental perfusion.", "The objective of this randomized prospective study was to compare the efficacy of 50 mcg vaginal misoprostol and 3 mg dinoprostone, administered every nine hours for a maximum of three doses, for elective induction of labor in a specific cohort of nulliparous women with an unfavorable cervix and more than 40 weeks of gestation.\n One hundred and sixty-three pregnant women with more than 285 days of gestation were recruited and analyzed. The main outcome measures were time from induction to delivery and incidence of vaginal delivery within 12 and 24 hours. Admission rate to the neonatal intensive care unit within 24 hours post delivery was a secondary outcome.\n The induction-delivery interval was significantly lower in the misoprostol group than in the dinoprostone group (11.9 h vs. 15.5 h, p < 0.001). With misoprostol, more women delivered within 12 hours (57.5% vs. 32.5%, p < 0.01) and 24 hours (98.7% vs. 91.4%, p < 0.05), spontaneous rupture of the membranes occurred more frequently (38.8% vs. 20.5%, p < 0.05), there was less need for oxytocin augmentation (65.8% vs. 81.5%, p < 0.05) and fewer additional doses were required (7.5% vs. 22%, p < 0.05). Although not statistically significant, a lower Caesarean section (CS) rate was observed with misoprostol (7.5% vs. 13.3%, p > 0.05) but with the disadvantage of higher abnormal fetal heart rate (FHR) tracings (22.5% vs. 12%, p > 0.05). From the misoprostol group more neonates were admitted to the intensive neonatal unit, than from the dinoprostone group (13.5% vs. 4.8%, p > 0.05). One woman had an unexplained stillbirth following the administration of one dose of dinoprostone.\n Vaginal misoprostol, compared with dinoprostone in the regimens used, is more effective in elective inductions of labor beyond 40 weeks of gestation. Nevertheless, this is at the expense of more abnormal FHR tracings and more admissions to the neonatal unit, indicating that the faster approach is not necessarily the better approach to childbirth.", "Our purpose was to compare the efficacy 25 micrograms and 50 micrograms dosage of intravaginal misoprostol for labor induction in patients with an unfavorable cervix. Fifty pregnant women were randomly assigned to receive either 25 micrograms (24 cases) or 50 micrograms (26 cases) of intravaginal misoprostol every 6 hours. The mean interval from induction to vaginal delivery was significantly shorter in the 50 micrograms group (13.8 +/- 6.6 hours) when compared with the 25 micrograms group (20.9 +/- 9.5 hours) (P = 004). The average number of misoprostol doses needed per patient was significantly fewer in the 50 micrograms group (1.6 +/- 0.7 versus 2.3 +/- 1.2, P = 0.018). The frequencies of uterine tachysystole were 4.2 per cent and 7.7 per cent in the 25 micrograms and 50 micrograms groups respectively which did not significantly differ. Requirement for oxytocin infusion in the 25 micrograms group was significantly more than in the 50 micrograms group (66.6% versus 23.1% respectively, P = 0.004). Analgesia requirement, delivery method, and perinatal outcomes were comparable in both groups. In summary, intravaginal application of 50 micrograms misoprostol at 6-hour interval is comparable in safety but more effective for labor induction than the 25 micrograms dosage.", "Although induction of labor in women with prior cesareans is controversial, we compared misoprostol to oxytocin in such women in a randomized trial. The investigation was terminated prematurely because of safety concerns.\n Disruption of the prior uterine incision was found in two of 17 misoprostol-treated women. The first woman underwent repeat cesarean delivery at 42 weeks because of fetal tachycardia and repetitive late decelerations. A 10-cm vertical rent in the anterior myometrium was discovered. The second woman underwent induction for fetal growth restriction. Loss of fetal heart tones and abnormal abdominal contour prompted emergent cesarean for suspected uterine rupture. An 8-cm longitudinal uterine defect was found.\n When misoprostol is used in women with previous cesareans, there is a high frequency of disruption of prior uterine incisions.", "Misoprostrol, a synthetic analogue of prostaglandin E(1), has been used for cervical preparation. Its ideal dose, route and frequency of administration are still under investigation. We conducted a randomised controlled trial, in a tertiary hospital in a developing country, to compare misoprostol 50 microg (low) and 100 microg (high) for effectiveness and safety in induction of labour at term. Women admitted for induction of labour with a singleton live fetus in cephalic presentation after 37 weeks' gestation were recruited. A misoprostol tablet was inserted in the posterior vaginal fornix at 8-hour intervals. Main outcomes were duration of induction, maternal and fetal complications. The mean duration of induction was 15.4 (SD 10.6) and 14.2 (SD 13.6) h in the low- and high-groups respectively (P = 0.095). There was no difference in need for augmentation with oxytocin (OR 0.82; 95% Cl 0.36-1.86) or operative delivery (OR 1.29; 95% CI 0.26-6.84). There were two uterine ruptures and four intrapartum stillbirths in the high misoprostol group. There was no difference in postpartum haemorrhage, 9.5% vs. 7.9% (P = 1.00) and admissions to the neonatal unit 18.8% vs. 17.0% (P = 0.980) in the 1ow- and high-groups) respectively. Misoprostol 50 microg was as effective as the 100 microg dose for induction of labour whereas the higher dose had an increased risk of serious complications.", "The aim of this prospective, randomized study was to investigate the changes in urinary cyclic guanosine 3',5'-monophosphate (cGMP) and cyclic adenosine 3',5'-monophosphate (cAMP) between the latent and the active phases of spontaneous and prostaglandin E(1) (PGE(1))-induced labor.\n Seventy singleton pregnant women at 36-41(+) weeks' gestation without signs of fetal distress were enrolled. The first group consisted of 35 pregnant women in whom labor was induced by PGE(1) applied intravaginally. The second group consisted of 35 women who had spontaneous active labor. Clinical data of the two groups were assessed as labor progressed.\n After the onset of active labor, urinary cGMP/creatinine (U cGMP/Cr) decreased in both groups with the percentage decline of 35.2 and 9.7, respectively, but this difference was only significant in the PGE(1)-induced group (P=0.033). After the onset of active labor, urinary cAMP/creatinine (U cAMP/Cr) decreased in both groups with the percentage decline of 36.5 and 15.6, respectively, but this difference was only significant in the PGE(1)-induced group (P=0.001). The duration of the latent phase was significantly shortened in the PGE(1)-induced group compared with the spontaneous labor group (P<0.05).\n Decreased U cGMP/Cr and U cAMP/Cr may be a transition from the latent to the active phase in PGE(1)-induced labor. Our results suggest that U cGMP/Cr and U cAMP/Cr can serve as easily obtained secondary messenger markers of myometrial contractility and cervical ripening at the onset of active labor. The NO-cGMP system and the G-protein alpha-cAMP system in the human uterus may concomitantly contribute to uterine quiescence during pregnancy and show downregulation in U cGMP/Cr and U cAMP/Cr at the initiation of active labor.", "The aim of this randomized trial was to compare the efficacy and safety of vaginal misoprostol and oxytocin for cervical ripening and labor induction in patients with premature rupture of membrane (PROM) at term.\n Ninety-seven women with PROM at term were assigned randomly to receive intravaginal misoprostol or oxytocin. The primary outcome measure was the induction-delivery interval. Secondary outcomes included the number of women who delivered vaginally within 12 hours of the start of the induction in the two groups, the cesarean, hyperstimulation, and failed induction rates, the mode of delivery, and the neonatal outcome.\n Forty-eight women were assigned to intravaginal misoprostol and 49 to oxytocin administration. The mean interval from induction to delivery was 10.61 +/- 2.45 hours in the misoprostol group and 11.57 +/- 1.91 hours in the oxytocin group (p = 0.063). The rates of vaginal delivery were 83.3% and 87.7% and cesarean delivery were 16.7% and 8.2% in the misoprostol and oxytocin groups, respectively. Neonatal outcomes were not significantly different. Of the cases, 8.3% in the misoprostol group and 8.2% in the oxytocin group revealed uterine contraction abnormalities.\n Our study demonstrates that, intravaginally, misoprostol results in a similar interval from induction of labor to delivery when compared to oxytocin.", "To compare the efficacy and safety of misoprostol (prostaglandin E(1) (PGE(1))) with dinoprostone (prostaglandin E(2) (PGE(2))) for third trimester cervical ripening and labor induction.\n Patients requiring induction of labor were randomly assigned to receive either 50 microg of intravaginal misoprostol every 4 h or 0.5 mg of intracervical dinoprostone gel every 6 h. Eligibility criteria included gestation = 36 weeks. Primary outcome was the time interval from induction to delivery; secondary outcomes were mode of delivery, perinatal outcome, and interpretation of cardiotocogram (CTG) records.\n Two hundred women were randomly enrolled to receive either misoprostol (n = 100) or dinoprostone (n = 100). Time induction-to-delivery at 12, 24 and 48 h and the need for oxytocin were reduced with misoprostol (P < 0.05). Pathological CTG tracing according to FIGO and Melchior scores were more frequent in the misoprostol-treated group (P < 0.001).\n Misoprostol shortened the induction-to-delivery interval, but is associated with a higher incidence of abnormal CTG than prostaglandin E(2).", "To compare the efficacy and complications of intravaginal misoprostol application with oxytocin infusion for induction of labor in great grandmultiparous pregnancies with a Bishop score of <6.\n Sixty-four great grandmultiparous (delivering the tenth, or greater, infant) pregnant patients with a Bishop score of <6 were randomized in two groups with 32 patients receiving 50 microg intravaginal misoprostol four times with 4h intervals, and 32 patients receiving oxytocin infusion for induction of labor starting from 2 mIU/min, increasing it every 30 min with 2 mIU/min increments up to maximum of 40 mIU/min. The time from induction to delivery, the route of delivery, fetal outcome and maternal complications were recorded. Statistical analyses were performed using Mann-Whitney U-test, Chi-Square test and hypothesis test about differences for two proportions (t-test) to determine differences between the two groups. P < or = 0.05 was considered significant.\n The mean time from induction to delivery was 9.91+/-4.30 and 10.88+/-4.72 h in the misoprostol and oxytocin administered group, respectively, with no significant difference between the groups. The rate of vaginal delivery was 84.4 and 87.5% in the misoprostol and oxytocin administered group, respectively, with no significant difference between the groups (P = 0.72). The rates of placental abruption and postpartum hemorrhage were similar in both groups and no case of uterine rupture occurred. The 1 and 5 min mean Apgar scores were 6.91+/-1.57-8.88+/-1.39 and 7.22+/-1.24-9.06+/-0.84 in the misoprostol and oxytocin administered group with no significant differences between the groups (P = 0.38 and 0.51). No case of asphyxia was present. The rate of admission to neonatal intensive care unit was higher in the misoprostol administered group, but the difference was not significant.\n Intravaginal misoprostol is an alternative method to oxytocin in induction of labor in great grandmultiparous pregnant women with low Bishop scores, as it is effective, cheap and easy to use. Safety about rare complications and neonatal morbidity needs clarifications with further studies." ]

[ "9121852", "10771973", "9835439", "8645387", "11195235", "15833887", "8429447" ]

[ "Effectiveness of budesonide aerosol in ventilator-dependent preterm babies: a preliminary report.", "Respiratory and systemic effects of inhaled dexamethasone on ventilator dependant preterm infants at risk for bronchopulmonary dysplasia.", "Inhaled salbutamol and beclomethasone for preventing broncho-pulmonary dysplasia: a randomised double-blind study.", "Trial of beclomethasone dipropionate by metered-dose inhaler in ventilator-dependent neonates less than 1500 grams.", "Budesonide delivered by dosimetric jet nebulization to preterm very low birthweight infants at high risk for development of chronic lung disease.", "Fluticasone inhalation in moderate cases of bronchopulmonary dysplasia.", "Controlled trial of beclomethasone dipropionate by nebulization in oxygen- and ventilator-dependent infants." ]

[ "The aim of this randomized, double-blind, placebo-controlled trial was to assess the short-term effect of a topical glucocorticoid (budesonide 600 mu g twice daily) vs. placebo administered by metered dose inhaler (MDL) and spacer (Aerochamber MV15) directly into endotracheal tube of intubated infants for 7 days. Twenty preterm infants (mean birthweight, 1,030 g; mean gestational age, 27.3 weeks)who still needed assisted ventilation at 14 days of age were randomly assigned to receive budesonide (n=9) or placebo (n=11) and completed the study. The primary outcome was the need for mechanical ventilation after 7 days of treatment. Other outcome variables included ventilator settings, blood gases, serum cortisol levels, and bronchoalveolar lavage inflammatory cell counts. No ventilated infant was extubated during the study period. The treatment group showed significant improvements in mean peak inspiratory pressure, ventilator efficiency index, and (A-a) oxygen difference. There were no changes in the placebo group. Serum cortisol levels and bronchoalveolar lavage cell counts did not change significantly during study period. There was no difference in side effects between the groups. This trial demonstrates that topical budesonide administered by MDL and Aerochamber produces clinical improvement in ventilated preterm infants, without glucocorticoid side effects.", "Short-term inhaled dexamethasone therapy was evaluated in a double blind placebo controlled trial in 36 ventilator dependent preterm neonates (BW < 1500 gm, postnatal age > 7 days) who were at risk for bronchopulmonary dysplasia. Pulmonary and systemic effects were compared at early (day 3), late (7-10 days) and post (14 days after initiation) phases of therapy. Airflow mechanics improved as demonstrated by a net 101% improvement in pulmonary resistance (a decrease from 139 to 101 cm H2O/L/s in the dexamethasone treated infants as compared to an increase from 153 to 267 cmH2O/L/s in the placebo treated infants during the early phase of therapy); this was associated with a 45% increase in inspiratory airflow (1.29 +/- 0.43 to 1.87 +/- 0.978 L/min; p < 0.01), and 37% increase in expiratory airflow. These changes resulted in a significant reduction in the work of breathing such that the mean tidal driving pressure significantly decreased from 13.6 cmH2O to 9.4 cm H2O with inhaled steroid administration. Though the brief duration of therapy did not result in cessation of ventilatory support, the level of support was significantly reduced (decreased values of oxygen supplementation, mean airway pressure and oxygenation index and increased ventilatory efficiency index). The inhaled dexamethasone therapy was also associated with systemic absorption of the drug as evidenced by transient but apparently reversible reduction in serum cortisol levels. No systemic side effects of hypertension, hyperglycemia or nosocomial sepsis were observed. These data demonstrate beneficial effects of short-term inhaled dexamethasone on the resistive airflow properties of preterm infants at risk for BPD and may provide adjunctive means to facilitate weaning in the ventilator dependent neonates.", "Early inflammatory lesions and bronchial hyperresponsiveness are characteristics of the respiratory distress in premature neonates and are susceptible to aggravation by assisted ventilation. We hypothesized that treatment with inhaled salbutamol and beclomethasone might be of clinical value in the prevention of bronchopulmonary dysplasia (BPD) in ventilator-dependent premature neonates. The study was double-blinded and placebo controlled. We studied 173 infants of less than 31 weeks of gestational age, who needed ventilatory support at the 10th postnatal day. They were randomised to four groups and received either placebo + placebo, placebo + salbutamol, placebo + beclomethasone or beclomethasone + salbutomol, respectively for 28 days. The major criteria for efficacy were: diagnosis of BPD (with score of severity), mortality, duration of ventilatory support and oxygen therapy. The trial groups were similar with respect to age at entry (9.8-10.1 days), gestational age (27.6-27.8 weeks), birth weight and oxygen dependence. We did not observe any significant effect of treatment on survival, diagnosis and severity of BPD, duration of ventilatory support or oxygen therapy. For instance, the odds-ratio (95% confidence interval) for severe or moderate BPD were 1.04 (0.52-2.06) for inhaled beclomethasone and 1.54 (0.78-3.05) for inhaled salbutamol.\n This randomised prospective trial does not support the use of treatment with inhaled beclomethasone, salbutamol or their combination in the prevention of BPD in premature ventilated neonates.", "Beclomethasone dipropionate administered by metered-dose inhaler to ventilated infants with early chronic lung disease was evaluated in a double-blind, placebo-controlled study to determine the feasibility and safety of administration. Patients selected for study were less than 1500 g birthweight, had previous radiographic evidence of respiratory distress syndrome with early changes of bronchopulmonary dysplasia (BPD), were greater than 2 weeks of age, and had failed attempts at extubation. The metered-dose inhaler was connected to the respirator circuit by an in-line spacer device and either saline placebo or beclomethasone was delivered for 7 days or until extubated. Beclomethasone was delivered in a dose calculated to be approximately 1 mg/kg/day in three divided doses. Nineteen infants were enrolled. Nine received placebo and 10 received beclomethasone. No adverse effects on blood pressure, heart rate, respiratory rate, ventilator settings, concentration or duration of oxygen therapy, incidence of retinopathy of prematurity (ROP) or infections, blood glucose, daily weight, or serum cortisol levels before and after adrenal stimulation tests were observed in the beclomethasone group compared with the placebo group. One infant in the placebo and six infants in the steroid group were extubated during the study period (p = 0.03). These data indicate that beclomethasone dipropionate may be administered safely to intubated neonates without adverse effects of hypertension, hyperglycemia, diminished weight gain, or adrenal suppression frequently seen with systemic steroid administration. Beclomethasone may enhance extubation in infants with early BPD, however, further data are required to substantiate this preliminary observation.", "We investigated the effect of an aerosolized corticosteroid (budesonide) on the oxygen requirement of infants at high risk for developing chronic lung disease (CLD) in a randomized, double-blind study. The study objective was to attain a 30% decrease in FiO2 levels in the budesonide treatment group after 14 d of therapy. Thirty very low birthweight (VLBW) infants (median (range)) gestational age 26 wk (23-29) and birthweight 805 g (525-1227) were randomized. Inclusion criteria were mechanical ventilation on day 6 of life, or if extubated on nasal continuous positive airway pressure with FiO2 > or = 0.3. The budesonide (Pulmicort) dose was 500 microg bid, or placebo. The aerosol was delivered with a dosimetric jet nebulizer, with variable inspiratory time and breath sensitivity. Inhalations were started on day 7 of life. Twenty-seven patients completed the study. A significant lowering of the FiO2 levels at 21 d of life was not detected. Infants who received budesonide were more often extubated during the study period (7/8 vs 2/9) and had a greater relative change from baseline in their oxygenation index (budesonide decreased 26% vs placebo increased 60%). Subsequent use of intravenous dexamethasone or inhaled budesonide in the treatment group was significantly less. All patients required O2 supplementation on day 28 of life. At 36 wk postconceptual age, 61% of infants in the budesonide group needed supplemental O2 as opposed to 79% in the placebo group. No side effects on growth or adrenal function were observed.\n We conclude that inhaled budesonide aerosol via dosimetric jet nebulizer started on day 7 of life for infants at high risk for developing CLD decreases the need for mechanical ventilation similar to intravenous dexamethasone, but without significant side effects.", "This randomized, controlled trial was designed to determine the efficacy of inhaled fluticasone propionate on oxygen therapy weaning in a population of preterm infants who were born at <32 weeks of gestation and experienced moderate bronchopulmonary dysplasia (BPD).\n Thirty-two infants who were < or =32 weeks of gestation, had moderate BPD that required supplemental oxygen (fraction of inspired oxygen > or =0.25), and were aged between 28 and 60 days were randomized. Fluticasone propionate 125 microg twice daily for 3 weeks and once daily for a fourth week was delivered to infants who weighed between 500 and 1200 g. The dosage was doubled for infants who weighed > or =1200 g.\n Compared with placebo, treatment had no effect on either duration of supplemental O2 therapy or ventilatory support as assessed by survival analysis. At 28 days, a trend toward a lower cortisol/creatinine ratio in the treatment group was noted compared with placebo (25.1 +/- 18.9 vs 43 +/- 14.4). In the fluticasone group at 28 days, the systolic arterial pressure (78 +/- 3 vs 68 +/- 3 mm Hg) and diastolic arterial pressure (43 +/- 3.4 mm Hg vs 38 +/- 2.0 mm Hg) were higher compared with baseline fluticasone values. The chest radiograph score was lower than baseline (2.8 +/- 1.4 vs 3.7 +/- 2.2) in the fluticasone group at 28 days. This study has a statistical power of 1.0 to detect a significant difference in the duration of oxygen supplementation of >21 days between the study groups.\n We conclude that fluticasone propionate reduces neither supplemental O2 use nor the need for ventilatory support in this patient population. However, fluticasone does have a positive radiologic effect in lowering chest radiograph scores. In addition, our data point to a possible association among inhaled fluticasone treatment and higher arterial blood pressure. Thus, the results of this investigation do not support the use of inhaled corticosteroids in the treatment of oxygen-dependent infants who have established moderate BPD.", "Parenteral glucocorticoids have been shown to be effective in the treatment of oxygen- and ventilator-dependent bronchopulmonary dysplasia. We conducted a randomized, prospective study using a nebulized, water-soluble form of beclomethasone dipropionate for the treatment of infants with oxygen- and ventilator-dependent lung disease. Newborn infants with chest x-ray changes consistent with bronchopulmonary dysplasia at 14 days of age were randomly assigned, in a paired sequential fashion by birth weight, to treatment (beclomethasone) or placebo (saline solution) groups. Treatment included three nebulized doses of beclomethasone (50 micrograms) or saline solution per day for 28 days. Measured variables included tidal volume, total dynamic compliance, and airway resistance. Weight gain, gender, and incidence of infection during therapy were also recorded. Pulmonary functions were measured before initiation of therapy and weekly thereafter. Thirteen infants, seven in the saline solution group and six in the beclomethasone group, met study criteria and completed treatment. Infants treated with beclomethasone had reductions in airway resistance that were significant in weeks 2, 3, and 4 (p < 0.05, p < 0.02, and p < 0.001, respectively). Dynamic lung compliance increased at weeks 3 and 4 (p < 0.01 and p < 0.05, respectively). As expected, tidal volume increased with weight and time, but there were no significant differences between groups. There were no differences between the groups in weight gain, gender, or infection. This study demonstrates that beclomethasone by nebulization (1) reduced airway resistance in oxygen-dependent neonates with bronchopulmonary dysplasia, (2) improved dynamic lung compliance, as reported with parenterally administered glucocorticoids, and (3) produced no apparent increase in the incidence of infection." ]

[ "17297614", "10839875", "19578227", "17551656", "12673261", "17597827" ]

[ "Transepidermal water loss and cerebral hemodynamics in preterm infants: conventional versus LED phototherapy.", "A new blue light-emitting phototherapy device: a prospective randomized controlled study.", "Light emitting diodes versus compact fluorescent tubes for phototherapy in neonatal jaundice: a multi center randomized controlled trial.", "Efficacy of new microprocessed phototherapy system with five high intensity light emitting diodes (Super LED).", "A prospective randomized controlled study of phototherapy using blue and blue-green light-emitting devices, and conventional halogen-quartz phototherapy.", "Randomized controlled trial of light-emitting diode phototherapy." ]

[ "The aim of our study was to evaluate whether high-intensity gallium nitride light-emitting diode (LED) phototherapy (LPT) influences transepidermal water loss (TEWL) and cerebral hemodynamics in preterm neonates in comparison with conventional phototherapy (CPT). Thirty-one preterm infants were randomized for conventional (n = 14) and for LED (n = 17) phototherapy. All infants were studied using a Tewameter TM 210 and cerebral Doppler ultrasound immediately before phototherapy (time 0), 30 min (time 1), 1-6 h (time 2), and 12-24 h (time 3) after the start of phototherapy, and 6-12 h after discontinuing phototherapy (time 4). The study shows that LPT does not induce significant changes in TEWL (time 0: 2.75 +/- 4.71 ml/m(2)/h; time 3: 14.45 +/- 3.68 ml/m(2)/h), in peak systolic, end diastolic and mean cerebral blood flow velocity (CBFV), and in the resistence index (RI). On the contrary, CPT is associated with a significant increase of TEWL (time 0: 13.22 +/- 5.61 ml/m(2)/h; time 3: 20.94 +/- 3.21 ml/m(2)/h), which disappeared at time 4, when phototherapy had stopped. The peak systolic and mean CBFV increased, respectively, from 0.11 +/- 0.03 m/s at time 0 to 0.16 +/- 0.07 m/s at time 3. We conclude that LPT, emitting light within the 450-470-nm spectrum for optimal bilirubin degradation, can be preferable to CPT for the therapy of hyperbilirubinemia in preterm infants.", "To evaluate the efficacy of a new phototherapy light source with a narrow luminous blue spectrum. The device, made with high-intensity gallium nitride light-emitting diodes (LEDs), was compared with conventional phototherapy at similar light intensities.\n Two university-affiliated community hospitals in Jerusalem.\n Prospective open randomized study.\n Sixty-nine jaundiced, but otherwise healthy, term infants who met the entry criteria for phototherapy set by the American Academy of Pediatrics' Practice Parameter.\n The duration of phototherapy and the rate of decrease in total serum bilirubin (TSB) concentration.\n The mean TSB concentrations at initiation and termination of treatment did not differ between newborns receiving LED and those receiving conventional phototherapy. The duration of phototherapy and the rate of decrease in TSB concentration were not statistically different in the 2 groups. The average rate of decrease in TSB after adjustment by a linear regression analysis for confounding factors was -3.16 micromol/L/h (95% confidence limits -4.81, -1.51) in newborns receiving LED phototherapy compared with -2.19 micromol/L/h (-3.99, -0.40) in those treated with conventional phototherapy (P <.14). No side effects were noted in any of the newborns.\n The blue gallium nitride LED device is as effective as conventional phototherapy and is readily accepted by nursing staff. Future LED phototherapy devices can provide much higher irradiance, and thus greater efficacy, and offer a new highly versatile approach to the treatment of jaundice.", "To evaluate whether light-emitting diode (LED) phototherapy is as efficacious as compact fluorescent tube (CFT) phototherapy for the treatment of non-hemolytic jaundice in healthy term and late preterm neonates.\n Multi centre open label randomized controlled trial.\n Four tertiary care neonatal units.\n Healthy term and late preterm neonates with non-hemolytic jaundice.\n Single-surface LED or CFT phototherapy. PRIMARY OUTCOME VARIABLE: Duration of phototherapy.\n A total of 272 neonates were randomized to receive LED (n=142) or CFT (n=130) phototherapy. The baseline demographic and biochemical variables were similar in the two groups. The median duration of phototherapy (IQR) in the two groups was comparable (26 (22-36) h vs. 25(22-36) h; P=0.44). At any time point, a similar proportion of neonates were under phototherapy in the two groups (log-rank test, P=0.38). The rate of fall of serum total bilirubin (STB) during phototherapy and the incidence of failure of phototherapy were also not different. An equal proportion of neonates had a rebound increase in STB needing restarting of phototherapy. Side effects were rare, comparable in the two groups and included hypothermia, hyperthermia, rash, skin darkening and dehydration.\n LED and CFT phototherapy units were equally efficacious in the management of non-hemolytic hyperbilirubinemia in healthy term and late preterm neonates.", "To evaluate the efficacy of a microprocessed phototherapy (PT) system with five high intensity light emitting diodes (Super LED) for the treatment of neonatal hyperbilirubinemia of premature infants.\n Randomized clinical trial using Super LED phototherapy in the study group and twin halogen spotlight phototherapy in the control group. A stratified blocked randomization, based on birth weight, was performed. The duration of phototherapy and the rate of decrease of total serum bilirubin (TSB) concentration in the first 24 hours of treatment were the main outcome measures.\n We studied 88 infants, 44 in the Super LED group and 44 in the halogen spotlight PT group. The demographic characteristics of the patients in both groups were similar. Infants in the Super LED group had a similar mean initial serum bilirubin level (10.1+/-2.4 mg%) to those receiving halogen spotlight treatment (10.9+/-2.0 mg%). After 24 hours of treatment, the decrease in total serum bilirubin levels was significantly greater in the Super LED group (27.9 vs. 10.7%, p<0.01) and duration of phototherapy was significantly shorter in this group (36.8 h vs. 63.8 h, p<0.01). After 24 hours of treatment, a significantly greater number of patients receiving Super LED phototherapy had reached serum bilirubin concentrations low enough to allow withdrawal of treatment (23 vs. 10, p<0.01).\n Our results demonstrate that the efficacy of Super LED phototherapy for treating hyperbilirubinemia in premature infants was significantly better than halogen phototherapy.", "To determine the efficacy of blue versus blue-green phototherapy using new light sources with narrow luminous spectra. The devices made of high-intensity gallium nitride light-emitting diodes (LEDs) were also compared to conventional halogen-quartz bulbs phototherapy.\n Prospective open randomized study.\n A total of 114 jaundiced, but otherwise healthy term infants who met the entry criteria for phototherapy set by the American Academy of Pediatrics' Practice Parameter.\n The duration of phototherapy and the rate of decrease in total serum bilirubin (TSB).\n The mean TSB concentrations at initiation and termination of treatment, as well as the duration of phototherapy and the rate of decrease in TSB, were not statistically different in newborns receiving blue LED, blue-green LED or conventional phototherapy. The average rate of decrease in TSB (slope), after adjustment by a linear regression analysis for confounding factors, was -3.61 micromol/hour (95% confidence limits -5.47, -1.75) in the 25 newborns receiving blue LED phototherapy compared with -2.57 micromol/hour (-4.32, -0.82) in the 22 newborns treated with blue-green LED phototherapy and -3.42 micromol/hour (-5.02, -1.81) in the 57 newborns who received conventional phototherapy.\n When using low light irradiance, there was no statistically significant difference in the effectiveness of phototherapy using blue-green LEDs, blue LEDs or conventional halogen-quartz bulbs.", "We wished to compare the efficacy of light-emitting diode (LED) phototherapy with special blue fluorescent (BB) tube phototherapy in the treatment of neonatal hyperbilirubinemia.\n We randomly assigned 66 infants >or=35 weeks of gestation to receive phototherapy using an LED device or BB. In addition to phototherapy from above, all infants also received phototherapy from below using four BB tubes or a fiberoptic pad.\n After 15+/-5 h of phototherapy, the rate of decline in the total serum bilirubin (TSB) was 0.35+/-0.25 mg/dl/h in the LED group vs 0.27+/-0.25 mg/dl/h in the BB group (P=0.20).\n LED phototherapy is as effective as BB phototherapy in lowering serum bilirubin levels in term and near-term newborns." ]

[ "10487307", "9037222" ]

[ "An investigation into the need for supplementary steroids in organ transplant patients undergoing gingival surgery. A double-blind, split-mouth, cross-over study.", "A double-blind study of perioperative steroid requirements in secondary adrenal insufficiency." ]

[ "Organ transplant patients are frequently medicated with triple immunosuppressive therapy that includes both cyclosporin and the corticosteroid, prednisolone. Many of these patients experience gingival overgrowth that necessitates surgical intervention. Chronic dosing with corticosteroids can lead to suppression of the hypothalamic-pituitary axis, and subsequent adrenocortical suppression. To circumvent possible suppression, supplementary steroids are administered to such patients prior to so-called \"stressful events\". We have examined the need for supplementary steroids in 20 organ transplant patients undergoing gingival surgery under local anaesthesia to correct their drug-induced gingival overgrowth. All patients were operated upon in the first half of the morning. Prior to gingival surgery, resting blood pressure (BP) and serum ACTH concentrations were determined. Immediately before surgery patients received either intravenous hydrocortisone 100 mg or placebo in random, double-blind order. Each patient required 2 gingivectomies and thus acted as their own placebo control. BP was measured at various time points throughout surgery and upto 2 h postoperatively. On completion of surgery, a further blood sample was taken to determine ACTH concentration. There was no significant difference (p>0.05) between placebo and hydrocortisone treatments for BP and ACTH measurements. No patient experienced any symptoms that were suggestive of adrenocortical suppression. One patient did experience postural hypotension prior to gingival surgery, but this is attributed to his antidepressant medication. We can conclude from this study that immunosuppressed organ transplant patients taking the maintenance dose of prednisolone (5-10 mg/day) do not require corticosteroid cover prior to gingival surgery under local anaesthesia. We would however, advocate monitoring of their blood pressure throughout the procedure.", "Patients treated long-term with supraphysiologic doses of glucocorticoids experience secondary adrenal insufficiency and are routinely given large doses of steroids in the perioperative period to prevent hypotension. Because the dose of steroids required to prevent hypotension is not known, we conducted a randomized, double-blind study to determine whether patients treated long-term with glucocorticoids actually require increased steroids in the perioperative period.\n Patients who had been taking at least 7.5 mg prednisone daily for several months and had secondary adrenal insufficiency as defined by adrenocorticotropic hormone testing formed the study population. Patients were randomized to two groups. One group received perioperative injections of saline solution alone; the other received perioperative saline solution and cortisol. All patients received their usual daily prednisone dose throughout the study.\n Six patients were in the steroid-treated group and 12 were in the saline-treated group. Most subjects underwent major operations such as joint replacements, abdominal operations, and miscellaneous other procedures. Two patients had hypotension, one in each group. Hypotension resolved with volume replacement in both patients. The average pulse rates and blood pressures were similar in both groups during the perioperative period.\n Patients with secondary adrenal insufficiency do not experience hypotension or tachycardia caused by inadequate glucocorticoid levels when given only their daily dose of steroids for surgical procedures." ]

[ "2319363" ]

[ "Recognizing the onset of labor." ]

[ "An experimental study compared the use of an educational technique based on patient participation with routine instructions to prepare patients to recognize the onset of active labor. The number of visits to the labor suite that resulted in the patient being discharged undelivered was significantly lower in patients who received the educational intervention. The study revealed that, without any increase in time, nurses can prepare patients to make judgments about the need for hospitalization." ]

[ "7791837" ]

[ "A comparison of conservative and aggressive transfusion regimens in the perioperative management of sickle cell disease. The Preoperative Transfusion in Sickle Cell Disease Study Group." ]

[ "Preoperative transfusions are frequently given to prevent perioperative morbidity in patients with sickle cell anemia. There is no consensus, however, on the best regimen of transfusions for this purpose.\n We conducted a multicenter study to compare the rates of perioperative complications among patients randomly assigned to receive either an aggressive transfusion regimen designed to decrease the hemoglobin S level to less than 30 percent (group 1) or a conservative regimen designed to increase the hemoglobin level to 10 g per deciliter (group 2).\n Patients undergoing a total of 604 operations were randomly assigned to group 1 or group 2. The severity of the disease, compliance with the protocol, and the types of operations were similar in the two groups. The preoperative hemoglobin level was 11 g per deciliter in group 1 and 10.6 g per deciliter in group 2. The preoperative value for hemoglobin S was 31 percent in group 1 and 59 percent in group 2. The most frequent operations were cholecystectomies (232), head and neck surgery (156), and orthopedic surgery (72). With the exception of transfusion-related complications, which occurred in 14 percent of the operations in group 1 and in 7 percent of those in group 2, the frequency of serious complications was similar in the two groups (31 percent in group 1 and 35 percent in group 2). The acute chest syndrome developed in 10 percent of both groups and resulted in two deaths in group 1. A history of pulmonary disease and a higher risk associated with surgery were significant predictors of the acute chest syndrome.\n A conservative transfusion regimen was as effective as an aggressive regimen in preventing perioperative complications in patients with sickle cell anemia, and the conservative approach resulted in only half as many transfusion-associated complications." ]

[ "11556409", "21051772", "12757574", "14687346", "17397426", "21479913", "12588572", "15368824", "20854564", "18259094", "20817936", "17605699", "12609940", "20060665", "7500174", "19675115", "17355644", "19011727", "21335296", "19392952", "20683707", "18509559", "16267192", "10023893", "15935015", "19933747", "20421240", "21680622", "9701104", "12588571", "11264206", "19124530", "15716246", "21350242", "18245764", "18195202", "19054193", "2354297", "15490272", "15885294", "12495822", "15664003", "18629569", "19507291", "16183652", "15615747", "14695863", "10841179", "8343668", "15591487", "11039967", "15144369", "16845754", "7977921", "21143436", "10591231", "10404919", "12403738", "10404930", "20101013", "18808597", "9366737", "12006310", "18795987", "14695864", "20460620", "16078954", "21450224", "11890582", "12851185", "14687345", "16238765", "15889312", "21499018", "21044715", "11207837", "21214623", "20492040", "12383144", "17302651", "14728632", "18829689", "10843351", "11953541", "20501583", "20306017", "8150304", "17302652", "11502787", "15785256", "18559634", "17174387", "12071273", "15195985", "16364936", "8201149", "7594152", "17397425", "20202271", "20823124", "21526229", "21098340", "9224433", "17998225", "16505262", "17726361", "1392755", "20460331", "8617895", "10143898", "20458090", "18755784", "8078528", "20510973", "16945613", "17356003", "15129393", "19925613", "17613583", "16645293", "12081122", "19483372", "18166695", "20722845", "16271907", "20395080", "20831723", "20625015", "15528779", "20128337", "15860827", "18400123", "11563205", "9623035", "9060344", "11691528", "21226674", "1427246", "10746118", "15341550", "15814861", "19767629", "18373136", "17661956", "15086643", "15501836" ]

[ "A randomised controlled trial of the outcome of health assessment of people aged 75 years and over.", "A randomized trial of a multifaceted intervention to reduce falls among community-dwelling adults.", "A randomized controlled trial of an enhanced balance training program to improve mobility and reduce falls in elderly patients.", "Intense tai chi exercise training and fall occurrences in older, transitionally frail adults: a randomized, controlled trial.", "A randomized, controlled trial of fall prevention programs and quality of life in older fallers.", "Randomized trial of alendronate plus vitamin D3 versus standard care in osteoporotic postmenopausal women with vitamin D insufficiency.", "Preventing falls in community-dwelling frail older people using a home intervention team (HIT): results from the randomized Falls-HIT trial.", "Evidence-based clinical practice in falls prevention: a randomised controlled trial of a falls prevention service.", "LiFE Pilot Study: A randomised trial of balance and strength training embedded in daily life activity to reduce falls in older adults.", "Injurious falls are associated with lower household but higher recreational physical activities in community-dwelling older male veterans.", "The Whitehorse NoFalls trial: effects on fall rates and injurious fall rates.", "A Quality Use of Medicines program for general practitioners and older people: a cluster randomised controlled trial.", "Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial.", "Does daily vitamin D 800 IU and calcium 1000 mg supplementation decrease the risk of falling in ambulatory women aged 65-71 years? A 3-year randomized population-based trial (OSTPRE-FPS).", "Randomized clinical trial of nutritional supplementation shows little effect on functional status among free-living frail elderly.", "Effectiveness of a video-based exercise programme to reduce falls and improve health-related quality of life among older adults discharged from hospital: a pilot randomized controlled trial.", "Feasibility and results of a randomised pilot-study of pre-discharge occupational therapy home visits.", "Preventative effect of exercise against falls in the elderly: a randomized controlled trial.", "Impact of enhanced pharmacologic care on the prevention of falls: a randomized controlled trial.", "Effect of a risk-based multifactorial fall prevention program on the incidence of falls.", "Economic evaluation of dose-response resistance training in older women: a cost-effectiveness and cost-utility analysis.", "A single home visit by an occupational therapist reduces the risk of falling after hip fracture in elderly women: a quasi-randomized controlled trial.", "Tailored group exercise (Falls Management Exercise -- FaME) reduces falls in community-dwelling older frequent fallers (an RCT).", "Prevention of falls in the elderly trial (PROFET): a randomised controlled trial.", "A simple gait-stabilizing device reduces outdoor falls and nonserious injurious falls in fall-prone older people during the winter.", "Carotid sinus syndrome, should we pace? A multicentre, randomised control trial (Safepace 2).", "Randomized trial of domiciliary versus center-based rehabilitation: which is more effective in reducing falls and improving quality of life in older fallers?", "Effectiveness of a multifaceted podiatry intervention to prevent falls in community dwelling older people with disabling foot pain: randomised controlled trial.", "A randomized walking trial in postmenopausal women: effects on physical activity and health 10 years later.", "A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the Frailty Interventions Trial in Elderly Subjects (FITNESS).", "Effectiveness and economic evaluation of a nurse delivered home exercise programme to prevent falls. 1: Randomised controlled trial.", "Pacing in elderly recurrent fallers with carotid sinus hypersensitivity: a randomised, double-blind, placebo controlled crossover trial.", "Patients with recurrent falls attending Accident & Emergency benefit from multifactorial intervention--a randomised controlled trial.", "A randomized trial of effects of health risk appraisal combined with group sessions or home visits on preventive behaviors in older adults.", "Square-stepping exercise and fall risk factors in older adults: a single-blind, randomized controlled trial.", "Effects of ergocalciferol added to calcium on the risk of falls in elderly high-risk women.", "Lack of effect of Tai Chi Chuan in preventing falls in elderly people living at home: a randomized clinical trial.", "Screening the elderly in the community: controlled trial of dependency surveillance using a questionnaire administered by volunteers.", "Randomized controlled trial of exercise intervention for the prevention of falls in community-dwelling elderly Japanese women.", "Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial.", "[Effectiveness of falls prevention strategies for elderly subjects who live in the community with performance assessment of physical activities (before-after)].", "Menatetrenone and vitamin D2 with calcium supplements prevent nonvertebral fracture in elderly women with Alzheimer's disease.", "Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals.", "An outpatient multifactorial falls prevention intervention does not reduce falls in high-risk elderly Danes.", "Randomised controlled trial of prevention of falls in people aged > or =75 with severe visual impairment: the VIP trial.", "Falls and health status in elderly women following first eye cataract surgery: a randomised controlled trial.", "A randomised, controlled comparison of different calcium and vitamin D supplementation regimens in elderly women after hip fracture: The Nottingham Neck of Femur (NONOF) Study.", "Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women.", "Effects of preventive home visits to elderly people.", "Results of a community-based weight-bearing resistance training programme for healthy Chilean elderly subjects.", "Effects of a programme of multifactorial home visits on falls and mobility impairments in elderly people at risk: randomised controlled trial.", "Effectiveness of home visit falls prevention strategy for Taiwanese community-dwelling elders: randomized trial.", "The effect of 15 weeks of exercise on balance, leg strength, and reduction in falls in 40 women aged 65 to 89 years.", "Preventing disability and falls in older adults: a population-based randomized trial.", "A randomized controlled trial of a multifactorial falls prevention intervention for older fallers presenting to emergency departments.", "Home visits by an occupational therapist for assessment and modification of environmental hazards: a randomized trial of falls prevention.", "Chronic care clinics: a randomized controlled trial of a new model of primary care for frail older adults.", "Community-based exercise program reduces risk factors for falls in 65- to 75-year-old women with osteoporosis: randomized controlled trial.", "Psychotropic medication withdrawal and a home-based exercise program to prevent falls: a randomized, controlled trial.", "Exercise effects on bone mineral density, falls, coronary risk factors, and health care costs in older women: the randomized controlled senior fitness and prevention (SEFIP) study.", "Effectiveness of a falls-and-fracture nurse coordinator to reduce falls: a randomized, controlled trial of at-risk older adults.", "Randomised controlled trial of a general practice programme of home based exercise to prevent falls in elderly women.", "Evaluation of a nurse-led falls prevention programme versus usual care: a randomized controlled trial.", "Otago home-based strength and balance retraining improves executive functioning in older fallers: a randomized controlled trial.", "The efficacy of a specific balance-strategy training programme for preventing falls among older people: a pilot randomised controlled trial.", "Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial.", "The effect of an individualized fall prevention program on fall risk and falls in older people: a randomized, controlled trial.", "Multifactorial fall prevention for pairs of frail community-dwelling older fallers and their informal caregivers: a dead end for complex interventions in the frailest fallers.", "Preventing falls in older people: outcome evaluation of a randomized controlled trial.", "Community-based group exercise improves balance and reduces falls in at-risk older people: a randomised controlled trial.", "The effect of group exercise on physical functioning and falls in frail older people living in retirement villages: a randomized, controlled trial.", "A randomized clinical trial of the effectiveness of a discharge planning intervention in hospitalized elders with hip fracture due to falling.", "Effect of impact exercise on bone mineral density in elderly women with low BMD: a population-based randomized controlled 30-month intervention.", "Community-based fall assessment compared with hospital-based assessment in community-dwelling older people over 65 at high risk of falling: a randomized study.", "Efficacy of a short multidisciplinary falls prevention program for elderly persons with osteoporosis and a fall history: a randomized controlled trial.", "Exercise training for rehabilitation and secondary prevention of falls in geriatric patients with a history of injurious falls.", "Reducing the fear of falling among community-dwelling elderly adults through cognitive-behavioural strategies and intense Tai Chi exercise: a randomized controlled trial.", "Community-based interventions to reduce falls among older adults in Taiwan - long time follow-up randomised controlled study.", "Improving medication use in newly admitted home healthcare patients: a randomized controlled trial.", "A randomized trial of a screening, case finding, and referral system for older veterans in primary care.", "Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimum calcium intake of more than 500 mg daily.", "The Winchester falls project: a randomised controlled trial of secondary prevention of falls in older people.", "Effects of a group exercise program on strength, mobility, and falls among fall-prone elderly men.", "Benefits of home visits for falls and autonomy in the elderly: a randomized trial study.", "Effect on falls of providing single lens distance vision glasses to multifocal glasses wearers: VISIBLE randomised controlled trial.", "Effects of whole body vibration on bone mineral density and falls: results of the randomized controlled ELVIS study with postmenopausal women.", "Preventing falls among community-dwelling older persons: results from a randomized trial.", "Improving vision to prevent falls in frail older people: a randomized trial.", "Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss.", "Balance, mobility, and falls among community-dwelling elderly persons: effects of a rehabilitation exercise program.", "Efficacy and effectiveness of a balance-enhancing insole.", "Pragmatic exercise-oriented prevention of falls among the elderly: a population-based, randomized, controlled trial.", "Testing the effect of the WALC intervention on exercise adherence in older adults.", "Effects of home exercises and group training on functional abilities in home-dwelling older persons with mobility and balance problems. A randomized study.", "Falls and health status in elderly women following second eye cataract surgery: a randomised controlled trial.", "An in-home preventive assessment program for independent older adults: a randomized controlled trial.", "The effect of a 12-month exercise trial on balance, strength, and falls in older women: a randomized controlled trial.", "Kenosha County falls prevention study: a randomized, controlled trial of an intermediate-intensity, community-based multifactorial falls intervention.", "The effects and costs of a multifactorial and interdisciplinary team approach to falls prevention for older home care clients 'at risk' for falling: a randomized controlled trial.", "A multicentre randomised controlled trial of day hospital-based falls prevention programme for a screened population of community-dwelling older people at high risk of falls.", "Effect of a nutrition supplement and physical activity program on pneumonia and walking capacity in Chilean older people: a factorial cluster randomized trial.", "Effect of music-based multitask training on gait, balance, and fall risk in elderly people: a randomized controlled trial.", "The effect of strength and endurance training on gait, balance, fall risk, and health services use in community-living older adults.", "Effect of annual intramuscular vitamin D on fracture risk in elderly men and women--a population-based, randomized, double-blind, placebo-controlled trial.", "Effect of cholecalciferol plus calcium on falling in ambulatory older men and women: a 3-year randomized controlled trial.", "Old women with a recent fall history show improved muscle strength and function sustained for six months after finishing training.", "Can health visitors prevent fractures in elderly people?", "Community falls prevention for people who call an emergency ambulance after a fall: randomised controlled trial.", "Reducing frailty and falls in older persons: an investigation of Tai Chi and computerized balance training. Atlanta FICSIT Group. Frailty and Injuries: Cooperative Studies of Intervention Techniques.", "Effects of preventive outpatient geriatric assessment: short-term results of a randomized controlled study.", "Effect of high-dosage cholecalciferol and extended physiotherapy on complications after hip fracture: a randomized controlled trial.", "Promotion of health in older people: a randomised controlled trial of health risk appraisal in British general practice.", "A multifactorial intervention to reduce the risk of falling among elderly people living in the community.", "Comparison of telecommunication, community, and home-based Tai Chi exercise programs on compliance and effectiveness in elders at risk for falls.", "Randomized controlled trial of calcium in healthy older women.", "A randomised controlled trial of Tai Chi and resistance exercise on bone health, muscle strength and balance in community-living elderly people.", "A randomized controlled trial of weight-bearing versus non-weight-bearing exercise for improving physical ability after usual care for hip fracture.", "Should oral nutritional supplementation be given to undernourished older people upon hospital discharge? A controlled trial.", "Effects of exercise and nutrition on postural balance and risk of falling in elderly people with decreased bone mineral density: randomized controlled trial pilot study.", "A five-week exercise program can reduce falls and improve obstacle avoidance in the elderly.", "Strategy to prevent falls in the Thai elderly: a controlled study integrated health research program for the Thai elderly.", "Effects on balance, falls, and bone mineral density of a home-based exercise program without home visits in community-dwelling elderly women: a randomized controlled trial.", "Effectiveness of a community-based multifactorial intervention on falls and fall risk factors in community-living older adults: a randomized, controlled trial.", "Two-year effects of interdisciplinary intervention for hip fracture in older Taiwanese.", "The effect of hormone replacement on physical performance in community-dwelling elderly women.", "A 12-month randomized controlled trial of balance training in elderly women with osteoporosis: improvement of quality of life.", "Trail-walking exercise and fall risk factors in community-dwelling older adults: preliminary results of a randomized controlled trial.", "Multifactorial intervention to reduce falls in older people at high risk of recurrent falls: a randomized controlled trial.", "Low-intensity exercise and reduction of the risk for falls among at-risk elders.", "Multifactorial intervention with balance training as a core component among fall-prone older adults.", "Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care.", "Cost-effectiveness of a multidisciplinary fall prevention program in community-dwelling elderly people: a randomized controlled trial (ISRCTN 64716113).", "A randomized controlled trial of a community-based consultation service to prevent falls.", "A randomised controlled trial of regular surveillance in Thai elderly using a simple questionnaire administered by non-professional personnel.", "Implementing strategies to decrease risk of falls in older women.", "Carotid sinus syndrome: a modifiable risk factor for nonaccidental falls in older adults (SAFE PACE).", "Environmental assessment and modification to prevent falls in older people.", "Attempts to prevent falls and injury: a prospective community study.", "A sustainable programme to prevent falls and near falls in community dwelling older people: results of a randomised trial.", "The effectiveness of a community-based program for reducing the incidence of falls in the elderly: a randomized trial.", "Tai Chi and fall reductions in older adults: a randomized controlled trial.", "Community-based intervention to optimise falls risk management: a randomised controlled trial.", "An electronic medical record (EMR)-based intervention to reduce polypharmacy and falls in an ambulatory rural elderly population.", "A randomized, controlled trial of tai chi for the prevention of falls: the Central Sydney tai chi trial.", "Resistance and agility training reduce fall risk in women aged 75 to 85 with low bone mass: a 6-month randomized, controlled trial.", "Vitamin D supplementation improves neuromuscular function in older people who fall." ]

[ "To measure the outcomes of a health assessment, conducted by a nurse, of people aged 75 years and older (75+HA) living independently in their own homes.\n Randomised controlled trial (RCT).\n A convenience sample of six general practices within the Adelaide Western Division of General Practice (AWDGP). A random sample of 100 participants was drawn from practice age-sex registers. Data were collected in initial visits between 1 August 1998 and February 1999, then in follow-up visits one year later.\n Participants were aged 75 years and over on 1 August 1998 and living independently in the community. 145 eligible patients were invited to join the study, and 100 of these consented to enrol (69%).\n A 75+HA conducted in the participant's home by a nurse and reported to their usual general practitioner.\n Primary: number of problems in each group; number of participants with problems; and mortality. Secondary: physical function; psychological (including cognitive) function; falls; and admission to institution.\n There were no significant differences between the control and intervention groups at follow-up in the number of problems, the number of participants with problems, or mortality. In the intervention group, there was significant improvement in self-rated health, geriatric depression score (GDS 15), and number of falls.\n This RCT has not demonstrated improvement in health status of the intervention group which received a 75+HA compared with a control group left to usual care.", "Using a randomized controlled trial, we tested the efficacy of a fall prevention intervention to reduce falls among adults in a community-based health promotion program. Adults aged 65 and older within two counties were recruited (control n = 257; intervention n = 286). After 12 months, there was a significant decrease in the number of falls in both groups (odds ratio = 0.45, p < .04), but the time by group membership interaction was not significant (χ(2) = 0.15, p < .69). Multivariate analysis did not find significant differences between the control and intervention groups for physical function as measured by a balance test or a sitting/standing test. Further research is needed on effective methods to deliver multifaceted fall interventions to older adults who are already being served by community health promotion programs.", "To evaluate the effectiveness of an enhanced balance training program in improving mobility and well-being of elderly people with balance problems.\n Prospective, single-blind, randomized, controlled trial.\n District general hospital.\n One hundred ninety-nine patients aged 60 and older with a Berg Balance Scale (BBS) score of less than 45.\n Six weeks enhanced balance training consisting of a series of repetitive tasks of increasing difficulty specific to functional balance. The control group received physiotherapy conforming to existing practice in elderly patients with mobility problems.\n Ten-meter timed walk test (TWT), BBS, Frenchay Activities Index (FAI), Falls Handicap Inventory (FHI), and European Quality of Life questionnaire (Euroqol) measured at 6, 12, and 24 weeks after intervention.\n The mean age +/- standard deviation of subjects was 82.7 +/- 5.6, and baseline characteristics were comparable between the groups. Both groups showed improvements in TWT (intervention: 22.5-16.5 seconds, P =.001; control: 20.5-15.8 seconds, P =.054), BBS (intervention: 33.3-42.7, P =.001; control: 33.4-42.0, P <.0001), FAI (18-21, P =.02 in both groups), FHI score (intervention: 31-17, P =.0001; control: 33-17, P =.0001) and Euroqol score (intervention: 58-65, P =.04; control: 60-65, P =.07). There were no intergroup differences at any time. More patients reported increased confidence in walking indoors (36% vs 28%; P =.04) and outdoors (27% vs 18%; P =.02) in the enhanced balance-training group.\n Exercise programs significantly improve balance and mobility in patients with balance problems, independent of strategy. Enhanced balance training may, in addition, improve confidence and quality of life but needs further investigation.", "To determine whether an intense tai chi (TC) exercise program could reduce the risk of falls more than a wellness education (WE) program in older adults meeting criteria for transitioning to frailty.\n Randomized, controlled trial of 48 weeks duration.\n Twenty congregate living facilities in the greater Atlanta area.\n Sample of 291 women and 20 men aged 70 to 97.\n Demographics, time to first fall and all subsequent falls, functional measures, Sickness Impact Profile, Centers for Epidemiologic Studies-Depression Scale, Activities-specific Balance Confidence Scale, Falls Efficacy Scales, and adherence to interventions.\n The risk ratio (RR) of falling was not statistically different in the TC group and the WE group (RR=0.75, 95% confidence interval (CI)=0.52-1.08), P=.13). Over the 48 weeks of intervention, 46% (n=132) of the participants did not fall; the percentage of participants that fell at least once was 47.6% for the TC group and 60.3% for the WE group.\n TC did not reduce the RR of falling in transitionally frail, older adults, but the direction of effect observed in this study, together with positive findings seen previously in more-robust older adults, suggests that TC may be clinically important and should be evaluated further in this high-risk population.", "To compare the effects of three fall-prevention programs (education (ED), home safety assessment and modification (HSAM), and exercise training (ET)) on quality of life (QOL), functional balance and gait, activities of daily living (ADLs), fear of falling, and depression in adults aged 65 and older.\n A 4-month randomized trial.\n Randomized, controlled trial.\n One hundred fifty participants who had experienced a recent fall.\n QOL was assessed according to the brief version of the World Health Organization Quality of Life instrument (WHOQOL-BREF), functional balance and gait according to functional reach and Tinetti balance and gait, ADLs according to the Older Americans Resources and Services questionnaire, fear of falling according to a visual analog scale, and depression level according to the Geriatric Depression Scale.\n The score changes for the ET group were 2.1 points greater on the physical domain (95% confidence interval (CI)=-1.2-5.3), 3.8 points greater on the psychological domain (95% CI=0.7-7.0), and for the WHOQOL-BREF, 3.4 points greater on the social domain (95% CI=0.7-6.1) and 3.2 points greater on the environmental domain (95% CI=0.6-5.7) than for the ED group. The score change for each domain of the WHOQOL-BREF for the HSAM group was greater than that for the ED group, although these results were not statistically significant. The ET group also had greater improvements in functional reach, Tinetti balance and gait, and fear of falling than the ED group.\n The QOL outcome supports the superiority of ET over the other two interventions in older people who have recently fallen. This finding also parallels those gathered from the functional measures.", "Vitamin D insufficiency is common in patients with osteoporosis. We conducted a randomized trial comparing alendronate 70 mg combined with vitamin D(3) 5,600 IU in a single tablet (ALN/D5600, n = 257) with standard care chosen by the patients' personal physicians (n = 258) in patients with postmenopausal osteoporosis (BMD T score ≤2.5 or ≤1.5 and a prior fragility fracture) who had vitamin D insufficiency (serum 25[OH]D values 8-20 ng/ml) and who were at risk of falls. Virtually all patients randomized to standard care received bisphosphonate therapy, and in approximately 70% of cases this was combined with vitamin D supplements. However, only 24% took ≥800 IU/day of supplemental vitamin D. At 6 months the proportion of patients with vitamin D insufficiency was 8.6% in the ALN/D5600 group compared with 31.0% in the standard care group (P < 0.001). Those in the ALN/D5600 group also had a greater reduction in urinary NTX/creatinine ratio (-57% vs. -46%, P < 0.001) and bone-specific alkaline phosphatase (-47% vs. -40%, P < 0.001). In the ALN/5600 group, by 12 months the increase in BMD was greater at the lumbar spine (4.9% vs. 3.9%, P = 0.047) and the total hip (2.2% vs. 1.4%, P = 0.035), significantly fewer patients were vitamin D-insufficient (11.3% vs. 36.9%, P < 0.001), and bone turnover marker (BTM) results were similar to those at 6 months. There was no difference between groups in those who experienced falls or fractures, and adverse events were similar. Based on the finding that ALN/D5600 was more effective than standard care at correcting vitamin D insufficiency, increasing BMD, and reducing BTMs in this patient group, greater attention needs to be directed toward optimizing the treatment of osteoporosis and correcting vitamin D deficiency in postmenopausal women.", "To evaluate the effect of an intervention by a multidisciplinary team to reduce falls in older people's homes.\n Randomized, controlled trial with follow-up of subjects for 1 year.\n University-affiliated geriatric hospital and older patients' homes.\n Three hundred sixty subjects (mean age +/- standard deviation = 81.5 +/- 6.4) admitted from home to a geriatric hospital and showing functional decline, especially in mobility.\n The participants were randomly assigned to receive a comprehensive geriatric assessment followed by a diagnostic home visit and home intervention or a comprehensive geriatric assessment with recommendations and usual care at home. The home intervention included a diagnostic home visit, assessing the home for environmental hazards, advice about possible changes, offer of facilities for any necessary home modifications, and training in the use of technical and mobility aids. An additional home visit was made after 3 months to reinforce the recommendations. After 12 months of follow-up, a home visit was made to all study participants.\n Number of falls, type of recommended home modifications, and compliance with recommendations.\n After 1 year, there were 163 falls in the intervention group and 204 falls in the control group. The intervention group had 31% fewer falls than the control group (incidence rate ratio (IRR) = 0.69, 95% confidence interval (CI) = 0.51-0.97). The intervention was most effective in a subgroup of participants who reported having had two or more falls during the year before recruitment into the study. In this subgroup, the proportion of frequent fallers and the rate of falls was significantly reduced for the intervention group compared with the control group (21 vs 36 subjects with recurrent falls, P =.009; IRR = 0.63, 95% CI = 0.43-0.94). The compliance rate varied with the type of change recommended from 83% to 33% after 12 months of follow-up.\n Home intervention based on home visits to assess the home for environmental hazards, providing information about possible changes, facilitating any necessary modifications, and training in the use of technical and mobility aids was effective in a selected group of frail older subjects with a history of recurrent falling.", "Evidence-based guidelines recommend a range of treatments for falls and injury prevention. We undertook a randomised trial of a falls prevention service to screen for falls risk factors and recommend to GPs an evidenced base prescription for falls prevention.\n All patients who presented with a fall to the Emergency Department at Flinders Medical Centre over a 22-week period were considered for the study. We excluded patients with dementia, resident in high care or those transferred to other hospitals and outside our catchment area. Of those who consented, we randomised patients between usual care or to an intervention consisting of a falls risk assessment and writing of an evidence-based prescription faxed to their GP for action. Patients were followed for six months and uptake of advice and fall rates were monitored.\n Four hundred and fifty patients presented with a fall-related attendance and of these 261 patients were eligible for inclusion in the trial. Of these 261 patients, 140 consented and were enrolled in the trial. Over the six months patients in the intervention group were more likely to uptake preventative advice (OR=12.3; 95%CI=4.2-35.9). We were unable to show a reduction in falls (OR= 1.7; 95%CI=0.7-4.4).\n A patient centered evidence-based approach is feasible and effective in increasing uptake of falls prevention advice. Long term compliance with advice needs further exploration.", "Exercise as a falls prevention strategy is more complex with people at risk than with the general population. The Lifestyle approach to reducing Falls through Exercise (LiFE) involves embedding balance and lower limb strength training in habitual daily routines.\n A total of 34 community-residing people aged ≥70 years were randomised either into the LiFE programme or into a no-intervention control group and followed up for six months. Inclusion criteria were two or more falls or an injurious fall in the past year.\n There were 12 falls in the intervention group and 35 in the control group. Therelative risk (RR) analysis demonstrated a significant reduction in falls (RR = 0.23; 0.07-0.83). There were indications that dynamic balance (P = 0.04 at three months) and efficacy beliefs (P = 0.04 at six months) improved for the LiFE programme participants. In general, secondary physical and health status outcomes, which were hypothesised as potential mediators of fall risk, improved minimally and inconsistently.\n LiFE was effective in reducing recurrent falls in this at-risk sample. However, there were minimal changes in secondary measures. The study was feasible in terms of recruitment, randomisation, blinding and data collection. A larger randomised trial is needed to investigate long-term efficacy, mechanisms of benefit and clinical significance of this new intervention.", "Physical activity (PA) and exercise have numerous beneficial effects in older adults. The effect of sustaining an injury from a fall on subsequent PA levels has received little research attention, even though about a quarter of older adults who fall sustain a serious injury. Even less is known about the effect of injurious falls on different PA categorizations.\n To examine the role of injurious falls on subsequent household and recreational PA levels in older community-dwelling males who were all Canadian veterans of World War II and the Korean War.\n Data from a fall risk-factor modification trial were used for the present study. Falls and related injuries were ascertained prospectively using fall calendars. A brief, valid and reliable PA interview for older adults (Phone-FITT) measured household and recreational PA approximately 1 year later. Covariates were measured as part of the screening questionnaire administered at the start of the study. Multiple linear regression models were computed using household and recreational PA as dependent variables.\n The present study included 200 males with a mean age 81 years (SD = 3.8). Half of the participants fell at least once and about one third reported at least one injury resulting from a fall. Multivariable analyses indicated that household PA scores were 3.1 points lower (95% CI = -5.8 to -0.3, p = 0.03) and recreational PA scores were 3.4 points higher (95% CI = 0.1 to 6.7, p = 0.04) among persons who had one or more falls leading to injury compared to those who did not fall or had one or more falls without injury. Analyses were adjusted for age, baseline PA, self-rated health, foot problems, balance problems, inability to stand without using armrests, vision and memory.\n Categorization of PA type (household vs. recreational) suggests distinct differences in PA response following an injurious fall. Use of an overall PA measure would obscure this finding. Following further research, the results from this study may help in the design of preventive strategies to maximize physical activity in those who have sustained an injurious fall.\n (c)2008 S. Karger AG, Basel.", "the burden of falls and fall-related injuries among older adults is well established. Contention surrounds the effectiveness, and hence value, of multi-component fall prevention interventions delivered in the community.\n using consensus-based analytic guidelines rather than time-to-first fall as the primary endpoint, the objective was to examine the effectiveness of the Whitehorse NoFalls trial on all falls, falls resulting in injury and falls requiring medical care to be sought. Design, setting and participants: the study was a community-based randomised controlled trial, with 1,090 participants assigned to one of eight groups, these being a combination of one or more of exercise, vision and or home hazard reduction or alternatively assignment to the control group.\n using negative binomial regression, the incidence of all falls, falls resulting in injury and those requiring medical care in the intervention groups were examined. Falls were reported using a monthly return calendar.\n exercise alone and in combination with vision and/or home hazard reduction was associated with fewer falls. For falls resulting in injury and the subset requiring medical care, the vision plus exercise intervention was associated with fewer falls.\n the findings confirm the effectiveness of exercise in preventing falls among community-dwelling older adults and supports contention that multi-component interventions do not prevent more falls than a single intervention. The results highlight the effectiveness of vision plus exercise in preventing more serious falls, a finding which warrants further consideration.", "To investigate the effectiveness of an educational Quality Use of Medicines program, delivered at the level of general practice, on medicines use, falls and quality of life in people aged > or = 65 years.\n Cluster randomised controlled trial conducted in 2002.\n General practices in the Hunter Region, New South Wales, Australia.\n Twenty general practitioners recruited 849 patients to participate in the study.\n Education (academic detailing, provision of prescribing information and feedback); medication risk assessment; facilitation of medication review; financial incentives.\n Primary measures: a composite score reflecting use of benzodiazepines, non-steroidal anti-inflammatory drugs (NSAIDs) and thiazide diuretics; secondary measures: use of medication reviews, occurrence of falls, quality of life (as assessed by SF-12 and EQ-5D survey scores.\n Compared with the control group, participants in the intervention group had increased odds of having an improved medication use composite score (odds ratio [OR], 1.86; 95% CI, 1.21-2.85) at 4-month follow-up but not at 12 months. At 4-month follow-up, the intervention group had reduced odds of using NSAIDs (OR, 0.62; 95% CI, 0.39-0.99) and showed a non-significant reduction in use of benzodiazepines (OR, 0.51; 95% CI, 0.20-1.30) and thiazide diuretics (OR, 0.70; 95% CI, 0.48-1.01). Changes in drug use were not significant at 12-month follow-up. At 12 months, intervention-group participants had lower adjusted ORs (AORs) for having a fall (AOR, 0.61; 95% CI, 0.41-0.91), injury (AOR, 0.56; 95% CI, 0.32-0.96), and injury requiring medical attention (AOR, 0.46; 95% CI, 0.30-0.70). Quality-of-life scores were unaffected by the intervention.\n Education and systems for medication review conducted by GPs can be used to improve use of medicines. These interventions are associated with a reduction in falls among older people, without adverse effects on quality of life.", "To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community.\n Randomised double blind controlled trial of 100 000 IU oral vitamin D3 (cholecalciferol) supplementation or matching placebo every four months over five years.\n 2686 people (2037 men and 649 women) aged 65-85 years living in the general community, recruited from the British doctors register and a general practice register in Suffolk.\n Fracture incidence and total mortality by cause.\n After five years 268 men and women had incident fractures, of whom 147 had fractures in common osteoporotic sites (hip, wrist or forearm, or vertebrae). Relative risks in the vitamin D group compared with the placebo group were 0.78 (95% confidence interval 0.61 to 0.99, P=0.04) for any first fracture and 0.67 (0.48 to 0.93, P=0.02) for first hip, wrist or forearm, or vertebral fracture. 471 participants died. The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 (0.74 to 1.06, P=0.18). Findings were consistent in men and women and in doctors and the general practice population.\n Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community.", "The hypothesis was that the calcium and vitamin D supplementation prevents falls at the population level.Study design: The OSTPRE-FPS was a randomized population-based open-trial with 3-year follow-up. The supplementation group (n=1566) received daily cholecalciferol 800IU+calcium carbonate 1000mg, while the control group (n=1573) received no supplementation or placebo. A randomly selected subsample of 593 subjects underwent a detailed measurement program including serum 25(OH)D measurements.\n The occurrence of falls was the primary outcome of the study. The participants in the subsample were telephoned at 4 months intervals and the rest of the trial population was interviewed by phone once a year.\n In the entire trial population (ETP), there were 812 women with 1832 falls in the intervention group and 833 women with 1944 falls in the control group (risk ratio was 0.98, 95% CI 0.92-1.05, P=0.160). The supplementation was not associated with single or multiple falls in the ETP. However, in the subsample, multiple fall incidence decreased by 30% (odds ratio (OR) 0.70, 95% CI 0.50-0.97, P=0.034) in the supplementation group. Further, the supplementation decreased the incidence of multiple falls requiring medical attention (OR 0.72, 95% CI 0.53-0.97, P=0.031) in the ETP. The mean compliance in the entire trial population was 78% and in the subsample 79%.\n Overall, the primary analysis showed no association between calcium and vitamin D supplementation and risk of falls. However, the results of a post hoc analysis suggested that there was a decreased risk of multiple falls requiring medical attention: this finding requires confirmation.\n Copyright 2009 Elsevier Ireland Ltd. All rights reserved.", "Nutritional deficiencies, frequently observed among the frail elderly, have been associated with increased morbidity and dependency. A randomized clinical trial was conducted to assess the impact of nutritional supplementation on the functional status of frail elderly living at home. Subjects (n = 50) over age 60 (mean 78 y) requiring community services and at elevated risk of undernutrition (excessive weight loss or body mass index < 24 kg/m2) were randomized to a high energy nutrient dense supplement provided by a dietitian or a control group receiving visits only. Outcome measures, including changes in handgrip strength, general well-being score, perception of health and number of falls, were measured by an investigator who was unaware of treatment assignment. After 12 wk, weight gain was greater in the supplemented group (2.1 +/- 2.3 vs. 0.6 +/- 1.6 kg; P < 0.01). Despite adequate statistical power, no functional measures differed except that the number of falls was lower among treated subjects vs. controls (0% vs. 21%; P = 0.05). Frail elderly can gain weight through oral supplementation, indicating the reversibility of weight loss in this group, but changes in functional status indicators may require a longer period of supplementation.", "Falls, loss of health-related quality of life and physical capacity, reduced participation in activities of daily living, and increased fear of falling are all potential outcomes for older adults discharged from hospital. A low-cost video based exercise programme may address this.\n This study was a randomized controlled trial with blinded outcomes assessment and a six-month follow-up.\n Participants were older adults (>65 years) using a mobility aid discharged from a tertiary hospital in Brisbane, Australia, without referral for community-based rehabilitation services.\n A digital video disk-based programme encompassing six exercise types each with six levels of difficulty. A home visit from a project physiotherapist was conducted to ensure patient safety. Control group patients received usual care.\n Falls, health-related quality of life, participation in activities of daily living, physical capacity and fear of falling.\n Study participants (n = 53, 19 intervention, 34 control) experienced decreasing health-related quality of life, several falls (72), and lower levels of participation in activities of daily living over the six-month follow-up. The intervention group did not differ significantly from the control group in terms of the outcomes examined, though a non-significant reduction in the rate of falls was observed. Intervention group participants complied with the exercise programme well during the first two weeks following discharge from hospital but then reduced their compliance levels thereafter.\n The intervention may be beneficial for reducing the rate of falls in this patient population though further research with a larger sample size is indicated.", "Pre-discharge home visits aim to maximise independence in the community. These visits involve assessment of a person in their own home prior to discharge from hospital, typically by an occupational therapist. The therapist may provide equipment, adapt the home environment and/or provide education. The aims of this study were to investigate the feasibility of a randomised controlled trial in a clinical setting and the effect of pre-discharge home visits on functional performance in older people undergoing rehabilitation.\n Ten patients participating in an inpatient rehabilitation program were randomly assigned to receive either a pre-discharge home visit (intervention), or standard practice in-hospital assessment and education (control), both conducted by an occupational therapist. The pre-discharge home visit involved assessment of the older person's function and environment, and education, and took an average of 1.5 hours. The hospital-based interview took an average of 40 minutes. Outcome data were collected by a blinded assessor at 0, 2, 4, 8 and 12 weeks. Outcomes included performance of activities of daily living, reintegration to community living, quality of life, readmission and fall rates.\n Recruitment of 10 participants was slow and took three months. Observed performance of functional abilities did not differ between groups due to the small sample size. Difference in activities of daily living participation, as recorded by the Nottingham Extended Activities of Daily Living scale, was statistically significant but wide confidence intervals and low statistical power limit interpretation of results.\n Evaluation of pre-discharge home visits by occupational therapists in a rehabilitation setting is feasible, but a more effective recruitment strategy for a main study is favored by application of a multi-centre setting.", "The present study was conducted to determine the effect of 5-month exercise program on the prevention of falls in the elderly. The exercise training, which consisted of calisthenics, body balance training, muscle power training, and walking ability training 3 days/week improved the indices of the flexibility, body balance, muscle power, and walking ability and reduced the incidence of falls compared with non-exercise controls. The present study showed the beneficial effect of the exercise program aimed at improving flexibility, body balance, muscle power, and walking ability in preventing falls in the elderly.\n The present study was conducted to determine the effect of exercise on the prevention of falls in the elderly.\n Sixty-eight elderly ambulatory volunteers were randomly divided into two groups: the exercise and control groups. The daily exercise, which consisted of calisthenics, body balance training (tandem standing, tandem gait, and unipedal standing), muscle power training (chair-rising training), and walking ability training (stepping), were performed 3 days/week only in the exercise group. No exercise was performed in the control group.\n After the 5-month exercise program, the indices of the flexibility, body balance, muscle power, and walking ability significantly improved in the exercise group compared with the control group. The incidence of falls was significantly lower in the exercise group than in the control group (0.0% vs. 12.1%, P = 0.0363). The exercise program was safe and well tolerated in the elderly.\n The present study showed the beneficial effect of the exercise program aimed at improving flexibility, body balance, muscle power, and walking ability in preventing falls in the elderly.", "Falls are the leading cause of both fatal and nonfatal injuries among older adults in the United States. Medications that affect the central nervous system are known to increase the risk of falling.\n The purpose of this study was to assess the effects of a community pharmacy-based falls-prevention program targeting high-risk older adults on the rates of recurrent falls, injurious falls, and filling prescriptions for medications that have been associated with an increased risk of falling.\n This was a randomized controlled trial of participants recruited through a community pharmacy chain in North Carolina. The 2-year study consisted of a 1-year \"look-back\" period before randomization and a 1-year follow-up period after randomization. Patients were eligible to participate if they were ≥65 years of age, had fallen at least once during the 1-year period preceding enrollment, and were taking medications associated with an increased risk of falling. Medications classified as high risk included benzodiazepines, antidepressants, anticonvulsants, sedative hypnotics, opioid analgesics, antipsychotics, and skeletal muscle relaxants. Participants were assigned to either the intervention arm or the control arm; participants in the intervention arm were invited to attend a face-to-face medication consultation conducted by a community pharmacy resident, whereas those in the control arm received no medication consultation. The primary end point was the rate of recurrent falls during the 1-year followup period. Secondary end points were the total number of prescriptions for high-risk medications filled during the follow-up period and either discontinued use or a reduction in the dosage of a high-risk medication during the follow-up period.\n One hundred eighty-six patients (132 women, 54 men; 88.7% white) were enrolled. Intention-to-treat (ITT) analyses revealed no significant differences in the rates of recurrent falls, injurious falls, or filling prescriptions for high-risk medications. However, 13 patients in the intervention group either discontinued use of a high-risk medication or had the dosage reduced during the follow-up period, compared with 5 patients in the control group (χ(2) = 3.94; P < 0.05). As-treated analyses revealed numeric reductions in the rates of falls (rate ratio [RR] = 0.76; 95% CI, 0.53-1.09), injurious falls (RR= 0.67; 95% CI, 0.43-1.05), and filling prescriptions for high-risk medications (RR= 0.85; 95% CI, 0.72-1.03) after receipt of the intervention, but the differences were not statistically significant.\n Results of this study support the feasibility of using community pharmacies to deliver a falls-prevention program targeting high-risk older adults. Although the ITT analyses revealed no significant reduction in the rate of recurrent falls, injurious falls, or overall use of high-risk medications, individuals in the intervention group were more likely than those in the control group to discontinue use of a high-risk medication or have the dosage reduced during the 1-year follow-up period. More work is needed to evaluate the intervention using a larger sample size that provides greater power to detect clinically meaningful effects of reduction in the use of high-risk medications on preventing or reducing falls in the high-risk population.\n Copyright © 2010 Elsevier HS Journals, Inc. Published by EM Inc USA. All rights reserved.", "To evaluate the effects of a multifactorial fall prevention program on falls and to identify the subgroups that benefit the most.\n Randomized controlled trial.\n Community-dwelling subjects who had fallen at least once during the previous 12 months.\n Five hundred ninety-one subjects randomized into intervention (IG) (n=293) and control (CG) (n=298) groups.\n A multifactorial 12-month fall prevention program.\n Incidence of falls.\n The intervention did not reduce the incidence of falls overall (incidence rate ratio (IRR) for IG vs CG=0.92, 95% confidence interval (CI)=0.72-1.19). In subgroup analyses, significant interactions between subgroups and groups (IG and CG) were found for depressive symptoms (P=.006), number of falls during the previous 12 months (P=.003), and self-perceived risk of falling (P=.045). The incidence of falls decreased in subjects with a higher number of depressive symptoms (IRR=0.50, 95% CI=0.28-0.88), whereas it increased in those with a lower number of depressive symptoms (IRR=1.20, 95% CI=0.92-1.57). The incidence of falls decreased also in those with at least three previous falls (IRR=0.59, 95% CI=0.38-0.91) compared to those with one or two previous falls (IRR=1.28, 95% CI=0.95-1.72). The intervention was also more effective in subjects with high self-perceived risk of falling (IRR=0.77, 95% CI=0.55-1.06) than in those with low self-perceived risk (IRR=1.28, 95% CI=0.88-1.86).\n The program was not effective in reducing falls in the total sample of community-dwelling subjects with a history of falling, but the incidence of falls decreased in participants with a higher number of depressive symptoms and in those with at least three falls.", "We estimated the incremental cost-effectiveness of a once-weekly or twice-weekly resistance training intervention compared with balance and tone classes in terms of falls prevented and quality-adjusted life years (QALYs) gained. Both resistance training interventions were more likely to save health care resource money and offer better health outcomes for falls prevention than balance and tone classes.\n This study aims to estimate the incremental cost-effectiveness and cost-utility of a once-weekly or twice-weekly resistance training intervention compared with twice-weekly balance and tone classes in terms of falls prevented and QALYs gained.\n Economic evaluation was conducted concurrently with a three-arm randomized controlled trial including 155 community-dwelling women aged 65 to 75 years, Mini Mental State Examination ≥24, and visual acuity 20/40 or better. Participants received the once-weekly resistance training (n = 54), the twice-weekly resistance training (n = 51) or the twice-weekly balance and tone (the comparator) classes (n = 50) for 1 year. Measurements included the number of falls for each participant, healthcare resource utilization, and associated costs over 9 months; health status was assessed using the EQ-5D and SF-6D to calculate QALYs.\n Based on the point estimates from our base case analysis, we found that both once- and twice-weekly resistance training groups were less costly (p < 0.05) and more effective than twice-weekly balance and tone classes. The incremental QALYs assessed using the SF-6D were 0.003 for both the once- and twice-weekly resistance training groups, compared with the twice-weekly balance and tone classes. The incremental QALYs assessed using the EQ-5D were 0.084 for the once-weekly and 0.179 for the twice-weekly resistance training groups, respectively, compared with the twice-weekly balance and tone classes.\n An individually tailored resistance training intervention delivered once or twice weekly provided better value for money for falls prevention than balance and tone classes.", "To assess the effectiveness of a single home visit by an occupational therapist in the reduction of fall risk after hip fracture in elderly women.\n Quasi-randomized controlled trial.\n Ninety-five women aged 60 years or older, living in the community, who sustained a fall-related hip fracture.\n The women were allocated alternately to intervention or control groups. All the women underwent a multidisciplinary programme targeted at fall prevention during in-patient rehabilitation. Additionally, the intervention group received a home visit by an occupational therapist a median of 20 days after discharge. Falls were recorded at a 6-month follow-up.\n Thirteen of the 50 women in the control group sustained 20 falls during 9231 days, whereas 6 of the 45 women in the intervention group sustained 9 falls during 8970 days. After adjustment for observation periods, Barthel Index scores, and body height, a significantly lower proportion of fallers was found in the intervention group: the odds ratio was 0.275 (95% confidence interval 0.081-0.937, p=0.039).\n A single home visit by an occupational therapist after discharge from a rehabilitation hospital significantly reduced the risk of falling in a sample of elderly women following hip fracture.", "nan", "Falls in elderly people are a common presenting complaint to accident and emergency departments. Current practice commonly focuses on the injury, with little systematic assessment of the underlying cause, functional consequences, and possibilities for future prevention. We undertook a randomised controlled study to assess the benefit of a structured inderdisciplinary assessment of people who have fallen in terms of further falls.\n Eligible patients were aged 65 years and older, lived in the community, and presented to an accident and emergency department with a fall. Patients assigned to the intervention group (n=184) underwent a detailed medical and occupational-therapy assessment with referral to relevant services if indicated; those assigned to the control group (n=213) received usual care only. The analyses were by intention to treat. Follow-up data were collected every 4 months for 1 year.\n At 12-month follow-up, 77% of both groups remained in the study. The total reported number of falls during this period was 183 in the intervention group compared with 510 in the control group (p=0.0002). The risk of falling was significantly reduced in the intervention group (odds ratio 0.39 [95% CI 0.23-0.66]) as was the risk of recurrent falls (0.33 [0.16-0.68]). In addition, the odds of admission to hospital were lower in the intervention group (0.61 [0.35-1.05]) whereas the decline in Barthel score with time was greater in the control group (p<0.00001).\n The study shows that an interdisciplinary approach to this high-risk population can significantly decrease the risk of further falls and limit functional impairment.", "To determine whether Yaktrax Walker (YW), a nonmedical gait-stabilizing device, prevents outdoor falls and injurious falls in fall-prone older people during the winter.\n Prospective, randomized, interventional trial.\n Community-based, northern United States, winter, outdoors.\n Ambulatory, community-dwelling, fall-prone people aged 65 and older.\n Participants were randomized to wear YW or their usual winter footwear (UWF) outdoors during the winter of 2003/2004.\n The number of indoor and outdoor slips, falls, and injurious falls was recorded daily in a fall diary. Winter footwear satisfaction survey was completed after study completion.\n One hundred nine subjects completed 10,724 diary days. Mean age was 74.2. There were 93 indoor slips, 13 indoor falls, 714 outdoor slips, and 62 outdoor falls. The tendency for both groups to slip/fall indoors was comparable. The relative risk (RR) of outdoor slip for YW was 0.50 (P<.04) for all diary days and 0.61 (P=.14) when only days walked on snow and ice was the exposure variable. The RR of outdoor fall for YW was 0.42 (P<.03) when only days walked on snow and ice was the exposure variable. RR of injurious falls per day walked on snow and ice for YW was 0.13 (P<.02). Twelve of 19 outdoor falls occurred when YW subjects were not wearing their assigned device. No serious injury or fracture occurred in either group. The number needed to treat for the YW to prevent one nonserious injurious fall in one winter was six.\n YW may reduce the risk of outdoor winter falls, and of nonserious injurious falls, in older community-dwelling people with a history of previous falls.", "Cardioinhibitory carotid sinus hypersensitivity (CICSH) is highly prevalent among older people with falls.\n To assess the efficacy of dual-chamber pacing in older patients with CICSH and unexplained falls.\n A multicentre, double blind, randomised controlled trial.\n Selection from emergency room, geriatric medicine and orthopaedic departments.\n Patients aged >50 years, with two unexplained falls and/or one syncopal event in the previous 12 months for which no other cause is evident apart from CICSH.\n Patients randomised to either a 700/400 kappa, rate responsive pacemaker or implantable loop recorder (Medtronic Reveal thera RDR, Medtronic, Minneapolis, Minnesota, USA).\n The primary outcome was the number falls after implantation. Secondary outcomes were time to fall event, presyncope, quality of life and cognitive function.\n 141 patients were recruited from 22 centres. Mean age was 78 years and mean follow-up 24 months. The overall relative risk of falling after device implantation compared with before was 0.23 (0.15 to 0.32). No significant reduction in falls was seen between paced and loop recorder groups (RR=0.79; 95% CI 0.41 to 1.50). Data were also consistent in both groups for syncope, quality of life and cognitive function. Conclusions These results question the use of pacing in CICSH. However, the study was underpowered and also patient characteristics differed from those in Safepace 1-participants were physically and cognitively frailer. Further work is necessary to assess cardiac pacing in this setting.", "To compare the effect of two modes of delivering a falls prevention service in reducing the rate of falls and improving quality of life, activity levels, and physical status among older adults with a history of recent falls.\n A randomized controlled trial was conducted with a total of 107 participants with blinded baseline and follow-up assessments. The participants were older community-dwelling adults referred for a falls prevention service located in Brisbane, Australia. The intervention was a multiple component falls prevention service delivered in either in a domiciliary or center-based mode of delivery. Both programs were similar apart from setting and consisted of three components, a balance and strength component, falls prevention education, and functional tasks. Physical and psychosocial assessments were administered at baseline, 8-week follow-up and 6-month follow-up. Falls data were collected by monthly telephone contact and by interview at 8 weeks and 6 months.\n The center-based service demonstrated significantly better results in preventing falls over the home-based service. Clients in the center-based arm of the trial experienced fewer total falls and this group also had a greater reduction in the total number of fallers after the intervention.\n This research demonstrates that delivering a similar service in different settings-home based or center based-impacts upon the effectiveness of the service. Community-dwelling older adults with a history of falls should be provided with center-based programs in preference to home-based programs where they are available.", "To determine the effectiveness of a multifaceted podiatry intervention in preventing falls in community dwelling older people with disabling foot pain.\n Parallel group randomised controlled trial.\n University health sciences clinic in Melbourne, Australia.\n 305 community dwelling men and women (mean age 74 (SD 6) years) with disabling foot pain and an increased risk of falling. 153 were allocated to a multifaceted podiatry intervention and 152 to routine podiatry care, with 12 months' follow-up.\n Multifaceted podiatry intervention consisting of foot orthoses, advice on footwear, subsidy for footwear ($A100 voucher; £65; €74), a home based programme of foot and ankle exercises, a falls prevention education booklet, and routine podiatry care for 12 months. The control group received routine podiatry care for 12 months.\n Proportion of fallers and multiple fallers, falling rate, and injuries resulting from falls during follow-up.\n Overall, 264 falls occurred during the study. 296 participants returned all 12 calendars: 147 (96%) in the intervention group and 149 (98%) in the control group. Adherence was good, with 52% of the participants completing 75% or more of the requested three exercise sessions weekly, and 55% of those issued orthoses reporting wearing them most of the time. Participants in the intervention group (n=153) experienced 36% fewer falls than participants in the control group (incidence rate ratio 0.64, 95% confidence interval 0.45 to 0.91, P=0.01). The proportion of fallers and multiple fallers did not differ significantly between the groups (relative risk 0.85, 0.66 to 1.08, P=0.19 and 0.63, 0.38 to 1.04, P=0.07). One fracture occurred in the intervention group and seven in the control group (0.14, 0.02 to 1.15, P=0.07). Significant improvements in the intervention group compared with the control group were found for the domains of strength (ankle eversion), range of motion (ankle dorsiflexion and inversion/eversion), and balance (postural sway on the floor when barefoot and maximum balance range wearing shoes).\n A multifaceted podiatry intervention reduced the rate of falls in community dwelling older people with disabling foot pain. The components of the intervention are inexpensive and relatively simple to implement, suggesting that the programme could be incorporated into routine podiatry practice or multidisciplinary falls prevention clinics.\n Australian New Zealand Clinical Trials Registry ACTRN12608000065392.", "It is important to determine if permanent lifestyle changes may result from physical activity interventions and whether health may be affected by these changes.\n To conduct a 10-year follow-up of physical activity and self-reported health status in participants of a randomized clinical trial of walking intervention.\n Of the original 229 volunteer postmenopausal women who participated in the original clinical trial, 196 (N = 96 intervention and 100 controls) completed the 10-year follow-up telephone interview. The interview protocol included questions on self-reported walking for exercise and purposes other than exercise, the Paffenbarger sport and exercise index, functional status, and various chronic diseases and conditions.\n The median values for both usual walking for exercise and total walking were significantly higher for walkers compared with controls (for both, P = .01), with median differences of 706 and 420 kcal/wk, respectively. After excluding women who reported heart disease during the original trial, 2 women in the walking group (2%) and 11 women in the control group (12%) reported physician-diagnosed heart disease over the last 10 years (P = .07). There were also fewer hospitalizations, surgeries, and falls among women in the walking group, although these differences were not statistically significant (P>.05).\n Although limited by self-report, this study may be the first to demonstrate long-term exercise compliance to a randomized control trial in older women and to suggest that health benefits may have ensued as a result of these increased activity levels.", "To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge.\n Multicenter, randomized, controlled trial with a factorial design.\n Five hospitals in Auckland, New Zealand, and Sydney, Australia.\n Two hundred forty-three frail older people.\n Patients were randomized to receive a single dose of vitamin D (calciferol, 300,000 IU) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits.\n The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months. Physical performance and self-rated function were secondary endpoints. Assessments took place in the participants' homes at 3 and 6 months after randomization and were performed by blinded assessors.\n There was no effect of either intervention on physical health or falls, but patients in the exercise group were at increased risk of musculoskeletal injury (risk ratio = 3.6, 95% confidence interval = 1.5-8.0). Vitamin D supplementation did not improve physical performance, even in those who were vitamin D deficient (<12 ng/mL) at baseline.\n Neither vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization. There was no effect of vitamin D on physical performance, and the exercises increased the risk of musculoskeletal injury. These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people.", "To assess the effectiveness of a trained district nurse individually prescribing a home based exercise programme to reduce falls and injuries in elderly people and to estimate the cost effectiveness of the programme.\n Randomised controlled trial with one year's follow up.\n Community health service at a New Zealand hospital.\n 240 women and men aged 75 years and older.\n 121 participants received the exercise programme (exercise group) and 119 received usual care (control group); 90% (211 of 233) completed the trial.\n Number of falls, number of injuries resulting from falls, costs of implementing the programme, and hospital costs as a result of falls.\n Falls were reduced by 46% (incidence rate ratio 0.54, 95% confidence interval 0.32 to 0.90). Five hospital admissions were due to injuries caused by falls in the control group and none in the exercise group. The programme cost $NZ1803 (523 pound sterling) (at 1998 prices) per fall prevented for delivering the programme and $NZ155 per fall prevented when hospital costs averted were considered.\n A home exercise programme, previously shown to be successful when delivered by a physiotherapist, was also effective in reducing falls when delivered by a trained nurse from within a home health service. Serious injuries and hospital admissions due to falls were also reduced. The programme was cost effective in participants aged 80 years and older compared with younger participants.", "While carotid sinus syndrome (CSS) is traditionally defined by the association of carotid sinus hypersensitivity (CSH) with syncope, uncertainty remains over the role, if any, of complex pacing in patients with CSH and unexplained or recurrent falls. We sought to clarify the role of dual chamber pacing in this patient group in the first placebo-controlled study in CSH.\n Randomised, double-blind, crossover, placebo-controlled trial.\n Specialist falls and syncope facility.\n Consecutive subjects aged over 55 years with CSH as the sole attributable cause of three or more unexplained falls in the 6 months preceding enrolment.\n Dual-chamber permanent pacing with rate-drop response programming. The pacemaker was switched on (DDD/RDR) or off (ODO (placebo)) for 6 months, then crossed over to the alternate mode for a further 6 months, in randomised, double-blind fashion.\n The primary outcome measure was number of falls in paced and non-paced modes.\n Twenty-five of 34 subjects (mean 76.8 years (SD 9.0), 27 (79%) female) recruited completed the study. Pacing intervention had no effect on number of falls (4.04 (9.54) in DDD/RDR mode, 3.48 (7.22) in ODO; relative risk of falling in ODO mode 0.82, 95% CI 0.62 to 1.10).\n Permanent pacing intervention had no effect on fall rates in older patients with CSH. Further work is urgently needed to clarify the role, if any, of complex pacing in this patient group.", "To determine the effectiveness of multifactorial intervention to prevent falls in cognitively intact older persons with recurrent falls.\n Randomised controlled trial of multifactorial (medical, physiotherapy and occupational therapy) post-fall assessment and intervention compared with conventional care.\n Accident & Emergency departments in a university teaching hospital and associated district general hospital.\n 313 cognitively intact men and women aged over 65 years presenting to Accident & Emergency with a fall or fall-related injury and at least one additional fall in the preceding year; 159 randomised to assessment and intervention and 154 to conventional care. Outcome measures: primary outcome was the number of falls and fallers in 1 year after recruitment. Secondary outcomes included injury rates, fall-related hospital admissions, mortality and fear of falling.\n There were 36% fewer falls in the intervention group (relative risk 0.64, 95% confidence interval 0.46-0.90). The proportion of subjects continuing to fall (65% (94/144) compared with 68% (102/149) relative risk 0.95, 95% confidence interval 0.81-1.12), and the number of fall-related attendances and hospital admissions was not different between groups. Duration of hospital admission was reduced (mean difference admission duration 3.6 days, 95% confidence interval 0.1-7.6) and falls efficacy was better in the intervention group (mean difference in Activities Specific Balance Confidence Score of 7.5, 95% confidence interval 0.72-14.2).\n Multifactorial intervention is effective at reducing the fall burden in cognitively intact older persons with recurrent falls attending Accident & Emergency, but does not reduce the proportion of subjects still falling.", "To explore effects of a health risk appraisal for older people (HRA-O) program with reinforcement, we conducted a randomized controlled trial in 21 general practices in Hamburg, Germany.\n Overall, 2,580 older patients of 14 general practitioners trained in reinforcing recommendations related to HRA-O-identified risk factors were randomized into intervention (n = 878) and control (n = 1,702) groups. Patients (n = 746) of seven additional matched general practitioners who did not receive this training served as a comparison group. Patients allocated to the intervention group, and their general practitioners, received computer-tailored written recommendations, and patients were offered the choice between interdisciplinary group sessions (geriatrician, physiotherapist, social worker, and nutritionist) and home visits (nurse).\n Among the intervention group, 580 (66%) persons made use of personal reinforcement (group sessions: 503 [87%], home visits: 77 [13%]). At 1-year follow-up, persons in the intervention group had higher use of preventive services (eg, influenza vaccinations, adjusted odds ratio 1.7; 95% confidence interval 1.4-2.1) and more favorable health behavior (eg, high fruit/fiber intake, odds ratio 2.0; 95% confidence interval 1.6-2.6), as compared with controls. Comparisons between intervention and comparison group data revealed similar effects, suggesting that physician training alone had no effect. Subgroup analyses indicated favorable effects for HRA-O with personal reinforcement, but not for HRA-O without reinforcement.\n HRA-O combined with physician training and personal reinforcement had favorable effects on preventive care use and health behavior.", "Decreased fitness of the lower extremities is a potentially modifiable fall risk factor. This study aimed to compare two exercise programs--square-stepping exercise (SSE), which is a low-cost indoor program, and walking--for improving the fitness of the lower extremities.\n We randomly allocated 68 community-dwelling older adults (age 65-74 years) to either the SSE or walking group (W group). During the 12-week regimen, the SSE group participated in 70-minute exercise sessions conducted twice a week at a local health center, and the W group participated in outdoor supervised walking sessions conducted weekly. The W group was instructed to increase the number of daily steps. Prior to and after the program, we obtained information on 11 physical performance tests for known fall risk factors and 3 self-reported scales. The fall incidence was followed-up for 8 months.\n At 12 weeks postregimen, significant differences were observed between the two exercise groups with respect to leg power (1 item), balance (2 items), agility (2 items), reaction time (2 items), and a self-reported scale (1 item); the SSE group demonstrated a marked improvement in the above-mentioned items with Group x Time interactions. Significant time effects were observed in the tests involving chair stands, functional reach, and standing up from a lying-down position without Group x Time interactions. During the follow-up period, the fall rates per person-year in the SSE and W groups were 23.4% and 33.3%, respectively (p =.31).\n Although further studies are required, SSE is apparently more effective than walking in reducing fall risk factors, and it appears that it may be recommended as a health promotion exercise in older adults.", "Ergocalciferol (vitamin D(2)) supplementation plays a role in fall prevention, but the effect in patients living in the community in sunny climates remains uncertain. We evaluated the effect of ergocalciferol and calcium citrate supplementation compared with calcium alone on the risk of falls in older women at high risk of falling.\n A 1-year population-based, double-blind, randomized controlled trial of 302 community-dwelling ambulant older women aged 70 to 90 years living in Perth, Australia (latitude, 32 degrees S), with a serum 25-hydroxyvitamin D concentration of less than 24.0 ng/mL and a history of falling in the previous year. Participants were randomized to receive ergocalciferol, 1000 IU/d, or identical placebo (hereinafter, ergocalciferol and control groups, respectively). Both groups received calcium citrate, 1000 mg/d. Fall data were collected every 6 weeks.\n Ergocalciferol therapy reduced the risk of having at least 1 fall over 1 year after adjustment for baseline height, which was significantly different between the 2 groups (ergocalciferol group, 53.0%; control group, 62.9%; odds ratio [OR], 0.61; 95% confidence interval [CI], 0.37-0.99). When those who fell were grouped by the season of first fall or the number of falls they had, ergocalciferol treatment reduced the risk of having the first fall in winter and spring (ergocalciferol group, 25.2%; control group, 35.8%; OR, 0.55; 95% CI, 0.32-0.96) but not in summer and autumn, and reduced the risk of having 1 fall (ergocalciferol group, 21.2%; control group, 33.8%; OR, 0.50; 95% CI, 0.28-0.88) but not multiple falls.\n Patients with a history of falling and vitamin D insufficiency living in sunny climates benefit from ergocalciferol supplementation in addition to calcium, which is associated with a 19% reduction in the relative risk of falling, mostly in winter.", "To evaluate the effectiveness of Tai Chi Chuan in fall prevention in elderly people living at home with a high risk of falling.\n Randomized controlled trial.\n Two industrial towns in the western part of the Netherlands.\n Two hundred sixty-nine elderly people (average age 77) living at home with a high risk of falling.\n The intervention group received Tai Chi Chuan training for 1 hour twice a week for 13 weeks; the control group received usual care. Both groups received a brochure containing general information on how to prevent fall incidents.\n Primary outcome was the number of falls over 12 months. Secondary outcomes were balance, fear of falling, blood pressure, heart rate at rest, forced expiratory volume during the first second, peak expiratory flow, physical activity, and functional status.\n After 12 months, no lower fall risk in the Tai Chi Chuan group was observed than in the control group (adjusted hazard ratio=1.16; 95% confidence interval=0.84-1.60), and there were no significant intervention effects on the secondary outcome measures.\n These results suggest that Tai Chi Chuan may not be effective in elderly people at a high risk of falling who live at home.", "To test the benefits of regular surveillance of the elderly at home using an activities of daily living questionnaire administered by volunteers.\n Randomised controlled study.\n 539 Subjects aged 75 and over from two general practices.\n All subjects were visited at the beginning and end of the study by volunteers, who completed a scored activity of daily living questionnaire. The study group were revisited at regular intervals. Individuals with an increase in score greater than 5 were referred to their general practitioners. All interactions with social services and health authorities were recorded for both groups.\n Mortality, activity of daily living score, total number of days in institutions, geriatric and psychogeriatric service contacts, primary health care team contacts, use of community support services.\n The study group were admitted to hospital more often than the controls (335 occasions v 252), but the control group spent 33% more days in institutions, mainly in long term admissions to residential accommodation. The number of falls reported in the control group doubled (from 17 before the first interview to 36 before the last) and in the study group remained unchanged (12 before both interviews). The study group received community support services sooner than the control group. There was no difference between the groups in mortality or activity of daily living score.\n Regular visiting of old people at home by non-professional volunteers using a simple activity of daily living questionnaire is a practical way of identifying problems and initiating action for this group.", "Falls are common in elderly people. Possible consequences include serious injuries and the post-fall syndrome, with functional decline and limitation of physical activity. The present randomized controlled study sought to clarify the benefits of a combined long-term and home-based fall prevention program for elderly Japanese women. The subjects were individuals aged over 73 years, living at home in a western suburb of Tokyo, who had attended a comprehensive geriatric health check. Persons with a marked decline in the basic activities of daily living (ADL), hemiplegia, or those missing baseline data were excluded. Fifty-two subjects who expressed a wish to participate in the trial were randomized, 28 to an exercise-intervention group and 24 to a control group. Baseline data for age, handgrip force, walking speed, total serum cholesterol, serum albumin, basic ADL, visual and auditory impairments, self-rated health, and experience of falls did not differ significantly between the two groups. Beginning from June 2000, the intervention group attended a 6-month program of fall-prevention exercise classes aimed at improving leg strength, balance, and walking ability; this was supplemented by a home-based exercise program that focused on leg strength. The control group received only a pamphlet and advice on fall prevention. The average rate of attendance at exercise class was 75.3% (range, 64% to 86%). Participants showed significant improvements in tandem walk and functional reach after the intervention program, with enhanced self confidence. At the 8-month follow-up, the proportion of women with falls was 13.6% (3/22) in the intervention group and 40.9% (9/22) in the control group. At 20 months, the proportion remained unchanged, at 13.6% in the intervention group, but had increased to 54.5% (12/22) in the control group, which showed a statistically significant difference between the two groups (Fisher's exact test; P = 0.0097). The total number of falls during the 20-month follow-up period was 6 in the intervention group and 17 in the control group. We conclude that a moderate exercise intervention program plus a home-based program significantly decreases the incidence of falls in both the short and the long term, contributing to improved health and quality of life in the elderly.\n Copyright 2004 Springer-Verlag", "Elderly people who have a fracture are at high risk of another. Vitamin D and calcium supplements are often recommended for fracture prevention. We aimed to assess whether vitamin D3 and calcium, either alone or in combination, were effective in prevention of secondary fractures.\n In a factorial-design trial, 5292 people aged 70 years or older (4481 [85%] of whom were women) who were mobile before developing a low-trauma fracture were randomly assigned 800 IU daily oral vitamin D3, 1000 mg calcium, oral vitamin D3 (800 IU per day) combined with calcium (1000 mg per day), or placebo. Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months. Analysis was by intention-to-treat and the primary outcome was new low-energy fractures.\n 698 (13%) of 5292 participants had a new low-trauma fracture, 183 (26%) of which were of the hip. The incidence of new, low-trauma fractures did not differ significantly between participants allocated calcium and those who were not (331 [12.6%] of 2617 vs 367 [13.7%] of 2675; hazard ratio (HR) 0.94 [95% CI 0.81-1.09]); between participants allocated vitamin D3 and those who were not (353 [13.3%] of 2649 vs 345 [13.1%] of 2643; 1.02 [0.88-1.19]); or between those allocated combination treatment and those assigned placebo (165 [12.6%] of 1306 vs 179 [13.4%] of 1332; HR for interaction term 1.01 [0.75-1.36]). The groups did not differ in the incidence of all-new fractures, fractures confirmed by radiography, hip fractures, death, number of falls, or quality of life. By 24 months, 2886 (54.5%) of 5292 were still taking tablets, 451 (8.5%) had died, 58 (1.1%) had withdrawn, and 1897 (35.8%) had stopped taking tablets but were still providing data for at least the main outcomes. Compliance with tablets containing calcium was significantly lower (difference: 9.4% [95% CI 6.6-12.2]), partly because of gastrointestinal symptoms. However, potentially serious adverse events were rare and did not differ between groups.\n The findings do not support routine oral supplementation with calcium and vitamin D3, either alone or in combination, for the prevention of further fractures in previously mobile elderly people.", "The development of falls prevention strategies is an essential health concern in elderly people. However, a global consensus does not exist for elderly subjects who live independently in the community. The aim of the study was to evaluate the benefit of an exercises program.\n A control group (153 subjects) and an \"Intervention\" group (150 subjects) were tested before and after a 1-year prospective study. The \"Intervention\" group performed ten training sessions of physical activity, based on balance, muscular activity and coordination. We compared the incidence of falls, and the performances in several tests between the two groups.\n The clinical features were similar between the two groups: mean age 71 years, 83% of females, subjects who were independent for activities of daily living. However, all subjects presented risk for factors for falls: 38% were not able to maintain the unipodal position more than five seconds, 29% had already fallen during the previous year. For the \"Intervention\" group, the comparison of the performances before and after the physical activity program showed significant increases (p < 0.001) for all the tests, and specifically for the unipodal position and for the exercises performed with eyes closed. After one year follow-up, the incidence rate of falls was lower in the \"Intervention\" group compared with the control group, but the difference was not significant (p = 0.32). However, falls occurred significantly latter in the \"Intervention\" group (p = 0.02).\n Ten training sessions of physical activity allowed to improve the performance of elderly people in several tests. This result suggests that a fall prevention program based on collective and regular exercises, may be efficient for elderly subjects who still have an active and independent way of live.", "A high incidence of fractures, particularly of the hip, represents an important problem in patients with Alzheimer's disease (AD), who are prone to falls and may have osteoporosis. We previously showed deficiency of vitamins D and K1 causes reduced bone mineral density (BMD) in female AD patients. The present study was undertaken to address the possibility that treatment with vitamin K2 (menatetrenone; MK-4) may maintain BMD and reduce the incidence of nonvertebral fractures in elderly female patients with AD. In a random and prospective study of AD patients, 100 patients received 45 mg menatetrenone, 1000 IU ergocalciferol and 600 mg calcium daily for 2 years, and the remaining 100 (untreated group) did not. At baseline, patients of both groups showed vitamin D and K1 deficiencies. They also had high serum levels of parathyroid hormone (PTH) and Glu osteocalcin (OC) and low serum ionized calcium, indicating that vitamin D deficiency stimulates compensatory PTH secretion. During the 2-year study period, BMD in the second metacarpals increased by 2.3% in the treated group and decreased by 5.2% in the untreated group (P < 0.0001). Serum levels of vitamin K2 and 25-hydroxyvitamin D increased by 284.9% and 147.9%, respectively, in the treated group. Correspondingly, a significant decrease in Glu OC and PTH were observed, in association with an increased calcium levels, in the treated group. Twenty-two patients in the untreated group sustained nonvertebral fractures (15 with hip fractures, two fractures each at the distal forearm and the proximal femur, each one fracture at the proximal humerus, ribs, and pelvis), and three fractures (2 with hip fractures, one fracture at the proximal femur) occurred among the treated patients (P = 0.0003; odds ratio = 7.5). Treatment with MK-4 and vitamin D2 with calcium supplements increases the BMD in elderly female patients with AD and leads to the prevention of nonvertebral fractures.", "In 242 community-dwelling seniors, supplementation with either 1000 mg of calcium or 1000 mg of calcium plus vitamin D resulted in a decrease in the number of subjects with first falls of 27% at month 12 and 39% at month 20. Additionally, parameters of muscle function improved significantly.\n The efficacy of vitamin D and calcium supplementation on risk of falling in the elderly is discussed controversially. Randomized controlled trials using falls as primary outcome are needed. We investigated long-term effects of calcium and vitamin D on falls and parameters of muscle function in community-dwelling elderly women and men.\n Our study population consisted of 242 individuals recruited by advertisements and mailing lists (mean [ +/- SD] age, 77 +/- 4 years). All serum 25-hydroxyvitamin D (25[OH]D) levels were below 78 nmol/l. Individuals received in a double blinded fashion either 1000 mg of calcium or 1000 mg of calcium plus 800 IU of vitamin D per day over a treatment period of 12 months, which was followed by a treatment-free but still blinded observation period of 8 months. Falls were documented using diaries. The study took place in Bad Pyrmont, Germany (latitude 52 degrees ) and Graz, Austria (latitude 46 degrees ).\n Compared to calcium mono, supplementation with calcium plus vitamin D resulted in a significant decrease in the number of subjects with first falls of 27% at month 12 (RR = 0.73; CI = 0.54-0.96) and 39% at month 20 (RR = 0.61; CI = 0.34-0.76). Concerning secondary endpoints, we observed significant improvements in quadriceps strength of 8%, a decrease in body sway of 28%, and a decrease in time needed to perform the TUG test of 11%.\n Combined calcium and vitamin D supplementation proved superior to calcium alone in reducing the number of falls and improving muscle function in community-dwelling older individuals.", "To evaluate the effect of multifactorial fall prevention in community-dwelling people aged 65 and older in Denmark.\n Randomized, controlled clinical trial.\n Geriatric outpatient clinic at Glostrup University Hospital.\n Three hundred ninety-two elderly people, mean age 74, 73.7%women, who had visited the emergency department or had been hospitalized due to a fall.\n Identification of general medical, cardiovascular, and physical risk factors for falls and individual intervention in the intervention group. Participants in the control group received usual care.\n Falls were registered prospectively in falls diaries, with monthly telephone calls for collection of data. Outcomes were fall rates and proportion of participants with falls, frequent falls, and injurious falls in 12 months.\n Groups were comparable at baseline. Followup exceeded 90.0%. A total of 422 falls were registered in the intervention group, 398 in the control group. Intention-to-treat analysis revealed no effect of the intervention on fall rates (relative risk=1.06, 95%confidence interval (CI)=0.75 -1.51), proportion with falls (odds ratio (OR)=1.20, 95% CI 0.81-1.79), frequent falls (OR=0.97, 95% CI=0.60-1.56), or injurious falls (OR=0.97, 95% CI=0.57-1.62).\n A program of multifactorial fall prevention aimed at elderly Danish people experiencing at least one injurious fall was not effective in preventing further falls.", "To assess the efficacy and cost effectiveness of a home safety programme and a home exercise programme to reduce falls and injuries in older people with low vision.\n Randomised controlled trial.\n Dunedin and Auckland, New Zealand.\n 391 women and men aged > or =75 with visual acuity of 6/24 or worse who were living in the community; 92% (361 of 391) completed one year of follow-up.\n Participants received a home safety assessment and modification programme delivered by an occupational therapist (n = 100), an exercise programme prescribed at home by a physiotherapist plus vitamin D supplementation (n = 97), both interventions (n = 98), or social visits (n = 96).\n Numbers of falls and injuries resulting from falls, costs of implementing the home safety programme.\n Fewer falls occurred in the group randomised to the home safety programme but not in the exercise programme (incidence rate ratios 0.59 (95% confidence interval 0.42 to 0.83) and 1.15 (0.82 to 1.61), respectively). However, within the exercise programme, stricter adherence was associated with fewer falls (P = 0.001). A conservative analysis showed neither intervention was effective in reducing injuries from falls. Delivering the home safety programme cost NZ650 dollars (234 pounds sterling, 344 euros, US432 dollars) (at 2004 prices) per fall prevented.\n The home safety programme reduced falls and was more cost effective than an exercise programme in this group of elderly people with poor vision. The Otago exercise programme with vitamin D supplementation was not effective in reducing falls or injuries in this group, possibly due to low levels of adherence. Trial registration number ISRCTN15342873.", "A third of elderly people fall each year. Poor vision is associated with increased risk of falls. The authors aimed to determine if first eye cataract surgery reduces the risk of falling, and to measure associated health gain.\n 306 women aged over 70, with cataract, were randomised to expedited (approximately 4 weeks) or routine (12 months wait) surgery. Falls were ascertained by diary, with follow up every 3 months. Health status was measured after 6 months.\n Visual function improved in the operated group (corrected binocular acuity improved by 0.25 logMAR units; 8% had acuity worse than 6/12 compared with 37% of controls). Over 12 months of follow up, 76 (49%) operated participants fell at least once, and 28 (18%) fell more than once. 69 (45%) unoperated participants fell at least once, 38 (25%) fell more than once. Rate of falling was reduced by 34% in the operated group (rate ratio 0.66, 95% confidence interval 0.45 to 0.96, p = 0.03). Activity, anxiety, depression, confidence, visual disability, and handicap all improved in the operated group compared with the control group. Four participants in the operated group had fractures (3%), compared with 12 (8%) in the control group (p = 0.04).\n First eye cataract surgery reduces the rate of falling, and risk of fractures and improves visual function and general health status.", "survivors of hip fracture are at 5- to 10-fold risk of a second hip fracture. There is little consensus about secondary prevention. Many are given calcium and vitamin D, but the evidence supporting this is circumstantial.\n to compare the effects of different calcium and vitamin D supplementation regimens on bone biochemical markers, bone mineral density and rate of falls in elderly women post-hip fracture.\n randomised controlled trial.\n orthogeriatric rehabilitation ward.\n 150 previously independent elderly women, recruited following surgery for hip fracture, were assigned to receive a single injection of 300,000 units of vitamin D(2), injected vitamin D(2) plus 1 g/day oral calcium, 800 units/day oral vitamin D(3) plus 1 g/day calcium, or no treatment. Follow-up was one year, with measurement of 25-hydroxyvitamin D, parathyroid hormone, bone mineral density, and falls.\n mean 25-hydroxyvitamin D increased and mean parathyroid hormone was suppressed in all the actively treated groups, more so in the group receiving combined oral vitamin D and calcium. Twenty per cent of participants injected with vitamin D were deficient in 25-hydroxyvitamin D a year later. Bone mineral density showed small but statistically significant differences of up to 4.6% between actively treated groups and placebo. Relative risk of falling in the groups supplemented with vitamin D was 0.48 (95% CI 0.26-0.90) compared with controls.\n Vitamin D supplementation, either orally or with injected vitamin D, suppresses parathyroid hormone, increases bone mineral density and reduces falls. Effects may be more marked with calcium co-supplementation. The 300,000 units of injected vitamin D may not last a whole year.", "Long-term vitamin D and calcium supplementation is effective in reducing nonvertebral fractures in elderly people. Increased bone fragility caused by secondary hyperparathyroidism (sHPT) and impaired balance are known risk factors for hip fractures. The hypothesis is that short-term therapy with calcium and vitamin D may improve body sway as well as sHPT more effectively than calcium monotherapy. The effects of 8 weeks of supplementation with vitamin D (cholecalciferol) and calcium on body sway and biochemical measures of bone metabolism were measured. The sample consisted of 148 women (mean [+/-SD] age, 74 +/- 1 years) with a 25-hydroxycholecalciferol level below 50 nmol/liter. They received either 1200 mg of calcium plus 800 IU of vitamin D or 1200 mg of calcium per day. We measured intact parathyroid hormone (PTH), markers of bone turnover, and body sway before and after treatment. Falls and fractures among the participants were followed over a 1-year period. Compared with calcium mono, supplementation with vitamin D and calcium resulted in an increase in serum 25-hydroxyvitamin D of 72% (p < 0.0001), a decrease in the serum PTH of 18% ( p = 0.0432), and a decrease in body sway of 9% (p = 0.0435). The mean number of falls per subject during a 1-year follow-up period was 0.45 for the calcium mono group and 0.24 for the calcium and vitamin D group (p = 0.0346). Short-term supplementation with vitamin D and calcium improves sHPT and body sway and therefore may prevent falls and subsequent nonvertebral fractures in elderly women.", "To assess the effect of preventive home visits by public health nurses on the state of health of and use of services by elderly people living at home.\n Randomised controlled trial.\n General population of elderly people in one of the southern regions of the Netherlands.\n 580 subjects aged between 75 and 84 years randomly allocated to intervention (292) or control (288) group.\n Four visits a year over three years in intervention group. Control group received no home visits.\n Self rated health, functional state, well being, loneliness, aspects of the mental state (depressive complaints, memory disturbances), and mortality. Use of services and costs.\n Visits had no effect on the health of the subjects. In the group visited no higher scores were seen on health related measures, fewer died (42 (14%) v 50 (17%)), and community care increased slightly. In the control group more were referred to outpatient clinics (166 (66%) v 132 (55%)), and they had a 40% increased risk of admission (incidence rate ratio 1.4; 90% confidence interval 1.2 to 1.6). No differences were found in long term institutional care, and overall expenditure per person in the intervention group exceeded that in the control group by 4%. Additional analyses showed that visits were effective for subjects who initially rated their health as poor.\n Preventive home visits are not beneficial for the general population of elderly people living at home but might be effective when restricted to subjects with poor health.", "nan", "To evaluate whether a programme of multifactorial home visits reduces falls and impairments in mobility in elderly people living in the community.\n Randomised controlled trial with 18 months of follow up.\n Six general practices in Hoensbroek, the Netherlands.\n 316 people aged 70 and over living in the community, with moderate impairments in mobility or a history of recent falls.\n Five home visits by a community nurse over a period of one year. Visits consisted of screening for medical, environmental, and behavioural factors causing falls and impairments in mobility, followed by specific advice, referrals, and other actions aimed at dealing with the observed hazards.\n Falls and impairments in mobility.\n No differences were found in falls and mobility outcomes between the intervention and usual care groups.\n Multifactorial home visits had no effects on falls and impairments in mobility in elderly people at risk who were living in the community. Because falls and impairments in mobility remain a serious problem among elderly people, alternative strategies should be developed and evaluated.", "The purpose of this research was to examine the effect of a multifactorial intervention to prevent falls by increasing self-efficacy to prevent falls, improving the knowledge of medication safety, and decreasing the number of environmental risks in older persons dwelling in the community. A sample of 120 cognitively intact residents of this community who were 65 years of age and older were recruited into a two-group pretest-post-test experimental design and randomly assigned to an experimental group and a comparison group (60 in each group). The intervention was delivered, and data were collected during three home visits in a 4-month period. (1) Experimental subjects improved their fall self-efficacy, environmental safety, and knowledge of medication safety significantly (p < 0.01) as compared with those in the comparison group at post-test; (2) the incidence of falls was reduced at post-test in both groups compared to pretest scores, and the falling was more serious in the comparison group at post-test compared to that in the experimental group. The results can help community health professionals to individualize their interventions to the specific needs of the elderly, thus helping to prevent falls among community-dwelling elders.", "Risk of falling increases as people age, and decreased leg strength and poor balance have been implicated as contributors. Our aims were to:1) assess the efficacy of a fall-prevention exercise program on balance and leg strength in women aged 65 to 89 years and 2) conduct a 1-year follow-up to determine the effect of exercise on fall rates.\n Forty women were classified by falling history and fear of falling and assigned to exercise and control groups using stratified randomization. We used the Berg Balance Scale, Get-up and Go, Functional Reach, and Wall-Sit Tests to evaluate changes in balance and leg strength before and after a supervised 15-week exercise program (31-hr sessions/week). We conducted 1-year follow-up telephone interviews and compared the number of falls reported by exercise and control groups.The study used a 2 x 2 (exercise/control by pretest/post-test) factorial design with the testing times being a repeated factor, so we used analysis of variance (ANOVA) to evaluate differences between the 2 groups across testing times. Power analysis computed a priori with STPLAN software (Version 4.2) showed that a sample size of 40 was necessary to determine statistical differences in balance and leg strength.\n Exercise subjects showed significant improvement on 5 of 14 items (5.2%, p < or = 05 to 34.4%, p < or = .01) in the Berg Balance Scale and on the total score (6.8%, p < or = .05). Leg strength increased significantly (p < or = .05) on post-test as measured by the Wall-Sit Test. Control subjects reported 6 falls and exercise subjects no falls during the follow-up year, but this difference was not significant using Fischer's exact test (p=.106).\n The exercise program resulted in increased balance and leg strength, but did not result in a significant difference in falls during the follow-up period. Further research with a larger and possibly older sample is needed to more adequately investigate this question. Health care providers who work with older women should provide exercise programs in which balance and leg strength are emphasized.", "Because preventing disability and falls in older adults is a national priority, a randomized controlled trial was conducted to test a multicomponent intervention program.\n From a random sample of health maintenance organization (HMO) enrollees 65 years and older, 1559 ambulatory seniors were randomized to one of three groups: a nurse assessment visit and follow-up interventions targeting risk factors for disability and falls (group 1, n = 635); a general health promotion nurse visit (group 2, n = 317); and usual care (group 3, n = 607). Data collection consisted of a baseline and two annual follow-up surveys.\n After 1 year, group 1 subjects reported a significantly lower incidence of declining functional status and a significantly lower incidence of falls than group 3 subjects. Group 2 subjects had intermediate levels of most outcomes. After 2 years of follow-up, the differences narrowed.\n The results suggest that a modest, one-time prevention program appeared to confer short-term health benefits on ambulatory HMO enrollees, although benefits diminished by the second year of follow-up. The mechanisms by which the intervention may have improved outcomes require further investigation.", "To investigate the effect of a referral-based targeted multifactorial falls prevention intervention on the occurrence of recurrent falls and injuries in older people presenting to an emergency department (ED) after a fall and discharged directly home from the ED.\n Randomized controlled trial. Assessors of outcomes were unaware of group allocation.\n Seven EDs in metropolitan Melbourne, Australia.\n Inclusion criteria were community dwelling, aged 60 and older, presenting to an ED after a fall, and discharged directly home. Exclusion criteria were unable to follow simple instructions or walk independently.\n Targeted referrals to existing community services and health promotion recommendations, based on the falls risk factors found in a baseline assessment.\n Primary outcome measures were falls and resultant injuries occurring over the 12-month follow-up period. Falls and injury data were collected using falls calendars supported by medical record reviews.\n Three hundred sixty-one participants were randomized to the standard care group and 351 to the intervention group. No significant difference was found between the two groups over the 12-month follow-up period in number of fallers (relative risk (RR)=1.11, 95% confidence interval (CI)=0.95-1.31] or number of participants sustaining an injury from a fall (RR=1.06, 95% CI=0.86-1.29).\n This study does not support the use of a referral-based targeted multifactorial intervention program to reduce subsequent falls or fall injuries in older people who present to an ED after a fall.\n © 2010, Copyright the Authors. Journal compilation © 2010, The American Geriatrics Society.", "To determine whether occupational therapist home visits targeted at environmental hazards reduce the risk of falls.\n A randomized controlled trial.\n Private dwellings in the community in Sydney, Australia.\n A total of 530 subjects (mean age 77 years), recruited primarily before discharge from selected hospital wards.\n A home visit by an experienced occupational therapist, who assessed the home for environmental hazards and facilitated any necessary home modifications.\n The primary study outcome was falls, ascertained over a 12-month follow-up period using a monthly falls calendar.\n Thirty six percent of subjects in the intervention group had at least one fall during follow-up, compared with 45% of controls (P = .050). The intervention was effective only among subjects (n = 206) who reported having had one or more falls during the year before recruitment into the study; in this group, the relative risk of at least one fall during follow-up was 0.64 (95% confidence interval, 0.50-0.83). Similar results were obtained when falls data were analyzed using survival analysis techniques (proportional and multiplicative hazards models) and fall rates (mean number of falls per person per year). About 50% of the recommended home modifications were in place at a 12-month follow-up visit.\n Home visits by occupational therapists can prevent falls among older people who are at increased risk of falling. However, the effect may not be caused by home modifications alone. Home visits by occupational therapists may also lead to changes in behavior that enable older people to live more safely in both the home and the external environment.", "To determine whether a new model of primary care, Chronic Care Clinics, can improve outcomes of common geriatric syndromes (urinary incontinence, falls, depressive symptoms, high risk medications, functional impairment) in frail older adults.\n Randomized controlled trial with 24 months of follow-up. Physician practices were randomized either to the Chronic Care Clinics intervention or to usual care.\n Nine primary care physician practices that comprise an ambulatory clinic in a large staff-model HMO in western Washington State.\n Those patients aged 65 and older in each practice with the highest risk for being hospitalized or experiencing functional decline.\n Intervention practices (5 physicians, 96 patients) held half-day Chronic Care Clinics every 3 to 4 months. These clinics included an extended visit with the physician and nurse dedicated to planning chronic disease management; a pharmacist visit that emphasized reduction of polypharmacy and high-risk medications; and a patient self-management/support group. Control practices (4 physicians, 73 patients) received usual care.\n Changes in self-reported urinary incontinence, frequency of falls, depressive symptoms, physical function, and satisfaction were analyzed using an intention-to-treat analysis adjusted for baseline differences, covariates, and practice-level variation. Prescriptions for high-risk medications and cost/utilization data obtained from administrative data were similarly analyzed.\n After 24 months, no significant improvements in frequency of incontinence, proportion with falls, depression scores, physical function scores, or prescriptions for high risk medications were demonstrated. Costs of medical care including frequency of hospitalization, hospital days, emergency and ambulatory visits, and total costs of care were not significantly different between intervention and control groups. A higher proportion of intervention patients rated the overall quality of their medical care as excellent compared with control patients (40.0% vs 25.3%, P = .10).\n Although intervention patients expressed high levels of satisfaction with Chronic Care Clinics, improved outcomes for selected geriatric syndromes were not demonstrated. These findings suggest the need for developing greater system-wide support for managing geriatric syndromes in primary care and illustrate the challenges of conducting practice improvement research in a rapidly changing delivery system.", "Exercise programs improve balance, strength and agility in elderly people and thus may prevent falls. However, specific exercise programs that might be widely used in the community and that might be \"prescribed\" by physicians, especially for patients with osteoporosis, have not been evaluated. We conducted a randomized controlled trial of such a program designed specifically for women with osteoporosis.\n We identified women 65 to 75 years of age in whom osteoporosis had been diagnosed by dual-energy X-ray absorptiometry in our hospital between 1996 and 2000 and who were not engaged in regular weekly programs of moderate or hard exercise. Women who agreed to participate were randomly assigned to participate in a twice-weekly exercise class or to not participate in the class. We measured baseline data and, 20 weeks later, changes in static balance (by dynamic posturography), dynamic balance (by a timed figure-eight run) and knee extension strength (by dynamometry).\n Of 93 women who began the trial, 80 completed it. Before adjustment for covariates, the intervention group tended to have greater, although nonsignificant, improvements in static balance (mean difference 4.8%, 95% confidence interval [CI] -1.3% to 11.0%), dynamic balance (mean difference 3.3%, 95% CI -1.7% to 8.4%) and knee extension strength (mean difference 7.8%, 95% CI -5.4% to 21.0%). Mean crude changes in the static balance score were -0.85 (95% CI -2.91 to 1.21) for the control group and 1.40 (95% CI -0.66 to 3.46) for the intervention group. Mean crude changes in figure-eight velocity (dynamic balance) were 0.08 (95% CI 0.02 to 0.14) m/s for the control group and 0.14 (95% CI 0.08 to 0.20) m/s for the intervention group. For knee extension strength, mean changes were -0.58 (95% CI -3.02 to 1.81) kg/m for the control group and 1.03 (95% CI -1.31 to 3.34) kg/m for the intervention group. After adjustment for age, physical activity and years of estrogen use, the improvement in dynamic balance was 4.9% greater for the intervention group than for the control group (p = 0.044). After adjustment for physical activity, cognitive status and number of fractures ever, the improvement in knee extension strength was 12.8% greater for the intervention group than for the control group (p = 0.047). The intervention group also had a 6.3% greater improvement in static balance after adjustment for rheumatoid arthritis and osteoarthritis, but this difference was not significant (p = 0.06).\n Relative to controls, participants in the exercise program experienced improvements in dynamic balance and strength, both important determinants of risk for falls, particularly in older women with osteoporosis.", "To assess the effectiveness of psychotropic medication withdrawal and a home-based exercise program in reducing falls in older people.\n A randomized controlled trial with a two by two factorial design.\n Seventeen general practices in Dunedin, New Zealand.\n Women and men aged 65 years registered with a general practitioner and currently taking psychotropic medication (n = 93).\n Two interventions: (1) gradual withdrawal of psychotropic medication versus continuing to take psychotropic medication (double blind) and (2) a home-based exercise program versus no exercise program (single blind).\n Number of falls and falls risk during 44 weeks of follow-up. Analysis was on an intent to treat basis.\n After 44 weeks, the relative hazard for falls in the medication withdrawal group compared with the group taking their original medication was .34 (95% CI, .16-.74). The risk of falling for the exercise program group compared with those not receiving the exercise program was not significantly reduced.\n Withdrawal of psychotropic medication significantly reduced the risk of falling, but permanent withdrawal is very difficult to achieve.", "Physical exercise affects many risk factors and diseases and therefore can play a vital role in general disease prevention and treatment of elderly individuals and may reduce costs. We sought to determine whether a single exercise program affects fracture risk (bone mineral density [BMD] and falls), coronary heart disease (CHD) risk factors, and health care costs in community-dwelling elderly women.\n We conducted a randomized, single-blinded, controlled trial from May 1, 2005, through July 31, 2008, recruiting women 65 years or older who were living independently in the area of Erlangen-Nuremberg, Germany. In all, 246 women were randomly assigned to an 18-month exercise program (exercise group) or a wellness program (control group). The exercise group (n = 123) performed a multipurpose exercise program with special emphasis on exercise intensity; the controls (n = 123) focused on well-being with a low-intensity, low-frequency program. The main outcome measures were BMD, the number of falls, the Framingham-based 10-year CHD risk, and direct health care costs.\n For the 227 women who completed the 18-month study, significant exercise effects were observed for BMD of the lumbar spine (mean [95% confidence interval (CI)] percentage of change in BMD [baseline to follow-up] for the exercise group: 1.77% [1.26% to 2.28%] vs controls: 0.33% [-0.24% to 0.91%]; P < .001), femoral neck (exercise group: 1.01% [0.37% to 1.65%] vs controls: -1.05% [-1.70% to -0.40%]; P < .001), and fall rate per person during 18 months (exercise group: 1.00 [0.76 to 1.24] vs controls: 1.66 [1.33 to 1.99]; P = .002). The 10-year CHD risk was significantly affected in both subgroups (absolute change for the exercise group: -1.96% [95% CI, -2.69% to -1.23%] vs controls: -1.15% [-1.69% to -0.62%]; P = .22), with no significant difference between the groups. The direct health care costs per participant during the 18-month intervention showed nonsignificant differences between the groups (exercise group: 2255 euros[95% CI, 1791 euros-2718 euros] vs controls: 2780 euros [2187 euros-3372 euros]; P = .20).\n Compared with a general wellness program, our 18-month exercise program significantly improved BMD and fall risk, but not predicted CHD risk, in elderly women. This benefit occurred at no increase in direct costs.\n clinicaltrials.gov Identifier: NCT00267839.", "To assess the effectiveness of a community-based falls-and-fracture nurse coordinator and multifactorial intervention in reducing falls in older people.\n Randomized, controlled trial.\n Screening for previous falls in family practice followed by community-based intervention.\n Three hundred twelve community-living people aged 75 and older who had fallen in the previous year.\n Home-based nurse assessment of falls-and-fracture risk factors and home hazards, referral to appropriate community interventions, and strength and balance exercise program. Control group received usual care and social visits.\n Primary outcome was rate of falls over 12 months. Secondary outcomes were muscle strength and balance, falls efficacy, activities of daily living, self-reported physical activity level, and quality of life (Medical Outcomes Study 36-item Short Form Questionnaire).\n Of the 3,434 older adults screened for falls, 312 (9%) from 19 family practices were enrolled and randomized. The average age was 81+/-5, and 69% (215/312) were women. The incidence rate ratio for falls for the intervention group compared with the control group was 0.96 (95% confidence interval=0.70-1.34). There were no significant differences in secondary outcomes between the two groups.\n This nurse-led intervention was not effective in reducing falls in older people who had fallen previously. Implementation and adherence to the fall-prevention measures was dependent on referral to other health professionals working in their usual clinical practice. This may have limited the effectiveness of the interventions.", "To assess the effectiveness of a home exercise programme of strength and balance retraining exercises in reducing falls and injuries in elderly women.\n Randomised controlled trial of an individually tailored programme of physical therapy in the home (exercise group, n = 116) compared with the usual care and an equal number of social visits (control group, n = 117).\n 17 general practices in Dunedin, New Zealand.\n Women aged 80 years and older living in the community and registered with a general practice in Dunedin.\n Number of falls and injuries related to falls and time between falls during one year of follow up; changes in muscle strength and balance measures after six months.\n After one year there were 152 falls in the control group and 88 falls in the exercise group. The mean (SD) rate of falls was lower in the exercise than the control group (0.87 (1.29) v 1.34 (1.93) falls per year respectively; difference 0.47; 95% confidence interval 0.04 to 0.90). The relative hazard for the first four falls in the exercise group compared with the control group was 0.68 (0.52 to 0.90). The relative hazard for a first fall with injury in the exercise group compared with the control group was 0.61 (0.39 to 0.97). After six months, balance had improved in the exercise group (difference between groups in change in balance score 0.43 (0.21 to 0.65).\n An individual programme of strength and balance retraining exercises improved physical function and was effective in reducing falls and injuries in women 80 years and older.", "to evaluate a nurse-led management plan and care pathway for older people discharged from an Accident and Emergency Department after a fall.\n randomized controlled trial.\n a large teaching hospital.\n 348 consecutive patients aged 65 or over attending the Accident and Emergency Department with a fall.\n we randomized patients to falls nurse intervention or usual care. Within 4 weeks, the intervention group received a home assessment to address easily modifiable risk factors for falls. This included assessments of medication, ECG, blood pressure, cognition, visual acuity, hearing, vestibular dysfunction, balance, mobility, feet and footwear. All patients were given advice and education about general safety in the home.\n Further falls, functional ability, re-attendance at the Accident and Emergency Department and admission to hospital.\n at 6 months post-Index fall, 36 patients in the intervention group and 39 patients in the control group had had 89 and 145 falls respectively. Although the intervention group had less falls, this was not significant (P>0.05). Similarly, the intervention group had fewer fall-related admissions and bed days (8 and 69 respectively) than the control group (10 and 233 respectively). The intervention group scored significantly higher in indicators of function (P<0.05) and mobility within the community (P<0.02).\n although the differences were not significant, patients in the intervention group had fewer falls, less hospital attendances and spent less time in hospital. Moreover, patients in the intervention group were more functionally independent at 6 months post-Index fall.", "To primarily ascertain the effect of the Otago Exercise Program (OEP) on physiological falls risk, functional mobility, and executive functioning after 6 months in older adults with a recent history of falls and to ascertain the effect of the OEP on falls during a 1-year follow-up period.\n Randomized controlled trial.\n Dedicated falls clinics.\n Seventy-four adults aged 70 and older who presented to a healthcare professional after a fall.\n The OEP, a home-based program that consists of resistance training and balance training exercises.\n Physiological falls risk was assessed using the Physiological Profile Assessment. Functional mobility was assessed using the Timed Up and Go Test. Three central executive functions were assessed: set shifting, using the Trail Making Test Part B; updating, using the verbal digits backward test; and response inhibition, using the Stroop Color-Word Test. Falls were prospectively monitored using daily calendars.\n At 6 months, there was no significant between-group difference in physiological falls risk or functional mobility (P>or= .33). There was a significant between-group difference in response inhibition (P=.05). A falls histogram revealed two outliers. With these cases removed, using negative binomial regression, the unadjusted incidence rate ratio of falls in the OEP group compared with the control group was 0.56. The adjusted incidence rate ratio was 0.47.\n The OEP may reduce falls by improving cognitive performance.", "older people participate in exercise programmes to reduce the risk of falls but no study has investigated a specific balance strategy training intervention presented in a workstation format for small groups.\n to determine whether a specific balance strategy training programmeme delivered in a workstation format was superior to a community based exercise class programme for reducing falls.\n a randomised controlled trial model.\n Neurological Disorders, Ageing and Balance Clinic, Department of Physiotherapy, The University of Queensland.\n 73 males and females over 60 years, living independently in the community and who had fallen in the previous year were recruited.\n all subjects received a falls risk education booklet and completed an incident calendar for the duration of the study. Treatment sessions were once a week for 10 weeks. Subject assessment before and after intervention and at 3 months follow-up included number of falls, co-morbidities, medications, community services and activity level, functional motor ability, clinical and laboratory balance measures and fear of falling.\n all participants significantly reduced the number of falls (P < 0.000). The specific balance strategy intervention group showed significantly more improvement in functional measures than the control group (P = 0.034). Separate group analyses indicated significantly improved performance in functional motor ability and most clinical balance measures for the balance group (P < 0.04). The control group only improved in TUG and TUGcog.\n the results provide evidence that all participants achieved a significant reduction in falls. Specific balance strategy training using workstations is superior to traditional exercise classes for improving function and balance.", "Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor.\n To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture.\n A double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years. The study concluded in 2008.\n 500,000 IU of cholecalciferol or placebo.\n Falls and fractures were ascertained using monthly calendars; details were confirmed by telephone interview. Fractures were radiologically confirmed. In a substudy, 137 randomly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels.\n Women in the cholecalciferol (vitamin D) group had 171 fractures vs 135 in the placebo group; 837 women in the vitamin D group fell 2892 times (rate, 83.4 per 100 person-years) while 769 women in the placebo group fell 2512 times (rate, 72.7 per 100 person-years; incidence rate ratio [RR], 1.15; 95% confidence interval [CI], 1.02-1.30; P = .03). The incidence RR for fracture in the vitamin D group was 1.26 (95% CI, 1.00-1.59; P = .047) vs the placebo group (rates per 100 person-years, 4.9 vitamin D vs 3.9 placebo). A temporal pattern was observed in a post hoc analysis of falls. The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months (test for homogeneity; P = .02). In the substudy, the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3% of the substudy participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group, 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L, were approximately 90 nmol/L at 3 months, and remained higher than the placebo group 12 months after dosing.\n Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures.\n anzctr.org.au Identifier: ACTRN12605000658617; isrctn.org Identifier: ISRCTN83409867.", "To determine whether an individualized falls prevention program comprising exercise, visual, and counseling interventions can reduce physiological falls risk and falls in older people.\n Randomized, controlled trial of 12 months' duration.\n Falls Clinic, Royal North Shore Hospital, Sydney, Australia.\n Six hundred twenty people aged 75 and older recruited from a health insurance company membership database. Interventions: Participants in the extensive intervention group (EIG) received individualized interventions comprising exercise and strategies for maximizing vision and sensation; the minimal intervention group (MIG) received brief advice; and the control group (CG) received no intervention.\n Accidental falls, vision, postural sway, coordinated stability, reaction time, lower limb muscle strength, sit-to-stand performance, and physiological profile assessment (PPA) falls risk scores.\n At the 6-month follow-up, PPA falls risk scores were significantly lower in the EIG than in the CG. EIG subjects assigned to the extensive exercise intervention group showed significant improvements in tests of knee flexion strength and sit-to-stand times but no improvements in balance. EIG subjects assigned to the extensive visual intervention group showed significant improvements in tests of visual acuity and contrast sensitivity. The rate of falls and injurious falls within the trial period were similar in the three groups.\n The individualized intervention program reduced some falls risk factors but did not prevent falls. The lack of an effect on falls may reflect insufficient targeting of the intervention to an at-risk group.", "To assess whether a multifactorial fall prevention program was more effective than usual geriatric care in preventing falls and reducing fear of falling in frail community-dwelling older fallers, with and without cognitive impairment, and in alleviating subjective caregiver burden in caregivers.\n A randomized, 2 parallel-group, single-blind, multicenter trial conducted in 36 pairs of frail fallers, who were referred to a geriatric outpatient clinic after at least 1 fall in the past 6 months, and their informal caregivers.\n Groups of 5 pairs of patients and caregivers received 10 twice-weekly, 2-hour sessions with physical and psychological components and a booster session.\n The primary outcome was the fall rate during a 6-month follow-up. Additionally, we measured fear of falling and subjective caregiver burden. Data on the secondary outcome measures were collected at baseline, directly after, and at 3 and 6 months after the last session of the intervention.\n Directly after the intervention and at the long-term evaluation, the rate of falls in the intervention group was higher than in the control group, although these differences were not statistically significant (RR = 7.97, P = .07 and RR = 2.12, P = .25, respectively). Fear of falling was higher in the intervention group, and subjective caregiver burden did not differ between groups.\n Although we meticulously developed this pairwise multifactorial fall prevention program, it was not effective in reducing the fall rate or fear of falling and was not feasible for caregivers, as compared with regular geriatric care. Future research initiatives should be aimed at how to implement the evidence-based principles of geriatric fall prevention for all frail fallers rather than developing more complex interventions for the frailest.\n Copyright © 2011 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.", "To evaluate the outcome of an intervention to reduce hazards in the home on the rate of falls in seniors.\n Randomized controlled trial, with follow-up of subjects for 1 year.\n Community-based study in Perth, Western Australia.\n People age 70 and older.\n One thousand eight hundred seventy-nine subjects were recruited and randomly allocated by household to the intervention and control groups in the ratio 1:2. Because of early withdrawals, 1,737 subjects commenced the study. All members of both groups received a single home visit from a research nurse. Intervention subjects (n = 570) were offered a home hazard assessment, information on hazard reduction, and the installation of safety devices, whereas control subjects (n = 1,167) received no safety devices or information on home hazard reduction.\n Both groups recorded falls on a daily calendar. Reported falls were confirmed by a semistructured telephone interview and were assigned to one of three overlapping categories: all falls, falls inside the home, and falls involving environmental hazards in the home. Analysis was by multivariate modelling of rate ratios and odds ratios for falls, corrected for household clustering, using Poisson regression and logistic regression with robust variance estimation.\n Overall, 86% of study subjects completed the 1 year of follow-up. The intervention was not associated with any significant reduction in falls or fall-related injuries. There was no significant reduction in the intervention group in the incidence rate of falls involving environmental hazards inside the home (adjusted rate ratio, 1.11; 95% CI = 0.82-1.50), or the proportion of the intervention group who fell because of hazards inside the home (adjusted odds ratio, 0.97; 95% CI = 0.74-1.28). No reduction was seen in the rate of all falls (adjusted rate ratio, 1.02; 95% CI = 0.83-1.27) or the rate of falls inside the home (adjusted rate ratio, 1.17; 95% CI = 0.85-1.60). There was no significant reduction in the rate of injurious falls in intervention subjects (adjusted rate ratio, 0.92; 95% CI = 0.73-1.14).\n The intervention failed to achieve a reduction in the occurrence of falls. This was most likely because the intervention strategies had a limited effect on the number of hazards in the homes of intervention subjects. The study provides evidence that a one-time intervention program of education, hazard assessment, and home modification to reduce fall hazards in the homes of healthy older people is not an effective strategy for the prevention of falls in seniors.", "recent studies have found that moderate intensity exercise is an effective intervention strategy for preventing falls in older people. However, research is required to determine whether supervised group exercise programmes, conducted in community settings with at-risk older people referred by their health care practitioner are also effective in improving physical functioning and preventing falls in this group.\n to determine whether participation in a weekly group exercise programme with ancillary home exercises over one year improves balance, muscle strength, reaction time, physical functioning, health status and prevents falls in at-risk community-dwelling older people.\n the sample comprised 163 people aged over 65 years identified as at risk of falling using a standardised assessment screen by their general practitioner or hospital-based physiotherapist, residing in South Western Sydney, Australia. Subjects were randomised into either an exercise intervention group or a control group. Physical performance and general health measures were assessed at baseline and repeated 6-months into the trial. Falls were measured over a 12-month follow-up period using monthly postal surveys.\n at baseline both groups were well matched in their physical performance, health and activity levels. The intervention subjects attended a median of 23 exercise classes over the year, and most undertook the home exercise sessions at least weekly. At retest, the exercise group performed significantly better than the controls in three of six balance measures; postural sway on the floor with eyes open and eyes closed and coordinated stability. The groups did not differ at retest in measures of strength, reaction time and walking speed or on Short-Form 36, Physical Activity Scale for the Elderly or fear of falling scales. Within the 12-month trial period, the rate of falls in the intervention group was 40% lower than that of the control group (IRR=0.60, 95% CI 0.36-0.99).\n these findings indicate that participation in a weekly group exercise programme with ancillary home exercises can improve balance and reduce the rate of falling in at-risk community dwelling older people.", "To determine whether a 12-month program of group exercise can improve physical functioning and reduce the rate of falling in frail older people.\n Cluster randomized, controlled trial of 12 months duration.\n Retirement villages in Sydney and Wollongong, Australia.\n Five hundred fifty-one people aged 62 to 95 (mean+/-standard deviation=79.5+/-6.4) who were living in self- and intermediate-care retirement villages.\n Accidental falls, choice stepping reaction time, 6-minute walk distance postural sway, leaning balance, simple reaction time, and lower-limb muscle strength.\n Two hundred eighty subjects were randomized to the weight-bearing group exercise (GE) intervention that was designed to improve the ability of subjects to undertake activities for daily living. Subjects randomized to the control arm (n=271) attended flexibility and relaxation (FR) classes (n=90) or did not participate in a group activity (n=181). In spite of the reduced precision of cluster randomization, there were few differences in the baseline characteristics of the GE and combined control (CC) subjects, although the mean age of the GE group was higher than that of the CC group, and there were fewer men in the GE group. The mean number of classes attended was 39.4+/-28.7 for the GE subjects and 31.5+/-25.2 for the FR subjects. After adjusting for age and sex, there were 22% fewer falls during the trial in the GE group than in the CC group (incident rate ratio=0.78, 95% confidence interval (CI)=0.62-0.99), and 31% fewer falls in the 173 subjects who had fallen in the past year (incident rate ratio=0.69, 95% CI=0.48-0.99). At 6-month retest, the GE group performed significantly better than the CC group in tests of choice stepping reaction time, 6-minute walking distance, and simple reaction time requiring a hand press. The groups did not differ at retest in tests of strength, sway, or leaning balance.\n These findings show that group exercise can prevent falls and maintain physical functioning in frail older people.", "The objective of this study was to examine the effectiveness of a discharge plan in hospitalized elderly patients with hip fracture due to falling.\n Hip fractures are an important cause of morbidity and mortality among older people. Hip fracture patients require ongoing medical and long-term care services. Discharge plan services can play a very important role for these patients, since the services improved their outcome conditions.\n Hip fracture patients aged 65 years and older (n = 126), hospitalized due to falling and discharged from a medical centre in northern Taiwan, were randomly assigned to either a comparison group (the routine care) or experimental group (the discharge planning intervention). The outcomes used to determine the effectiveness of the intervention were: length of hospitalized stay, rate of readmission, repeat falls and survival, and activities of daily living.\n The discharge planning intervention decreased length of stay, rate of readmission and rate of survival and improved activities of daily living for intervention group compared with those of control group. Mean total SF-36 scores of patients in the experimental group were higher than for the control group and both groups had improved quality of life.\n The discharge planning benefited older people with hip fractures.\n A discharge planning intervention by a nurse can improve physical outcomes and quality of life in hip fracture patients.", "Evidence of the effect of exercise on bone loss comes mainly from studies in voluntary postmenopausal women, and no population-based, long-term interventions have been performed. The purpose of this population-based, randomized, controlled trial was to determine the effect of long-term impact exercise on bone mass at various skeletal sites in elderly women with low bone mineral density (BMD) at the radius and hip. Participants (n=160) were randomly assigned to 30 months either of supervised and home-based impact exercise training or of no intervention. The primary outcome measures were femoral neck, trochanter and total hip BMD, and the secondary outcomes were bone density measures at the radius and calcaneum. Outcomes were assessed at baseline, 12 months and 30 months using blinded operators. The analyses were performed on an intention-to-treat analysis. Mean femoral neck and trochanter BMD decreased in the control group [-1.1%, 95% confidence interval (CI) -0.1% to -2.1% and -1.6%, 95% CI -0.4% to -2.7%], while no change occurred in the exercise group. Mean trochanter BMC decreased more in the control group (-7.7%, 95% CI -9.7% to -5.6% vs. -2.9%, 95% CI -5.3 to -0.9). There were six falls that resulted in fractures in the exercise group and 16 in the control group during the 30-month intervention (P=0.019). A significant bone loss occurred in both groups at the radius and calcaneum. In multivariate analysis, weight gain was associated with increased BMD and BMC at all femur sites both in the exercise group and in the pooled groups. In conclusion, impact exercise had no effect on BMD, while there was a positive effect on BMC at the trochanter. Exercise may prevent fall-related fractures in elderly women with low bone mass.", "The effectiveness of community-based fall assessment programs in older people is unclear. In this study, we examined the effectiveness of community-based fall assessment compared with hospital-based assessment.\n A randomized un-blind study was conducted in 369 older adults aged 65 years and over at high risk of falling. Participants were drawn from a larger cohort of community-dwelling older people. Eligible participants were identified by means of a simple five-item screening tool. A randomly chosen subset population of people at high risk of falling was then randomized into two arms, community-based and hospital-based fall assessments. The total number of falls in both groups was recorded by following up subjects' diaries and telephone interviews at 3, 6 and 12 months. Incidence Rate Ratios (IRR) for the rate of falls at 12 months between community- and hospital-based assessments were analysed as primary outcome, by intention-to-treat analysis.\n A total of 349 participants completed the study. Attendance to community-based assessment was significantly higher compared with hospital-based assessment in this older population (p=0.012). There were no statistically significant differences between the two groups in total number of falls at the 12 month follow-up. According to Negative Binomial regression, the adjusted IRR of falls in the community based arm was not significantly different from the hospital-based one (IRR 0.95; 95% CI 0.58-1.45, p=0.83).\n This study showed the increased risk of falling according to community-based fall assessment program with respect to a traditional hospital-based one in community-dwelling older adults at high risk of falling.", "To evaluate the efficacy of the Nijmegen Falls Prevention Program (NFPP) for persons with osteoporosis and a fall history in a randomized controlled trial. Persons with osteoporosis are at risk for fall-related fractures because of decreased bone strength. A decrease in the number of falls therefore is expected to be particularly beneficial for these persons.\n Randomized controlled trial.\n Hospital.\n Persons with osteoporosis and a fall history (N=96; mean ± SD age, 71.0±4.7y; 90 women).\n After baseline assessment, participants were randomly assigned to the exercise (n=50; participated in the NFPP for persons with osteoporosis [5.5wk]) or control group (n=46; usual care).\n Primary outcome measure was fall rate, measured by using monthly fall calendars for 1 year. Secondary outcomes were balance confidence (Activity-specific Balance Confidence Scale), quality of life (QOL; Quality of Life Questionnaire of the European Foundation for Osteoporosis), and activity level (LASA Physical Activity Questionnaire, pedometer), assessed posttreatment subsequent to the program and after 1 year of follow-up.\n The fall rate in the exercise group was 39% lower than for the control group (.72 vs 1.18 falls/person-year; risk ratio, .61; 95% confidence interval, .40-.94). Balance confidence in the exercise group increased by 13.9% (P=.001). No group differences were observed in QOL and activity levels.\n The NFPP for persons with osteoporosis was effective in decreasing the number of falls and improving balance confidence. Therefore, it is a valuable new tool to improve mobility and independence of persons with osteoporosis.\n Copyright © 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.", "To determine the safety and efficacy of an exercise protocol designed to improve strength, mobility, and balance and to reduce subsequent falls in geriatric patients with a history of injurious falls.\n A randomized controlled 3-month intervention trial, with an additional 3-month follow-up.\n Out-patient geriatric rehabilitation unit.\n Fifty-seven female geriatric patients (mean age 82 +/- 4.8 years; range 75-90) admitted to acute care or inpatient rehabilitation with a history of recurrent or injurious falls including patients with acute fall-related fracture.\n Ambulatory training of strength, functional performance, and balance 3 times per week for 3 months. Patients of the control group attended a placebo group 3 times a week for 3 months. Both groups received an identical physiotherapeutic treatment 2 times a week, in which strengthening and balance training were excluded.\n Strength, functional ability, motor function, psychological parameters, and fall rates were assessed by standardized protocols at the beginning (T1) and the end (T2) of intervention. Patients were followed up for 3 months after the intervention (T3).\n No training-related medical problems occurred in the study group. Forty-five patients (79%) completed all assessments after the intervention and follow-up period. Adherence was excellent in both groups (intervention 85.4 +/- 27.8% vs control 84.2 +/- 29.3%). The patients in the intervention group increased strength, functional motor performance, and balance significantly. Fall-related behavioral and emotional restrictions were reduced significantly. Improvements persisted during the 3-month follow-up with only moderate losses. For patients of the control group, no change in strength, functional performance, or emotional status could be documented during intervention and follow-up. Fall incidence was reduced nonsignificantly by 25% in the intervention group compared with the control group (RR:0.753 CI:0.455-1.245).\n Progressive resistance training and progressive functional training are safe and effective methods of increasing strength and functional performance and reducing fall-related behavioral and emotional restrictions during ambulant rehabilitation in frail, high-risk geriatric patients with a history of injurious falls.", "To examine the effectiveness of cognitive-behavioural strategies with/without intense Tai Chi exercise in reducing fear of falling among community-dwelling elderly adults. Background.  Fear of falling is a major health problem among community-dwelling older persons. The prevalence of this fear ranges from 29% to 77%, indicating the importance of developing effective strategies to reduce fear of falling among elderly adults.\n Data were collected from January to December 2007. A randomized controlled trial with three groups (control, cognitive-behavioural and cognitive-behavioural with Tai Chi). Participants were assessed at baseline for demographic data, falls-related history, and fear of falling. Data on these variables plus falls, mobility, social support behaviour and satisfaction, and quality of life were also collected at 2 and 5 months after interventions.\n Participants in the three groups differed significantly in both measures of fear of falling (F = 20·89, P < 0·001; F = 6·09, P < 0·001) and mobility (F = 30·33, P < 0·001), social support behaviour and satisfaction (F = 3·32, P < 0·05 and F = 6·35, P < 0·001, respectively), and quality of life (F = 16·66, P< 0·001). In addition, participants who received the cognitive-behavioural intervention with Tai Chi had significantly lower fear of falling scores (P < 0·001) and higher mobility (P < 0·001), social support satisfaction (P < 0·01) and quality of life (P < 0·001) than the cognitive-behavioural alone and control groups at 5 months. The three groups did not differ significantly in falls.\n The results of this trial suggest that the cognitive-behavioural intervention with Tai Chi exercise helped community-dwelling elderly adults to enhance their mobility, to manage their fear of falling and to increase their quality of life.\n © 2011 Blackwell Publishing Ltd.", "The aim of the study was to examine the effects of different interventions that are used to prevent falls. These were education, Tai Chi Chuan and education plus Tai Chi Chuan; the study involved a five-month implantation period and a one-year follow-up period.\n With advancing years, a fall can be very serious and an increased number of falls/re-falls among older adults has been noted. Hence, both education about risk factors and balance exercise programs such as Tai Chi Chuan may help to prevent falls.\n This study adopted a randomised case-controlled design with a two-by-two factorial approach. It included three intervention groups and one control group in a community-based program.\n Cluster-randomised sampling was used and four villages in Taiwan City were selected. Three interventions groups and one control group were involved over five-months from late July 2000-January 2001 and each participant was followed up one year later (n = 163).\n The intervention involving education plus Tai Chi Chuan resulted in a statistically significant reduction in falls and the risk factors of falls over the five-month intervention. After one-year follow-up, participants receiving any one of the interventions showed a reduction in falls compared with the control group.\n Tai Chi Chuan was able to improve gait balance significantly. Education may also help participants to prevent falls-by eliminating related risk factors present in their environment. However, it was found that at the one-year follow-up, any one of the three interventions had reduced falls significantly.\n The prevention of falls among older adults seems to needs multiple interventions. Education plus Tai Chi Chuan has both an immediately and a long-term effect and it is possible that a shorter intervention period using this approach would also be successful.", "To test the efficacy of a medication use improvement program developed specifically for home health agencies. The program addressed four medication problems identified by an expert panel: unnecessary therapeutic duplication, cardiovascular medication problems, use of psychotropic drugs in patients with possible adverse psychomotor or adrenergic effects, and use of nonsteroidal antiinflammatory drugs (NSAIDs) in patients at high risk of peptic ulcer complications. It used a structured collaboration between a specially trained clinical pharmacist and the patients' home-care nurses to improve medication use.\n Parallel-group, randomized controlled trial.\n Two of the largest home health agencies in the United States.\n Study subjects were consenting Medicare patients aged 65 and older admitted to participating agency offices from October 1996 through September 1998, with a projected home healthcare duration of at least 4 weeks and at least one study medication problem.\n Qualifying patients were randomized to usual care or usual care with the medication improvement program.\n Medication use was measured during an in-home interview, with container inspection at baseline and at follow-up (between 6 and 12 weeks) by interviewers unaware of treatment assignment. The trial endpoint was the proportion of patients with medication use improvement according to predefined criteria at follow-up.\n There were 259 randomized patients with completed follow-up interviews: 130 in the intervention group and 129 with usual care. Medication use improved for 50% of intervention patients and 38% of control patients, an attributable improvement of 12 patients per 100 (95% confidence interval (CI) = 0.0-24.0, P =.051). The intervention effect was greatest for therapeutic duplication, with improvement for 71% of intervention and 24% of control patients, an attributable improvement of 47 patients per 100 (95% CI = 20-74, P =.003). Use of cardiovascular medications also improved more frequently in intervention patients: 55% vs 18%, attributable improvement 37 patients per 100 (95% CI = 9-66, P =.017). There were no significant improvements for the psychotropic medication or NSAID problems. There was no evidence of adverse intervention effects: new medication problems, more agency nurse visits, or increased duration of home health care.\n A program congruent with existing personnel and practices of home health agencies improved medication use in a vulnerable population and was particularly effective in reducing therapeutic duplication.", "To test whether a system of screening, assessment, referral, and follow-up provided within primary care for high-risk older outpatients improves recognition of geriatric conditions and healthcare outcomes.\n Controlled clinical trial with 3-year follow-up; intervention versus control group allocation based on practice group assignment.\n Department of Veterans Affairs (VA) ambulatory care center.\n Seven hundred ninety-two community-dwelling patients aged 65 and older identified by postal screening survey.\n The intervention combined a structured telephone geriatric assessment by a physician assistant, individualized referrals and recommendations, selected referral to outpatient geriatric assessment, and ongoing telephone case management.\n Main outcomes were VA medical record evidence of recognition and evaluation of target geriatric conditions (depression, cognitive impairment, urinary incontinence, falls, functional impairment), functional status (Functional Status Questionnaire, FSQ), and hospitalization (VA databases and self-reported non-VA usage).\n Intervention participants were more likely to have target conditions recognized, evaluated, and referred to specialized services within 12 months of enrollment, although there were no significant differences in FSQ scores or acute hospitalization between intervention and control groups at 1, 2, or 3 years follow-up. Subgroup analyses suggested improvements in depression symptoms and functional impairment at 1-year follow-up in intervention participants with these problems at baseline, but these findings were not evident at later follow-up.\n The intervention increased recognition and evaluation of target geriatric conditions but did not improve functional status or decrease hospitalization. Innovative screening methods can identify older people in need of geriatric services, but achieving measurable improvement in functional status or hospitalization rates will likely require a more-intensive intervention than a program involving primarily unsolicited referrals and short-term consultations.", "To study the effect of alfacalcidol (1alpha(OH)D3) on fall risk in community-dwelling elderly men and women.\n Randomized, double-blind, placebo-controlled intervention trial.\n Basel, Switzerland.\n Three hundred seventy-eight community-dwelling elderly (191 women/187 men).\n Participants were randomly assigned to receive 1 microg of alfacalcidol or matched placebo daily for 36 weeks.\n Serum 25-hydoxyvitamin D3 (25(OH) D,1,25-dihydroxyvitamin D3 (D-hormone), and intact parathormone (iPTH) levels were measured using radioimmunoassay at baseline and every 12 weeks. Numbers of fallers and falls were assessed using a questionnaire during each study site visit. Dietary calcium intake was assessed at baseline using a food frequency questionnaire.\n At baseline, participants had, on average, normal vitamin D and D-hormone serum levels. Over 36 weeks, alfacalcidol treatment was associated with fewer fallers (odds ratio (OR)=0.69, 95% confidence interval (CI)=0.41-1.16) than placebo. In a post hoc subgroups analysis by medians of total calcium intake, this reduction reached significance in alfacalcidol-treated subjects with a total calcium intake of more than 512 mg/d (OR=0.45, 95% CI=0.21-0.97, P=.042) but not in those who consumed less than 512 mg/d (OR=1.00, 95% CI= 0.47-2.11, P=.998). Alfacalcidol treatment was also, independent of total calcium intake, associated with a significant 37.9% reduction in iPTH serum levels (P<.0001). No cases of clinically relevant hypercalcemia were observed.\n Provided a minimal calcium intake of more than 512 mg/d, alfacalcidol treatment significantly and safely reduces number of fallers in an elderly community dwelling population.", "the mortality and morbidity of falls in older people is significant, with recurrent fallers being at an increased risk. The most effective way to reduce falls in this group is not clear.\n to determine the effectiveness of two interventions, one based in primary care and the other in secondary care, at preventing further falls in recurrent fallers.\n cluster randomised controlled trial.\n sixty-five years or over, living in the community, two or more falls in the previous year and not presenting to an emergency department with index fall.\n Mid Hampshire, UK.\n eighteen general practices were randomly allocated to one of three groups. The primary care group was assessed by nurses in the community, using a risk factor review and subsequent targeted referral to other professionals. The secondary care group received a multi-disciplinary assessment in a day hospital followed by identified appropriate interventions. The control group received usual care. Follow-up was for 1 year.\n five hundred and five participants were recruited. Follow-up was completed in 83% (421/505). The proportion of participants who fell again was significantly lower in the secondary care group (75%, 158/210) compared to the control group [84%, 133/159, adjusted odds ratio (OR) 0.52 (95% CI 0.35-0.79) P = 0.002]. The primary care group showed similar results to the control group [87%, 118/136, adjusted OR 1.17 (95% CI 0.57-2.37) P = 0.673].\n a structured multi-disciplinary assessment of recurrent fallers significantly reduced the number experiencing further falls, but a community-based nurse-led assessment with targeted referral to other professionals did not.", "This randomized controlled trial studied the effects of a low- to moderate-intensity group exercise program on strength, endurance, mobility, and fall rates in fall-prone elderly men with chronic impairments.\n Fifty-nine community-living men (mean age = 74 years) with specific fall risk factors (i.e., leg weakness, impaired gait or balance, previous falls) were randomly assigned to a control group (n = 28) or to a 12-week group exercise program (n = 31). Exercise sessions (90 minutes, three times per week) focused on increasing strength and endurance and improving mobility and balance. Outcome measures included isokinetic strength and endurance, five physical performance measures, and self-reported physical functioning, health perception, activity level, and falls.\n Exercisers showed significant improvement in measures of endurance and gait. Isokinetic endurance increased 21% for right knee flexion and 26% for extension. Exercisers had a 10% increase (p < .05) in distance walked in six minutes, and improved (p < .05) scores on an observational gait scale. Isokinetic strength improved only for right knee flexion. Exercise achieved no significant effect on hip or ankle strength, balance, self-reported physical functioning, or number of falls. Activity level increased within the exercise group. When fall rates were adjusted for activity level, the exercisers had a lower 3-month fall rate than controls (6 falls/1000 hours of activity vs 16.2 falls/1000 hours, p < .05).\n These findings suggest that exercise can improve endurance, strength, gait, and function in chronically impaired, fall-prone elderly persons. In addition, increased physical activity was associated with reduced fall rates when adjusted for level of activity.", "To investigate whether home visits by a occupational therapist reduces the risk of falling and improves the autonomy of older patients hospitalized for falling.\n In this randomized, controlled trial set in a geriatric hospital, 60 patients (mean age, 83.5 yr) who were hospitalized for falling were recruited from the acute medicine department. A home visit from an occupational therapist and an ergotherapist assessed patients' homes for environmental hazards and recommended modifications. The outcomes measured were falls, autonomy, hospitalization for falling, institutionalization, and death.\n During the follow-up period, the rate of falls, hospitalization for falls, institutionalization, and death were not significantly different between the two groups. Both groups had a loss of dependence at 12 mo. This loss of dependence was significant in the control group but not in the intervention group.\n Home visits from occupational therapists during hospitalization of older patients at risk for falling can help to preserve the patient's autonomy.", "To determine whether the provision of single lens distance glasses to older wearers of multifocal glasses reduces falls.\n Parallel randomised controlled trial stratified by recruitment site and source of referral, with 13 months' follow-up and outcome assessors blinded to group allocation.\n Community recruitment and treatment room assessments in Sydney and Illawarra regions of NSW, Australia.\n 606 regular wearers of multifocal glasses (mean age 80 (SD 7) years). Inclusion criteria included increased risk of falls (fall in previous year or timed up and go test >15 seconds) and outdoor use of multifocal glasses at least three times a week.\n Provision of single lens distance glasses with recommendations for wearing them for walking and outdoor activities compared with usual care.\n Number of falls and injuries resulting from falls during follow-up.\n Single lens glasses were provided to 275 (90%) of the 305 intervention group participants within two months; 162 (54%) of the intervention group reported satisfactory use of distance glasses for walking and outdoor activities for at least 7/12 months after dispensing. In the 299 intervention and 298 control participants available to follow-up, the intervention resulted in an 8% reduction in falls (incidence rate ratio 0.92, 95% confidence interval 0.73 to 1.16). Pre-planned sub-group analyses showed that the intervention was effective in significantly reducing all falls (incidence rate ratio 0.60, 0.42 to 0.87), outside falls, and injurious falls in people who regularly took part in outside activities. A significant increase in outside falls occurred in people in the intervention group who took part in little outside activity.\n With appropriate counselling, provision of single lens glasses for older wearers of multifocal glasses who take part in regular outdoor activities is an effective falls prevention strategy. The intervention may be harmful, however, in multifocal glasses wearers with low levels of outdoor activity.\n Clinical trials NCT00350855.", "We determined whether the effect of exercise on bone mineral density (BMD) and falls can be enhanced by whole body vibration (WBV). In summary, the multi-purpose exercise training was effective to increase lumbar BMD but added WBV did not enhance this effect. However, falls were lowest in the exercise program combined with WBV.\n WBV is a new approach to reduce the risk of osteoporotic fractures. In the \"Erlangen Longitudinal Vibration Study\" (ELVIS), we investigated whether WBV enhances the effect of multifunctional exercise on BMD and falls.\n One hundred fifty-one postmenopausal women (68.5 ± 3.1 years) were randomly assigned to a: (1) conventional training group (TG); (2) conventional training group including vibration (TGV); and (3) wellness control group (CG). TG conducted an exercise program consisting of 20 min dancing aerobics, 5 min balance training, 20 min functional gymnastics, and 15 min dynamic leg-strength training on vibration plates (without vibration) twice a week. TGV performed an identical exercise regimen with vibration (25-35 Hz) during the leg-strengthening sequence. CG performed a low-intensity wellness program. BMD was measured at the hip and lumbar spine at baseline and follow-up using the DXA method. Falls were recorded daily via the calendar method.\n After 18 months, an increase in BMD at the lumbar spine was observed in both training groups (TGV: +1.5% vs. TG: +2.1%). The difference between the TG and the CG (1.7%) was significant. At the hip no changes were determined in either group. The fall frequency was significantly lower in TGV (0.7 falls/person) compared with CG (1.5), whereas the difference between TG (0.96) and CG was not significant.\n A multifunctional training program had a positive impact on lumbar BMD. The application of vibration did not enhance these effects. However, only the training including WBV affected the number of falls significantly.", "A randomized trial of falls prevention program that addressed home safety, exercise, and behavioral risks was conducted with 3,182 independently living HMO members age 65 and older. The intervention decreased the odds of falling by 0.85, but only reduced the average number of falls among those who fell by 7%. The effect was strongest among men age 75 and older. The likelihood of avoiding falls requiring medical treatment was not significantly affected by the intervention. We conclude that the intervention dose was not of sufficient intensity or duration to have a marked protective effect on older persons. Future research should focus on more intensive intervention approaches because serious falls do not appear to be amendable to low-intensity environment/behavioral efforts.", "To determine the efficacy of vision and eye examinations, with subsequent treatment of vision problems, for preventing falls and fractures in frail older people.\n Randomized, controlled trial.\n Community in Sydney, Australia.\n Six hundred sixteen men and women aged 70 and older (mean age 81) recruited mainly from people attending outpatient aged care services.\n The intervention group received comprehensive vision and eye examinations conducted by a study optometrist. The optometrist arranged for new eyeglasses for 92 subjects and referred 24 for a home visit with an occupational therapist, 17 for glaucoma management, and 15 for cataract surgery. The control group received usual care.\n Falls and fractures during 12 months of follow-up were ascertained according to self-report using a monthly postcard system.\n Fifty-seven percent of subjects fell at least once during follow-up. Falls occurred more frequently in the group randomized to receive the vision intervention (65% fell at least once; 758 falls in total) than in the control group (50% fell at least once; 516 falls in total). The falls rate ratio using the negative binomial model was 1.57 (95% confidence interval (CI)=1.20-2.05, P=.001). Fractures were also more frequent in the intervention group (31 fractures) than the control group (18 fractures; relative risk from proportional hazards model 1.74, 95% CI=0.97-3.11, P=.06).\n In frail older people, comprehensive vision and eye assessment, with appropriate treatment, does not reduce, and may even increase, the risk of falls and fractures.", "Estrogen deficiency and declining calcium absorption due to reduced calcitriol levels or intestinal resistance to calcitriol, are important factors in the pathogenesis of age-related bone loss. The main objective of this study was to examine the effect of estrogen and 1,25-dihydroxyvitamin D therapy given individually or in combination on bone loss in elderly women. Four hundred eighty-nine elderly women with normal bone density for their age, aged 65-77 yr, were entered into a randomized double blind, placebo-controlled trial. Women were randomized to one of four groups: conjugated estrogens (0.625 mg, daily) to women without a uterus (estrogen replacement therapy) plus medroxyprogesterone acetate (2.5 mg, daily) to women with a uterus (hormone replacement therapy), calcitriol (0.25 microg twice daily), a combination of hormone replacement therapy/estrogen replacement therapy plus calcitriol, or placebos for 3 yr. The primary outcome was the change in bone mineral density of the femoral neck and spine. In the intent to treat analysis, hormone therapy (hormone replacement therapy/estrogen replacement therapy) produced a mean (+/-1 SD) increase in bone mineral density of 2.98% (+/-5.45%) at the femoral neck (P < 0.0001) and 4.36% (+/-6.42%) at the spine (P < 0.0001). There were parallel increases in total hip and trochanter bone mineral density. Calcitriol increased bone mineral density 0.10% (+/- 4.27%) at the femoral neck (P = 0.57) and 1.65% (+/- 4.83%) at the spine (P < 0.0124). The combination of hormone replacement therapy/estrogen replacement therapy + calcitriol increased bone mineral density 3.80% (+/-4.95%) at the femoral neck (P < 0.001), 4.91% (+/-6.0%) at the spine (P < 0.0001), and parallel changes at the total hip and trochanter. All three treatment groups differed significantly from placebo at the spine and for the hormone replacement therapy/estrogen replacement therapy groups at the femoral neck, spine, total hip and trochanter. There were no significant differences between combination therapy and hormone replacement therapy/estrogen replacement therapy alone on bone mineral density at any site in the intent to treat analysis. In a secondary analysis of the effect in women who were adherent to treatment, calcitriol had a more significant effect on spine (P = 0.003) and total hip (P = 0.004). The increase in bone mineral density in the adherent groups of women was always higher compared with the intent to treat groups. Combination therapy compared with hormone replacement therapy/estrogen replacement therapy alone produced a significantly greater response in trochanter (P = 0.007) and total hip bone mineral density (P = 0.0017). In summary, hormone replacement therapy/estrogen replacement therapy alone and in combination with calcitriol therapy was highly effective in reducing bone resorption and increasing bone mineral density at the hip and other clinically relevant sites in a group of elderly women, with normal bone density for their age. Calcitriol was effective in increasing spine bone mineral density. In the adherent women, combination therapy with hormone replacement therapy/estrogen replacement therapy and calcitriol increased bone mineral density significantly more in the total hip and trochanter than did hormone replacement therapy/estrogen replacement therapy alone.", "To assess the short-term effect of an exercise-based rehabilitation intervention on balance, mobility, falls and injuries.\n This randomized, controlled trial with repeated measures was performed at an outpatient rehabilitation center. Elderly, ambulatory, community-dwelling volunteers underwent 6 wks of supervised stretching, balance, endurance, coordination, and strengthening exercises. Controls attended seminars. Data were recorded for time and quality performance on a functional obstacle course and for self-reported falls and injuries.\n From baseline through 6-mo follow-up, participants in the exercise group (n = 122) significantly outperformed those in the control group (n = 83). The exercise group's functional obstacle course quality improved 2.3% postintervention and 1.57% at follow-up compared with 0.3% for the control group for each time period (P = 0.001). Functional obstacle course completion time improved 7.69% at postintervention and 8.35% at follow-up for the exercise group compared with 4.0% and 3.4% for the control group. Of baseline fallers in the intervention group, 87% (compared with 34.5% for the controls) reported no falls in the subsequent 6 mos. Of those reporting injuries in the 6 mos preintervention, 89.7% in the intervention group (compared with 55.6% for controls) reported no injury at 6 mos postintervention.\n Our intervention can improve functional performance and protect against falls and fall-related injuries.", "Age-related loss of foot-sole cutaneous sensation is very common and is associated with impaired balance control. This study investigated the effect of a balance-enhancing insole (designed to facilitate foot-sole sensation) on lateral gait stability and evaluated its effectiveness in daily life.\n Forty community-dwelling older adults (age 65-75) with moderate loss of foot-sole sensation (unrelated to neuropathy) were fitted with the same model of walking shoes. Half of the participants were assigned, at random, to wear the shoes with a facilitatory insole for 12 weeks; the other participants wore a conventional insole. A gait perturbation protocol, simulating uneven terrain, was performed at baseline and after wearing the assigned insoles for 12 weeks. Participants were tested with both types of insoles during each gait-testing session and sent in weekly postcards with information pertaining to insole comfort, hours of wear, and falls.\n The facilitatory insole improved lateral stability during gait, and this benefit did not habituate after 12 weeks of wearing the insole in daily life. Nine participants who wore conventional insoles experienced one or more falls, whereas only five of the facilitatory group fell. Although there were initial reports of mild discomfort in 10 cases, all but one participant tolerated the facilitatory insole, and most indicated that they would like to continue wearing the insole on a long-term basis.\n A relatively simple change in insole design can help to counter effects of age-related (non-neuropathic) decline in foot-sole sensitivity, and is a viable intervention to enhance balance control.", "To assess the effectiveness of an intervention planned and implemented by regional geriatric care teams in order to prevent falls in an elderly population.\n The study was conducted among 555 (67%) home-dwelling Finnish persons aged 85 years or older of a representative population sample (N=827) in 2000-2003. Altogether 486 subjects (88%) had a history of recurrent falls or at least one risk factor for disability in the activities of daily living or mobility and were randomly assigned to receive suggestions for a programme consisting of home exercise, walking exercise, group activities or self-care exercise or alternatively routine care. Falls were monitored for a median of 16 months during the intervention.\n The time to first four falls and all falls did not significantly differ in the targeted intervention group (N=217); compared to controls (N=220), hazard ratio 0.88 (95% CI 0.74 to 1.04) and 0.93 (0.80-1.09), respectively. Among those able to move outdoors, the corresponding hazard ratios in the intervention group (N=168) compared to the controls (N=178) were 0.78 (0.64-0.94) and 0.88 (0.74-1.05). After the intervention period, impaired balance was less common in the intervention than in the control subjects; 64 (45%) and 89 (59%) (p<0.05).\n A pragmatic intervention was not effective in reducing the falling risk at the population level, but slowed down the reduction of balance performance. Among those able to move outdoors, the intervention was also effective in reducing the risk of first four falls.", "The purpose of this study was to test the feasibility of the WALC intervention (Walk; Address pain, fear, fatigue during exercise; Learn about exercise; Cue by self-modeling), and determine its effects on self-efficacy and outcome expectations, exercise activity and free living activity, physical and mental health status, and falls and fall-related injuries. A total of 17 sedentary older women with a mean age of 88 +/- 3.7 years were randomly assigned to receive either the WALC intervention or routine care. Ninety percent of those in the treatment group initiated and engaged in a regular exercise program during the 6 months of the study. There was a statistically significant difference in self-efficacy expectations, exercise behavior, and overall activity between the two groups. Those in the treatment group had stronger self-efficacy expectations related to exercise; engaged in more exercise and more free living activity; and although not statistically significant, had stronger outcome expectations following exposure to the WALC intervention when compared with those who received routine care. To help older adults initiate and adhere to an exercise program, nurses can easily implement the WALC intervention in a variety of settings.", "Exercise in older people may reduce falls and improve functional abilities. Less is known about the optimal amount of training. The aim of this study was to determine the effectiveness of home training, and whether group training in addition to home training enhances the effect.\n This randomized trial included 77 persons aged 75 years and older (mean 81, SD 4.5), living at home. Home training (HT) comprised twice-daily functional balance and strength exercises and 3 group meetings. Combined training (CT) included group training twice weekly and the same home exercises. The trial lasted 12 weeks. Physical therapists ran both programs. Exercises and falls were recorded daily. We assessed function at baseline, 3 and 9 months, and falls at one year.\n Mean participation for group meetings was 2.5 out of 3 (HT group) and, for group training sessions, 21 out of 24 (CT group). The mean numbers of daily home sessions were 1.29 and 1.35 in the HT and CT groups. Overall improvement, but no group differences, were found at 3 months for walking speed, Figure of Eight, Timed Up & Go, Maximum Step Length, Timed Pick-up and Sit-to-stand (p<0.02). Posturography (p=0.85) and isometric quadriceps strength (p=0.26) showed no improvement. Function at 9 months was equivalent to baseline level. There were no group differences in fall rate (p=0.78) or time to first fall (p=0.84).\n Daily home training supervised by physical therapists improved functional abilities. Supplementary individualized group training gave no additional effect. The effect on function was not present 6 months after the end of the intervention.", "first eye cataract surgery reduces the risk of falling. Most cataracts in elderly people are bilateral. Some binocular functions (e.g. stereopsis) are associated with falls. We aimed to determine if second eye cataract surgery reduces the risk of falling and to measure associated health gain.\n we randomised 239 women over 70, who had been referred to a hospital ophthalmology department, with one unoperated cataract, to expedited (approximately 4 weeks) or routine (12 months wait) surgery. Falls were ascertained by diary, with follow-up every 3 months for 12 months. We measured health status after 6 months.\n visual function (especially stereopsis) improved in the operated group. Over 12 months follow-up, 48 (40%) operated participants fell at least once, 22 (18%) fell more than once. Forty-one (34%) unoperated participants fell at least once, 22 (18%) fell more than once. Rate of falling was reduced by 32% in the operated group, but this was not statistically significant (rate ratio 0.68, 95% CI 0.39, 1.19, P = 0.18). Confidence, visual disability and handicap all improved in the operated compared with the control group.\n second eye cataract surgery improves visual disability and general health status. The effect on rate of falling remains uncertain.", "To evaluate the effectiveness of in-home geriatric assessments as a means of providing preventive health care and improving health and functional status of community-living elderly veterans.\n Randomized controlled trial with 1-year follow-up.\n Home visits performed in a suburb of Los Angeles.\n Community-living veterans 70 years and older not currently receiving health care at the Sepulveda VA Medical Center (n = 131 intervention; 123 controls).\n A home visit by a physician's assistant or nurse, to screen for medical, functional and psychosocial problems, followed by a letter describing findings and recommendations, and follow-up visits by trained volunteers at 4-month intervals for 1 year. Controls received only telephone interviews at 4-month intervals to collect outcome data.\n Compliance with recommendations was studied for the intervention group. Outcome comparisons between the two groups included: mortality, medication usage, functional status, immunization rates, and nursing home and hospital utilization.\n A mean of four new or suboptimally treated problems was identified for intervention subjects. Subjects complied with 76% of recommendations to see a physician or initiate a specific health practice. At 12-month follow-up, intervention subjects had significantly increased their immunization rates (P < 0.001) and had a significantly increased likelihood of having a primary care physician (P < 0.05). Twelve-month functional status (IADL) scores were significantly higher for intervention subjects than for controls; intervention subjects maintained their functional status, while controls experienced significant decline during the follow-up year (P < 0.05). Non-prescription drug use increased significantly among controls, but not among intervention subjects (P < 0.05).\n A brief geriatric screening assessment performed in the home can detect unrecognized and treatable problems, even among relatively healthy older adults. The use of trained volunteers is a feasible strategy for providing health education and follow-up contacts. These results support the concept that preventive gerontological approaches can help maintain important aspects of health and function.", "To determine whether a 12-month program of regular exercise can improve balance, reaction time, neuromuscular control, and muscle strength and reduce the rate of falling in older women.\n A randomized, controlled trial of 12 months duration.\n Conducted as part of the Randwick Falls and Fractures Study in Sydney, Australia.\n One hundred ninety-seven women aged 60 to 85 years (mean age 71.6, SD = 5.4) who were randomly recruited from the community.\n Accidental falls, postural sway, reaction time, neuromuscular control, and lower limb muscle strength.\n Exercise and control subjects were tested before, midway through, and at the end of the trial. At initial testing, exercisers and controls performed similarly in all tests and were well matched in relevant health and lifestyle factors. The mean number of classes attended for the 75 exercise subjects who completed the program was 60.0 (range 26-82). At the end of the trial, the exercise subjects showed improved performance in all five strength measures, in reaction time, neuromuscular control, body sway on a firm surface with the eyes open, and body sway on a compliant surface with the eyes open and closed. In contrast, there were no significant improvements in any of the test measures in the controls. In one test measure, hip flexion strength, the exercisers showed continued improvement throughout the study year. There was no significant difference in the proportion of fallers between the exercise and control subjects. Interesting trends were evident, however, between falls frequency and adherence to the exercise program.\n These findings show that exercise can produce long-term benefits with regard to improving sensorimotor function in older persons. The findings also suggest that high compliance to an exercise program may reduce falls frequency, although further studies are required to conclusively demonstrate that exercise offers an effective means of preventing falls.", "To decrease the rate of falls in high-risk community-dwelling older adults.\n Randomized, controlled trial.\n Community-based.\n Three hundred forty-nine adults aged 65 and older with two falls in the previous year or one fall in the previous 2 years with injury or balance problems.\n Subjects received two in-home visits from a trained nurse or physical therapist who assessed falls risk factors using an algorithm. The intervention consisted of recommendations to the subject and their primary physician, referrals to physical therapy and other providers, 11 monthly telephone calls, and a balance exercise plan. Control subjects received a home safety assessment.\n The primary outcome was rate of falls per year in the community. Secondary outcomes included all-cause hospitalizations and nursing home admissions per year.\n There was no difference in rate of falls between the intervention and control groups (rate ratio (RR)=0.81, P=.27). Nursing home days were fewer in the intervention group (10.3 vs 20.5 days, P=.04). Intervention subjects with a Mini-Mental State Examination (MMSE) score of 27 or less had a lower rate of falls (RR=0.55; P=.05) and, if they lived with someone, had fewer hospitalizations (RR=0.44, P=.05), nursing home admissions (RR=0.15, P=.003), and nursing home days (7.5 vs 58.2, P=.008).\n This multifactorial intervention did not decrease falls in at-risk community-living adults but did decrease nursing home utilization. There was evidence of efficacy in the subgroup who had an MMSE score of 27 or less and lived with a caregiver, but validation is required.", "This study determined the effects and costs of a multifactorial, interdisciplinary team approach to falls prevention. Randomized controlled trial of 109 older adults who are at risk for falls. This was a six-month multifactorial and evidence-based prevention strategy involving an interdisciplinary team. The primary outcome was number of falls during the six-month follow-up. At six months, no difference in the mean number of falls between groups. Subgroup analyses showed that the intervention effectively reduced falls in men (75-84 years old) with a fear of falling or negative fall history. Number of slips and trips was greatly reduced; and emotional health had a greater improvement in role functioning related to emotional health in the intervention group. Quality of life was improved, slips and trips were reduced, as were falls among males (75-84 years old) with a fear of falling or negative fall history.", "to determine the clinical effectiveness of a day hospital-delivered multifactorial falls prevention programme, for community-dwelling older people at high risk of future falls identified through a screening process.\n multicentre randomised controlled trial.\n eight general practices and three day hospitals based in the East Midlands, UK. Participants: three hundred and sixty-four participants, mean age 79 years, with a median of three falls risk factors per person at baseline. Interventions: a day hospital-delivered multifactorial falls prevention programme, consisting of strength and balance training, a medical review and a home hazards assessment. Main outcome measure: rate of falls over 12 months of follow-up, recorded using self-completed monthly diaries.\n one hundred and seventy-two participants in each arm contributed to the primary outcome analysis. The overall falls rate during follow-up was 1.7 falls per person-year in the intervention arm compared with 2.0 falls per person-year in the control arm. The stratum-adjusted incidence rate ratio was 0.86 (95% CI 0.73-1.01), P = 0.08, and 0.73 (95% CI 0.51-1.03), P = 0.07 when adjusted for baseline characteristics. There were no significant differences between the intervention and control arms in any secondary outcomes.\n this trial did not conclusively demonstrate the benefit of a day hospital-delivered multifactorial falls prevention programme, in a population of older people identified as being at high risk of a future fall.", "Ageing is associated with increased risk of poor health and functional decline. Uncertainties about the health-related benefits of nutrition and physical activity for older people have precluded their widespread implementation. We investigated the effectiveness and cost-effectiveness of a national nutritional supplementation program and/or a physical activity intervention among older people in Chile.\n We conducted a cluster randomized factorial trial among low to middle socioeconomic status adults aged 65-67.9 years living in Santiago, Chile. We randomized 28 clusters (health centers) into the study and recruited 2,799 individuals in 2005 (~100 per cluster). The interventions were a daily micronutrient-rich nutritional supplement, or two 1-hour physical activity classes per week, or both interventions, or neither, for 24 months. The primary outcomes, assessed blind to allocation, were incidence of pneumonia over 24 months, and physical function assessed by walking capacity 24 months after enrollment. Adherence was good for the nutritional supplement (~75%), and moderate for the physical activity intervention (~43%). Over 24 months the incidence rate of pneumonia did not differ between intervention and control clusters (32.5 versus 32.6 per 1,000 person years respectively; risk ratio = 1.00; 95% confidence interval 0.61-1.63; p = 0.99). In intention-to-treat analysis, after 24 months there was a significant difference in walking capacity between the intervention and control clusters (mean difference 33.8 meters; 95% confidence interval 13.9-53.8; p = 0.001). The overall cost of the physical activity intervention over 24 months was US$164/participant; equivalent to US$4.84/extra meter walked. The number of falls and fractures was balanced across physical activity intervention arms and no serious adverse events were reported for either intervention.\n Chile's nutritional supplementation program for older people is not effective in reducing the incidence of pneumonia. This trial suggests that the provision of locally accessible physical activity classes in a transition economy population can be a cost-effective means of enhancing physical function in later life.\n Current Controlled Trials ISRCTN 48153354.", "Falls occur mainly while walking or performing concurrent tasks. We determined whether a music-based multitask exercise program improves gait and balance and reduces fall risk in elderly individuals.\n We conducted a 12-month randomized controlled trial involving 134 community-dwelling individuals older than 65 years, who are at increased risk of falling. They were randomly assigned to an intervention group (n = 66) or a delayed intervention control group scheduled to start the program 6 months later (n = 68). The intervention was a 6-month multitask exercise program performed to the rhythm of piano music. Change in gait variability under dual-task condition from baseline to 6 months was the primary end point. Secondary outcomes included changes in balance, functional performances, and fall risk.\n At 6 months, there was a reduction in stride length variability (adjusted mean difference, -1.4%; P < .002) under dual-task condition in the intervention group, compared with the delayed intervention control group. Balance and functional tests improved compared with the control group. There were fewer falls in the intervention group (incidence rate ratio, 0.46; 95% confidence interval, 0.27-0.79) and a lower risk of falling (relative risk, 0.61; 95% confidence interval, 0.39-0.96). Similar changes occurred in the delayed intervention control group during the second 6-month period with intervention. The benefit of the intervention on gait variability persisted 6 months later.\n In community-dwelling older people at increased risk of falling, a 6-month music-based multitask exercise program improved gait under dual-task condition, improved balance, and reduced both the rate of falls and the risk of falling. Trial Registration clinicaltrials.gov Identifier: NCT01107288.", "The study tested the effect of strength and endurance training on gait, balance, physical health status, fall risk, and health services use in older adults.\n The study was a single-blinded, randomized controlled trial with intention-to-treat analysis. Adults (n = 105) age 68-85 with at least mild deficits in strength and balance were selected from a random sample of enrollees in a health maintenance organization. The intervention was supervised exercise (1-h sessions, three per week, for 24-26 weeks), followed by self-supervised exercise. Exercise groups included strength training using weight machines (n = 25), endurance training using bicycles (n = 25), and strength and endurance training (n = 25). Study outcomes included gait tests, balance tests, physical health status measures, self-reported falls (up to 25 months of follow-up), and inpatient and outpatient use and costs.\n There were no effects of exercise on gait, balance, or physical health status. Exercise had a protective effect on risk of falling (relative hazard = .53, 95% CI = .30-.91). Between 7 and 18 months after randomization, control subjects had more outpatient clinic visits (p < .06) and were more likely to sustain hospital costs over $5000 (p < .05).\n Exercise may have beneficial effects on fall rates and health care use in some subgroups of older adults. In community-living adults with mainly mild impairments in gait, balance, and physical health status, short-term exercise may not have a restorative effect on these impairments.", "Low trauma fractures in older people incur enormous physical, social and economic costs. Previous research indicates that an annual intramuscular injection of vitamin D may reduce fracture rates in this group. This strategy requires validation in a population setting.\n Randomized, double-blind, placebo-controlled trial of 300,000 IU intramuscular (i.m.) vitamin D2 (ergocalciferol) injection or matching placebo every autumn over 3 years. 9440 people (4354 men and 5086 women) aged 75 yrs and over were recruited from general practice registers in Wessex, England. Primary outcome measure was all non-vertebral fracture. Secondary outcomes were hip and wrist fractures, and all falls.\n 585 subjects had incident non-spine fractures (hip 110, wrist 116, ankle 37). Hazard ratios (HRs) for fracture in the vitamin D group were: 1.09 [95% confidence interval (CI) 0.93-1.28, P = 0.29] for any first fracture, 1.49 (95% CI 1.02-2.18, P = 0.04) for hip and 1.22 (95% CI 0.85-1.76, P = 0.28) for wrist. There was no effect on falls: HR 0.98 (0.93-1.04). No protective effect was observed in any subgroup when the cohort was stratified by sex, age, previous fracture or mobility.\n An annual i.m. injection of 300,000 IU vitamin D2 is not effective in preventing non-vertebral fractures among elderly men and women resident in the general population.", "A recent meta-analysis found that cholecalciferol (vitamin D) should reduce falls by more than 20%. However, little is known about whether supplemental cholecalciferol plus calcium citrate malate will lower the long-term risk of falling in men, active older individuals, and older individuals with higher 25-hydroxyvitamin D levels.\n We studied the effect of 3-year supplementation with cholecalciferol-calcium on the risk of falling at least once in 199 men and 246 women 65 years or older and living at home. Individuals received 700 IU of cholecalciferol plus 500 mg of calcium citrate malate per day or placebo in a randomized double-blind manner. Subjects were classified as less physically active if physical activity was below the median level. Low 25-hydroxyvitamin D levels were classified as those below 32 ng/mL (<80 nmol/L).\n In 3 years, 55% of women and 45% of men reported at least 1 fall. Mean +/- SD baseline 25-hydroxyvitamin D levels were 26.6 +/- 12.7 ng/mL (66.4 +/- 31.7 nmol/L) in women and 33.2 +/- 14.2 ng/mL (82.9 +/- 34.9) in men. Cholecalciferol-calcium significantly reduced the odds of falling in women (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.30-0.97), but not in men (OR, 0.93; 95% CI, 0.50-1.72). Fall reduction was most pronounced in less active women (OR, 0.35; 95% CI, 0.15-0.81). Baseline 25-hydroxyvitamin D level did not modulate the treatment effect.\n Long-term dietary cholecalciferol-calcium supplementation reduces the odds of falling in ambulatory older women by 46%, and especially in less active women by 65%. Supplementation had a neutral effect in men independent of their physical activity level.", "Restricted physical activity as a consequence of chronic disease or injury is a predictor of functional decline. The aim of this study was to test the hypothesis that a 6- month multidimensional training program would have sustained beneficial effects upon the physiological, functional and psychological condition of old women with a recent history of falls.\n Participants were 65 home-dwelling women (70-90 years) identified from hospital records as having had an accidental fall. After assessment of muscle strength, balance performance, walking speed, balance confidence, and physical activity level, the participants were randomly assigned to a control group (n=33) or a training group (n=32), who performed a multidimensional training program including moderate resistance exercise and balance exercise twice weekly for 6 months. Measurements were repeated after 6 and 12 months.\n Six months of multidimensional training resulted in significant improvements and between-group differences in isometric knee extension strength (p<0.05), trunk extension/ flexion strength (p<0.001), habitual/maximal walking speed (p<0.001) and balance performance (p<0.001). At follow-up, 6 months after intervention, these improvements were preserved in the training group and there was also a significant between- group difference with regard to balance confidence. No between-group differences were found concerning number of falls or physical activity level during the one-year study period.\n A multi-dimensional training program produced significant improvements in physiological and functional risk factors for falls and disability in women aged 70-90 years with a recent history of falls.", "To assess whether intervention by a health visitor could reduce the number of fractures, over a four year period, in those aged 70 and over.\n Randomised, controlled trial; randomisation by household.\n General practice in a market town.\n Of 863 patients aged 70 and over on the practice records, 674 were traced and successfully interviewed; 350 were assigned to the intervention group, 324 as controls.\n The people in the intervention group were allocated to the care of a health visitor. The approach was four pronged: assessment and correction of nutritional deficiencies, including reducing smoking and alcohol intake; assessment and referral of medical conditions such as heart block or inappropriate medication; assessment and correction of environmental hazards in the home such as poor lighting; assessment and improvement of fitness--for example, exercise classes for the moderately fit. The intervention continued for four years.\n Fracture rate over four years.\n The incidence of fractures was 5% (16/350) in the intervention group and 4% (14/324) in the control group (difference not significant).\n A health visitor visiting a group of people aged 70 and over and using simple preventive measures had no effect on the incidence of fractures.", "To evaluate whether a service to prevent falls in the community would help reduce the rate of falls in older people who call an emergency ambulance when they fall but are not taken to hospital.\n Randomised controlled trial.\n Community covered by four primary care trusts, England.\n 204 adults aged more than 60 living at home or in residential care who had fallen and called an emergency ambulance but were not taken to hospital.\n Referral to community fall prevention services or standard medical and social care.\n The primary outcome was the rate of falls over 12 months, ascertained from monthly diaries. Secondary outcomes were scores on the Barthel index, Nottingham extended activities of daily living scale, and falls efficacy scale at baseline and by postal questionnaire at 12 months. Analysis was by intention to treat.\n 102 people were allocated to each group. 99 (97%) participants in the intervention group received the intervention. Falls diaries were analysed for 88.6 person years in the intervention group and 84.5 person years in the control group. The incidence rates of falls per year were 3.46 in the intervention group and 7.68 in the control group (incidence rate ratio 0.45, 95% confidence interval 0.35 to 0.58, P<0.001). The intervention group achieved higher scores on the Barthel index and Nottingham extended activities of daily living and lower scores on the falls efficacy scale (all P<0.05) at the 12 month follow-up. The number of times an emergency ambulance was called because of a fall was significantly different during follow-up (incidence rate ratio 0.60, 95% confidence interval 0.40 to 0.92, P=0.018).\n A service to prevent falls in the community reduced the fall rate and improved clinical outcome in the high risk group of older people who call an emergency ambulance after a fall but are not taken to hospital.\n Current Controlled Trials ISRCTN67535605.", "To evaluate the effects of two exercise approaches, Tai Chi (TC) and computerized balance training (BT), on specified primary outcomes (biomedical, functional, and psychosocial indicators of frailty) and secondary outcomes (occurrence of falls).\n The Atlanta FICSIT (Frailty and Injuries: Cooperative Studies of Intervention Techniques), a prospective, randomized, controlled clinical trial with three arms (TC, BT, and education [ED]. Intervention length was 15 weeks, with primary outcomes measured before and after intervention and at 4-month follow-up. Falls were monitored continuously throughout the study.\n Persons aged 70 and older living in the community.\n A total of 200 participants, 162 women and 38 men; mean age was 76.2.\n Biomedical (strength, flexibility, cardiovascular endurance, body composition), functional (IADL), and psychosocial well-being (CES-D scale, fear of falling questionnaire, self-perception of present and future health, mastery index, perceived quality of sleep, and intrusiveness) variables.\n Grip strength declined in all groups, and lower extremity range of motion showed limited but statistically significant changes. Lowered blood pressure before and after a 12-minute walk was seen following TC participation. Fear of falling responses and intrusiveness responses were reduced after the TC intervention compared with the ED group (P = .046 and P = .058, respectively). After adjusting for fall risk factors, TC was found to reduce the risk of multiple falls by 47.5%.\n A moderate TC intervention can impact favorably on defined biomedical and psychosocial indices of frailty. This intervention can also have favorable effects upon the occurrence of falls. Tai Chi warrants further study as an exercise treatment to improve the health of older people.", "nan", "Care of elderly patients after hip fracture is not well established.\n We enrolled 173 patients with acute hip fracture who were 65 years or older (79.2% women; mean age, 84 years; 77.4% living at home). Using a factorial design, we randomly allocated patients to extended physiotherapy (PT) (supervised 60 min/d during acute care plus an unsupervised home program) vs standard PT (supervised 30 min/d during acute care plus no home program; single-blinded), and to cholecalciferol therapy, 2000 vs 800 IU/d (double-blinded). Primary outcome was rate of falls; secondary outcome was rate of hospital readmissions during the 12-month follow-up. All analyses included 173 individuals and used multivariate Poisson regression analyses.\n At baseline, 50.9% of participants had 25-hydroxyvitamin D levels of less than 12 ng/mL and 97.7% of less than 30 ng/mL. We documented 212 falls and 74 hospital readmissions. Because this was a factorial design trial, all analyses tested the main effect of each treatment while controlling for the other in 173 participants. Extended vs standard PT reduced the rate of falls by 25% (95% confidence interval [CI], -44% to -1%). Cholecalciferol treatment, 2000 vs 800 IU/d, did not reduce falls (28%; 95% CI, -4% to 68%), but reduced the rate of hospital readmissions by 39% (95% CI, -62% to -1%).\n Extended PT was successful in reducing falls but not hospital readmissions, whereas cholecalciferol treatment, 2000 IU/d, was successful in reducing hospital readmission but not falls. Thus, the 2 strategies may be useful together because they address 2 different and important complications after hip fracture.", "there is inadequate evidence to support currently formulated NHS strategies to achieve health promotion and preventative care in older people through broad-based screening and assessment in primary care. The most extensively evaluated delivery instrument for this purpose is Health Risk Appraisal (HRA). This article describes a trial using HRA to evaluate the effect on health behaviour and preventative-care uptake in older people in NHS primary care.\n a randomised controlled trial was undertaken in three London primary care group practices. Functionally independent community-dwelling patients older than 65 years (n = 2,503) received a self-administered Health Risk Appraisal for Older Persons (HRA-O) questionnaire leading to computer-generated individualised written feedback to participants and general practitioners (GPs), integrated into practice information-technology (IT) systems. All primary care staff received training in preventative health in older people. The main outcome measures were self-reported health behaviour and preventative care uptake at 1-year follow-up.\n of 2,503 individuals randomised, 2,006 respondents (80.1%) (intervention, n = 940, control n = 1,066) were available for analysis. Intervention group respondents reported slightly higher pneumococcal vaccination uptake and equivocal improvement in physical activity levels compared with controls. No significant differences were observed for any other categories of health behaviour or preventative care measures at 1-year follow-up.\n HRA-O implemented in this way resulted in minimal improvement of health behaviour or uptake of preventative care measures in older people. Supplementary reinforcement involving contact by health professionals with patients over and above routine clinical encounters may be a prerequisite to the effectiveness of IT-based delivery systems for health promotion in older people.", "Since falling is associated with serious morbidity among elderly people, we investigated whether the risk of falling could be reduced by modifying known risk factors.\n We studied 301 men and women living in the community who were at least 70 years of age and who had at least one of the following risk factors for falling: postural hypotension; use of sedatives; use of at least four prescription medications; and impairment in arm or leg strength or range of motion, balance, ability to move safely from bed to chair or to the bathtub or toilet (transfer skills), or gait. These subjects were given either a combination of adjustment in their medications, behavioral instructions, and exercise programs aimed at modifying their risk factors (intervention group, 153 subjects) or usual health care plus social visits (control group, 148 subjects).\n During one year of follow-up, 35 percent of the intervention group fell, as compared with 47 percent of the control group (P = 0.04). The adjusted incidence-rate ratio for falling in the intervention group as compared with the control group was 0.69 (95 percent confidence interval, 0.52 to 0.90). Among the subjects who had a particular risk factor at base line, a smaller percentage of those in the intervention group than of those in the control group still had the risk factor at the time of reassessment, as follows: at least four prescription medications, 63 percent versus 86 percent, P = 0.009; balance impairment, 21 percent versus 46 percent, P = 0.001; impairment in toilet-transfer skills, 49 percent versus 65 percent, P = 0.05; and gait impairment, 45 percent versus 62 percent, P = 0.07.\n The multiple-risk-factor intervention strategy resulted in a significant reduction in the risk of falling among elderly persons in the community. In addition, the proportion of persons who had the targeted risk factors for falling was reduced in the intervention group, as compared with the control group. Thus, risk-factor modification may partially explain the reduction in the risk of falling.", "To compare the adherence to and effectiveness of Tai Chi exercise program through a live, interactive, telecommunication-based exercise (Tele-ex) with that of a similar program through a community center-based exercise (Comm-ex) and a home video-based exercise (Home-ex) among community-dwelling elders who are at risk for falls.\n Three groups randomized controlled trial with pretests and posttests.\n Exercise programs were community-based, and the outcome measures were laboratory-based.\n Adults (N=64) age 65+ years with positive fall history in the previous year and/or significant fear of falling.\n A 24-form, Yang-style Tai Chi for 15 weeks, 3 hours a week.\n Exercise compliance, number of falls, fear of falling (Activities-specific Balance Confidence [ABC] score), self-perceived health (Medical Outcomes Study 36-Item Short Form Health Survey [SF-36]), Timed Up & Go (TUG), single leg stance (SLS), and body sway during quiet stance (medial-lateral foot center of pressure [ML-COP]).\n Tele-ex and Comm-ex groups demonstrated significantly higher exercise attendance and in-class practice time than the Home-ex group (P<.01) and significant reductions in the mean number of falls and injurious falls (P<.01). There were significant improvements posttraining in SLS, ABC, ML-COP, and Physical Health subscore of the SF-36 (P<.05). Both Tele-ex and Comm-ex groups demonstrated larger improvements than the Home-ex group in TUG, ML-COP, and the Social Function, Mental Health, and Physical Health subscores of the MOS SF-36.\n Compared with the Home-ex, the Tele-ex and Comm-ex groups are better in exercise compliance, fall reduction and balance and health improvements. Tele-ex is an effective, affordable, and acceptable choice of exercise for elders.\n Copyright 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.", "Calcium has been shown to have positive effects on bone mineral density in postmenopausal women. However, these effects are small, it is unknown whether they are sustained with long-term use, they have not been shown with intention-to-treat analyses, and the evidence for fracture prevention with calcium monotherapy is inconsistent.\n A randomized controlled trial of calcium (1 g/day as the citrate) in 1471 healthy postmenopausal women (aged 74+/-4 years) was performed to assess the effects on bone density and fracture incidence over 5 years.\n Follow-up was complete in 90% of subjects, and average medication compliance was 55% to 58%. Calcium had a significant beneficial effect on bone density (intention-to-treat analysis), with between-groups differences at 5 years of 1.8% (spine), 1.6% (total hip), and 1.2% (total body). Effects were greater in a per-protocol analysis (5-year differences of 2.3%, 2.8%, and 1.8%, respectively). A total of 425 fractures occurred in 281 women. Hazard ratios, based on time to first fracture, were 0.90 (95% confidence interval [CI], 0.71-1.16) for any symptomatic fracture, 0.72 (95% CI, 0.44-1.18) for vertebral, 3.55 (95% CI, 1.31-9.63) for hip, and 0.65 (95% CI, 0.41-1.04) for forearm fracture. Per-protocol analysis found respective hazard ratios of 0.86 (95% CI, 0.64-1.17), 0.62 (95% CI, 0.33-1.16), 3.24 (95% CI, 0.65-16.1), and 0.45 (95% CI, 0.24-0.87). Height loss was reduced by calcium in the per-protocol population (P=.03). Serum alkaline phosphatase and procollagen type-I N-terminal propeptide were lower in the calcium group at 5 years, but constipation was more common.\n Calcium results in a sustained reduction in bone loss and turnover, but its effect on fracture remains uncertain. Poor long-term compliance limits its effectiveness.", "The beneficial role of exercise in improving bone mineral density, muscle strength and balance, has been documented predominantly in younger populations. These findings may not apply to elderly populations with limited ability to perform exercises of high intensity.\n To examine the effects of Tai Chi (TC) and resistance exercise (RTE) on bone mineral density (BMD), muscle strength, balance and flexibility in community living elderly people.\n Randomised controlled trial, using blocked randomization with stratification by sex.\n A community in the New Territories Region of Hong Kong, China.\n One hundred eighty subjects (90 men, 90 women) aged 65-74, were recruited through advertisements in community centres.\n Subjects were assigned to participate in TC, RTE three times a week, or no intervention (C) for 12 months. Measurements were carried out at baseline, 6 and 12 months. Analyses of covariance (ANCOVA) adjusted for age, and baseline values of variables that were significantly different between groups: i.e. smoking and flexibility for men; quadriceps strength for women.\n Compliance was high (TC 81%, RTE 76%). In women, both TC and RTE groups had less BMD loss at total hip compared with controls. No effect was observed in men. No difference in either balance, flexibility or the number of falls was observed between either intervention or controls after 12 months.\n The beneficial effects of TC or RTE on musculoskeletal health are modest and may not translate into better clinical outcomes.", "To compare the effects of weight-bearing and non-weight-bearing home exercise programs and a control program on physical ability (strength, balance, gait, functional performance) in older people who have had a hip fracture.\n Randomized controlled trial with 4-month follow-up.\n Australian community-dwellers (82%) and residents of aged care facilities who had completed usual care after a fall-related hip fracture.\n One hundred twenty older people entered the trial, 40 per group (average age +/- standard deviation, 79+/-9y) and 90% completed the 4-month retest.\n Home exercise prescribed by a physical therapist.\n Strength, balance, gait, and functional performance.\n At the 4-month retest, there were differences between the groups in the extent of improvement since the initial assessment for balance (F(10,196)=2.82, P<.001) and functional performance (F(6,200)=3.57, P<.001), but not for strength (F(12,190)=1.09, P=.37) or gait (F(8,200)=.39, P=.92). The weight-bearing exercise group showed the greatest improvements in measures of balance and functional performance (between-group differences of 30%-40% of initial values).\n A weight-bearing home exercise program can improve balance and functional ability to a greater extent than a non-weight-bearing program or no intervention among older people who have completed usual care after a fall-related hip fracture.", "To determine whether the oral nutritional supplementation of undernourished older people upon discharge from hospital improves muscle function and reduces disability.\n Randomized controlled trial.\n Community-based study in two centers in Scotland.\n Two hundred fifty-three people.\n Randomization to oral nutritional supplementation (600 kcal/d) or control supplement of 200 kcal/d.\n Primary outcome (20-point activity of daily living Barthel Index) and secondary outcomes (handgrip strength, Sit-to-Stand test, and Euroquol) were measured at baseline (after discharge from the hospital and before supplement was commenced) and 8 and 16 weeks and accelerometry-measured physical activity levels at baseline and 16 weeks. Falls were recorded prospectively.\n Mean age was 82. There was no significant difference in change in Barthel score between supplement and control groups (adjusted mean difference=0.28, 95% confidence interval (CI)=-0.28-0.84). Handgrip strength improved more in the supplemented group (adjusted mean difference=1.52 kg, 95% CI=0.50-2.55; P=.004). The supplemented group exhibited modestly greater vector movement (overall activity) than controls (P=.02). There were no significant between-group differences in Sit-to-Stand test, health-related quality of life, or falls. Adherence was 38.2% in the nutritional supplement group and 50.0% in the control supplement group. Weight did not increase in the nutritional supplement group as a whole, but on-treatment analysis adjusting for adherence showed a mean weight gain of 1.17 kg (95% CI=0.07-2.27; P=.04) more than in controls.\n Oral nutritional supplementation of undernourished older people upon hospital discharge did not reduce disability, despite improving handgrip strength and modestly increasing objectively measured physical activity levels. Lack of an effect of the nutritional supplement used in this study may have been due to low adherence, suggesting that different approaches to nutritional supplementation need to be tested in this population.", "To compare the effect of calcium/vitamin D supplements with a combination of calcium/vitamin D supplements and exercise/protein on risk of falling and postural balance.\n Randomized clinical trial.\n University hospital physiotherapy department.\n Twenty-four independently living elderly females aged 65 years and older with osteopenia or osteoporosis and mean total hip T-score (SD) of -1.8 (0.8).\n A three-month programme consisting of exercise/protein including training of muscular strength, co-ordination, balance and endurance. Calcium/ vitamin D was supplemented in all participants for a 12-month period.\n Assessment took place prior to and following the months 3, 6, 9 and at the end of the study; primary dependent variables assessed were risk of falling (Berg Balance Test) and postural balance (forceplate). Secondary measures included body composition, strength, activity level, number of falls, bone mineral content, biochemical indices, nutritional status and general health.\n Significant reductions of risk of falling (repeated measures ANOVA F = 8.90, P = 0.008), an increase in muscular strength (ANOVA F = 3.0, P = 0.03), and an increase in activity level (ANOVA F = 3.38, P = 0.02) were found in the experimental group as compared to the control group. Further on, there was 89% reduction of falls reported in the experimental group (experimental pre/post 8/1 falls; control group pre/post 5/6 falls).\n This study provides support for our intervention programme aimed at reducing the risk of falling in elderly participants diagnosed with osteopenia or osteoporosis. The data obtained from the pilot study allow the calculation of the actual sample size needed for a larger randomized trial.", "Falls in the elderly are a major health problem. Although exercise programs have been shown to reduce the risk of falls, the optimal exercise components, as well as the working mechanisms that underlie the effectiveness of these programs, have not yet been established.\n To test whether the Nijmegen Falls Prevention Program was effective in reducing falls and improving standing balance, balance confidence, and obstacle avoidance performance in community-dwelling elderly people.\n A total of 113 elderly with a history of falls participated in this study (exercise group, n = 79; control group, n = 28; dropouts before randomization, n = 6). Exercise sessions were held twice weekly for 5 weeks. Pre- and post-intervention fall monitoring and quantitative motor control assessments were performed. The outcome measures were the number of falls, standing balance and obstacle avoidance performance, and balance confidence scores.\n The number of falls in the exercise group decreased by 46% (incidence rate ratio (IRR) 0.54, 95% confidence interval (CI) 0.36-0.79) compared to the number of falls during the baseline period and by 46% (IRR 0.54, 95% CI 0.34-0.86) compared to the control group. Obstacle avoidance success rates improved significantly more in the exercise group (on average 12%) compared to the control group (on average 6%). Quiet stance and weight-shifting measures did not show significant effects of exercise. The exercise group also had a 6% increase of balance confidence scores.\n The Nijmegen Falls Prevention Program was effective in reducing the incidence of falls in otherwise healthy elderly. There was no evidence of improved control of posture as a mechanism underlying this result. In contrast, an obstacle avoidance task indicated that subjects improved their performance. Laboratory obstacle avoidance tests may therefore be better instruments to evaluate future fall prevention studies than posturographic balance assessments.\n Copyright (c) 2006 S. Karger AG, Basel.", "Instability or falls are one of the important warning symptoms of underlying serious illness among the elderly, so many studies have concentrated on the risk factors for falls. However, a study involving a strategic method to reduce the incidence of falls is the next step and is the main objective of this study. 1,043 elderly subjects living in the urban area around Siriraj Hospital Medical School, Bangkok, were recruited, 585 of them were allocated to the study group and 458 subjects to the control group. A leaflet containing information on important risk factors of falls within their community was enclosed with a follow-up postcard in the study group only. In addition, this particular group was allowed free access to the geriatric clinic at Siriraj Hospital if there was any health problem. All of them received a postcard asking about any falls which had occurred over the previous 2 months on 6 occasions and a telephone call if the postcards were not returned to the team. The percentage of elderly who kept in contact was 92.5 per cent, 90.6 per cent, 89.3 per cent, 89.2 per cent, 86.2 per cent and 85.45 per cent for the first to final follow-up respectively. After one year of longitudinal study, the overall incidence of falls was 6.6 per cent in the study group and 10.1 per cent in the control group. The incidence of falls began to show a statistically significant difference between the two groups at the fourth and sixth episodes of follow-up (P = 0.002 and 0.004). The Kaplan-Meier survival analysis also revealed a statistically significant difference in the incidence of falls between the two groups (P =0.01). In conclusion, the incidence of falls was significantly reduced in the study group and a repeated campaign to alert the elderly to the risk of falling is a cost-effective way of fall prevention among the healthy elderly in the community.", "The aim of the present study was to investigate the effects of home-based exercise without home visits on physical function, falls, and bone mineral density in community-dwelling elderly women. Sixty community-dwelling, elderly (> or =65 years of age) women were recruited from a Japanese community. Subjects were randomly assigned to a home-based exercise group or a control group. The subjects assigned to the home-based exercise group performed home-based exercise without home visits 3 times per week for 6 months in their homes. Assessments of physical function and bone mineral density were carried out before and after intervention in both groups. Muscle strength, gait velocity, the timed up and go test (TUGT), single leg stance time, the bend reach performance test, and reaction time were measured to assess physical function. The patients' history of falls was also assessed before and after the 12-month follow-up. To determine bone mineral density, the speed of sound (SOS) at the right calcaneus was measured using a quantitative ultrasound device. There were no significant differences between the two groups in baseline characteristics. 82.6% of subjects completed the prescribed exercise program in the home-based exercise group. Compared to the control group, TUGT improved significantly (p<0.05) in the home-based exercise group. Home-based exercise without home visits can be adopted for community-dwelling elderly women, particularly since no specific place or instructor is needed.", "The purpose of this study was to evaluate the effectiveness of a 12-month community-based intervention on falls and risk factors (balance, lower extremity strength, and mobility) in community-living older adults.\n Four hundred fifty-three sedentary adults (65 years old or older) were randomized to either a multifaceted intervention (3 times a week group exercise, 6 hours of fall prevention education, comprehensive falls risk assessment results sent to primary health care provider) or control group (written materials on falls prevention). Primary outcome was fall incidence rates calculated from self-reported falls reported monthly for 12 months. Secondary outcomes were tests of leg strength, balance, and mobility prior to and following the 12-month intervention.\n Twelve-month follow-up was completed on 95% of participants. Intent-to-treat analysis found that the incidence rate of falls was 25% lower among those in the intervention group compared with control group (1.33 vs 1.77 falls/person-year, rate ratio 0.75, 95% confidence interval [CI], 0.52-1.09). This difference was not statistically significant. The risk ratio for any fall was 0.96 (95% CI, 0.82-1.13). Small but significant improvements were found on the Berg Balance Test (adjusted mean difference +1.5 points, 95% CI, 0.8-2.3), the Chair Stand Test (adjusted mean difference +1.2, 95% 0.6-1.9), and the Timed Up and Go Test (adjusted mean difference -0.7, 95% CI, -1.2 to -0.2).\n A community-based multifaceted intervention was effective in improving balance, mobility, and leg strength, all known fall risk factors. Although the incidence of falls was lower, the confidence interval included the possibility of no intervention effect on falls.", "To explore the 2-year outcomes of an interdisciplinary intervention for elderly patients with hip fracture.\n Randomized experimental design.\n A 3,000-bed medical center in northern Taiwan.\n Patients with hip fracture (N=162): 80 in the intervention group and 82 in the usual care control group.\n An interdisciplinary program of geriatric consultation, continuous rehabilitation, and discharge planning.\n Outcomes (clinical outcomes, self-care ability, health-related quality of life (HRQoL), service utilization, and depressive symptoms) were assessed 1, 3, 6, 12, 18, and 24 months after discharge. Self-care ability (ability to perform activities of daily living (ADLs)) was measured using the Chinese Barthel Index. HRQoL was measured using the Medical Outcomes Study 36-item Short Form Survey, Taiwan version (SF-36). Depressive symptoms were measured using the Chinese Geriatric Depression Scale, short form.\n Subjects in the intervention group had significantly better ratios of hip flexion (beta=5.43, P<.001), better performance on ADLs (beta=9.22, P<.001), better recovery of walking ability (odds ratio (OR)=2.23, P<.001), fewer falls (OR=0.56, P=.03), fewer depressive symptoms (beta=-1.31, P=.005), and better SF-36 physical summary scores (beta=6.08, P<.001) than the control group during the first 24 months after discharge. The intervention did not affect the peak force of the fractured limb's quadriceps, mortality, service utilization, or SF-36 mental summary score.\n The interdisciplinary intervention for hip fracture benefited elderly persons with hip fracture by improving clinical outcomes, self-care ability, and physical health-related outcomes and by decreasing depressive symptoms during the first 24 months after hospital discharge.", "Our aim was to determine the effect of hormone replacement on physical performance measures, functional ability, physical activity, falls, and cognitive function in elderly women.\n Following a 3-month, open-label, run-in phase, we randomized 373 community-dwelling women aged 65 years and older to receive conjugated equine estrogen 0.625 mg/day plus or minus medroxyprogesterone 2.5 mg/day vs placebo for 3 years in a double-blind fashion. We assessed time to rise from a chair, timed walking, balance, Instrumental Activities of Daily Living, Physical Activity Scale of the Elderly, Folstein Mini-Mental State Examination, and falls.\n Over 3 years, except for balance scores, performance measures declined significantly (all P<.05). There were no significant mean differences between women on hormone replacement versus placebo for rising time (0.1, -0.5 to 0.7 seconds [mean, 95% confidence interval]), walking normal (0.0, -0.4 to 0.4 seconds), and walking fast (0.2, -0.1 to 0.6 seconds). There were no significant mean differences between the two groups for the Instrumental Activities of Daily Living (0.1, -0.1 to 0.3 points), Physical Activity Scale of the Elderly (-3, -15 to 8 points), Folstein Mini-Mental State Examination (-0.1, -0.3 to 0.3 points), or the proportion of participants reporting falls (-1, -11 to 9%).\n In elderly women, hormone replacement had no statistically significant effect on cognition or balance, nor did it prevent the age-related decline in physical measures of mobility, ability to rise from a chair, self-reported activities of daily living, physical activity scores, or falls.", "Physical and psychological incapacity, including fear of falling is related to decreased satisfaction with life in osteoporosis (OP). The impact of a balance exercise program on improving the quality of life is not well established. We have, therefore, investigated the effect of 12-month Balance Training Program in quality of life, functional balance and falls in elderly OP women.\n Sixty consecutive women with senile OP were randomized into a Balance Training Group (BT) of 30 patients and no intervention control group (CG) of 30 patients. The BT program included techniques to improve balance over a period of 12 months (1h exercise session/week and home-based exercises). The quality of life was evaluated before and at the end of the trial using the Osteoporosis Assessment Questionnaire (OPAQ), functional balance was evaluated by Berg Balance Scale (BBS). Falls in the preceding year were noted and compared to the period of study.\n The comparison of OPAQ variations (INITIAL-FINAL) revealed a significant improvement in quality of life in all parameters for BT compared to CG: well-being (1.61+/-1.44 vs. -1.46+/-1.32, p<0001), physical function (1.30+/-1.33 vs. -0.36+/-0.82, p<0.001), psychological status (1.58+/-1.36 vs. -1.02+/-0.83, p<0.001), symptoms (2.76+/-1.96 vs. -0.63+/-0.87, p<0.001), social interaction (1.01+/-1.51 vs. 0.35+/-1.08, p<0.001). Of note, this overall benefit was paralleled by an improvement of BBS (-5.5+/-5.67 vs. +0.5+/-4.88 p<0.001) and a reduction of falls in 50% in BT group vs. 26.6% for the CG (RR: 1.88, p<0.025).\n The long-term Balance Training Program of OP women provides a striking overall health quality of life improvement in parallel with improving functional balance and reduced falls.\n Copyright 2010 Elsevier Ireland Ltd. All rights reserved.", "To evaluate the effects of a trail-walking exercise (TWE) program on the rate of falls in community-dwelling older adults.\n Pilot randomized controlled trial (RCT).\n This trial was conducted in Japan and involved community-dwelling older adults as participants.\n Sixty participants randomized into a TWE group (n=30) and a walking (W) group (n=30).\n Exercise class combined with multicomponent trail walking program, versus exercise class combined with simple indoor walking program.\n Measurement was based on the difference in fall rates between the TWE and W groups.\n Six months after the intervention, the incidence rate ratio (IRR) of falls for the TWE group compared with the W group was 0.20 (95% confidence interval (CI)=0.04-0.91); 12 months after the intervention, the IRR of falls for the TWE group compared with the W group was 0.45 (95% CI=0.16-1.77).\n The results of this pilot RCT suggest that the TWE program was more effective in improving locomotion and cognitive performance under trail-walking task conditions than walking. In addition, participants who took part in the TWE demonstrated a decrease in the incidence rate of falls 6 months after trial completion. Further confirmation is needed, but this preliminary result may promote a new understanding of accidental falls in older adults.\n © 2010, Copyright the Authors. Journal compilation © 2010, The American Geriatrics Society.", "Falls occur frequently in older people and strongly affect quality of life. Guidelines recommend multifactorial, targeted fall prevention. We evaluated the effectiveness of a multifactorial intervention in older persons with a high risk of recurrent falls.\n A randomized controlled trial was conducted from April 3, 2005, to July 21, 2008, at the geriatric outpatient clinic of a university hospital and regional general practices in the Netherlands. Of 2015 persons identified, 217 persons aged 65 years or older were selected to participate. They had a high risk of recurrent falls and no cognitive impairment and had visited the emergency department or their family physician after a fall. The geriatric assessment and intervention were aimed at reduction of fall risk factors. Primary outcome measures were time to first and second falls after randomization. Secondary outcome measures were fractures, activities of daily living, quality of life, and physical performance.\n Within 1 year, 55 (51.9%) of the 106 intervention participants and 62 (55.9%) of the 111 usual care (control) participants fell at least once. No significant treatment effect was demonstrated for the time to first fall (hazard ratio, 0.96; 95% confidence interval, 0.67-1.37) or the time to second fall (1.13; 0.71-1.80). Similar results were obtained for secondary outcome measures and for per-protocol analysis. One intervention participant died vs 7 in the control group (hazard ratio, 0.15; 95% confidence interval, 0.02-1.21).\n This multifactorial fall-prevention program does not reduce falls in high-risk, cognitively intact older persons. Trial Registration isrctn.org Identifier: ISRCTN11546541.", "Among elderly persons, falls account for 87% of all fractures and are contributing factors in many nursing home admissions. This study evaluated the effect of an easily implemented, low-intensity exercise program on the incidence of falls and the time to first fall among a clinically defined population of elderly men and women.\n This community-based, randomized trial compared the exercise intervention with a no-intervention control. The participants were 294 men and women, aged 60 years or older, who had either a hospital admission or bed rest for 2 days or more within the previous month. Exercise participants were scheduled to attend exercise sessions lasting 45 minutes, including warm-up and cool-down, 3 times a week for 8 weeks (24 sessions). Assessments included gait and balance measures, self-reported physical function, the number of medications being taking at baseline, participant age, sex, and history of falling. Falls were tracked for 1 year after each participant's baseline assessment.\n 29% of the study participants reported a fall during the study period. The effect of exercise in preventing falls varied significantly by baseline physical function level (p < or =.002). The risk for falls decreased for exercise participants with low baseline physical functioning (hazard ratio,.51) but increased for exercise participants with high baseline physical functioning (hazard ratio, 3.51).\n This easily implemented, low-intensity exercise program appears to reduce the risk for falls among elderly men and women recovering from recent hospitalizations, bed rest, or both who have low levels of physical functioning.", "The purpose of this randomized controlled trial was to measure the effectiveness of A Matter of Balance, a small-group based balance program, on muscle strength, gait, balance, and fall risk among older community-dwelling adults at risk for falls. A secondary aim was to measure the effects of the program on actual fall rates over the 3-month study.\n Twenty-three older adults were randomly assigned to either an experimental group that participated in a 12-week small-group based balance program or a control group. Subjects were assessed at baseline and following an intervention using the following outcome measures: lower extremity manual muscle testing (MMT) and range of motion; gait analysis on the GAITRite system; balance parameters on the SMART EquiTest, the Timed Up and Go test, the Berg Balance Scale, and incidence of falls.\n A repeated measures ANOVA revealed that there was a significant interaction between groups over time in the Berg Balance Scale scores, P < or = .05. The experimental group improved over time (48.1 to 52.9/56, respectively), whereas the control group decreased in performance (49.1 to 47.8/56, respectively), P < or = .05. The mean number of falls was significantly less in the experimental group during the intervention compared with the control group (0.09 and 0.50, respectively), P < or = .05.\n A community-based multifactorial intervention including individualized fall risk assessment, exercise, and home assessment appears to safely and effectively reduce the number of falls, resulting in significant improvements in functional balance ability and decreased fall risk.", "To assess whether supplementation with calcium and cholecaliferol (vitamin D3) reduces the risk of fracture in women with one or more risk factors for fracture of the hip.\n Pragmatic open randomised controlled trial.\n Practice nurse led clinics in primary care.\n 3314 women aged 70 and over with one or more risk factors for hip fracture: any previous fracture, low body weight (< 58 kg), smoker, family history of hip fracture, or fair or poor self reported health.\n Daily oral supplementation using 1000 mg calcium with 800 IU cholecaliferol and information leaflet on dietary calcium intake and prevention of falls, or leaflet only (control group).\n Primary outcome measure was all clinical fractures and secondary outcome measures were adherence to treatment, falls, and quality of life (measured with the SF-12).\n 69% of the women who completed the follow-up questionnaire at 24 months were still taking supplements (55% with inclusion of randomised participants known to be alive). After a median follow-up of 25 months (range 18 to 42 months), clinical fracture rates were lower than expected in both groups but did not significantly differ for all clinical fractures (odds ratio for fracture in supplemented group 1.01, 95% confidence interval 0.71 to 1.43). The odds ratio for hip fracture was 0.75 (0.31 to 1.78). The odds of a woman having a fall at six and 12 months was 0.99 and 0.98, respectively. Quality of life did not significantly differ between the groups.\n We found no evidence that calcium and vitamin D supplementation reduces the risk of clinical fractures in women with one or more risk factors for hip fracture. Registration ISRCTN26118436, controlled trials registry.", "Multidisciplinary and multifactorial interventions seem to be effective in preventing falls. We aimed to assess the cost-effectiveness of a multidisciplinary fall prevention program compared with usual Dutch healthcare in community-dwelling people 65 years of age or older who experienced a fall.\n Cost-effectiveness and cost-utility analysis were performed from a societal perspective. Falls and healthcare utilization were continuously measured for 12 months. Daily functioning and quality of life were measured at baseline, after 4 and 12 months. Bootstrap analyses were performed to estimate uncertainty of the findings and sensitivity analysis to assess the generalizability of assumptions made.\n One hundred sixty-six participants were randomly allocated to the experimental group and 167 to the control group. The overall response rate was 74 percent. Healthcare and patient and family costs of both groups were comparable. Our analyses showed no effect of the intervention program on falls, daily functioning, or quality of life measures.\n The multidisciplinary intervention program to prevent falls was not cost-effective compared with usual care in the Netherlands. Notwithstanding our findings, however, falls still have an important impact on society and individuals in terms of costs and effects. Economic evaluations studying promising interventions to prevent falls, therefore, remain necessary.", "Multifaceted programs that combine assessment with interventions have been shown to reduce subsequent falls in some clinical trials. We tested this approach to see whether it would be effective if offered as a consultation service using existing health care resources.\n The subjects of this randomized controlled trial had to be aged 65 years or more and had to have fallen within the previous 3 months. They were randomly assigned to receive either usual care or the intervention, which consisted of in-home assessment in conjunction with the development of an individualized treatment plan, including an exercise program for those deemed likely to benefit. The primary outcomes were the proportion of participants who fell and the rate of falling during the following year. Visits to the emergency department and admissions to hospital were secondary outcomes.\n One hundred and sixty-three subjects were randomly assigned to either the control or the intervention group, and 152 provided data about their falls. There were no significant differences between the control and intervention groups in the cumulative number of falls (311 v. 241, p = 0.34), having one or more falls (79.2% v. 72.0%, p = 0.30) or in the mean number of falls (4.0 v. 3.2, p = 0.43). Analysis of secondary outcomes (health care use) also showed no significant differences between the intervention group and the control group. In the Cox regression analysis, there was no significant difference between the groups in the proportion of subjects having one or more falls (p = 0.55), but there was a significantly (p < 0.001) longer time between falls in the intervention group. In a post hoc subgroup analysis, subjects with more than 2 falls in the 3 months preceding study entry who had been assigned to the intervention group were less likely to fall (p = 0.046) and had a significantly longer time between falls (p < 0.001), when compared with the group who received usual care.\n The intervention did not decrease significantly the cumulative number of falls, the likelihood of participants having at least one fall over the next year or the mean number of falls. It did increase significantly the time between falls in a survival analysis when age, sex and history of falling were used as covariates.", "To test the benefits of regular surveillance of the elderly at home using a simple-questionnaire, 142 randomly selected subjects aged 70 years or over and living in a slum area of Bangkok were recruited and were designated as cases (n = 70) and controls (n = 72). At the beginning of the study period all subjects were visited and their characteristics, including morbidity data, activities of daily living (Barthle ADL Index, Chula ADL Index) and number of falls during the last three months, were collected. Over three years the cases were visited every three months, in their own home, by non-professional personnel. They and/or their care-givers were interviewed using a short questionnaire designed for the home visiting programme. The elderly who had problems according to the criteria were visited and assessed by nurses and/or a geriatrician. Appropriate management was provided to these elderly. After three years, all subjects were visited and outcome data were collected. Rates of service use among the cases were higher than among the controls but there was not a statistically significant difference. The rate of declining in Chula ADL Index score of the cases was significantly less than that of the controls. (p < 0.05) There was no statistically significant difference between other main outcomes of the case and control groups. However, regular home visiting of old people at home by non-professional personnel using a simple questionnaire is a practical way for community care of the elderly population living in poor areas.", "1. Seventy-three percent of older women attending a fall prevention program made at least one low cost change in either their personal behavior or living environment to decrease their likelihood of falls. 2. Older women educated in small group sessions made more fall prevention changes than those educated individually. 3. When conducting a fall prevention program, having examples of safety devices available for participants to examine enhances the presentation.", "The aim of the study was to determine whether cardiac pacing reduces falls in older adults with cardioinhibitory carotid sinus hypersensitivity (CSH).\n Cardioinhibitory carotid sinus syndrome causes syncope, and symptoms respond to cardiac pacing. There is circumstantial evidence for an association between falls and the syndrome.\n A randomized controlled trial was done of consecutive older patients (>50 years) attending an accident and emergency facility because of a non-accidental fall. Patients were randomized to dual-chamber pacemaker implant (paced patients) or standard treatment (controls). The primary outcome was the number of falls during one year of follow-up.\n One hundred seventy-five eligible patients (mean age 73 +/- 10 years; 60% women) were randomized to the trial: pacemaker 87; controls 88. Falls (without loss of consciousness) were reduced by two-thirds: controls reported 669 falls (mean 9.3; range 0 to 89), and paced patients 216 falls (mean 4.1; range 0 to 29). Thus, paced patients were significantly less likely to fall (odds ratio 0.42; 95% confidence interval: 0.23, 0.75) than were controls. Syncopal events were also reduced during the follow-up period, but there were much fewer syncopal events than falls-28 episodes in paced patients and 47 in controls. Injurious events were reduced by 70% (202 in controls compared to 61 in paced patients).\n There is a strong association between non-accidental falls and cardioinhibitory CSH. These patients would not usually be referred for cardiovascular assessment. Carotid sinus hypersensitivity should be considered in all older adults who have non-accidental falls.", "To assess the effectiveness of an environmental falls prevention intervention delivered by qualified occupational therapists or unqualified trained assessors.\n A pilot three-armed randomized controlled trial.\n Airedale National Health Service Trust catchment, North and West Yorkshire, England.\n Two hundred thirty-eight community-dwelling adults aged 70 and older with a history of falls in the previous year.\n Assessment and modification of the home environment of people at greater risk of falls.\n Fear of falling was the primary outcome measure, and an analysis of covariance was conducted on the area under the curve at 12 months. As a secondary outcome, falls were analysed using negative binomial regression. Quality of life and independence in activities of daily living (ADLs) were also measured.\n The intervention had no effect on fear of falling (P=.63). The occupational therapy group had significantly fewer falls than controls 12 months after the assessment (incidence rate ratio (IRR)=0.54, 95% confidence interval (CI)=0.36-0.83, P=.005). There was no significant effect on falls in the trained assessor group (IRR=0.78, 95% CI=0.51-1.21, P=.34).\n Environmental assessment had no effect on fear of falling. Environmental assessment prescribed by an occupational therapist significantly reduced the number of falls in high-risk individuals whereas that prescribed by a trained assessor did not. Further research in other settings is needed to confirm this, to explore the mechanisms, and to estimate cost-effectiveness.\n © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.", "At 16 senior centers, we studied the effectiveness of exercise and cognitive-behavioral programs, compared with a discussion control program, in reducing falls and injuries among 230 older adults. After 1 year of the programs, we observed no significant difference in time to first fall. Even though a relatively high percentage (38.6%) suffered at least one fall, only 7.8% of these community-residing elderly required medical attention. Secondary outcome measures such as strength, balance, fear of falling, and perceived health did not significantly change.", "In the causative mechanism of falls among older community dwellers, slips and trips have been found to be significant precursors. The purpose of the two year trial was to assess the effectiveness of multi-component interventions targeting major risk factors for falls in reducing the incidence of slips, trips and falls among the well, older community.\n Four groups with approximately equal numbers of participants were randomly allocated to interventions. The prevention strategies included education and awareness raising of falls risk factors, exercise sessions to improve strength and balance, home safety advice to modify environmental hazards, and medical assessment to optimise health. The interventions combined the strategies in an add on approach. The first intervention group receiving the information session only was regarded as the control. The outcome of interest was the occurrence of a slip, trip or fall, monitored prospectively using a daily calendar diary.\n Two hundred and fifty two members of the National Seniors Association in the Brisbane district agreed to participate. National Seniors clubs provide a forum for active, community dwelling Australians aged 50 and over to participate in policy, personal development and recreation.\n Using Cox's proportional hazards regression model, adjusted hazard ratios comparing intervention groups with the control ranged from 0.35 (95% CI 0.17, 0.73) to 0.48 (0.25, 0.91) for slips; 0.29 (0.16, 0.51) to 0.45 (0.27, 0.74) for trips; and 0.60 (0.36, 1.01) to 0.82 (0.51, 1.31) for falls. While calendar monitoring recorded outcome, it was also assessed as a prevention strategy by comparing the intervention groups with a hypothetical nonintervened group. At one year after intervention, reductions in the probability of slips, trips and falls (61 (95% CI 54, 66)%; 56 (49, 63)%; 29 (22, 36)% respectively) were demonstrated.\n This study makes an important contribution to the priority community health issue of falls prevention by showing that effective, sustainable, low cost programmes can be introduced through community-based organisations to reduce the incidence of slips, trips and falls in well older people.", "To test whether Stepping On, a multifaceted community-based program using a small-group learning environment, is effective in reducing falls in at-risk people living at home.\n A randomized trial with subjects followed for 14 months.\n The interventions were conducted in community venues, with a follow-up home visit.\n Three hundred ten community residents aged 70 and older who had had a fall in the previous 12 months or were concerned about falling.\n The Stepping On program aims to improve fall self-efficacy, encourage behavioral change, and reduce falls. Key aspects of the program are improving lower-limb balance and strength, improving home and community environmental and behavioral safety, encouraging regular visual screening, making adaptations to low vision, and encouraging medication review. Two-hour sessions were conducted weekly for 7 weeks, with a follow-up occupational therapy home visit.\n The primary outcome measure was falls, ascertained using a monthly calendar mailed by each participant.\n The intervention group experienced a 31% reduction in falls (relative risk (RR)=0.69, 95% confidence interval (CI)=0.50-0.96; P=.025). This was a clinically meaningful result demonstrating that the Stepping On program was effective for community-residing elderly people. Secondary analysis of subgroups showed that it was particularly effective for men (n=80; RR=0.32, 95% CI=0.17-0.59).\n The results of this study renew attention to the idea that cognitive-behavioral learning in a small-group environment can reduce falls. Stepping On offers a successful fall-prevention option.\n Copyright 2004 American Geriatrics Society", "The authors' objective was to evaluate the efficacy of a 6-month Tai Chi intervention for decreasing the number of falls and the risk for falling in older persons.\n This randomized controlled trial involved a sample of 256 physically inactive, community-dwelling adults aged 70 to 92 (mean age, 77.48 years; standard deviation, 4.95 years) who were recruited through a patient database in Portland, Oregon. Participants were randomized to participate in a three-times-per-week Tai Chi group or to a stretching control group for 6 months. The primary outcome measure was the number of falls; the secondary outcome measures included functional balance (Berg Balance Scale, Dynamic Gait Index, Functional Reach, and single-leg standing), physical performance (50-foot speed walk, Up&Go), and fear of falling, assessed at baseline, 3 months, 6 months (intervention termination), and at a 6-month postintervention follow-up.\n At the end of the 6-month intervention, significantly fewer falls (n=38 vs 73; p=.007), lower proportions of fallers (28% vs 46%; p=.01), and fewer injurious falls (7% vs 18%; p=.03) were observed in the Tai Chi group compared with the stretching control group. After adjusting for baseline covariates, the risk for multiple falls in the Tai Chi group was 55% lower than that of the stretching control group (risk ratio,.45; 95% confidence interval, 0.30 to 0.70). Compared with the stretching control participants, the Tai Chi participants showed significant improvements (p<.001) in all measures of functional balance, physical performance, and reduced fear of falling. Intervention gains in these measures were maintained at a 6-month postintervention follow-up in the Tai Chi group.\n A three-times-per-week, 6-month Tai Chi program is effective in decreasing the number of falls, the risk for falling, and the fear of falling, and it improves functional balance and physical performance in physically inactive persons aged 70 years or older.", "falls are the leading causes of accidental death and fragility fractures in older adults. Interventions that assess and reduce falls risk are underutilised.\n to evaluate the impact of a multifaceted community-based programme aimed at optimising evidence-based management of patients at risk for fall-related fractures.\n this was a randomised trial performed from 2003 to 2006.\n community-based intervention in Ontario, Canada.\n eligible patients were community-dwelling, aged > or =55 years and identified to be at risk for fall-related fractures. A total of 201 patients were allocated to the intervention group or to usual care.\n components of the intervention included assessment of falls risk, functional status and home environment, and patient education.\n primary outcome was the implementation of appropriate falls risk assessment at 6 months. Secondary outcomes included falls and fractures at 6 and 12 months.\n the mean age of participants was 72 years, and 41% had fallen with injury in the previous year. Compared to usual care, the intervention increased the number of referrals made to physiotherapy [21% (21/101) vs 6.0% (6/100); relative risk (RR) 3.47, 95% confidence interval (CI) 1.46-8.22] and occupational therapy [15% (15/101) vs 0%; RR 30.7, 95% CI 1.86 to >500]. At 12 months, the number of falls in the intervention group was greater than in the usual care group [23% (23/101) vs 11% (11/100); RR 2.07, 95% CI 1.07-4.02].\n compared to usual care, a multi-faceted intervention increased referrals to physiotherapy and occupational therapy but did not reduce risk of falls. Similar falls reduction interventions cannot be recommended based on the results of this study.", "Falls are the leading cause of injury-related deaths in the aging population. Electronic medical record (EMR) systems can identify at-risk patients and enable interventions to decrease risk factors for falls.\n The objectives of this study were to evaluate an EMR-based intervention to reduce overall medication use, psychoactive medication use, and occurrence of falls in an ambulatory elderly population at risk for falls.\n Prospective, randomized by clinic site.\n Six-hundred twenty community-dwelling patients over 70 at risk for falls based on age and medication use.\n A standardized medication review was conducted and recommendations made to the primary physician via the EMR.\n Patients were contacted to obtain self reports of falls at 3-month intervals over the 15-month period of study. Fall-related diagnoses and medication data were collected through the EMR. A combination of descriptive analyses and multivariate regression models were used to evaluate differences between the 2 groups, adjusting for baseline medication patterns and comorbidities. Although the intervention did not reduce the total number of medications, there was a significant negative relationship between the intervention and the total number of medications started during the intervention period (p < .01, regression estimate -0.199) and the total number of psychoactive medications (p < .05, regression estimate -0.204.) The impact on falls was mixed; with the intervention group 0.38 times as likely to have had 1 or more fall-related diagnosis (p < .01); when data on self-reported falls was included, a nonsignificant reduction in fall risk was seen.\n The current study suggests that using an EMR to assess medication use in the elderly may reduce the use of psychoactive medications and falls in a community-dwelling elderly population.", "To determine the effectiveness of a 16-week community-based tai chi program in reducing falls and improving balance in people aged 60 and older.\n Randomized, controlled trial with waiting list control group.\n Community in Sydney, Australia.\n Seven hundred two relatively healthy community-dwelling people aged 60 and older (mean age 69).\n Sixteen-week program of community-based tai chi classes of 1 hour duration per week.\n Falls during 16 and 24 weeks of follow-up were assessed using a calendar method. Balance was measured at baseline and 16-week follow-up using six balance tests.\n Falls were less frequent in the tai chi group than in the control group. Using Cox regression and time to first fall, the hazard ratio after 16 weeks was 0.72 (95% confidence interval (CI)=0.51-1.01, P=.06), and after 24 weeks it was 0.67 (95% CI=0.49-0.93, P=.02). There was no difference in the percentage of participants who had one or more falls. There were statistically significant differences in changes in balance favoring the tai chi group on five of six balance tests.\n Participation in once per week tai chi classes for 16 weeks can prevent falls in relatively healthy community-dwelling older people.", "To compare the effectiveness of group resistance and agility-training programs in reducing fall risk in community-dwelling older women with low bone mass.\n A randomized, controlled, single-blind 25-week prospective study with assessments at baseline, midpoint, and trial completion.\n Community center.\n Community-dwelling women aged 75 to 85 with low bone mass.\n Participants were randomly assigned to one of three groups: resistance training (n=32), agility training (n=34), and stretching (sham) exercises (n=32). The exercise classes for each study arm were held twice weekly.\n The primary outcome measure was fall risk (derived from weighted scores from tests of postural sway, reaction time, strength, proprioception, and vision), as measured using a Physiological Profile Assessment (PPA). Secondary outcome measures were ankle dorsiflexion strength, foot reaction time, and Community Balance and Mobility Scale score.\n Attendance at the exercise sessions for all three groups was excellent: resistance training (85.4%), agility training (87.3%), and stretching program (78.8%). At the end of the trial, PPA fall-risk scores were reduced by 57.3% and 47.5% in the resistance and agility-training groups, respectively, but by only 20.2% in the stretching group. In the resistance and agility groups, the reduction in fall risk was mediated primarily by improved postural stability, where sway was reduced by 30.6% and 29.2%, respectively. There were no significant differences between the groups for the secondary outcomes measures. Within the resistance-training group, reductions in sway were significantly associated with improved strength, as assessed using increased squat load used in the exercise sessions.\n These findings support the implementation of community-based resistance and agility-training programs to reduce fall risk in older women with low bone mass. Such programs may have particular public health benefits because it has been shown that this group is at increased risk of falling and sustaining fall-related fractures.", "vitamin D supplementation reduces the incidence of fractures in older adults. This may be partly mediated by effects of vitamin D on neuromuscular function.\n to determine the effects of vitamin D supplementation on aspects of neuromuscular function known to be risk factors for falls and fractures.\n randomised, double-blind, placebo-controlled study.\n falls clinic taking referrals from general practitioners and accident and emergency department.\n 139 ambulatory subjects (>/=65 years) with a history of falls and 25-hydroxyvitamin D (25OHD) </=12 microg/l. Intervention: patients were randomised to receive a single intramuscular injection of 600,000 i.u. ergocalciferol or placebo.\n assessments including biochemistry, postural sway, choice reaction time (CRT), aggregate functional performance time (AFPT), and quadriceps strength were carried out at baseline and 6 months post-intervention.\n baseline characteristics were comparable between both groups. 25OHD in the treatment group increased significantly at 6 months. AFPT deteriorated in the control group and improved in the intervention group, representing a significant difference between groups (+6.6 s versus -2.0 s, t = 2.80, P < 0.05). Similar changes were observed for CRT (-0.06 s versus +0.41 s, t = -2.52, P < 0.01) and postural sway (+0.0025 versus -0.0138, t = 2.35, P < 0.02). There was no significant difference in muscle strength change between groups (-10 N versus -2 N, t = -1.26, ns). A significant correlation between change in AFPT and change in 25OHD levels was observed (r = 0.19, P = 0.03). There was no significant difference in the number of falls (0.39 versus 0.24, t = 1.08, P = 0.28) or fallers (14 versus 11, P = 0.52) between two groups.\n vitamin D supplementation, in fallers with vitamin D insufficiency, has a significant beneficial effect on functional performance, reaction time and balance, but not muscle strength. This suggests that vitamin D supplementation improves neuromuscular or neuroprotective function, which may in part explain the mechanism whereby vitamin D reduces falls and fractures." ]

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[ "Posterior capsule opacification after implantation of a hydrophilic or a hydrophobic acrylic intraocular lens: one-year follow-up.", "Heparin eyedrops to prevent posterior capsule opacification.", "Incidence of postoperative posterior capsular opacification following treatment with diclofenac 0.1% and ketorolac 0.5% ophthalmic solutions: 3-year randomized, double-masked, prospective clinical investigation.", "Long-term effect of optic edge design in an acrylic intraocular lens on posterior capsule opacification.", "Effect of a silicone intraocular lens with a sharp posterior optic edge on posterior capsule opacification.", "Long-term effect of optic edge design in a silicone intraocular lens on posterior capsule opacification.", "Comparison of posterior capsule opacification rates between hydrophilic and hydrophobic single-piece acrylic intraocular lenses.", "Efficacy and safety of capsular bending ring implantation to prevent posterior capsule opacification: three-year results of a randomized clinical trial.", "Effect of an acrylic intraocular lens with a sharp posterior optic edge on posterior capsule opacification.", "Quantitative comparison of posterior capsule opacification after polymethylmethacrylate, silicone, and soft acrylic intraocular lens implantation.", "Double-masked prospective ocular safety study of a lens epithelial cell antibody to prevent posterior capsule opacification.", "Posterior capsule opacification: comparison of 3 intraocular lenses of different materials and design.", "Position of anterior capsulorhexis and posterior capsule opacification.", "Posterior capsule opacification after implantation of a hydrogel intraocular lens.", "Inhibition of posterior capsule opacification with an immunotoxin specific for lens epithelial cells: 24 month clinical results.", "Posterior capsule opacification in the presence of an intraocular lens with a sharp versus rounded optic edge.", "Effect of 1-piece and 3-piece AcrySof intraocular lenses on the development of posterior capsule opacification after cataract surgery.", "Effect of anterior capsule polishing on the posterior capsule opacification-inhibiting properties of a sharp-edged, 3-piece, silicone intraocular lens: three- and 5-year results of a randomized trial.", "Posterior capsule opacification after phacoemulsification: silicone CeeOn Edge versus acrylate AcrySof intraocular lens.", "[Long-term outcome after implantation of various intraocular lenses through a corneal tunnel].", "Prospective intrapatient comparison of 6.0-millimeter optic single-piece and 3-piece hydrophobic acrylic foldable intraocular lenses.", "Influence on posterior capsule opacification and visual function of intraocular lens optic material.", "A prospective, randomised comparison of single and three piece acrylic foldable intraocular lenses.", "Posterior capsular opacification in pseudophakic eyes with a silicone or acrylic intraocular lens.", "The effect of capsulorhexis size on development of posterior capsule opacification: small (4.5 to 5.0 mm) versus large (6.0 to 7.0 mm).", "Silicone versus polymethylmethacrylate intraocular lenses with regard to capsular opacification.", "Anterior capsule relationship of the AcrySof intraocular lens optic and posterior capsule opacification: a prospective randomized clinical trial.", "Long-term efficacy of adding a sharp posterior optic edge to a three-piece silicone intraocular lens on capsule opacification: five-year results of a randomized study.", "Posterior capsule opacification after phacoemulsification in patients with postoperative steroidal and nonsteroidal treatment.", "Posterior capsule opacification after implantation of CeeOn Edge 911A, PhacoFlex SI-40NB, and AcrySof MA60BM lenses: one-year results of an intraindividual comparison multicenter study.", "Effect of anterior capsule polishing on fibrotic capsule opacification: three-year results.", "Effect of posterior chamber intraocular lens design and surgical placement on postoperative outcome.", "Posterior capsule opacification 3 years after implantation of an AcrySof and a MemoryLens in fellow eyes.", "Clinical evaluation of posterior capsule opacification in eyes with different small-incision intraocular lenses.", "Posterior capsular opacification with hydrogel, polymethylmethacrylate, and silicone intraocular lenses: two-year results of a randomized prospective trial.", "Digital retroilluminated photography to analyze posterior capsule opacification in eyes with intraocular lenses.", "Long-term results of sealed capsule irrigation using distilled water to prevent posterior capsule opacification: a prospective clinical randomised trial.", "Three-year follow-up of posterior capsule opacification with two different silicone intraocular lenses.", "[Quantitative evaluation of acrylic and silicone intraocular lenses with a sharp optic edge design].", "The effect of capsulorhexis size on posterior capsular opacification: one-year results of a randomized prospective trial.", "Factors influencing the formation of posterior capsular opacities after extracapsular cataract extraction with posterior chamber lens implant.", "Effect of intraocular lens haptic compressibility on the posterior lens capsule after cataract surgery.", "Fellow-eye comparison of posterior capsule opacification with AcrySof SN60AT and AF-1 YA-60BB blue-blocking intraocular lenses.", "The effect of polymethylmethacrylate, silicone, and polyacrylic intraocular lenses on posterior capsular opacification 3 years after cataract surgery.", "Long-term effect of sharp optic edges of a polymethyl methacrylate intraocular lens on posterior capsule opacification: a randomized trial.", "Randomized intraindividual comparison of posterior capsule opacification between a microincision intraocular lens and a conventional intraocular lens.", "Fellow-eye comparison of posterior capsule opacification rates after implantation of 1CU accommodating and AcrySof MA30 monofocal intraocular lenses.", "Posterior capsule opacification after extra capsular cataract extraction in Indian rural population: foldable acrylic vs poly (methyl-methacrylate) intraocular lenses a randomized clinical trial.", "[Postoperative cataract following intraocular lenses with and without laser ridge].", "Effect of a plano-convex posterior chamber lens on capsular opacification from Elschnig pearl formation.", "Optic edge design as long-term factor for posterior capsular opacification rates.", "Effects of dexamethasone, diclofenac, or placebo on the inflammatory response after cataract surgery.", "Effect of optic material on posterior capsule opacification in intraocular lenses with sharp-edge optics: randomized clinical trial.", "Effect of intraocular lens optic edge design and material on fibrotic capsule opacification and capsulorhexis contraction.", "Influence of optic edge design and anterior capsule polishing on posterior capsule fibrosis.", "The effects of three-piece or single-piece acrylic intraocular lens implantation on posterior capsule opacification.", "Comparison of posterior capsule opacification between the 1-piece and 3-piece Acrysof intraocular lenses: two-year results of a randomized trial.", "Prevention of posterior capsule opacification using different intraocular lenses (results of one-year clinical study).", "Influence of three-piece and single-piece designs of two sharp-edge optic hydrophobic acrylic intraocular lenses on the prevention of posterior capsule opacification: a prospective, randomised, long-term clinical trial.", "Long-term effect of 1-piece and 3-piece hydrophobic acrylic intraocular lens on posterior capsule opacification: a randomized trial.", "Three-year prospective randomized study of incidence of posterior capsule opacification in eyes treated with topical diclofenac and betamethasone." ]

[ "To evaluate the effect of hydrophilic and hydrophobic single-piece acrylic intraocular lenses (IOLs) on posterior capsule opacification (PCO) after cataract surgery.\n St. Erik's Eye Hospital, Stockholm, Sweden.\n In a prospective study, 120 patients having cataract surgery were randomized to implantation of a hydrophilic acrylic IOL (BL27, Bausch & Lomb) or a hydrophobic acrylic IOL (AcrySof SA60AT, Alcon). Surgery was performed according to a standardized protocol by 1 of 3 surgeons. Best corrected visual acuity, contrast sensitivity, glare, intraocular pressure, and flare were measured 1 week, 3 months, and 1 year after surgery. Posterior capsule opacification was assessed by digital retroillumination photography and analysis using POCOman software at 1 year. The rate of neodymium:YAG (Nd:YAG) capsulotomy for each IOL was also recorded.\n At 1 year, the hydrophilic acrylic IOL group had a significantly greater percentage area and severity of PCO than the hydrophobic acrylic IOL group (P<.001). Two patients in the hydrophilic acrylic IOL group and 4 in the hydrophobic acrylic IOL group had an Nd:YAG capsulotomy within the first year (P>.05). Contrast sensitivity was significantly better in the hydrophilic acrylic group at 3 months (P<.05); however, at 12 months no difference between the IOLs was observed. There was no significant difference in the other measured parameters.\n Patients with the hydrophilic acrylic BL27 IOL had a significantly greater percentage area and severity of PCO than those with the hydrophobic acrylic SA60AT IOL 1 year after surgery.", "To evaluate whether heparin eyedrops prevent or reduce posterior capsule opacification (PCO) after extracapsular cataract extraction (ECCE) with intraocular lens (IOL) implantation.\n Institute of Ophthalmology, University G. d'Annunzio, Chieti, Italy.\n This 4 year, prospective, case-controlled study evaluated 200 patients who had ECCE and implantation of the same type of posterior chamber IOL. Patients were randomly assigned to receive topical heparin eyedrops postoperatively (heparin group, n = 100) or not to receive the eyedrops (control group, n = 100). Postoperative cell response, cellular precipitates on the IOL, and presence of PCO were evaluated.\n There were no significant differences between groups in postoperative inflammation. The incidence of cellular precipitates was significantly lower in the heparin group than in the control group (P < .001). A neodymium:YAG (Nd:YAG) posterior capsulotomy was done in 7 patients in the heparin group and 14 in the control group (P = .15). During the first 24 months after surgery, the heparin group had a significantly lower incidence of Nd:YAG capsulotomy (P < .05) and fibrotic PCO (P = .02).\n Topical heparin eyedrops were effective in reducing fibrotic PCO in the long term, indicating their usefulness in the postoperative management of ECCE.", "Laboratory studies in experimental animals suggest that use of nonsteroidal anti-inflammatory drugs decreases the incidence of posterior capsular opacification (PCO) following cataract surgery. Recently the incidence of PCO following cataract surgery and intraocular lens implantation was reported to be no different following postoperative treatment with diclofenac sodium 0.1% (Voltaren, Ciba Vision) or with dexamethasone 0.1% (Maxidex, Alcon). We studied the incidence of PCO in patients following treatment with diclofenac 0.1% and ketorolac tromethamine 0.5% (Acular, Allergan) ophthalmic solutions 3 years after cataract surgery and implantation of a foldable silicone intraocular lens.\n A total of 120 patients underwent phacoemulsification and implantation of a foldable silicone intracular lens. Patients were treated with either diclofenac 0.1% ophthalmic solution or 0.5% ketorolac ophthalmic solution 4 times daily for 30 days in a double-masked, randomized fashion during the postoperative period. Patients were examined 3 years following surgery by a masked observer who determined which patients received YAG capsulotomies and graded any existing PCO.\n Each treatment group had 12% YAG capsulotomies 3 years following surgery. Although PCO was present more often with diclofenac treatment (25/62) than with ketorolac treatment (16/58), this difference is not statistically significant (P = .142). Patients tolerated both treatments well without a difference in toxic effects or tolerability.\n This study did not demonstrate a difference in the ability of diclofenac or ketorolac ophthalmic solutions to prevent PCO following cataract extraction and implantation of an intraocular lens. Both treatment regimens were equally well tolerated.", "To compare the posterior capsule opacification (PCO) inhibiting effect of the sharp posterior optic edge design of the Sensar OptiEdge AR40e intraocular lens (IOL) with that of the double-round edge design of the Sensar AR40 IOL over a period of 3 years.\n Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.\n Fifty-three patients with bilateral age-related cataract (106 eyes) were included in this randomized prospective bilateral patient- and examiner-masked clinical trial with intraindividual comparison. Each study patient had cataract surgery in both eyes and received a Sensar AR40 IOL (anterior and posterior round optic edges) in 1 eye and a Sensar OptiEdge AR40e IOL (round anterior and sharp posterior optic edge) in the other eye. Follow-up examinations were at 1 week, 1 and 6 months, and 1, 2, and 3 years. Digital retroillumination images were taken of each eye. The amount of PCO was assessed subjectively at the slitlamp and objectively using automated image-analysis software (AQUA) 1, 2, and 3 years after surgery.\n The sharp-edged AR40e lens showed significantly less regeneratory and fibrotic PCO 1, 2, and 3 years after surgery. The mean AQUA PCO score was 2.18 for the AR40 and 1.00 for the AR40e lens after 1 year; 2.94 and 1.56 after 2 years, and estimated at 3.13 and 1.77, respectively, after 3 years (scale 0 to 10; P<.001). The neodymium:YAG laser capsulotomy rate was significantly higher in the AR40 group. The AR40e lens also led to less peripheral fibrotic PCO. There was no significant difference in complaints concerning edge glare between the groups.\n Compared with the AR40 IOL, the sharp posterior optic edge design of the Sensar OptiEdge AR40e IOL led to significantly less PCO 1, 2, and 3 years postoperatively. In contrast with most past studies on PCO-preventative factors, this study varied only 1 parameter, namely the optic edge design, and the main outcome measure (PCO) was assessed with an objective image-analysis system.", "To compare the inhibiting effect on posterior capsule opacification (PCO) of a silicone intraocular lens (IOL) with a sharp posterior optic edge (ClariFlex OptiEdge, Advanced Medical Optics) and a silicone IOL with a round optic edge (PhacoFlex SI-40, Advanced Medical Optics). Setting: Department of Ophthalmology, University of Vienna, Vienna, Austria.\n This prospective randomized patient- and examiner-masked study comprised 104 eyes of 52 patients with bilateral age-related cataract. All patients had cataract surgery in both eyes and received a sharp-edged IOL in 1 eye and a round-edged IOL in the other eye. Postoperative examinations were at 1 week, 1 and 6 months, and 1 year. Digital slitlamp and retroillumination images were taken of each eye. The amount of PCO was assessed subjectively at the slitlamp and objectively using Automated Quantification of After-Cataract (AQUA) automated-image analysis software.\n The sharp-edged IOL group had significantly less regeneratory and fibrotic PCO 1 month, 6 months, and 1 year after surgery. The mean AQUA PCO score (scale 0 to 10) was 0.71 in the sharp-edged IOL group and 1.40 in the round-edged IOL group (P<.001). The sharp-edged IOL group had less peripheral fibrotic PCO. There was no significant difference between the 2 IOL groups in patient reports of edge glare.\n The sharp-edged design of the ClariFlex OptiEdge silicone IOL led to significantly less PCO than the round-edged PhacoFlex SI-40 IOL 1 year postoperatively.", "To compare the posterior capsule opacification (PCO) inhibiting effect of the round anterior and sharp posterior optic edge profile of the Clariflex silicone intraocular lens (IOL) [AMO Inc, Santa Ana, California, USA] with that of the double-round edge profile of the SI40 (Phacoflex; AMO Inc, Santa Ana, California, USA) silicone IOL over a period of three years.\n Prospective, randomized, double-masked, bilateral clinical trial.\n The study took place at the Department of Ophthalmology, Medical University of Vienna, Austria. Fifty-two patients with age-related cataracts (104 eyes) were included in the study. Each patient received an SI40 IOL (round edges) in one eye and a Clariflex IOL with OptiEdge (sharp posterior optic edge) in the other eye. Follow-up examinations were at one week, one month, six months, and one, two, and three years. Digital retroillumination images were taken of each eye. The amount of PCO was subjectively assessed with the slit-lamp and objectively assessed by automated image analysis software (the computer program Automated Quantification of After-Cataract [AQUA]; Vienna, Austria) one, two, and three years after surgery.\n The Clariflex lens showed markedly less PCO at one, two, and three years after surgery. The mean AQUA PCO score was 1.39 for the SI40 and 0.56 for the Clariflex lens after one year, estimated at 1.64 and 0.57 after two years, and at 2.04 and 0.64, respectively, after three years (scale zero to 10; P < .001). The Nd:YAG laser capsulotomy rate was far higher in the SI40 group (Five cases vs one case at three years).\n The sharp posterior optic edge profile of the Clariflex silicone IOL led to marked and consistently less PCO than the round-edged SI40 IOL one, two, and three years after surgery.", "To determine the effect of intraocular lens (IOL) material on the development of posterior capsule opacification (PCO) at 1 year.\n Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom.\n One hundred six eyes of 53 patients with bilateral cataract and no other ocular comorbidity were prospectively randomized to receive a hydrophobic acrylic or hydrophilic acrylic single-piece IOL in the first eye to have surgery. The alternate IOL was implanted in the fellow eye 4 to 6 weeks later. All surgery was performed by a single surgeon. Postoperative follow-up was 1 day, 1 and 6 months, and 1 year. At each visit, the best corrected high- and low-contrast visual acuities were assessed and a high-intensity digital retroillumination photograph was taken. Posterior capsule opacification was assessed from the digital images by a single operator using a dedicated software program and calculated as the percentage area of opacified capsule.\n One year postoperatively, the median percentage area of PCO was 50.3% in the hydrophilic IOL group and 4.9% in the hydrophobic IOL group (P<.001). The difference in PCO was not accounted for by loss of contact between the capsulorhexis and IOL surface. Further analysis showed that lens epithelial cells tended to invade the posterior capsule at the haptic-optic junction. This was more marked in the hydrophilic IOL group.\n The rate of PCO was significantly higher with the hydrophilic IOL. However, the results cannot be attributed to the IOL material alone as they show the importance of both IOL material and design.", "To determine whether a capsular bending ring (CBR) with a rectangular cross-section and sharp edges moves the barrier to the very equator and avoids contact between the capsulorhexis and optic to prevent posterior capsule opacification (PCO) and anterior capsule fibrosis.\n Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.\n A 0.7 mm high, open poly(methyl methacrylate) CBR was implanted in 60 eyes (patients) in a prospective randomized intraindividual trial. The impact of additional CBR implantation on PCO and anterior capsule fibrosis was compared to that of intraocular lens (IOL) implantation alone using objective scoring.\n No CBR-related surgical complications occurred. The objective PCO score and area were statistically significantly reduced in the CBR group. In patients with complete follow-up, the mean PCO score (scale 1 to 10) at 1, 2, and 3 years was 0.8, 1.7, and 2.1, respectively, in the CBR group and 2.6, 3.9, and 4.6, respectively, in the no-CBR group. The number of quadrants affected by PCO was 0.9, 1.5, and 1.8 versus 3.2, 3.8, and 3.8. Barrier failures with the CBR were caused by the inherent slight edge blunting and occasional eyelet gaping. Laser capsulotomies were performed in the no-CBR group only. Capsule stress folds and fibrotic anterior capsule opacification were also greatly reduced. The best corrected visual acuity was better in the CBR group.\n Capsular bending ring implantation was an effective and safe adjunct to in-the-bag IOL fixation. With improvements in technology and design securing exquisitely sharp edges and circumferential capsular bending independent of the capsular bag diameter, this concept has the potential to prevent PCO and anterior capsule fibrosis.", "To compare the posterior capsule opacification (PCO) inhibiting effect of the sharp posterior optic edge design of the Sensar OptiEdge AR40e intraocular lens (IOL) (Allergan Surgical) with that of the round-edged design of the Sensar AR40 IOL. Setting Department of Ophthalmology, University of Vienna, Vienna, Austria.\n This prospective randomized patient- and examiner-masked study comprised 106 eyes of 53 patients with bilateral age-related cataract. Each patient had cataract surgery in both eyes and received an AR40 IOL in 1 eye and an AR40e IOL in the other eye. Postoperative examinations were at 1 week, 2 and 6 months, and 1 year. Digital slitlamp and digital retroillumination images of each eye were taken. The amount of PCO was assessed subjectively at the slitlamp and objectively using automated image-analysis software.\n The AR40e group had significantly less regeneratory and fibrotic PCO 1 year after surgery. The mean automated image-analysis software PCO score (scale 0 to 10) was 2.19 in the AR40 group and 1.10 in the AR40e group (P <.001). The AR40e group had less peripheral fibrotic PCO. There was no significant difference in patient-reported edge glare between the 2 IOL groups.\n The sharp-edged design of the Sensar OptiEdge AR40e IOL led to significantly less PCO than the round-edged AR40 IOL 1 year postoperatively.", "To quantitatively compare the extent of posterior capsule opacification (PCO) after polymethylmethacrylate (PMMA), silicone, and soft acrylic intraocular lens implantation.\n A total of 240 eyes from 240 patients undergoing implant surgery were randomized into 3 groups based on the type of lens implanted: PMMA, silicone, and soft acrylic. The density value of PCO in 185 eyes was quantitated approximately 2 years after surgery by a new measurement method using the Scheimpflug videophotography system.\n Twenty-one eyes (30.4%) in the PMMA group, 4 (5.7%) in the silicone group, and 2 (2.7%) in the acrylic group had already undergone Nd:YAG laser posterior capsulotomy. The mean +/- SD PCO values were 26.3 +/- 12.2 computer-compatible tape steps (CCT) in the PMMA group, 12.0 +/- 8.3 CCT in the silicone group, and 16.0 +/- 10.3 CCT in the acrylic group. The PCO value in the PMMA group was significantly greater than that in the silicone or acrylic group (P < .001). The visual acuity loss in the PMMA group was also greater than that in the silicone or acrylic group (P < .001).\n Based on the PCO value and capsulotomy rate, the PCO was more extensive with the PMMA lens than with either the silicone or soft acrylic lens, which led to visual acuity loss.", "To evaluate the intraocular safety of an immunoconjugate (MDX-RA) developed to prevent posterior capsule opacification (PCO) in human eyes.\n St. Thomas's Hospital Eye Department, London, United Kingdom.\n Twenty-six patients had phacoemulsification and implantation of an intraocular lens (IOL). All were randomly allocated at the end of surgery to receive a 0.1 mL placebo or 0.1 mL of the immunotoxin MDX-RA intracamerally. Two doses of the drug were tested: 8 patients with a low dose (50 units), 9 patients with a high dose (100 units), and 9 with placebo. Follow-up at days 1, 14, 30, 60, 90, and 180 consisted of visual acuity measured by the Early Treatment of Diabetic Retinopathy Study test, contrast sensitivity, aqueous flare, specular microscopy of the IOL's anterior surface, and corneal endothelial counts. The percentage area of PCO was measured from retroillumination images of the posterior capsule.\n There was no decrease in corneal endothelial cell count in toxin-treated patients. Early postoperative flare, anterior chamber cell count, and corneal pachymetry were higher in toxin-treated patients. The median percentage area of PCO at 1 year was 32.0 in the placebo group, 3.8 in the low-dose group, and 7.4 in the high-dose group (P = .06).\n This prospective, randomized, placebo-controlled trial confirmed that MDX-RA is safe for intraocular use and is of potential value for further clinical trials of the prevention of PCO.", "To compare posterior capsule opacification (PCO) after cataract surgery with implantation of 3 intraocular lenses (IOLs) of different materials and design.\n St. Erik's Eye Hospital, Stockholm, Sweden.\n In this prospective clinical study, 180 patients had standardized phacoemulsification performed by a single surgeon and were randomized to have implantation of a heparin-surface-modified (HSM) poly(methyl methacrylate) (PMMA) IOL (809C, Pharmacia & Upjohn), a silicone IOL (SI-40NB, Allergan), or an acrylic IOL (AcrySof MA60BM, Alcon). To morphologically evaluate PCO, retroillumination photographs were obtained and analyzed using Evaluation of Posterior Capsule Opacification computer software. The neodymium:YAG (Nd:YAG) capsulotomy rate was recorded.\n After 2 years, the HSM PMMA IOL group had significantly more PCO than the silicone and AcrySof IOL groups; the silicone group had significantly more PCO than the AcrySof group (P<.05). The Nd:YAG capsulotomy rate was 20% in the HSM PMMA group, 22% in the silicone group, and 8% in the AcrySof group.\n Patients with an AcrySof IOL developed significantly less PCO than those with a silicone or HSM PMMA IOL with a round-edged design.", "To evaluate whether the position of the anterior continuous curvilinear capsulorhexis influences the rate of posterior capsule opacification (PCO).\n A total of 119 patients, aged 61-86 years, underwent cataract surgery with phacoemulsification performed by a single surgeon. The patients were randomized to implantation with either a silicone intraocular lens (IOL) (SI40NB, Allergan) or an AcrySof IOL (MA60BM, Alcon). Three years after surgery, the rate of PCO was analysed using the evaluation of posterior capsule opacification computer software (EPCO). The results were related to the capsulorhexis position, which was assessed with a retroillumination photograph.\n If the capsulorhexis was located partially or completely off the optics of the IOL, compared to totally on the IOL, significantly more PCO was found (p = 0.0014). When comparing within each IOL type, patients with AcrySof IOLs were found to have significantly less PCO when the capsulorhexis was totally on the optic (p = 0.0048). This difference was also significant in the silicone group (p = 0.041).\n A relatively small and central capsulorhexis allowing for the complete covering of the IOL optics by the rhexis edges seems to protect against PCO in cataract surgery, with both round-edged silicone IOLs and sharp-edged hydrophobic acrylic IOLs.", "To compare the degree of posterior capsule opacification (PCO) in eyes with a hydrophilic hydrogel intraocular lens (IOL) with that in eyes with a hydrophobic acrylic IOL.\n Ninety five patients underwent a hydrogel IOL implantation in one eye and an acrylic IOL implantation in the opposite eye. The PCO value of these patients was measured using the Scheimpflug videophotography system at 1, 6, 12, 18, and 24 months postoperatively. The rate of neodymium:YAG (Nd:YAG) laser posterior capsulotomy and visual acuity were also evaluated.\n The mean PCO value in the hydrogel group increased significantly (p<0.0001), while that in the acrylic group did not show significant change. The PCO value in the hydrogel group was significantly greater than that in the acrylic group throughout the follow up period. Kaplan-Meier survival analysis determined that the Nd:YAG capsulotomy rate in the hydrogel group was significantly higher than that in the acrylic group (p<0.0001). Mean visual acuity in the hydrogel group decreased significantly with time (p<0.0001), and became significantly worse than that in the acrylic group at 18 and 24 months postoperatively.\n Posterior capsule opacification in eyes with a hydrophilic hydrogel IOL is significantly more extensive than that in eyes with a hydrophobic acrylic IOL, and results in a significant impairment of visual acuity.", "To assess the safety and effectiveness of an immunotoxin, MDX-RA, designed to inhibit posterior capsule opacification (PCO).\n Eleven private practices in the United States.\n This study comprised 63 eyes of 63 patients having extracapsular cataract extraction by phacoemulsification; these patients were enrolled in a Phase I/II clinical investigation of the immunotoxin MDX-RA. At the close of surgery, 21 patients were treated with placebo, 23 patients with 50 units of the immunotoxin, and 19 patients with 175 units of the immunotoxin as an aqueous solution. The patients were monitored for 24 months after primary cataract surgery using external eye and slitlamp examinations, visual acuity assessment, ophthalmoscopy, pachymetry, tonometry, endothelial cell counts, and lens capsule photography. Posterior capsule opacification, recorded on lens capsule photographs, was graded independently by a committee of 3 cataract surgeons. The incidence of neodymium:YAG (Nd:YAG) capsulotomy was projected from the opacification results.\n The immunotoxin, at the 50 unit dose, was well tolerated and effective in inhibiting PCO. At the 175 unit dose, there was a trend toward increased postoperative inflammation that was transient with no residua. From 6 to 24 months postoperatively, the 50 unit dose significantly inhibited PCO compared with the placebo (P < .05). This significant reduction in PCO translated into a significantly lower projected need for Nd:YAG capsulotomy in the 50 unit than the placebo group (P < .004). About 60% in the placebo group and 4% in the 50 unit group were projected to need an Nd:YAG capsulotomy by 3 years postoperatively.\n The immunotoxin was well tolerated and was effective in reducing PCO for up to 24 months after cataract surgery. Although these preliminary results are encouraging, a larger study is underway to determine whether the reduction in PCO by the immunotoxin decreases the need for Nd:YAG capsulotomy.", "To compare the degree of posterior capsule opacification (PCO) and visual function in eyes implanted with an acrylic intraocular lens (IOL) with a sharp posterior optic edge with that in eyes implanted with an IOL with a rounded optic edge.\n Randomized clinical trial.\n Seventy-five consecutive patients scheduled for bilateral phacoemulsification were assigned randomly to 1 of 2 groups. One group received an acrylic IOL with a sharp edge (Sensar AR40e, AMO, Santa Ana, CA) in the left eye and an acrylic IOL of the same optic material and loops but with a rounded-edge optic (Sensar AR40) in the right eye. The other group received the sharp-edged IOL in the right eye and the rounded-edge IOL in the left eye. Sixty-nine patients (92%) completed follow-up.\n All patients underwent implantation of a sharp-edged IOL in 1 eye and a rounded-edge IOL in the fellow eye.\n The PCO value of these patients was measured using the Scheimpflug videophotography system at 1, 3, 6, 12, 18, and 24 months after surgery. The incidence of eyes that required a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser posterior capsulotomy was examined. Visual acuity and contrast sensitivity with and without a glare source also were evaluated.\n The mean PCO value in the sharp-edge IOL group was significantly less than that in the rounded-edge IOL group throughout the follow-up period. The incidence of Nd:YAG capsulotomy also was significantly less in the sharp-edge group than in the rounded-edge group (P = 0.0095). No significant difference was found in mean visual acuity during the 24 months of follow-up. However, contrast visual acuity with and without glare was significantly better in the sharp-edge group than in the rounded-edge group at 24 months after surgery.\n The degree of posterior capsule opacification in eyes with an acrylic IOL with a sharp posterior optic edge is significantly less than that in eyes with a rounded-edge IOL, and the sharp-edge optic led to better contrast sensitivity with and without glare.", "To evaluate the effect of 1-piece and 3-piece hydrophobic acrylic intraocular lenses (IOLs) on posterior capsule opacification (PCO) after cataract surgery.\n Ophthalmology departments of 3 hospitals in the United Kingdom and Germany and the Department of Physics at a United Kingdom university.\n A series of 131 patients having cataract surgery had implantation of an acrylic 1-piece (SA30AL) or an acrylic 3-piece (MA30BA) IOL (AcrySof, Alcon). Surgery was performed according to standardized protocol by a single surgeon at each hospital. Posterior capsule opacification was assessed using digital retroillumination photography. All images were analyzed at a single center according to a standard protocol. Data were analyzed 6 months and 1 year after surgery.\n There was no statistically significant difference in the percentage area of PCO between the 1-piece (mean 16.0% +/- 15.7% [SD]) and 3-piece (mean 13.6% +/- 19.8%) cohorts 6 months and 1 year after surgery (P =.0664).\n There was no evidence of a difference in the area of PCO after cataract surgery between 1-piece and 3-piece IOLs, which were otherwise matched for material and lens geometry.", "To evaluate the long-term effects of anterior capsule polishing on regeneratory posterior capsule opacification (PCO), anterior capsule opacification (ACO), and fibrotic PCO with a silicone intraocular lens (IOL) with sharp optic edges.\n Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.\n This prospective bilateral randomized patient- and examiner-masked clinical trial comprised 130 eyes of 65 patients with bilateral age-related cataract. All eyes had implantation of a 3-piece silicone IOL with a truncated, sharp-edged optic (CeeOn Edge 911A, Advanced Medical Optics). In 1 eye, the anterior capsule was extensively polished using an aspiration curette after phacoemulsification and cortex aspiration. Regenerative PCO was quantified objectively, while ACO and fibrotic PCO were graded subjectively 1, 2, 3, and 5 years postoperatively.\n The mean ACO score was significantly lower in the eyes in which the anterior capsule had been polished (1 year, P<.02; 2 years, P<.03; 3 years, P<.01; 5 years, P<.01). The mean difference in regeneratory PCO and fibrotic PCO scores between the 2 groups was not statistically significant.\n Three years after cataract surgery, eyes in which the anterior capsule had been polished had significantly less ACO. However, polishing did not lower PCO intensity when a sharp-edged CeeOn 911A IOL was implanted in the bag. Although results indicate that anterior capsule polishing may enhance the development of regeneratory PCO, this trend did not reach statistical significance.", "To compare the rates and morphologic features of posterior capsule opacification (PCO) after small-incision phacoemulsification and in-the-bag implantation of 2 foldable intraocular lenses (IOLs) over an 18-month follow-up.\n Departments of Ophthalmology, Hospital of Conegliano, Conegliano, and Maggiore Hospital of Bologna, Bologna, Italy.\n In an open clinical study, 78 cataract patients were randomly selected to have implantation of a silicone CeeOn Edge (Pharmacia) or acrylate AcrySof (Alcon) IOL after phacoemulsification cataract surgery. All the patients were operated on using a standard technique and in-the-bag IOL implantation. One eye in each patient was studied. Morphologic evaluation of PCO was performed using Evaluation of Posterior Capsule Opacification software.\n At 18 months in the CeeOn Edge group, 36 eyes (90%) had a clear posterior capsule and 4 (10%) had PCO that did not affect visual acuity. In the AcrySof group, 26 eyes (68%) had a clear posterior capsule, 11 (29%) had PCO that did not affect visual acuity, and 1 (3%) had PCO with a decrease of 2 or more lines of visual acuity that required a neodymium:YAG laser capsulotomy. No eye developed Elschnig pearls or stretched folds in the bag. The postoperative best corrected visual acuity ranged from 0.8 to 1.0 in 96% in the CeeOn Edge group and in 92% in the AcrySof group. No IOL haze or discoloration was observed in the CeeOn Edge group. Mild IOL decentration and tilting occurred in 4 AcrySof eyes; however, no glistenings were found any AcrySof IOL.\n Both the CeeOn Edge and AcrySof groups had a low incidence of PCO after an 18-month follow-up. The CeeOn Edge group had significantly less PCO than the AcrySof group. These results confirm that IOLs with square truncated edges create a barrier effect at the optic edge, reducing the overall incidence of PCO.", "A prospective, randomized study was carried out to evaluate functional and biomicroscopic long-term results of different posterior chamber intraocular lenses (IOLs) over a period of two years after clear corneal cataract surgery.\n 2 years after phacoemulsification through a temporal two-step clear corneal incision a total of 67 patients were examined. In 26 eyes (group A) a foldable plate-haptic silicone IOL (Chiron Adatomed, C10), in 25 eyes (group B) a foldable disc silicone IOL (Chiron Adatomed, 90D) had been implanted through a 3.5 (group A) or 4 mm (group B) corneal incision using a cartridge injector. In 16 eyes (group C) a one-piece PMMA-IOL (Pharmacia & Upjohn, 809C) had been implanted through a 5 mm incision. All eyes underwent functional and biomicroscopic examinations, as well as computerized videokeratographic analysis to obtain corneal topography data.\n In group A uncorrected visual acuity valued 0.64 (+/-0.29 SD), in group B 0.59 (+/-0.24) and in group C 0.56 (+/-0.27). Median of uncorrected visual acuity was 0.6 for all groups. Corrected visual acuity was 0.81 (+/-0.29) in group A, 0.8 (+/-0.25) in group B and 0.83 (+/-0.3) in group C. Intraocular pressure (mm Hg) was 13 (+/-2.5) in group A, 14.7 (+/-2) in group B and 15.1 (+/-2.5) in group C. Fibrosis of the anterior capsular rim occurred in 42% of the cases. One eye demonstrated folds in the posterior capsule (group B). Posterior capsular opacification valued 11.9% for all groups. In one eye a Nd:YAG-capsulotomy had already been performed. In group A a decentration of more than 1 mm was objected in one case, in group B in two cases and in group C in one case, but no patient complained about any functional impairment. Two years postoperatively, no signs of a re-flattening in the incision area could be detected using difference mapping tools in the videokeratographic analysis.\n Two years after implantation of foldable silicone IOLs and PMMA-IOLs via a temporal clear corneal tunnel incision after phacoemulsification only slight functional and morphologic differences between the three IOL-types could be observed.", "To compare postoperative performance and stability of 6.0-mm optic single- and 3-piece acrylic foldable intraocular lenses (IOLs).\n Prospective, randomized, self-controlled trial.\n Eighty eyes of 40 patients with bilateral senile cataracts.\n Phacoemulsification and IOL implantation were performed. One eye of a patient was randomly assigned to the SA60AT single-piece IOL, and the contralateral eye was allocated to the MA60AC 3-piece IOL.\n Best-corrected visual acuity (BCVA), spherical equivalent, aqueous flare intensity, anterior chamber depth, amount of IOL decentration and tilt, area of anterior capsule opening, and degree of posterior capsule opacification (PCO) were measured 2 days, 1 week, and 1, 3, 6, and 12 months after surgery. Specular microscopy was performed at 12 months postoperatively.\n In the SA60AT group, the anterior chamber depth did not show significant changes after surgery (P>0.05; paired t test), and the refraction remained highly stable throughout the 1-year study period. The MA60AC group showed significant shallowing of the anterior chamber (P<0.05) and a myopic shift (P<0.05) up to 1 month after surgery. There were no significant differences between the 2 groups (P>0.05) in BCVA, aqueous flare intensity, the amount of IOL decentration, IOL tilt, area of anterior capsule opening, and degree of PCO throughout the 12-month follow-up period.\n Both the SA60AT single-piece and MA60AC 3-piece lenses showed a minimum amount of decentration, tilt, anterior capsule contraction, and PCO. Although the MA60AC showed significant forward shift and myopic refractive changes after surgery, the SA60AT displayed little axial movement associated with highly stable refraction after surgery. This feature of the SA60AT should facilitate earlier spectacle prescription and quicker visual/social rehabilitation of patients after cataract surgery.", "To examine the influence of optic material on posterior capsule opacification (PCO) by comparing PCO and visual functions between eyes with an acrylic intraocular lens (IOLs) and those with a silicone IOL of the same optic design and with the same haptics.\n Randomized clinical trial.\n One hundred patients scheduled for phacoemulsification surgery underwent implantation of an acrylic IOL (AMO Sensar; AR40e) in one eye and implantation of a silicone IOL (ClariFlex) of the same optic design and loops in the fellow eye. Eighty-nine patients (89%) remained for analysis. The PCO value was measured using the Scheimpflug videophotography system at one, three, six, 12, 18, 24, 30, and 36 months postoperatively. The incidence of eyes that required a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser capsulotomy was examined; visual acuity and contrast sensitivity with and without a glare source were also evaluated.\n The mean PCO value did not increase significantly during follow-up in either the acrylic or silicone IOL group. When comparing the groups, no statistically significant difference was found in the PCO or in the incidence of Nd:YAG capsulotomy, although both tended to be slightly better in the silicone group than in the acrylic group. There was also no significant difference between the groups in visual acuity or in photopic and mesopic contrast sensitivity with or without glare.\n When acrylic and silicone IOLs are of the same optic design and with the same haptics, the optic material does not influence the development of PCO enough to impair visual function.", "To compare the postoperative performance of single and three piece acrylic foldable intraocular lenses (IOLs).\n 20 patients underwent bilateral cataract surgery with a single piece SA30AL IOL in one eye and a three piece MA30BA IOL in the other eye. The eyes were randomly assigned to either a single or three piece lens. The amount of IOL decentration and tilt, area of anterior capsule opening, and degree of posterior capsule opacification were measured using the Scheimpflug anterior segment analysis system (Nidek EAS-1000). Visual acuity and contrast sensitivity were examined. Measurements were performed by masked examiners before and 1 day, 1 week, 1, 3, 6, and 18 months after surgery.\n There were no significant differences between the two groups (p>0.05, paired t test) in the amount of IOL decentration, IOL tilt, area of anterior capsule opening, degree of posterior capsule opacification, best corrected visual acuity, and contrast sensitivity throughout the 18 month follow up period.\n The single and three piece acrylic foldable IOLs are equally stable in the eye after surgery.", "To compare posterior capsular opacification in eyes with IOL of two different materials--silicone or acrylic.\n Eighty consecutive eyes undergoing cataract surgery were prospectively randomized in two groups, 40 eyes receiving a silicone (Sl--30NB) and 40 eyes an acrylic (Acrysof MA60BM) intraocular lens (IOL). The same surgeon performed phacoemulsification and the intraocular lens (PHACO IOL) operation in all cases. Patients were re-examined on the first postoperative day, after one week, four months, and 1-2.4 years. Seven eyes were lost to late control.\n Clinically significant posterior capsular opacification (PCO) (including eyes with capsulotomy already performed) was equally common in both groups; 25% in the silicone group and 19% in the acrylic group (p=0.53). The posterior capsule remained clear in 61% of the silicone and 76% of the acrylic IOL eyes (p=0.18). In the whole study group, 29% of eyes with and 14% without concurrent ocular diseases had significant PCO (p=0.13). In the silicone IOL group, PCO was more common in eyes with concurrent ocular diseases (44%) than eyes without other diseases (10%) (p=0.049). Eyes with acrylic IOL showed no difference in significant PCO, with or without other diseases (18% and 20%, respectively).\n In a consecutive series of 80 cataract eyes central PCO was equally common in eyes receiving a silicone or an acrylic IOL. In the silicone IOL group, however, significant PCO was more common if there was concurrent ocular disease, while with the acrylic IOL concurrent ocular disease did not seem to increase the risk of PCO.", "The most common surgically related cause of reduced vision after extracapsular cataract extraction is posterior capsule opacification (PCO), which occurs in up to 50% of eyes following cataract extraction. This study examined whether small capsulorhexes of 4.5 to 5.0 mm, which lie completely on the 5.5 mm intraocular lens (IOL), and large capsulorhexes of 6.0 to 7.0 mm, which lie completely off the lens optic, are effective in preventing PCO development.\n In this prospective study, 496 eyes of 367 patients underwent standardized phacoemulsification with capsulorhexis and capsular bag foldable acrylic IOL implantation. The patients were randomly assigned to receive either a small capsulorhexis of 4.5 to 5 mm to lie completely on the IOL optic or a large capsulorhexis of 6 to 7 mm to lie completely off the lens optic. Retroillumination photographs were taken at 6 months and then yearly.\n Throughout the follow-up, there was less PCO in the small capsulorhexis group than in the large capsulorhexis group. CONCLUSIONS.:Small capsulorhexes were associated with less wrinkling of the posterior capsule and less PCO than were large capsulorhexes. PCO after IOL implantation has a multifactored pathogenesis. Small (4.5 to 5.0 mm) capsulorhexis and capsular bag implantation of 5.5 mm acrylic IOL are likely to reduce the PCO incidence when compared with the 6.0 to 7.0 mm capsulorhexis. The significance of the IOL optic diameter in association with the capsulorhexis size should also be documented by further studies.", "The authors conducted a 3-year randomized trial to compare silicone intraocular lenses (IOLs) with polymethylmethacrylate (PMMA) IOLs, to determine any differences in laser capsulotomy rates, capsular opacification light scatter, and subjective scoring.\n A total of 119 patients were enrolled, 84 of whom were examined at 3 years. The authors designed a prospective, masked, and randomized trial to compare the objective (lens opacity meter), subjective (slit-lamp scoring), and clinical parameters of the posterior capsular opacification (PCO) of these patients.\n The silicone group had less PCO than the PMMA group, according to objective (8.6% vs. 10.4%; P = .02, Student's t test) and subjective scoring (0.88 vs. 1.79; P = .0001, Student's t test). The laser capsulotomy rate was 24% for the silicone group and 33% for the PMMA group; however, this difference was not statistically significant.\n The silicone IOL was associated with less PCO than the PMMA IOL.", "To evaluate the relationship of the anterior capsule and the AcrySof MA30BA intraocular lens (IOL) and its impact on the development of central posterior capsule opacification (PCO).\n Prospective, randomized, controlled trial.\n Two hundred two patients with senile cataracts received an AcrySof IOL between July and December 1998 at Iladevi Cataract and IOL Research Center, Ahmedabad, India.\n Patients were randomized prospectively to receive 1 of the 3 possibilities of anterior capsule and IOL optic relationship: group 1, total anterior capsule cover (360 degrees ) of the optic; group 2, no anterior capsule cover (360 degrees ) of the optic; group 3, partial anterior capsule cover (<360 degrees ) of the optic. After surgery, slit-lamp video photography was performed every 6 months for 3 years. Analyses of variance and chi-square tests were used to compare treatment groups.\n Incidence of PCO in the 3 groups. The posterior capsule was divided into 3 zones: peripheral, central 3 mm, and midperipheral (the space between the peripheral and the central zones).\n The average follow-up was 35.3 +/- 1.52 months in all the groups. At 3 years, the rate of central PCO was 6.4% in group 1, 7.1% in group 2, and 5.9% in group 3 (P = 0.9). Midperipheral PCO was present in 24.2% in group 1, 16% in group 2, and 20.6% in group 3 (P = 0.9). Peripheral PCO was seen in 100% of patients in all groups. The neodynium:yttrium-aluminum-garnet laser (Nd:YAG) posterior capsulotomy rate was 0% in all groups.\n There was no significant difference in the incidence of development of central PCO among the 3 groups. No patient experienced central PCO that required Nd:YAG capsulotomy. When using the AcrySof IOL model MA30BA, the relationship of the anterior capsule and the IOL does not seem to be a factor that relates to the development of central PCO.", "To compare the intensity of capsule opacification with the sharp and the round optic edge variant of an open-loop hydrophobic silicone intraocular lens (IOL).\n Randomized, controlled, double-blind clinical trial with intraindividual comparison.\n Fifty-one patients with bilateral age-related cataract were included (102 eyes). Each patient had had cataract surgery in both eyes and received a Microsil IOL with a sharp optic edge design (model S) in one eye and a Microsil IOL with a round optic edge design (model R) in the fellow eye. Both IOLs had an identical haptic design (nonangulated polymethylmethacrylate) and silicone optic material. The patients were examined at the slit lamp, best-corrected visual acuity was assessed, and standardized high-resolution digital retroillumination images of the posterior capsule were taken 5 years after surgery. The intensity of regeneratory posterior capsule opacification (rPCO), fibrotic PCO (fPCO), and anterior capsule opacification (ACO) was assessed subjectively at the slit lamp, and of rPCO, objectively using automated image analysis software (AQUA). The need for an Nd:YAG laser capsulotomy (Nd:YAG-LCT) was noted.\n The mean AQUA PCO score was 1.2 for the model S and 2.4 for the model R lens (P = .001). The model S lens also led to less peripheral fPCO (P = .003). Concerning ACO, there was no significant difference between both IOL groups (P = .72). Whereas no capsulotomy was required with the model S, four cases (16%) had been performed in the model R group.\n Five years postoperatively, the sharp-edged silicone IOL showed less rPCO and fPCO than the round-edged IOL. However, regarding ACO, there was no significant difference between both IOL styles.", "To evaluate the effect of dexamethasone, diclofenac, and a placebo given for 3 weeks after phacoemulsification and intraocular lens (IOL) implantation on the formation of posterior capsule opacification (PCO).\n St. Erik's Eye Hospital, Stockholm, Sweden.\n In a 2-year prospective randomized double-blind study, a laser flare meter was used to measure aqueous flare intensity preoperatively and 3 days, 2 weeks, and 2 years after phacoemulsification and IOL implantation. Posterior capsule opacification was evaluated 2 years postoperatively using retroillumination images taken with a Scheimpflug camera. The Evaluation of Posterior Capsule Opacification system was used to score the areas of PCO density.\n The median rate of PCO 2 years after phacoemulsification was 0.72 (range 0.32 to 1.57) in the dexamethasone group, 0.78 (range 0.19 to 2.14) in the diclofenac group, and 0.70 (range 0.35 to 1.70) in the placebo group. The differences were not statistically significant (P>.05; Kruskal-Wallis analysis of variance, multiple comparisons). The rate of neodymium:YAG laser posterior capsulotomy during the 2 years after surgery was not statistically different between groups (P>.05, chi-square test). There was no correlation (Spearman rank coefficient) between laser flare measurements and PCO formation in any group during the study (P>.05).\n Topical instillation of diclofenac, dexamethasone, or a placebo in the immediate period after phacoemulsification and IOL implantation did not seem to influence the formation of PCO 2 years after cataract surgery.", "To perform an intraindividual comparison of posterior capsule opacification (PCO) with 2 foldable intraocular lenses (IOLs) and a foldable acrylic IOL 1 year after in-the-bag implantation.\n Seven German ophthalmology centers.\n In an open prospective randomized multicenter study, each center intraindividually compared a high-refractive-index, sharp-edged optic silicone IOL (CeeOn Edge 911A, Pharmacia) with a high-refractive-index, round-edged optic silicone IOL (PhacoFlex SI-40NB, Allergan) or a sharp-edged optic acrylic IOL (AcrySof MA60BM, Alcon). Of 288 randomized patients, 247 had standard phacoemulsification with in-the-bag IOL implantation in both eyes by the same surgeon. One eye of each patient received a CeeOn Edge IOL and the fellow eye, an AcrySof or PhacoFlex IOL. A morphologic evaluation of PCO was performed using the Evaluation of Posterior Capsule Opacification (EPCO) system 1 to 2 weeks and 11 to 14 months after surgery. The digital pictures were evaluated by an independent investigator who was blind to the type of IOL. Intraindividual differences in EPCO scores were statistically evaluated by a 1-sided binomial test at an alpha-level of 5%.\n One year after surgery, 127 patients with the AcrySof IOL and 102 patients with the PhacoFlex IOL in the control eye were reexamined. Functional results, safety, and handling were not significantly different between the 3 IOLs. All reexamined eyes had a very low PCO grade. The EPCO values revealed less PCO in eyes with the CeeOn Edge IOL than in eyes with the AcrySof or PhacoFlex IOL, but the difference was not statistically significant. A neodymium:YAG laser capsulotomy was performed in 1 eye with a CeeOn Edge IOL, 1 eye with an AcrySof IOL, and 2 eyes with a PhacoFlex IOL.\n The EPCO PCO grade was low 1 year after implantation of CeeOn Edge 911A, PhacoFlex SI-40NB, and AcrySof MA60BM IOLs; there was no statistically significant difference between the IOLs. The impact of IOL material and edge design on PCO development might be relevant in a long-term follow-up of this study.", "To evaluate the long-term effect of anterior capsule polishing on anterior capsule opacification (ACO) and peripheral fibrotic posterior capsule opacification (PCO).\n Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.\n This randomized double-blind study comprised 104 eyes of 52 patients with bilateral age-related cataract. All patients received round-edged intraocular lenses (IOLs); 26 received an SI-40 IOL (Advanced Medical Optics Inc.) in both eyes, and 26 received a Silens6 IOL (Domilens) in both eyes. Both IOLs consist of different silicone material and have different haptic angulation. The SI-40 IOL has 13.0 mm open-loop poly(methyl methacrylate) (PMMA) haptics angulated by 10 degrees. The Silens6 IOL has 12.5 mm open-loop PMMA haptics with no angulation. In 1 eye, the anterior capsule was extensively polished. The anterior capsule was left unpolished in the contralateral eye, which acted as a control. Digital slitlamp photographs of the ACO and fibrotic PCO were taken with a standardized technique for 3 years postoperatively. The intensity of ACO was measured objectively (score 0% to 100%) using Adobe Photoshop software. Fibrotic PCO was graded subjectively (score 0 to 4).\n The mean ACO was 17% in the polished eyes and 26% in the control eyes (P = .0001). The mean fibrotic PCO score was 0.5 and 1.0, respectively (P = .0007). The mean ACO was 15% in the polished SI-40 eyes and 26% in the control SI-40 eyes (P = .01). It was 19% in the polished Silens6 eyes and 26% in the control Silens6 eyes (P = .003). The mean fibrotic PCO score was 0.4 in the polished SI-40 eyes and 1.1 in the control SI-40 eyes (P = .0006). It was 0.6 in the polished Silens6 eyes and 0.9 in the control Silens6 eyes (P = .08).\n Three years after surgery, eyes in which the anterior capsule was extensively polished had less ACO and fibrotic PCO with both round-edged silicone IOLs. In eyes with Silens6 IOLs, however, the reduction in fibrotic PCO was not significant.", "Intraocular lens (IOL) design, optical configuration, and placement have potential effects on postoperative outcome. Laboratory studies have suggested that one-piece, biconvex designs may reduce or delay posterior capsular opacification and that in-the-bag fixation of the posterior chamber IOL may reduce inflammation. To document the clinical significance of IOL design and placement, we conducted a randomized, prospective, clinical trial. Six hundred uncomplicated capsulorhexis and phacoemulsification patients were randomized in a three-factor design to receive an IOL that was one-piece or three-piece, had a biconvex, plano-convex, or laser ridge optic, and was bag-or sulcus-fixated. Treatment differences were related to lens placement. Patients with bag-fixated IOLs had less posterior capsular opacification, fewer YAG laser capsulotomies, a higher percentage of centered lenses, less inflammation, and fewer late posterior capsular striae than those with sulcus-fixated IOLs. In the latter group, patients with three-piece IOLs had fewer posterior capsular striae at three months postoperatively. All six occurrences of haptic loop distortion were in patients with three-piece IOLs. Patients with the one-piece design had less late inflammation than those with the three-piece design. Fewer YAG capsulotomies were necessary at one year in patients with the biconvex design than in those with the plano-convex or laser ridge configurations. Operative complications, endothelial cell loss, and postoperative complications were not IOL-related.", "To compare the rates of lens epithelial cell (LEC) migration and posterior capsule opacification (PCO) 1 and 3 years after sutureless small incision phacoemulsification and in-the-bag implantation of 2 acrylic polymer intraocular lenses (IOLs)-the AcrySof and MemoryLens-in fellow eyes of patients.\n Eye Clinic, Beyoğlu Education and Research Hospital, Istanbul, Turkey.\n Fifty patients with no systemic or ocular problems that would interfere with postoperative visual acuity were included in this prospective study. Each patient had in-the-bag implantation of an AcrySof IOL in 1 eye and a MemoryLens in the fellow eye in a randomized fashion after uneventful phacoemulsification through a sutureless clear corneal incision.\n At 1 year (n = 32 patients), there was no significant difference between fellow eyes in postoperative best corrected visual acuity (BCVA) and contrast sensitivity. In the MemoryLens group, 10 eyes (31.3%) had PCO and 9 (28.1%), LEC migration. In the AcrySof group, no eye had PCO and 2 eyes (6.3%) had LEC migration (P <.001). At 3 years (n = 21 patients), 1 eye (4.7%) in the AcrySof group had PCO and 3 eyes (14.4%) had LEC migration without PCO. In the MemoryLens group, 1 eye (4.7%) had a clear posterior capsule, 11 eyes (52.4%) had LEC migration, and 9 eyes (42.9%) had PCO (P <.001). A neodymium:YAG capsulotomy was required in 4 eyes (19.0%) in the MemoryLens group but no eye in the AcrySof group. At 3 years, BCVA was lower in the MemoryLens group than in the AcrySof group (P <.05).\n The 3 year clinical data of fellow eyes indicate that the AcrySof IOL causes less PCO than the MemoryLens.", "To present a new method to quantify posterior capsular opacity with an anterior eye segment image analyzer (EAS 1000, NIDEK).\n This study was comprised of patients who underwent phacoemulsification intraocular lens (IOL) implantation. Three types of IOLS, acrylic, silicone, and polymethylmethacrylate (PMMA) were allocated to 30 eyes and clinically evaluated. Patients were observed for 3 years postoperatively using an anterior eye segment image analyzer (EAS1000). Opacity was determined by calculating the area of opacity from a retroillumination image. In the retroillumination mode of analysis, the measurement was limited to a 4-mm-diameter region of the pupillary zone to eliminate the influence of anterior capsular opacity. For color map analysis, the threshold level was expressed as the color tone of 0-255 CCT (computer compatible tape). The glare disability was measured to evaluate the three types of IOLs.\n The color map analysis revealed a time-related increase in the opacity level of patients receiving the PMMA IOL implant. Three years after surgery, the levels were significantly higher in the PMMA group (P < 0.01) compared to the acryl and silicone groups: acryl (17.5 +/- 3.8), silicone (18.0 +/- 6.2%), and PMMA 36.5 +/- 32.9%.\n Quantitative evaluation using an anterior eye segment image analyzer is effective for observing the degree of posterior capsule opacification. The color map analysis using an anterior eye segment image correlated with the visual function revealed that the time-related increase in the opacity level was significant during the third year in patients receiving PMMA IOL implantation.", "To compare the visual outcome, percentage of posterior capsular opacification, and laser capsulotomy rates with polymethylmethacrylate, silicone, and hydrogel intraocular lens implants at 1 and 2 years postoperatively.\n Ninety-three eyes of 93 patients were randomized to receive a polymethylmethacrylate, silicone, or hydrogel intraocular lens implant. A standardized surgical protocol was followed by a single surgeon using phacoemulsification with capsulorhexis; any patients with surgical complications were excluded, and all patients received standardized medication and follow-up. Patients were examined at days 1 and 7, months 1, 3, and 6, and years 1 and 2 after surgery. At each assessment, best-corrected logMAR visual acuity and Pelli-Robson contrast sensitivity were measured. Posterior capsular opacification was objectively assessed by digital retroillumination imaging with the use of a dedicated software program and calculated as the percentage area of opacified capsule. Laser capsulotomy was performed if the eye had lost 2 lines of visual acuity with a clinically opaque capsule.\n At 2 years postoperatively, the mean percentage area of posterior capsular opacification for hydrogel lenses was 63%; for polymethylmethacrylate, 46%; and for silicone, 17%. Hydrogel intraocular lenses were associated with 17% more posterior capsule opacification than were polymethylmethacrylate lenses (95% confidence interval, 1-33; P =. 037) and 45% more than were silicone lenses (95% confidence interval, 33-58; P <.0001) at 2 years. Polymethylmethacrylate lenses had 28% more posterior capsule opacification than silicone lenses (95% confidence interval, 13-43; P <.0001) at 2 years. Twenty-eight percent of patients with hydrogel intraocular lenses required an Nd:YAG laser posterior capsulotomy at 2 years, compared with 14% with polymethylmethacrylate, whereas no patients with silicone lenses needed a capsulotomy (P =.014). Visual acuity was not significantly different among the three groups, but patients with silicone intraocular lenses had significantly better contrast sensitivity than those with hydrogel lenses (P =.046).\n Intraocular lenses made of this specific hydrogel were associated with a significantly higher degree of posterior capsular opacification and more laser capsulotomies than polymethylmethacrylate and silicone intraocular lenses.", "To compare the formation and rates of posterior capsule opacification (PCO) in eyes with poly(methyl methacrylate) (PMMA) versus silicone intraocular lenses (IOLs) using an in vivo objective method.\n Taipei Municipal Yang-Ming Hospital, Taipei, Taiwan, Republic of China.\n This prospective study comprised 40 eyes with senile cataract receiving phacoemulsification with capsular implantation of an IOL from March to April 1997. The uneventful surgeries were performed using the stop and chop method by the same surgeon. Twenty eyes received a PMMA IOL (Pharmacia 812A) and 20, a silicone IOL (AMO SI-30NB). One year later, digital retroillumination images taken with the EAS-1000 anterior segment analysis system (Nidek) were used to analyze posterior capsule transparency over the central 3.0 and 5.0 mm optic zones and evaluate the degree of PCO over the central and peripheral zones.\n Over the central 5.0 mm optic zone, mean transparency of the capsule was 87.71% +/- 11.35% (SD) in the silicone group and 79.22% +/- 21.10% in the PMMA group (P = .17). Over the central 3.0 mm optic zone, the means were 97.17% +/- 5.96% and 86.32% +/- 19.60%, respectively (P = .048). Mean opacity in the central zone was 75.18 +/- 13.22 digital opacity units (OUs) in the silicone group and 80.24 +/- 7.93 OUs in the PMMA group (P = .18). The means in the peripheral zone were 88.49 +/- 18.47 OUs and 90.35 +/- 9.98 OUs, respectively (P = .71).\n The posterior capsule in the silicone IOL group was more transparent than in the PMMA IOL group over the central 3.0 mm optic zone after 1 year follow-up.", "We investigated long-term safety and efficacy of sealed capsule irrigation (SCI) during cataract surgery to prevent posterior capsule opacification (PCO).\n One eye of each of 17 patients (mean age: 70.1+/-9.7 years) who presented with bilateral cataracts was randomly chosen for SCI treatment. After phacoemulsification, the capsular bag was vacuum sealed with the PerfectCapsule device (Milvella) followed by SCI using distilled water for two minutes. No vacuum loss occurred during irrigation. Each patient's fellow eye served as a control. One hydrophilic acrylic intraocular lens model was implanted in all eyes. Five patients had to be excluded due to deep anterior chamber, small pupil or unilateral surgery. Follow-up examinations took place one day and one, three, six, 12 and 24 months after surgery. We evaluated safety parameters, anterior capsule (AC) overlapping and PCO.\n Postoperatively, mean best corrected visual acuity, pachymetry, endothelial cell count, intraocular pressure, AC overlapping and PCO showed no statistically significant difference between SCI and the control group (p>0.05, Wilcoxon test).\n SCI is a safe procedure and enables the specific pharmacological targeting of lens epithelial cells inside the capsular bag. Using distilled water, however, it is not possible to reduce PCO development significantly. Thus, alternative substances should be evaluated.", "To compare posterior capsule opacification (PCO) after cataract surgery with implantation of two silicone intraocular lenses (IOLs) with different designs.\n We carried out a prospective, clinical study of 116 patients randomized to standardized phacoemulsification with implantation of CeeOn Edge (n = 57) or SI40NB (n = 59) IOLs. The follow-up period was 3 years. To evaluate PCO morphologically, digital images were obtained and analysed using evaluation of posterior capsule opacification computer software (epco). The neodymium:YAG (Nd:YAG) capsulotomy rate was recorded.\n At 2 and 3 years, the eyes with SI40NB IOLs had significantly more PCO than those with the CeeOn Edge IOLs (p = 0.00014 and p = 0.002). Nine Nd:YAG capsulotomies were performed in the SI40NB group and none in the CeeOn Edge group. This difference was statistically significant (p = 0.003). In some patients a regression of PCO was noticed and confirmed using epco. Statistically less PCO was noted when the capsulorhexis rim was placed so that it covered all 360 degrees of the optic of the IOL.\n A clinically and statistically significant difference in PCO development between CeeOn Edge and SI40NB IOLs at 2 and 3 years postoperatively was found. These findings support earlier studies indicating that a sharp edge of the optic is a more important factor in IOL design than IOL material in the prevention of PCO.", "At the Department of Ophthalmology, Heidelberg, Germany, posterior capsule opacification (PCO) of a silicone and an acrylic intraocular lens (IOL) with a sharp optic edge design was evaluated.\n In a prospective study either the AMO ClariFlex silicone IOL or the Sensar AR40e hydrophobic acrylic IOL were implanted in 47 patients following uneventful phacoemulsification. Mean patient age was 76.2+/-7.8 (ClariFlex) and 73.4+/-12.9 years (AR40e), respectively. The mean follow-up time was 19.7+/-5.34 in the ClariFlex and 21.9+/-1.89 months in the AR40e group. PCO development was evaluated postoperatively using the EPCO 2000 analysis software (scale 0-4). Areas of interest were the total IOL optic, the central 3-mm zone as well as the capsulorhexis.\n In both groups, all patients achieved a BCVA of 20/32 (AR40e) and 20/25 (ClariFlex), respectively. There was a very low incidence of PCO development with a mean EPCO score of 0.07+/-0.2 (ClariFlex and 0.15+/-0.2 (AR40e). Within the 3-mm zone and the capsulorhexis, there was a tendency for even lower EPCO scores in both groups. We calculated a statistically significant difference for the two lens materials for all investigated IOL areas (Wilcoxon's test, p<0.05).\n Both IOLs with a sharp edge design showed good functional results, a stable position in the capsular bag as well as a low incidence of PCO development. However, the silicone IOL showed statistically significantly lower PCO scores.", "Posterior capsular opacification is the most common surgically related cause of reduced vision after cataract surgery. We studied the effect of capsulorhexis size on the pattern and severity of posterior capsular opacification.\n In this prospective study 75 patients underwent standardized phacoemulsification with capsulorhexis and in-the-bag placement of a 5.5-mm polymethylmethacrylate intraocular lens implant. The patients were randomly assigned to receive either a small capsulorhexis of 4.5 to 5 mm to lie completely on the intraocular lens optic or a large capsulorhexis of 6 to 7 mm to lie completely off the lens optic. Patients were examined at days 1, 14, 30, 90, and 180 and at year 1 with logMAR visual acuity assessment, Pelli-Robson contrast sensitivity testing, anterior chamber flare and cell measurement, and high-resolution digital retroillumination imaging of the posterior capsule. The pattern of posterior capsular opacification was determined, and the percentage area of posterior capsular opacification was calculated for each image with dedicated image analysis software.\n Large capsulorhexes were associated with significantly more wrinkling of the posterior capsule and worse posterior capsular opacification than small capsulorhexes. At 1 year the average percentage area of posterior capsular opacification was 32.7% for small capsulorhexes (95% confidence interval, 19.8 to 45.6) and 66.2% for large capsulorhexes (95% confidence interval, 57.7 to 74.6) (P = .0001). The patients with large capsulorhexes had significantly poorer visual acuities and a trend toward worse contrast sensitivities.\n This study demonstrated significantly greater wrinkling and opacification of the posterior capsule and worse visual acuity with large capsulorhexes than with small capsulorhexes. In cataract surgery with a polymethylmethacrylate intraocular lens, a small capsulorhexis with the edge completely on the surface of the implant is preferable to a large capsulorhexis in reducing posterior capsular opacification.", "This study was designed to determine whether different factors could influence the formation of posterior capsular opacities. The study group comprised 271 patients who had undergone an extracapsular cataract extraction with implantation of a posterior chamber lens either with or without laser ridge. Between 12 and 25 months after surgery, a statistically significant difference was found with a lower rate of secondary cataract in the laser ridge group, but with respect to advanced secondary cataract, i.e. eyes which needed YAG capsulotomy, no statistically significant difference was found (P-value 0.99). No association was found between age or sex of patients, different surgeons or complications during or after surgery and the risk of getting a secondary cataract.", "To evaluate the effect of intraocular lens (IOL) haptic compressibility on the posterior capsule after cataract surgery.\n Teaching hospital, London, United Kingdom.\n In this randomized prospective study, 60 patients had standardized phacoemulsification with in-the-bag placement of a poly(methyl methacrylate) (PMMA) (Storz P497UV) or hydrogel (Storz Hydroview H60M) IOL. Both IOLs had PMMA haptics of identical configuration and length. The IOL haptic compressibility was measured in air and then during incubation in saline at 37 degrees C over 1 month. Digital retroillumination imaging was performed 1, 7, 28, 90, 180, 360, and 720 days postoperatively. The presence and duration of postoperative capsule folds were recorded and correlated with the haptic compressibility measurements, lens epithelial cell (LEC) growth patterns on the posterior capsule at 6 months, and the extent of posterior capsule opacification.\n On the first postoperative day, 21 patients (88%) in the Hydroview group had posterior capsule folds that persisted in 12 patients (50%) for 2 years. Nineteen patients (68%) in the PMMA group had folds at day 1 (P =.01), with 1 patient (3%) still having folds at 1 month (P =.0002) and no patient having folds at 3 months. At 6 months, 11 patients (46%) in the Hydroview group and no patient in the PMMA group had LEC growth in the direction of the folds. The PMMA IOLs showed a greater decrease in haptic compressibility during incubation.\n Haptic compressibility should be an important consideration in IOL design. The results suggest that to avoid posterior capsule folds, the compressibility should be less than 2.5 mN.", "To evaluate intraindividual differences in posterior capsule opacification (PCO) and visual performance of AcrySof SN60AT (Alcon Laboratories) and AF-1 YA-60BB (Hoya Corp.) intraocular lenses (IOLs).\n Ophthalmology Department, St. Thomas' Hospital, London, United Kingdom.\n In this prospective single-surgeon standardized-surgical-procedure fellow-eye comparison, an AcrySof SN60AT or an AF-1 YA-60BB IOL was randomized to the first eye of 36 patients and fellow-eye surgery was performed within 4 to 6 weeks. Follow-up was at 1, 3, 6, 12, and 24 months. Best distance- corrected logMAR visual acuity was measured at 100% and 9% contrast. Contrast sensitivity was measured using the Functional Acuity Contrast Test (FACT) on the Optec 3500 instrument (Stereo Optical Company, Inc.). Color vision was assessed with the Farnsworth Munsell 100-hue test. After pupil dilation, digital retroillumination photographs were taken and the percentage area of PCO was calculated using POCO software.\n Posterior capsule opacification was significantly greater in the AF-1 YA-60BB group than in the AcrySof SN60AT group at all time points (P<.0001), with the difference greatest at 24 months. At 24 months, 100% contrast visual acuity was significantly better in the AcrySof SN60AT group than in the AF-1 YA-60BB group (P = .0313); 9% contrast visual acuity was significantly better in the AcrySof SN60AT group from 6 months onward. There was no significant difference between groups in color vision or contrast sensitivity. Electron microscopy showed the AcrySof SN60AT IOL has a much sharper posterior edge profile.\n The AcrySof SN60AT IOL had better PCO performance and thus visual performance than the AF-1 YA-60BB IOL. This is attributable to the differences in optic edge design.", "To compare the visual outcome, neodymium:YAG (Nd:YAG) capsulotomy rates, and percentage of posterior capsular opacification (PCO) seen with polymethylmethacrylate (PMMA), silicone, and polyacrylic intraocular lens implants 3 years after surgery.\n Randomized, prospective trial.\n Ninety eyes of 81 patients were examined at a British teaching hospital.\n Ninety eyes were prospectively randomized to receive a PMMA, silicone, or polyacrylic (AcrySof, Alcon, Fort Worth, TX) implant. All lenses had 6-mm disc optics with PMMA haptics. A standardized surgical protocol was performed by a single surgeon using an extracapsular technique with capsulorhexis; any surgical complications were excluded and all patients had standardized postoperative medication and follow-up.\n Patients were seen at 6 months and 1, 2, and 3 years after surgery. At 3 years, logarithm of the minimum angle of resolution (LogMAR) visual acuity and Pelli-Robson contrast sensitivity were measured and YAG capsulotomy rates determined. Posterior capsular opacification was assessed objectively by digital retroillumination imaging using dedicated software and calculated as the percentage area of opacified capsule.\n At 3 years, the overall follow-up rate was 71%: 19 patients were available for examination with polyacrylic lens implants, 22 with silicone, and 23 with PMMA. There was a significant difference in percentage PCO at 3 years among the lens types (P = 0.0001). Polyacrylic lenses were associated with less PCO (10%) than silicone (40%) and PMMA lenses (56%). The YAG capsulotomy rate was 0% for polyacrylic, 14% for silicone, and 26% for PMMA (P = 0.05). The visual acuity and contrast sensitivity were not significantly different among the three groups if patients with age-related macular degeneration and those requiring YAG capsulotomies are excluded.\n Intraocular lenses made from polyacrylic are associated with a significantly reduced degree of PCO and lower YAG rates.", "To compare the posterior capsule opacification (PCO) inhibiting effect of a 3-piece polymethyl methacrylate (PMMA) intraocular lens (IOL) with a sharp optic edge design with that of the round-edged version of the same IOL during a 5-year period.\n Randomized patient- and examiner-masked clinical trial with intraindividual comparison.\n Thirty-two patients with bilateral age-related cataract (64 eyes).\n Each study patient had phacoemulsification cataract surgery in both eyes and received a sharp optic edge PMMA IOL in one eye and a round optic edge PMMA IOL in the fellow eye (both by Dr Schmidt in Germany). Follow-up examinations were at 1 week, 1 month, 1 year, 3 years, and 5 years. Digital retroillumination images were taken from each eye. The amount of posterior capsule opacification was assessed objectively by means of automated image analysis software (Automated Quantification of After-Cataract) at 1 year, 3 years, and 5 years after surgery.\n Posterior capsule opacification score: 0-10.\n The sharp optic edge IOL showed significantly less regeneratory and fibrotic PCO at 1 year, 3 years, and 5 years after surgery. The mean AQUA PCO score was 5.12 for the round-edge and 2.49 for the sharp-edge IOL (scale, 0-10; P<0.001) at 5 years. The mean difference among patients for the PCO score in the eye implanted with the sharp optic edge versus the score in the eye with the round optic edge was 2.83 at 5 years (95% confidence interval, 1.66-4.00). Due to the large number of neodymium:yttrium-aluminum-garnet laser capsulotomies that were performed (12 in the round-edge group and 4 in the sharp-edge group), there was no significant difference in visual acuity between both groups at any time point.\n Compared with the round-edge version, the sharp optic edge design of a 3-piece PMMA IOL led to significantly less PCO at 1 year, 3 years, and 5 years after surgery. However, the sharp optic edge did not lead to complete PCO prevention during this follow-up period. This finding has implications for the design of PMMA IOLs used for cataract surgery, especially in the developing world.", "To evaluate the differences in posterior capsule opacification (PCO) and visual and optical performance between a microincision intraocular lens (IOL) and a conventional IOL.\n Ophthalmology Department, St. Thomas' Hospital, London, United Kingdom.\n Patients with bilateral cataract were prospectively randomized to receive a HumanOptics MC611MI microincision IOL (microlens group) or an Alcon AcrySof MA60AC 3-piece IOL (control group) in either eye and were followed for 24 months. Best corrected visual acuity (BCVA) (logMAR) was measured; PCO was quantified by POCO software analysis of retroillumination images. Aberrations and modulation transfer function (MTF) were measured at the 24-month visit.\n The study enrolled 32 patients. The mean percentage area PCO was greater in the microlens group than in the control group from 3 months onward and was statistically significant from 12 months onward. The greatest difference in PCO between groups was at 24 months: mean 25.45%+/-34.51% (SD) in the microlens group versus 7.82%+/-13.35% in the control group (P= .029). The BCVA in the control group was slightly better at all time points; the difference between groups was statistically significant at 3, 6, and 12 months. No significant difference in aberrations was detected. The MTF curves were comparable for both IOLs.\n Both IOLs provided good visual performance. There was no evidence of distortion of the microincision IOL in the capsular bag. The microincision IOL had poorer PCO performance, which was visually significant and was caused by migration of lens epithelial cells through its broad optic-haptic junctions.", "To measure posterior capsule opacification (PCO) and neodymium:YAG (Nd:YAG) capsulotomy rates between the AcrySof MA30 intraocular lens (IOL) (Alcon) and the 1CU IOL (HumanOptics) in a fellow-eye comparison.\n Ophthalmology Department, St. Thomas' Hospital, London, United Kingdom.\n Thirty patients who had bilateral cataract surgery with a 1CU IOL prospectively randomly allocated to 1 eye and an AcrySof MA30 monofocal IOL to the other eye were examined. Best corrected distance visual acuity was recorded using the Early Treatment Diabetic Retinopathy Study logMAR chart. Digital retroillumination images of the posterior capsule were taken with the pupil dilated and analyzed with POCO software.\n Eyes with the 1CU IOL had significantly higher PCO rates than eyes with the MA30 IOL at all time points. By 2 years after surgery, 50% of eyes with a 1CU IOL had required Nd:YAG capsulotomy compared with no eyes with an MA30 IOL. There was no significant difference in visual acuity at any time point when post Nd:YAG capsulotomy was taken in to account.\n The 1CU IOL has 4 broad optic-haptic junctions where the square-edged barrier is breached; this appeared to allow passage of lens epithelial cells, leading to an increase in PCO. However, the increased PCO cannot be attributed to this alone as the 1CU is hydrophilic, a factor known to be associated with higher PCO rates.", "To compare the performance of single-piece acrylic vspoly (methylmethacrylate) intraocular lenses (IOL) on the development of posterior capsule opacification (PCO) after conventional extra capsular cataract extraction (ECCE).\n One hundred and eighty-two eyes of 91 patients with bilateral senile cataract undergoing ECCE were prospectively randomized to receive a single-piece Alcon AcrySof SA60AT IOL or a single-piece EPOCH polymethylmethacrylate IOL in the first eye to have surgery. At 1, 6 and 12 months post-operative follow-up, digital retro illumination images of the posterior capsule were taken for PCO assessment semi-objectively using PCO (POCO automated analysis software) system. Relationship of anterior capsule contact (total off and partial cover) on optic for PCO was analyzed.\n The AcrySof IOL was associated with less PCO than EPOCH lens at 6 months (10.01+/-8.75% vs 32.26+/-27.44%; P<0.001) and 1-year (11.65+/-10.55% vs 38.38+/-29.62%; P<0.001) follow-up. The EPOCH IOL showed a remarkably significant difference on development of PCO with anterior capsule overlap on IOL optic (total off and part on) 1 year (P<0.039), whereas no such difference was observed with the AcrySof IOL (P=0.197).\n The AcrySof IOL led to significantly less PCO than the EPOCH IOL post-operatively after extracapsular cataract extraction.", "In this randomized, prospective clinical study, a convex plane intraocular lens (IOL) with a laser ridge was compared with a convex plane IOL without a laser ridge. No difference was found in the reduction of capsular opacification 1 year after surgery. The 100 patients (40 males/60 females) with senescent cataracts were treated with ECCE by a single surgeon from November 1986 to March 1987. The operative technique consisted of capsulorhexis, irrigation-aspiration and in-the-bag-implantation. The first group of 50 patients (50 eyes) had an IOL without a laser ridge and the second group an IOL with a laser ridge. When considering after-cataracts in combination with minor visual deterioration we had secondary cataract rate of 15% in the IOL group with a laser ridge and of 16% in the IOL group without a laser ridge. When we considered only the cases in which visual acuity worsened and YAG laser capsulotomy was required, the secondary cataract rate was 1.5%.", "Opacification of the posterior capsule occurs most commonly from Elschnig pearl migration or fibrosis. The physical contact of a posterior chamber lens, particularly one with a reverse optic, has been postulated to decrease the rate of capsular opacification by creating a barrier to Elschnig pearl migration. This randomized prospective clinical study comparing the 3M style 34S convex-plano optic and style 34R plano-convex (reverse) optic posterior chamber lens demonstrated a statistically significant reduction in capsular opacification by Elschnig pearls at one year in the reverse optic lenses (18.2% versus 7.6%, P = .03). No statistically significant difference in capsular fibrosis rates was noted (2.5% versus 4.5%, P = .48). The reverse optic implant also demonstrated greater iris to implant optic clearance.", "To compare the difference in posterior capsular opacification (PCO) between highly refractive silicone and hydrophobic acrylic foldable intraocular lenses (IOLs) with sharp and round edge designs 3 years after in-the-bag IOL implantation in subjects undergoing bilateral cataract surgery.\n Open-label, prospective, randomized, multicenter clinical trial.\n Two hundred and eighty-eight patients with bilateral surgery for senile cataract operated in German university clinics, eye hospitals, and private ophthalmic surgical centers (Aachen, Ahaus, Bad Hersfeld, Frankfurt/Main, Jena, Rosenheim, and Sulzbach/Saar).\n At each center, a highly refractive index silicone IOL with a sharp optic edge (CeeOn) was intraindividually compared either with a high-refractive index silicone IOL with a round optic edge (PhacoFlex) in 108 patients or with an acrylic IOL with a sharp optic edge (AcrySof) in 139 patients. All patients received standard phacoemulsification with IOL implantation in the bag in both eyes from the same surgeon. A morphological evaluation of PCO was performed by the Evaluation of the Posterior Capsule Opacification (EPCO) system 1 to 2 weeks and 11 to 14 and 35 to 37 months after surgery. The blinded digital pictures were evaluated by an independent investigator. Posterior capsular opacification was statistically evaluated by paired comparisons of 3-year cumulative incidences of neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treatment and EPCO scores.\n Posterior capsular opacification.\n The 3-year cumulative incidences of Nd:YAG laser capsulotomy were 2.1% (CeeOn), compared with 2.1% (AcrySof) (risk difference, 0%; 90% confidence interval, -3.4% to 3.4%), and 5.7% (CeeOn), compared with 17.0% (PhacoFlex) (risk difference, -11.4%; 90% confidence interval, -18.1% to -4.7%). In patients without Nd:YAG laser treatment, medians of the total area EPCO score were 0.0005 (CeeOn) versus 0.0440 (AcrySof) and 0 (CeeOn) versus 0.0700 (PhacoFlex) at 3 years. Functional results, safety, and handling did not significantly differ for the 3 lenses.\n Our results suggest that modern foldable IOLs have a low incidence of PCO after 3 years. There is less PCO for sharp optic edge designs independent of IOL material.", "To compare the inflammatory response after phacoemulsification and intraocular lens (IOL) implantation using postoperative treatment with dexamethasone, diclofenac, or placebo.\n A prospective, randomised, controlled double masked study including 180 patients enrolled for cataract surgery. The patients were 64-85 years old and had no eye disease other than cataract. After phacoemulsification and IOL implantation the patients were randomised to topical treatment with dexamethasone phosphate 0.1% (group I), diclofenac sodium 0.1% (group II), or placebo (saline 0.9%) (group III). The drops were administered four times daily during the first week and twice daily during the second, third, and fourth weeks. The inflammatory reaction in the anterior chamber was measured with laser flare photometry preoperatively and 1, 3, and 8 days, 2 and 4 weeks, 2 and 6 months, and 1, 2, and 4 years postoperatively. Inflammatory symptoms were registered. Biomicroscopy and visual acuity determinations were performed. The rate of Nd:YAG laser posterior capsulotomies after 2 and 4 years was determined.\n After 3 and 8 days (p <0.0001), 2 weeks (p <0.0001), and 1 month (p = 0.0013) median flare was highest in group III. There were no significant differences between group I and II. Inflammatory symptoms and striate keratopathy were more common in group III.\n Dexamethasone and diclofenac were equally effective in reducing postoperative inflammation after phacoemulsification and IOL implantation in eyes with no other disease than cataract. Both substances were more effective than placebo.", "Comparison of the intensity of posterior capsule opacification (PCO) between a silicone intraocular lens (IOL) and a hydrophobic acrylic IOL, both of them 3-piece and open-loop and having truncated optics with sharp edges.\n Randomized, controlled, patient- and examiner-masked trial with intrapatient comparison.\n One hundred six eyes of 53 patients with age-related bilateral cataract.\n Each patient had cataract surgery in both eyes and received a silicone IOL in one eye and a hydrophobic acrylic IOL in the fellow eye. Follow-up examinations were at 1 and 3 years after surgery. The patients were examined at the slit lamp, visual acuity (VA) was assessed, and standardized high-resolution digital retroillumination images of the posterior capsule were taken. The amount of PCO was assessed subjectively at the slit lamp and objectively using automated image analysis software. Data of 56 eyes of 28 patients, who were examined at each follow-up, were analyzed.\n Posterior capsule opacification intensity at 3 years as measured with automated image analysis.\n At 1 and 3 years after surgery, PCO did not differ between the silicone (1.6 and 1.9 [image analysis scores, 0-10 scale], respectively) and acrylic IOLs (1.7 and 2.2) (P > 0.24). Furthermore, there was no significant difference in best-corrected VA, rhexis/IOL overlap, capsular folds, and amount of anterior capsule opacification during the follow-up period. In each group, one neodymium:yttrium-aluminum-garnet (YAG) laser capsulotomy was performed during the entire study duration.\n Silicone and hydrophobic acrylic are similarly effective in inducing the PCO-inhibiting effect of a rectangular, sharp optic edge. Three years after surgery, the PCO intensity and the YAG rate were low with both IOL models.", "To examine the influence of intraocular lens (IOL) optic edge design and optic material on fibrosis of the anterior and peripheral posterior capsules and on capsulorhexis contraction.\n Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.\n This randomized controlled patient- and examiner-masked study comprised 210 eyes of 105 patients with bilateral age-related cataract. In Group 1 (n = 53), the Sensar OptiEdge AR40e hydrophobic acrylic IOL with a sharp posterior optic edge was compared with the AR40 acrylic IOL with a round edge. In Group 2 (n = 52), the ClariFlex OptiEdge silicone IOL with a sharp posterior optic edge was compared with the PhacoFlex SI-40 silicone IOL with a round edge All IOLs were manufactured by Advanced Medical Optics, Inc. Standardized digital slitlamp images of anterior capsule opacification (ACO) and fibrotic posterior capsule opacification (PCO) were taken 1 year postoperatively, and digital retroillumination images were taken at 1 week and 1 year. The intensity of fibrotic PCO was graded subjectively (score 0 to 4), ACO was graded objectively (score 0% to 100%), and the capsulorhexis area (mm(2)) was determined objectively.\n One year after surgery, the mean ACO score was 32% in eyes with the sharp-edged acrylic IOL and 29% in eyes with the round-edged acrylic IOL (P<.05). In the silicone group, the mean was 31% and 26%, respectively (P<.05). The mean fibrotic PCO score was lower in eyes with a sharp-edged acrylic IOL than in eyes with a round-edged acrylic IOL (0.26 and 0.93, respectively; P<.05) and in eyes with a sharp-edged silicone IOL than in eyes with a round-edged silicone IOL (0.24 and 0.82, respectively; P<.001). At 1 year, the mean capsulorhexis area was statistically significantly smaller in eyes with a sharp-edged silicone IOL than in eyes with a round-edged silicone IOL (P<.05).\n Acrylic and silicone IOLs with the sharp OptiEdge design led to significantly less fibrotic PCO but more ACO than round-edged acrylic and silicone IOLs. The sharp-edged silicone IOL caused significantly more capsulorhexis contraction than the round-edged silicone IOL and both acrylic IOLs.", "To evaluate the role of posterior optic edge design and the effect of anterior capsule polishing on peripheral fibrotic posterior capsule opacification (PCO).\n Department of Ophthalmology, University of Vienna, Vienna, Austria.\n This randomized prospective study comprised 144 eyes of 72 patients with bilateral age-related cataract. Each patient had standardized cataract surgery in both eyes by the same surgeon. Group 1 (46 patients) received a round-edged hydrophobic acrylic IOL (AMO Sensar AR40) in 1 eye and a sharp-edged hydrophobic acrylic IOL (AMO Sensar OptiEdge AR40e) in the other eye. Group 2 (26 patients) received a silicone IOL (Pharmacia CeeOn 911A) with a truncated optic in both eyes. In this group, the anterior capsule was extensively polished in 1 eye and was left unpolished in the other eye. Digital slitlamp photographs were taken 1 year postoperatively using a standardized photographic technique for fibrotic PCO. The intensity of PCO was subjectively graded (score 0 to 4) by 2 masked examiners.\n Subjective PCO scores correlated well between the 2 examiners (r = 0.88). In Group 1, the mean PCO score was 0.26 for the OptiEdge AR40e IOL and 0.90 for the AR40 IOL (P<.01). In Group 2, the mean PCO score was 0.24 in eyes with a polished capsule and 0.17 in eyes in which the capsule was not polished (P =.31).\n The sharp-edged OptiEdge AR40e IOL led to significantly less peripheral fibrotic PCO 1 year postoperatively than the round-edged AR40 IOL. In eyes with the sharp-edged silicone 911A IOL, anterior capsule polishing caused no significant difference in fibrotic PCO.", "To evaluate the development of posterior capsule opacification (PCO) in patients implanted with 5.5 mm optics, single-piece or three-piece acrylic intraocular lens (IOL) in cataract surgery prospectively.\n This study was carried out on 267 eyes of 249 patients implanted with three-piece, 5.5 mm optics, acrylic IOL and 252 eyes of 244 patients implanted with single-piece, 5.5 mm optics, acrylic IOL by phacoemulsification technique between September 2001 and February 2003. A total of 519 eyes of 493 patients were prospectively evaluated for PCO development during the 25-month period. All the patients were analyzed periodically with anterior segment retroillumination photography. The data provided were analyzed with chi-square method.\n The results between the two groups for PCO development were not statistically significant. However, there was a prominent opacification of the posterior capsule where the optic and haptic junction of IOL was positioned in some patients implanted with single-piece IOL. During the follow-up period, no patients implanted with either three-piece or single-piece acrylic IOL required Nd:YAG laser capsulotomy.\n Biocompatibility and reduced rate of PCO development are among the leading features of new generation IOLs. The intracapsular implantation of 5.5 mm optics acrylic IOLs resulted in decreased incidence of PCO and therefore greater patient satisfaction. Further studies investigating the effects of IOL optics, haptic structure and length, capsulorrhexis size, and IOL material and design features on PCO development will clarify the subject.", "To compare intensity of posterior capsule opacification (PCO) between the 1-piece and 3-piece haptic designs of an open-loop hydrophobic acrylic intraocular lens (IOL).\n A randomized, patient- and examiner-masked clinical trial with intraindividual comparison.\n Fifty-two patients with bilateral age-related cataract (104 eyes).\n Each patient had cataract surgery in both eyes and received a 1-piece Acrysof IOL in one eye and a 3-piece Acrysof IOL in the fellow eye. Follow-up examinations were at 1 week, 1 month, 6 months, 1 year, and 2 years. Patients were examined at the slit lamp, visual acuity (VA) was determined, and standardized high-resolution digital retroillumination images of the posterior capsule were taken. The intensity of PCO was assessed subjectively at the slit lamp and objectively using automated image analysis software.\n Posterior capsule opacification score (scale, 0-10).\n There was no significant difference between IOL styles in best-corrected VA, rhexis/IOL overlap, capsular folds, and amount of anterior capsule opacification during the follow-up period. One year postoperatively, the amount of regeneratory PCO was higher for the 1-piece Acrysof eyes (image analysis software score: 1.3) than for the 3-piece Acrysof eyes (score: 0.9; P = 0.002). However, 2 years postoperatively, there was no significant difference between the 2 IOL styles (1-piece: 1.5; 3-piece: 1.3; P = 0.3). Neodymium:yttrium-aluminum-garnet capsulotomy was not performed in the study.\n One year postoperatively, the 1-piece Acrysof showed slightly more regeneratory PCO than the 3-piece Acrysof. However, 2 years postoperatively, the barrier effect of the 1-piece design was comparable to that of the 3-piece haptic design, with low PCO intensity.", "To evaluate and to compare the preventive effect of different intraocular lenses from different material with a round or sharp optic edge design on posterior capsule opacification.\n Our clinical study included 165 patients. Mean follow-up was 12.4+/-0.9 months, mean patient age was 67.5+/-7.8 years. Patients in the group 1 (n=46) were implanted acrylic three-piece hydrophobic intraocular lenses, sharp optic edge (AcrySof, MA3OBA, Alcon), in the group 2 (n=38)--acrylic hydrophobic single piece intraocular lenses, sharp optic edge (AcrySof, SA3OAL, Alcon), in the group 3 (n=39)--silicone three-piece intraocular lenses, sharp optic edge (CeeOn 911A, Pharmacia), and in the group 4 (n=42)--polymethyl methacrylate single piece intraocular lenses, round optic edge (Crystal, 5T, Alcon). The posterior capsule opacification was evaluated for the entire optic and in the central 3-mm zone using EPCO 2000 Software.\n Posterior capsule opacification values of the entire optic were 0.002+/-0.001 in the AcrySof MA3OBA group, 0.007+/-0.002 in the AcrySof SA3OAL group, 0.002+/-0.001 in the CeeOn 911A group, 0.029+/-0.008 in the polymethyl methacrylate intraocular lens group 6 months after surgery. The values were 0.011+/-0.005, 0.025+/-0.006, 0.014+/-0.005 and 0.122+/-0.021, respectively, one year after surgery. The intraocular lenses types with sharp-edge design (acrylic and silicone) showed significantly lower posterior capsule opacification values than round-edge optic design polymethyl methacrylate lenses (p<0.05). Posterior capsule opacification values of the central 3-mm zone were 0.000+/-0.000 in the AcrySof MA3OBA group, 0.001+/-0.001 in the AcrySof SA3OAL group, 0.000+/-0.000 in the CeeOn 911A group, 0.002+/-0.001 in the polymethyl methacrylate intraocular lens group 6 months after surgery. The values were 0.0001+/-0.0001, 0.018+/-0.007, 0.004+/-0.002 and 0.028+/-0.009, respectively, one year after surgery. Posterior capsule opacification values differences between AcrySof MA3OBA and polymethyl methacrylate intraocular lenses' groups and between CeeOn 911A and polymethyl methacrylate intraocular lenses' groups one year after cataract surgery were established (p<0.05).\n The sharp-edge foldable intraocular lenses types (AcrySof MA3OBA, AcrySof SA3OAL, CeeOn 911A) showed statistically significant difference in posterior capsule opacification values in one-year follow-up time. The effect of these foldable lenses for prevention of posterior capsule opacification is mainly a result of rectangular, sharp-edged optic design, which creates a sharp capsular bend. A role of material of intraocular lenses (hydrophobic acrylate and silicone) in prevention of posterior capsule opacification during one-year follow-up was not established.", "Posterior capsule opacification (PCO) is still a major long-term complication of modern cataract surgery. We evaluated the impact of sharp-edged intraocular lenses (IOLs) with different haptic designs made from the same hydrophobic acrylic material on posterior and anterior lens capsule opacification.\n Eye clinic of Kaunas University of Medicine, Lithuania. Prospective randomised clinical study.\n Seventy-four eyes of 74 patients scheduled for cataract surgery were included in a prospective randomised clinical study. Thirty-seven eyes of 37 patients received a three-piece acrylic hydrophobic (AcrySof, MA3OBA, Alcon) IOL; and thirty-seven eyes of 37 patients received a one-piece acrylic hydrophobic (AcrySof, SA3OAL, Alcon) IOL. Visual acuity, anterior capsule opacification (ACO), capsular folds, capsulorrhexis/optic overlapping and posterior capsule opacification (PCO) were evaluated. ACO was assessed subjectively. PCO values in the entire IOL optic area and in the central 3 mm optic zone were assessed using a photographic image-analysis system (EPCO2000). Follow-ups were performed postoperatively at 1 day, 6 months, 1 year and 2 years.\n There were no significant differences in best corrected visual acuity, grade of ACO and capsulorrhexis/optic overlapping between IOL types during the follow-up period. Patients in the one-piece acrylic hydrophobic IOL group more frequently presented with capsular folds behind the IOL optic area than those in the three-piece IOL group. In the three-piece acrylic hydrophobic IOL group, PCO values (mean (SD)) of the entire IOL optic area were significantly lower six months postoperative (three-piece: 0.002 (0.009); one-piece: 0.007 (0.017); p=0.04), one year postoperative (three-piece: 0.004 (0.016); one-piece: 0.026 (0.041); p=0.001) as well as one year postoperative in the central 3 mm optic zone (three-piece: 0.000 (0.0002); one-piece: 0.019 (0.049); p=0.001). However, two years postoperative, the PCO values of the groups did not show significant differences (entire IOL optic area: three-piece, 0.136 (0.223); one-piece, 0.154 (0.190); p=0.18; central zone: three-piece, 0.023 (0.065); one-piece: 0.020 (0.039); p=0.44).\n The 2 year follow-up after cataract surgery showed no significant difference in ACO and PCO development between three-piece and one-piece acrylic hydrophobic intraocular lenses.", "To compare the intensity of posterior capsule opacification (PCO) between the 1-piece and 3-piece haptic designs of the foldable hydrophobic acrylic AcrySof intraocular lens (IOL) over a 5-year period.\n Randomized, prospective, patient- and examiner-masked clinical trial with intraindividual comparison.\n Fifty-two patients with bilateral age-related cataract (104 eyes).\n Each study patient had cataract surgery in both eyes and received a 1-piece AcrySof IOL in 1 eye and a 3-piece AcrySof IOL in the other eye. Follow-up examinations were performed at 1 week, 1 month, 6 months, and 1, 2, and 5 years. Digital retroillumination images were obtained of each eye. The amount of posterior capsule opacification (score range, 0-10) was assessed subjectively at the slit lamp and objectively using automated image analysis software 1, 2, and 5 years after surgery.\n Posterior capsule opacification score (scale, 0-10).\n There was no significant difference between the 1-piece and 3-piece AcrySof IOL in best-corrected visual acuity, overlap of rhexis and IOL, capsular folds, anterior capsule opacification, and posterior capsule opacification (1-piece AcrySof PCO score, 1.7+/-1.7; 3-piece AcrySof PCO score, 1.3+/-1.4; P = 0.30).\n Modification of the IOL haptic design of the sharp optic edged AcrySof IOL from a 3-piece to a 1-piece haptic design caused no significant change in PCO intensity and neodymium:yttrium-aluminium-garnet laser treatment rate 5 years after surgery.", "To investigate the incidence of posterior capsule opacification (PCO) in eyes treated with diclofenac sodium (DFNa) and betamethasone phosphate (BMS) ophthalmic solutions.\n A total of 200 eyes with silicone intraocular lens implantation were treated with topical agents for 3 months postoperatively. Twenty-six cases of the DFNa group and 34 of the BMS group met the criteria, and the severity of PCO was evaluated after 3 years.\n The results of axial densitometry by Scheimpflug photography were 27.8 computer-compatible tapes (CCT) in the DFNa-treated group and 32.6 CCT in the BMS-treated group (p = 0.1539). Posterior capsulotomy was performed in 11.5% of the DFNa group and 17.6% of the BMS group (p = 0.8375). The photographic grading of PCO showed no difference.\n The incidence of PCO in eyes treated with DFNa appears to be equal to that after BMS treatment.\n Copyright 2003 S. Karger AG, Basel" ]

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[ "Premature infant responses to noise reduction by earmuffs: effects on behavioral and physiologic measures.", "Effects of rocking on neuromuscular development in the premature.", "Individualized developmental care for the very low-birth-weight preterm infant. Medical and neurofunctional effects.", "Effect of an oral stimulation program on sucking skill maturation of preterm infants.", "Developmental intervention for low birth weight infants: improved early development outcome.", "Maternally administered tactile, auditory, visual, and vestibular stimulation: relationship to later interactions between mothers and premature infants.", "Longitudinal follow-up of prematurely born children: predischarge outcomes of hospital stimulation programme.", "Developmental intervention program for high-risk premature infants: effects on development and parent-infant interactions.", "Randomized clinical trial of an oscillating air mattress in preterm infants: effect on apnea, growth, and development.", "Nursery-based intervention with prematurely born babies and their mothers: are there effects?", "The use of waterbeds for very low-birthweight infants: effects on neuromotor development.", "A modified newborn intensive care unit environment may shorten hospital stay.", "Weight gain and movement patterns of very low birthweight babies nursed on lambswool.", "Neurobehavioral and autonomic effects of hammock positioning in infants with very low birth weight.", "Premature infants seek rhythmic stimulation, and the experience facilitates neurobehavioral development.", "Use of neonatal boundaries to improve outcomes.", "Effectiveness of individualized developmental care for low-risk preterm infants: behavioral and electrophysiologic evidence.", "Effects of vestibular-proprioceptive stimulation on the neurobehavioral development of preterm infants: a pilot study.", "Outcome of 100 randomly positioned children of very low birthweight at 2 years.", "Individualized behavioral and environmental care for the very low birth weight preterm infant at high risk for bronchopulmonary dysplasia: neonatal intensive care unit and developmental outcome.", "The effects of a prefeeding stimulation program on preterm infants.", "The impact of temporally patterned stimulation on the development of preterm infants.", "Effects of vestibular stimulation on sleep states in premature infants.", "The effects of swaddling versus standard positioning on neuromuscular development in very low birth weight infants.", "Responses of preterm infants to unimodal and multimodal sensory intervention.", "Effects of waterbed flotation on premature infants: A pilot study.", "Patterns of physiologic and behavioral response of intermediate care preterm infants to intervention.", "Rocking waterbeds and auditory stimuli to enhance growth of preterm infants. Preliminary report.", "Effect of auditory, tactile, visual, and vestibular intervention on length of stay, alertness, and feeding progression in preterm infants.", "Effect of night and day on preterm infants in a newborn nursery: randomised trial.", "Early experience alters brain function and structure.", "A three-center, randomized, controlled trial of individualized developmental care for very low birth weight preterm infants: medical, neurodevelopmental, parenting, and caregiving effects.", "A randomized, controlled trial to evaluate the effects of the newborn individualized developmental care and assessment program in a Swedish setting." ]

[ "The continuous high-intensity noise in the neonatal intensive care unit (NICU) is both stressful and harmful for the premature infant. Although some researchers have found evidence that loud noise can cause hearing loss and alter physiologic and behavioral responses, no study to date has investigated the benefits of noise reduction by the use of earmuffs. In this study earmuffs were placed over the premature infants' ears to reduce noise intensity in the NICU while physiologic and behavioral responses were measured. Two sites were used to collect data: in the first setting, 17 low birth weight infants were randomly assigned to an experimental and a control group, whereas 13 infants from a second hospital acted as their own controls and were tested with and without earmuffs. Earmuffs that reduced the intensity of noise by 7 to 12 dB were worn by infants in the experimental group only during the observation periods. Infants in the control group were exposed to the usual noise in the NICU. The infant's physiologic and behavioral responses were observed for four 2-hour intervals, morning and evening, on two consecutive days. Most of the significant results were from the site at which infants acted as their own controls. When infants wore the earmuffs, they had significantly higher mean oxygen saturation levels and less fluctuation in oxygen saturation. Furthermore, these infants had less frequent behavioral state changes, spent more time in the quiet sleep state, and had longer bouts in the sleep state. It is imperative that NICUs develop aggressive antinoise policies to substantially and consistently reduce noise.", "It has been postulated that motion stimulation accelerates postnatal development. To test this hypothesis, 26 premature infants participated in a randomized controlled study of the effects of rocking on body weight gain and measures of neuromuscular development. Treatment infants were exposed to 15-min sessions of sinusoidal oscillation about the longitudinal axis, three times a day for 2 weeks. Infants were evaluated at the beginning and end of the 2-week treatment period and 2 weeks later. Neuromuscular development at these three times was measured with the comprehensive Dubowitz examination. Following treatment, large as compared with small premature infants showed a marked, but not statistically significant increase in weight gain. Duration of treatment appears to be a critical factor in influencing weight gain. All infants exposed to motion stimulation showed significant gains over controls in overall neuromuscular development. Passive muscle tone (posture, arm recoil and popliteal angle) and active motility (arm traction, head lag and ventral suspension) showed significant improvement in the treatment group at posttest. Similar results were recorded with auditory and visual orientation, alertness and defensive reaction. These specific areas of behavior have been recognized to be delayed in premature infants not exposed to a program of sensory stimulation.", "To investigate the effectiveness of individualized developmental care in reducing medical and neurodevelopmental sequelae for very low-birth-weight infants.\n Randomized controlled trial.\n Newborn intensive care unit.\n Thirty-eight singleton preterm infants, free of known congenital abnormalities, weighing less than 1250 g, born before 30 weeks' gestation, mechanically ventilated within 3 hours of delivery and for more than 24 hours in the first 48 hours, randomly assigned to a control or an experimental group.\n Caregiving by nurses specifically trained in individualized developmental care; observation and documentation of the infants' behavior within 12 hours of admission, and subsequently every 10th day; developmental care recommendations and ongoing clinical support for the nurses and parents based on regular observation of the infant by developmental specialists; and the availability of special caregiving accessories.\n Medical outcome, including average daily weight gain; number of days the infant required mechanical ventilation, oxygen, gavage tube feeding, and hospitalization; severity of retinopathy of prematurity, bronchopulmonary dysplasia, pneumothorax, and intraventricular hemorrhage; pediatric complications; age at discharge; and hospital charges. Neurodevelopmental outcome, including Assessment of Preterm Infants' Behavior scale and quantified electroencephalography (2 weeks after due date); and Bayley Scales of Infant Development and Kangaroo Box Paradigm (9 months after due date).\n The infants in the experimental group had a significantly shorter duration of mechanical ventilation and supplemental oxygen support; earlier oral feeding; reduced incidence of intraventricular hemorrhage, pneumothorax, and severe bronchopulmonary dysplasia; improved daily weight gain; shorter hospital stays; younger ages at hospital discharge; and reduced hospital charges compared with the infants in the control group. At 2 weeks after their due dates, these infants also showed improved autonomic regulation, motor system functioning, self-regulatory abilities, and visual evoked potential measures; and at 9 months, they had improved Bayley Mental and Psychomotor Developmental Index scores, as well as Kangaroo Box Paradigm scores.\n Very low-birth-weight preterm infants may benefit from individualized developmental care in the neonatal intensive care unit in terms of medical and neurodevelopmental outcome.", "This study assessed the effect of an oral stimulation program on the maturation of sucking skills of preterm infants. Thirty-two preterm infants (13 males, 19 females), appropriate size for gestational age (gestational age at birth 28 wks, SD 1.2wks; birthweight 1002g, SD 251g), were randomly placed into experimental and control groups. The experimental group received a daily 15-minute oral stimulation program, consisting of stroking the peri- and intra-oral structures, for 10 days before the start of oral feedings. Sucking measures were monitored with a specially-designed nipple-bottle apparatus. Results indicate that the experimental group achieved full oral feedings 7 days sooner than the control group, and demonstrated greater overall intake (%), rate of milk transfer (mL/min), and amplitude of the expression component of sucking (mmHg). There was no difference in sucking stage maturation, sucking frequency, and amplitude of the suction component of sucking. Endurance, defined as ability to sustain the same sucking stage, sucking burst duration, and suction and expression amplitudes throughout a feeding session, was not significantly different between the two groups. The stimulation program enhanced the expression component of sucking, resulting in better oral feeding performance.", "This prospective longitudinal study was designed to evaluate the effects of a multidisciplinary infant development program (IDP) on the mental and physical development of low birth weight infants (less than 1,800 g). Infants in the neonatal intensive care were randomly assigned to the IDP or to traditional care (control group). IDP infants received developmental interventions in the hospital and at home through the first 2 years of life. Counseling and parenting education were provided to their parents during this same period. The control group received all the postnatal care and referrals customarily given in traditional care. Both IDP and control infants were enrolled in an independent follow-up program, which used the Bayley Scales of Infant Development in a blind evaluation design. The IDP group had a significantly lower incidence of developmental delay (P less than .05) and scored significantly higher than the control group (P less than .05) on mean mental and physical indices at 12 and 24 months of adjusted age.", "Thirty-three mother-infant pairs were randomly assigned to one of three groups: control, talking, or interactive (RISS). The later treatment included massage, talking, eye contact and rocking. The intervention (RISS) was administered to determine whether mothers and their preterm infants who actively interacted with each other would differ on later maternal and infant behaviors. The talking and RISS treatments were administered at specified time intervals 24 hours after delivery. Prior to hospital discharge, mother-infant interaction was assessed during a feeding. Significant differences were identified among the three groups for maternal (p less than .03) and infant (p less than .05) behaviors. These results suggest that active maternal interaction with the premature infant may enhance specific components of mother-infant interaction.", "nan", "Developmental follow-up studies have documented that low birth weight infants are at high risk for mental and physical disabilities, despite recent advances in neonatal intensive care. Moreover, parent-infant bonding is hampered by the barriers created by technical equipment. This study evaluated a program of hospital and home-based developmental interventions designed to enhance the development of high-risk, preterm infants and the quality of communication between infants and their caregivers. Treatment and contrast groups consisted of 41 premature infants weighing less than 1800 g at birth. Treatment took a preventive approach, consisting of daily multimodal interventions in-hospital and twice-monthly interventions by child development specialists in the child's home, through 12 months adjusted age. Infants in the contrast group received traditional, remedially oriented care. The Bayley Scales of Infant Development were used to measure mental and psychomotor development, and the Greenspan-Lieberman Observations System (GLOS) was used to analyze the behavioral characteristics of infant-caregiver interactions. Developmental interventions had positive, significant effects on mental development and on the quality of caregiver-infant interactions. Changes in mental development were not independent of changes in the GLOS.", "To investigate claims that oscillating mattresses reduce apnea of prematurity and improve growth and neurobehavioural development, we performed a randomized clinical trial using a predetermined sample size. Preterm infants weighing from 750 to 1750 gm at birth were randomly assigned, by 250 gm strata, to either a conventional mattress (n = 63) or to an air mattress (n = 59) oscillating at 14 to 16 regular pulses per minute. Infants remained on the oscillating air mattress for at least 7 days or until 34 weeks postmenstrual age. Apneic episodes occurred and required treatment equally in the two groups; this lack of an effect was seen for both sexes and all weight groups. Both weight and energy intake were similar. Neurobehavioral development as shown by sleep state, habituation testing, and behavioral assessment at term, 3, 6, and 12 months was similar in the two groups. There was no difference in the incidence of neurologic abnormalities. We conclude that an oscillating air mattress has no prophylactic value in reducing apnea and does not enhance growth and development.", "The effects of nursery-based intervention with healthy, prematurely born babies and their socially disadvantaged mothers were evaluated. Mother-infant dyads were randomly assigned to one of three intervention groups: In group one, the babies received special stimulation designed to make them more active contributors to the interactions with their mothers; in group two, mothers received special training to help them become more responsive to cues from their babies; in group three, infants received stimulation and mothers received training. In addition, a fourth group of preterm babies who received regular hospital care served as a comparison group to assess the short-term effects of the stimulation program. Outcome measures designed to evaluate various aspects of mother-infant interaction and infant development failed to reflect any effects of the interventions, either at the time the babies were discharged from the hospital or one year later. We attribute the lack of positive findings to the fact that the mothers faced numerous crises in their social environments. We conclude, therefore, that nothing short of massive social change is likely to result in measurable effects.", "One hundred and seven infants aged < 32 weeks of gestation were stratified according to birthweight and randomly assigned to either a waterbed group (N = 53) or a mattress group (N = 54). All the infants were assessed on removal from the surface: 68 infants at 40 weeks gestation and 52 infants at four, eight, 12 and 18 months adjusted age. At the 18-month assessment, outcome was classified as normal, suspicious or abnormal. There were no significant differences between the groups at any age. The results suggest that the use of the waterbed as a positional surface in the neonatal intensive-care unit has no influence on the motor development of very low-birthweight infants.", "Premature infants with birth weights from 1121 to 2000 gm were assigned randomly to two groups. Experimental group infants were placed on a microprocessor-controlled cradle that provided levels of motion and sound analogous to those of the third-trimester intrauterine environment. Periods of motion totaling 50% of the time were randomized on and off; motion speed was reduced 35% during a 12-hour night period. A uterine souffle sound was generated continuously but varied in pulse rate and volume with the motion and speed of the bed. Experimental group infants (n = 20) were placed on the cradle under a radiant warmer as soon as their condition was stable clinically. Control group infants (n = 18) were usually placed initially under a radiant warmer and transferred to an incubator when their condition was stable. Otherwise, both groups received standard newborn intensive care unit care. The mean length of hospital stay was significantly shorter for experimental group infants than for control group infants after controlling for gestational age and weight on entry to the study. Experimental group infants began nippling earlier and stopped requiring gavage feedings sooner. Experimental group infants had a decreased incidence of apnea. Blinded Brazelton Neonatal Behavioral Assessment Scale scores for the Orientation and Range of State cluster scales were significantly better for experimental group infants. A retrospective contrast group of preterm infants who met study criteria had an average length of stay similar to that of the control group infants. These data support the hypothesis that appropriate levels and kinds of stimulation may facilitate the maturation of preterm infants.", "34 very low birthweight babies (mean 1143 g) in incubators were randomly assigned to be continuously nursed on lambswool (n = 17) or ordinary cotton sheets (n = 17). The weight gain for the periods when babies were well was significantly larger for the wool group, 22.7 g/day vs 18.6 g/day for cotton control (p less than 0.02). The overall weight gain (which included weight change during periods of illness) revealed a similar picture in favour of the wool group, 21.5 g/day vs 18.2 g/day (p less than 0.05). Movement patterns for the two groups showed no differences, but for all babies a strong correlation was noted between moving and lying suspine (p less than 0.001), having eyes open (p less than 0.001), a cooler incubator (p less than 0.01), and faster weight gain (p less than 0.01). Lambswool seems to have advantages over cotton sheets as a bedding material for very low birth weight babies.", "This study was designed to determine whether supine positioning of infants born preterm in a hammock instead of the prone position affects their neuromuscular maturity, growth, and autonomic stability.\n Twenty healthy infants who were born premature with very low birth weight (VLBW) (<1500 g) were randomized into two groups. Subjects were pair-matched for weight (difference less than 100 g), gestational age (difference less than eight days), and postnatal age (difference less than eight days). Ten infants were placed supine in a hammock for three hours daily for ten consecutive days, and ten infants were maintained nested in the prone position. Neuromuscular maturity (based on three neurological parameters adopted from the Ballard examination), heart rate, respiratory rate, and weight gain (g/cal) were compared between the groups.\n Compared with nested prone positioning, supine positioning in a hammock was associated with a higher neuromuscular maturity score (p < 0.003) and a more relaxed condition, as expressed by lower heart rate and respiratory rate (p < 0.05 and p < 0.01, respectively).\n Maintaining infants who were born preterm with VLBW in the supine position in a hammock may positively affect their autonomic stability and neuromuscular maturity.", "This was a clinical trials study of self-regulation of rhythmic stimulation in preterm infants. Infants were enrolled in three regional hospitals and followed in four outlying hospitals. Forty-five premature infants, 22 males and 23 females, enrolled at 29-33 weeks conceptional age (CA) received in the isolette either a \"breathing\" teddy bear (set to breathe at one-half the infant's quiet sleep respiration rate) or a nonbreathing bear. Using time-lapse videorecording at a 60:1 ratio, subjects were recorded for 3 days at the beginning of the Intervention period and again for 3 days, 2 weeks later. After discharge from the hospital, the sleep of the subjects was monitored in the home for a 24-hour period on weeks 1, 2, 3, 4, and 5 after expected date of birth (postterm). Infants with a breathing bear spent more time in contact with the bear, and increased their contact over the two weeks. Postterm, the \"breathing bear babies\" showed more quiet sleep and a greater increase in quiet sleep over weeks. The results indicate that premature infants (\"prematures\") are capable of organizing their motility to express a preference for rhythmic stimulation, and that the experience facilitates neurobehavioral development.", "Technological advances have dramatically improved survival rates for the high-risk infant, yet developmental delays are common due to complications resulting from immature organ systems. The neonatal intensive care unit environment itself may pose barriers to optimal development of these infants. The purpose of this study was to investigate the effects of an oval-shaped cloth nest to make the environment less stressful and enhance neonatal development. Specifically, the study hypothesized that infants who were placed in the cloth nest would gain more weight and would have shorter lengths of hospital stay than would infants receiving routine care. A total of 102 healthy infants ranging from 26 to 31 weeks of gestation were recruited into the study. No significant differences were found in the groups on amount of weight gained. Infants who were placed in the cloth nest actually had longer hospital stays than did infants receiving routine care. Perhaps infants who received routine care received more touch than did nested infants, and the touch may have facilitated development as measured by length of stay.", "We assessed the effectiveness of individualized developmental support in the special care nursery for low-risk preterm infants.\n A university-affiliated teaching hospital.\n Twelve healthy full-term infants, and 24 low-risk preterm infants randomly assigned to a control or an experimental group.\n The preterm control group received standard care and the preterm experimental group received individualized developmental care at the same special care nursery.\n Medical, behavioral (Assessment of Preterm Infants' Behavior and Prechtl's Neurological Examination of the Full-Term Newborn Infant), and electrophysiologic outcome (using quantitative electroencephalography with topographic mapping) of all three groups was assessed 2 weeks after the expected due date.\n No between- or among-group medical differences were seen for this low-risk, healthy sample. The preterm experimental group showed behavioral and electrophysiologic performances comparable to those of the full-term group, whereas the preterm control group performed significantly less well. Behavioral measures suggested significantly poorer attentional functioning for the preterm control group. Electrophysiologic results implicated the frontal lobe.\n Individualized developmental intervention supports neurobehavioral functioning as measured at 2 weeks post-term. It appears to prevent frontal lobe and attentional difficulties in the newborn period, the possible causes of behavioral and scholastic disabilities often seen in low-risk preterm infants at later ages.", "This paper reports the results of an intervention study which assessed the effects of compensatory vestibular-proprioceptive stimulation provided by waterbed flotation on the neurobehavioral development of preterm infants. The subjects, who were randomly assigned to experimental and control groups before they were four days old, consisted of infants who were on ventilators for severe RDS. Twenty infants were tested with a new neurobehavioral assessment procedure when they were between 34 and 35 weeks conceptional age. The examiner, a pediatric neurologist, was unaware of the group status of the subjects he examined. The results showed that infants in the experimental group performed significantly better in attending and pursuing animate and inanimate visual and auditory stimuli, demonstrated more mature spontaneous motor behavior, showed significantly fewer signs of irritability and/or hypertonicity and were more than twice as often in th visually alert, inactive state. The assessment procedure, which can be used for longitudinal evaluation of infants ranging between 24 and 36 weeks conceptional age, shows promise of becoming generally useful as a research instrument. Our preliminary results show that the procedure discriminated between an experimental and control group, that inter-observer reliability was readily established and that test-retest reliability is very high in a number of important areas of neurobehavioral functioning.", "Prematurely born children often show a tendency to adopt extensor motor patterns during the first years of life. These children and especially those children of very low birthweight are considered to be at high risk for abnormal development. Positioning in an ordinary manner or in a more flexed position imposed at random during the neonatal period until discharge from hospital did not have a statistically significant influence on the development of these children at 24 months after term. Analysis of the optimality score of the 100 randomly selected children, born consecutively at the University Women's Hospital, Bern, showed a significant influence of prenatal optimality and congenital malformations on their later outcome.", "We hypothesize that the respiratory and functional states of the very low birth weight infant with bronchopulmonary dysplasia can be improved in the neonatal intensive care unit by prevention of inappropriate sensory input. To test this hypothesis, we developed for preterm newborns a behavior observation method that catalogues specific reaction patterns according to putative stress and relaxation behaviors. We then collected behavioral information and heart rate, respiratory rate, and transcutaneous PO2 readings before, during, and after routine care-giving interventions. Eight control and eight experimental infants were selected for study based on the following criteria: birth weight less than 1,250 g, gestational age less than 28 weeks, on the respirator greater than 24 hours in first 48 hours of life at greater than or equal to 0.60 FiO2 for more than two hours during first 48 hours of life. Additionally, the two groups were comparable on other medical and demographic variables, including severity of respiratory status for the first ten days and incidence of intraventricular hemorrhage, patent ductus arteriosus, and socioeconomic status. Systematic observations were conducted on days 10, 20, and 30 after birth and at 36 and 40 weeks postconception. For the intervention infants, our observations were discussed with the infants' primary nurses, and individualized modifications for each infant's care plan were implemented based on these observations. Experimental infants showed significantly briefer stays on the respirator (P less than .01) and in increased FiO2 (P less than .05). Their feeding behavior was normalized significantly earlier (P less than .01). Experimental infants also showed significantly better behavioral regulation scores at 1 month after their mothers' estimated dates of confinement (post-EDC), as measured with the Assessment of Preterm Infants' Behavior, significantly better Mental and Psychomotor Developmental Indices at 3, 6, and 9 months post-EDC, as measured with the Bayley Scales of Infant Development, and significantly better behavioral regulation scores at 9 months post-EDC, as measured in a videotaped play observation. Measurements of weight, height, and head circumference at 3, 6, and 9 months post-EDC showed no differences. All assessments were performed by one of two trained testers not familiar with the goals of the study or the group status of the infant. These results support the hypothesis that very low birth weight preterm babies profit significantly both medically and developmentally from individualized behavioral care in the neonatal intensive care unit.", "This study examined the effects of stroking and a perioral and intraoral prefeeding stimulation program on healthy, growing, preterm infants in a Level II special care nursery. Only infants without cardiac, gastrointestinal, or central nervous system problems were included in the study.\n Two groups of nine randomly assigned, medically stable preterm infants, born between 30 weeks and 34 weeks gestation, were selected for the study. All infants were introduced to nipple feeding at approximately 34 weeks postconceptual age. The infants in the control group received a 5-min stroking protocol before feeding; the infants in the experimental group received a 5-min stroking protocol in addition to a perioral and intraoral stimulation program.\n Compared with the control group, the experimental group had a decreased number of gavage feedings, greater weight gain, and fewer days of hospitalization. The experimental group also had higher scores on the Revised-Neonatal Oral Motor Assessment nutritive suck scale than the control group.\n On a preliminary basis, the findings from this study establish the efficacy of occupational therapy in a Level II special care nursery for healthy, growing, preterm infants. Further, the specific treatment strategies conducted with the infants receiving the experimental procedures have also been preliminary established as effective in enhancing the infants' feeding skills, resulting in weight gain and decreased hospital stays as compared with their counterparts in the control group. However, our findings cannot be generalized to preterm infant populations who are at greater medical risk than the infants in our study because of the potentially hazardous effects that could result. Implications of the results for intervention programs and future research are discussed.", "To test the efficacy of temporally patterned kinesthetic and auditory stimulation for promoting development of infants born prior to term, 88 preterm infants, below 35 weeks gestation, were assigned to 1 of 4 experimental or control groups. Control subjects received regular hospital care; fixed interval subjects received 15 min of rocking/heartbeat stimulation each hour; self-activating subjects received 15 min rocking/heartbeat when inactive for 90 sec, but only for 1 stimulation period per hour. Assessments included measures of neurological functioning, sleep-wake activity, mother-infant interaction, and mental and motor development at 8 and 24 months. All experimental infants, compared to controls, showed decreased rates of activity while in the hospital, fewer abnormal reflexes, and better orienting responses. At 24 months, experimental infants scored significantly higher on the Mental Development Index of the Bayley Scales. Few differences were found in parent-infant interaction patterns. The results indicate that both temporal patterning and contingent responsiveness in the preterm infant's early environment contribute positively to some aspects of the development of such infants.", "Seventeen appropriate-for-gestational-age premature infants (birthweights 1000-1530 gm) were randomly assigned to control (7) and vestibular stimulation (10) groups. Those in the treatment group were exposed daily to three 15-minute sessions of sinusoidal vestibular stimulation over a 2-week period. At the end of that period, postconceptional age ranged from 34 to 37 weeks. As a measure of neurologic maturation, behavioral and physiologic parameters characterizing sleep states were recorded at the onset and termination of the 2-week period. The ratio of active-to-quiet sleep did not change significantly in control patients. Those exposed to vestibular stimulation showed a significant decrease in proportion of active and a concomitant increase in the proportion of quiet sleep. These results may indicate that vestibular stimulation, even at this early postconceptional age, results in a more mature sleep pattern.", "A randomized control design was used to compare the effect of swaddling to standard positioning on neuromuscular development in very low birth weight (VLBW) infants (< 1,250 gm). The outcome of neuromuscular development was measured at 34 weeks postconceptional age using the Morgan Neonatal Neurobehavioral Exam (MNNE). The sample included 50 infants who met criteria for birth weight, age and who were classified as appropriate for gestational age. Exclusion criteria were also used. The infants were randomly assigned to the experimental group or the comparison group. Data analysis included descriptive and inferential statistical techniques. The results demonstrated that swaddled infants had higher total scores on the MNNE as compared to infants with standard positioning. Swaddling appears to be a positioning technique that can enhance neuromuscular development of the very low birth weight infant.", "To examine the immediate responses of preterm infants to two forms of unimodal [auditory only (A) and tactile only (T)] and two forms of multimodal sensory stimulation [auditory, tactile and visual (ATV); auditory, tactile, visual and vestibular (ATVV)].\n A convenience sample of 54 clinically stable preterm infants (33-34 postconceptional weeks) was randomly assigned to 1 of 5 experimental groups [Control (C); (A); (T); (ATV); and (ATVV)]. Stimulation was applied for 15 minutes once daily for 4 consecutive days.\n Outcome measures included pulse (PR) and respiratory rate (RR), oxygen saturation, behavioral state (BS), and body temperature. Repeated measures ANOVA identified significant differences among the groups during intervention for PR (p < .001), RR (p = .01), and BS (p < .02). Infants receiving any intervention with a tactile component showed increasing arousal (change in BS), and increased PR and RR during stimulation. Group T infants had higher proportions of PR > 180 while Group ATVV had higher proportions of PR < 140 (p = .0001). Group ATVV showed increased alertness following stimulation (24%) in contrast to having the least alertness during stimulation (11%).\n Tactile stimulation alone may be too arousing for these infants while the addition of vestibular stimulation may modulate arousal and facilitate optimal arousal prior to feeding.", "Two types of waterbeds were developed to impart compensatory vestibular-proprioceptive stimulation to premature infants. Twenty-one infants ranging in gestational age from 27 to 34 weeks and birthweights from 1,050 to 1,920 gm were included in this pilot study. Assignment to experimental and control groups was made by random design. The experimental group consisted of ten infants who were placed on a gently oscillating waterbed before the sixth postnatal day, where they remained for seven days. Their clinical progress was compared with that of a control group of 11 similar babies. Waterbed flotation was found to be a safe procedure; there was no significant effects on the infants' vital signs, weight, or frequency of emesis. Highly significant differences were found in the incidence of apnea between the two groups, with infants on the oscillating waterbed having significantly fewer apneic spells. Infants placed on the waterbed during the first four postnatal days benefited more than those placed later. A non-oscillating waterbed was found clinically useful for very small prematures with severe skin problems, for infants recovering from abdominal surgery, and for infants receiving parenteral nutrition.", "To determine the safety of a developmental intervention for use with preterm infants and feasibility of a time sampling procedure.\n An experimental design was used to test an intervention with clinically stable 33-34-week postconceptional age infants over a 4-day period. Repeated outcome measures included pulse rate, oxygen saturation levels, and infant behavioral state.\n The intervention resulted in significant differences in infant behavioral state with the experimental group achieving more alertness. Physiologic parameters remained within normal limits both during and after the intervention.\n The protocol was found to be safe for implementation with clinically stable preterm infants. Behavioral state findings suggest the potential for the intervention to promote alertness. Results suggest that changes in oxygen saturation and pulse rate were dependent upon changes in behavioral state.", "In this study certain features of intrauterine environment were stimulated. Preterm infants were placed on waterbeds, gently rocked, and exposed to auditory stimuli. The stimulated group exhibited significantly better growth for weight, head circumference, and biparietal diameter of the head than did the control infants. Healthy preterm infants placed on rocking waterbeds and exposed to auditory stimuli had growth characteristics comparable to fetuses during the thirty-second to the thirty-sixth week of gestation.", "This study determined whether an auditory, tactile, visual, and vestibular intervention (ATVV) reduced the length of hospitalization of 37 preterm infants by increasing the proportion of alert behavioral states, thereby improving their feeding progression. Participants comprised 12 infants born between 23 and 26 weeks' gestation with normal head ultrasounds and 25 CNS-injured infants born between 23 and 31 weeks' gestation. Infants were randomly assigned to the control group (11 males, five females) or study group (seven males, 14 females) at 32 weeks' postconceptional age. ATVV intervention was administered to the study group for 15 minutes, twice daily, 5 days per week, from 33 weeks of age until discharge. The study group demonstrated increased alertness during the first 5 minutes of intervention, which was significantly correlated to length of stay (p<0.05). The proportion of nippled (teat) intake increased significantly faster for the study group (p=0.0001). Infants in the study group were discharged at a mean of 36.54 weeks, 1.6 weeks earlier than control infants (p<0.05). ATVV intervention facilitated increased alertness, faster transition to complete nipple feeding, and decreased length of hospitalization.", "The effect of alternating night and day on sleep, feeding, and weight gain in 41 healthy preterm infants was examined in a randomised controlled trial. Twenty infants from a night and day nursery, where the intensity of light and noise was reduced between 7 pm and 7 am, spent longer sleeping and less time feeding and gained more weight than 21 infants from a control nursery, where the intensity of light and noise was not reduced. Differences were significant and became apparent only after discharge home; they were still present three months after the expected date of delivery, when infants from the night and day nursery were an average of 0.5 kg heavier (p less than 0.02). These findings suggest that physical environment has an effect (either direct or indirect) on the subsequent behaviour of preterm infants and that exposure to night and day is beneficial.", "To investigate the effects of early experience on brain function and structure.\n A randomized clinical trial tested the neurodevelopmental effectiveness of the Newborn Individualized Developmental Care and Assessment Program (NIDCAP). Thirty preterm infants, 28 to 33 weeks' gestational age (GA) at birth and free of known developmental risk factors, participated in the trial. NIDCAP was initiated within 72 hours of intensive care unit admission and continued to the age of 2 weeks, corrected for prematurity. Control (14) and experimental (16) infants were assessed at 2 weeks' and 9 months' corrected age on health status, growth, and neurobehavior, and at 2 weeks' corrected age additionally on electroencephalogram spectral coherence, magnetic resonance diffusion tensor imaging, and measurements of transverse relaxation time.\n The groups were medically and demographically comparable before as well as after the treatment. However, the experimental group showed significantly better neurobehavioral functioning, increased coherence between frontal and a broad spectrum of mainly occipital brain regions, and higher relative anisotropy in left internal capsule, with a trend for right internal capsule and frontal white matter. Transverse relaxation time showed no difference. Behavioral function was improved also at 9 months' corrected age. The relationship among the 3 neurodevelopmental domains was significant. The results indicated consistently better function and more mature fiber structure for experimental infants compared with their controls.\n This is the first in vivo evidence of enhanced brain function and structure due to the NIDCAP. The study demonstrates that quality of experience before term may influence brain development significantly.", "Medical, neurodevelopmental, and parenting effects of individualized developmental care were investigated in a three-center, randomized, controlled trial. A total of 92 preterm infants, weighing less than 1250 g and aged less than 28 weeks, participated. Outcome measures included medical, neurodevelopmental and family function. Quality of care was also assessed. Multivariate analysis of variance investigated group, site, and interaction effects; correlation analysis identified individual variable contributions to significant effects. The results consistently favored the experimental groups. The following contributed to the group effects: shorter duration of parenteral feeding, transition to full oral feeding, intensive care, and hospitalization; lower incidence of necrotizing enterocolitis; reduced discharge ages and hospital charges; improved weight, length, and head circumferences; enhanced autonomic, motor, state, attention, and self-regulatory functioning; reduced need for facilitation; and lowered family stress and enhanced appreciation of the infant. Quality of care was measurably improved. Very low birth weight infants and their parents, across diverse settings, may benefit from individualized developmental care.", "Family-centered developmentally supportive care of very low birth weight infants, provided by the Newborn Individualized Developmental Care and Assessment Program (NIDCAP) has been reported to have positive medical and economic impacts. Our aim was to investigate its effect on need of ventilatory assistance, growth, and hospitalization in a Swedish setting.\n Preterm infants born between September 1994 and April 1997 with a gestational age <32 weeks and with a need of ventilatory assistance at 24 hours were randomly assigned to either NIDCAP (n = 12) or conventional care (n = 13). The 2 groups were comparable (median [range]) with respect to birth weight (1083 [630-1411] vs 840[636-1939 g]), head circumference (24.0 [22.3-26.5] vs 24.0 [21. 1-30.0 cm]), gestational age (27.6 [24.0-28.7] vs 26.1 [23.9-30.3] weeks), female/male ratio (3/9 vs 9/8) and Clinical Risk Index for Babies (4.0 [0-11] vs 6.0 [2-15]). The infants in the intervention group were cared for in a separate room by a group of specially trained nurses. Formal weekly observations of these infants starting within 3 days after birth and continuing until 36 weeks postconception were used to develop individualized care plans. These plans provided recommendations as to how care might be attuned to the current developmental stage of the infant and how the family might be supported and stimulated to participate in this care. The treatment of the 2 groups was in all other respects identical.\n The duration of mechanical ventilation (median [range] was 2.8 [0-36.7] days in the intervention group vs 4.8 [.1-29.8] days; not significant [NS]) among the controls and continuous positive airway pressure was applied for 26.1 (6.9-52.0) vs 43.9 (5.0-65.1) days. Supplementary oxygen was withdrawn at 33.0 (29.3-35.7) vs 38.1 (33.1-44.9) weeks of postconceptional age (PCA). The weight gain up to 35 weeks of PCA was 13.0 (6.7-21.0) vs 9.8 (6.8-16.6) g/day (NS). The head growth up to 35 weeks of PCA was.73 (.56-1.3) vs.63 (.56-. 77) cm/week (NS). The age of the infant at discharge was 38.3 (36. 1-57.7) vs 41.0 (36.9-48.4) weeks of PCA (NS).\n NIDCAP does not seem to have detrimental effects on Swedish very low birth weight infants in comparison with conventional care. Indeed, NIDCAP might even be advantageous." ]

[ "20008945", "18843564", "18552625" ]

[ "A randomized trial of medical care management for community mental health settings: the Primary Care Access, Referral, and Evaluation (PCARE) study.", "Physical health--a cluster randomized controlled lifestyle intervention among persons with a psychiatric disability and their staff.", "Clinical trial of wellness training: health promotion for severely mentally ill adults." ]

[ "Poor quality of healthcare contributes to impaired health and excess mortality in individuals with severe mental disorders. The authors tested a population-based medical care management intervention designed to improve primary medical care in community mental health settings.\n A total of 407 subjects with severe mental illness at an urban community mental health center were randomly assigned to either the medical care management intervention or usual care. For individuals in the intervention group, care managers provided communication and advocacy with medical providers, health education, and support in overcoming system-level fragmentation and barriers to primary medical care.\n At a 12-month follow-up evaluation, the intervention group received an average of 58.7% of recommended preventive services compared with a rate of 21.8% in the usual care group. They also received a significantly higher proportion of evidence-based services for cardiometabolic conditions (34.9% versus 27.7%) and were more likely to have a primary care provider (71.2% versus 51.9%). The intervention group showed significant improvement on the SF-36 mental component summary (8.0% [versus a 1.1% decline in the usual care group]) and a nonsignificant improvement on the SF-36 physical component summary. Among subjects with available laboratory data, scores on the Framingham Cardiovascular Risk Index were significantly better in the intervention group (6.9%) than the usual care group (9.8%).\n Medical care management was associated with significant improvements in the quality and outcomes of primary care. These findings suggest that care management is a promising approach for improving medical care for patients treated in community mental health settings.", "The objective was to explore the impact on physical health of a lifestyle programme among persons with psychiatric disabilities, and their caregivers. Their satisfaction with the intervention was also assessed. Somatic comorbidity and an increased mortality related to the lifestyle among persons with psychiatric disabilities are well known. Few randomized controlled trials have been aimed specifically at lifestyle issues among persons with a psychiatric disability. This trial includes clients with psychiatric disabilities living in supported housing and their staff. Forty-one persons with a DSM-?V diagnosis of severe mental illness from psychiatric disability from 10 supported housing facilities and 41 of their caregivers participated in this 12-month study during 2005-2006 in Sweden. The supported housing facilities with residents and staff were randomly assigned to either a health intervention programme or a control programme with an aesthetic content. The presence of metabolic syndrome and changes in the mean of physiological parameters such as Hba1c, P-glucose, P-insulin, lipids, blood pressure, physical working capacity, body mass index, Heart Score were investigated and participants' satisfaction assessed. There was a significant reduction in the mean of metabolic syndrome criteria in the intervention group compared with the control group at the follow-up. The participants expressed satisfaction with the programme. The results indicate that health interventions on lifestyle issues when involving carers are appreciated, feasible and could be successful in reducing some health-related risk factors among persons with psychiatric disabilities.", "This randomized controlled trial examined benefits of adding active health promotion to basic primary care (BPC) services for SMI adults. It compared BPC with BPC plus wellness training (WT), a 12 months intervention promoting individual skills in self-management. Three hundred nine participants enrolled during short-term residential treatment completed baseline assessments and were assigned to treatment groups, before discharge. Outcomes of perceived health status (SF-36), global assessment of function, and ratings of self-efficacy were assessed at follow-up interviews at 6, 12, and 18 months. The intent-to-treat analysis employed multilevel regression to examine differences by group on outcomes across time, controlling for health related covariates. The WT group showed significantly better outcomes on the SF-36 physical functioning and general health scales. Findings affirm ability of SMI adults to benefit from active health promotion." ]

[ "20234138", "16027693", "6472970" ]

[ "Oral versus nasal route for placing feeding tubes: no effect on hypoxemia and bradycardia in infants with apnea of prematurity.", "Continuous feeding promotes gastrointestinal tolerance and growth in very low birth weight infants.", "An investigation into the benefits of resiting nasoenteric feeding tubes." ]

[ "Raised upper airway resistance may be involved in apnea of prematurity (AOP).\n To determine the effects of an oral versus a nasal gastric tube on episodes of hypoxemia and bradycardia in infants with AOP.\n In a randomized controlled cross-over trial, 32 infants (median gestational age 29 (range 24-31) weeks, postmenstrual age at study 32 (range 30-35) weeks) with the need for tube feeding and symptoms of AOP underwent a 24-hour recording of breathing movements, nasal airflow, heart rate, pulse oximeter saturation and pulse waveforms. A 5-Fr feeding tube was placed orally or nasally for 12 h each, the position selected first was randomly assigned. When the feeding tube was placed nasally, always the smaller nostril was selected. Each infant acted as his/her own control. Recordings were analyzed for the summed rate of bradycardia and desaturation (heart rate <2/3 of baseline, saturation <or=80%).\n The route of placing the feeding tube had no significant effect on the summed rate of bradycardia and desaturation (nasal route: median 1.6, CI 0.8-1.9; oral route: median 1.0, CI 0.9-1.6, p = 0.25).\n We could not confirm an advantage of placing a feeding tube orally in these infants with AOP, as the oral route did not improve their symptoms of AOP. Possible explanations include: (i) the increase in nasal airway resistance by the 5-Fr nasogastric tube, inserted into the smaller nostril, is too small to have any effect on AOP; (ii) any benefit of the oral route is neutralized by the negative effects of an enhanced vagal stimulation, or (iii) study duration was too short to detect a difference in AOP.\n Copyright 2010 S. Karger AG, Basel.", "To compare the effects of continuous versus intermittent feeding on gastrointestinal tolerance and growth in very low birth weight (VLBW) infants.\n In a randomized, controlled trial conducted at 3 neonatal units, 70 premature infants with a gestational age 24 to 29 weeks and birth weight < 1200 g were assigned to 1 of 3 feeding methods: continuous nasogastric feeding, intermittent nasogastric feeding, or intermittent orogastric feeding. Feeding was initiated within 30 hours of birth. Daily enteral and parenteral volumes, caloric and protein intakes, growth, enteral intolerance, and clinical complications were recorded. Cox regression analysis was used to determine primary outcome, the time to achieve full enteral feeding.\n The continuously fed infants achieved full enteral feeding significantly faster than the intermittently fed infants (hazard ratio [HR] = 1.86; 95% confidence interval [CI] = 1.07 to 3.22). In stratified analysis according to birth weight, the improvement was even more pronounced in the smallest infants, those with birth weight < or = 850 g (adjusted HR = 4.13; 95% CI = 1.48 to 11.53). Growth rate was significantly faster in the continuously fed infants ( P = .002).\n In VLBW infants, continuous feeding seems to be better than intermittent feeding with regard to gastrointestinal tolerance and growth.", "Partial nasal obstruction in preterm infants increases the airway resistance. In spite of this, nasal feeding tubes are often used, if only because oral tubes are difficult to secure. A palatal appliance has been devised that maintains the position of oroenteric feeding tube(s) and is not associated with local complications. In order to assess the effects of resiting feeding tubes, two related studies were carried out. The first study, a trial, included respiratory monitoring of 29 infants on the third and/or seventh day after either the appliance and oroenteric tubes had been inserted, or, in the control group, after the nasoenteric tubes had been passed. After seven days, the infants using the palatal appliance had significantly less periodic breathing, central apnea, and movement than the control group. The second study showed that the removal of feeding tubes that had been in situ for several days reduced apnea rates and produced a significant increase in transcutaneous PO2." ]

[ "16125588", "21062666", "12830403", "20850004", "1287904", "9231212" ]

[ "Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial.", "Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial.", "Randomized comparison of artesunate and quinine in the treatment of severe falciparum malaria.", "Comparison of artesunate and quinine in the treatment of Sudanese children with severe Plasmodium falciparum malaria.", "Comparison of artemisinin suppositories with intravenous artesunate and intravenous quinine in the treatment of cerebral malaria.", "Comparison of artemisinin suppositories, intramuscular artesunate and intravenous quinine for the treatment of severe childhood malaria." ]

[ "In the treatment of severe malaria, intravenous artesunate is more rapidly acting than intravenous quinine in terms of parasite clearance, is safer, and is simpler to administer, but whether it can reduce mortality is uncertain.\n We did an open-label randomised controlled trial in patients admitted to hospital with severe falciparum malaria in Bangladesh, India, Indonesia, and Myanmar. We assigned individuals intravenous artesunate 2.4 mg/kg bodyweight given as a bolus (n=730) at 0, 12, and 24 h, and then daily, or intravenous quinine (20 mg salt per kg loading dose infused over 4 h then 10 mg/kg infused over 2-8 h three times a day; n=731). Oral medication was substituted when possible to complete treatment. Our primary endpoint was death from severe malaria, and analysis was by intention to treat.\n We assessed all patients randomised for the primary endpoint. Mortality in artesunate recipients was 15% (107 of 730) compared with 22% (164 of 731) in quinine recipients; an absolute reduction of 34.7% (95% CI 18.5-47.6%; p=0.0002). Treatment with artesunate was well tolerated, whereas quinine was associated with hypoglycaemia (relative risk 3.2, 1.3-7.8; p=0.009).\n Artesunate should become the treatment of choice for severe falciparum malaria in adults.", "Severe malaria is a major cause of childhood death and often the main reason for paediatric hospital admission in sub-Saharan Africa. Quinine is still the established treatment of choice, although evidence from Asia suggests that artesunate is associated with a lower mortality. We compared parenteral treatment with either artesunate or quinine in African children with severe malaria.\n This open-label, randomised trial was undertaken in 11 centres in nine African countries. Children (<15 years) with severe falciparum malaria were randomly assigned to parenteral artesunate or parenteral quinine. Randomisation was in blocks of 20, with study numbers corresponding to treatment allocations kept inside opaque sealed paper envelopes. The trial was open label at each site, and none of the investigators or trialists, apart from for the trial statistician, had access to the summaries of treatment allocations. The primary outcome measure was in-hospital mortality, analysed by intention to treat. This trial is registered, number ISRCTN50258054.\n 5425 children were enrolled; 2712 were assigned to artesunate and 2713 to quinine. All patients were analysed for the primary outcome. 230 (8·5%) patients assigned to artesunate treatment died compared with 297 (10·9%) assigned to quinine treatment (odds ratio [OR] stratified for study site 0·75, 95% CI 0·63-0·90; relative reduction 22·5%, 95% CI 8·1-36·9; p=0·0022). Incidence of neurological sequelae did not differ significantly between groups, but the development of coma (65/1832 [3·5%] with artesunate vs 91/1768 [5·1%] with quinine; OR 0·69 95% CI 0·49-0·95; p=0·0231), convulsions (224/2712 [8·3%] vs 273/2713 [10·1%]; OR 0·80, 0·66-0·97; p=0·0199), and deterioration of the coma score (166/2712 [6·1%] vs 208/2713 [7·7%]; OR 0·78, 0·64-0·97; p=0·0245) were all significantly less frequent in artesunate recipients than in quinine recipients. Post-treatment hypoglycaemia was also less frequent in patients assigned to artesunate than in those assigned to quinine (48/2712 [1·8%] vs 75/2713 [2·8%]; OR 0·63, 0·43-0·91; p=0·0134). Artesunate was well tolerated, with no serious drug-related adverse effects.\n Artesunate substantially reduces mortality in African children with severe malaria. These data, together with a meta-analysis of all trials comparing artesunate and quinine, strongly suggest that parenteral artesunate should replace quinine as the treatment of choice for severe falciparum malaria worldwide.\n The Wellcome Trust.\n Copyright © 2010 Elsevier Ltd. All rights reserved.", "A randomized, open-label comparison of artesunate and quinine was conducted in 113 adults with clinically severe falciparum malaria in western Thailand. Mortality was 12% with artesunate and 22% with quinine treatment (relative risk, 0.53; 95% confidence interval, 0.23-1.26; P=.22). Multiple logistic regression analysis found admission plasma lactate level, Glasgow Coma Scale score, and total serum bilirubin level to be independent risk factors for death. Coma recovery and times to normalize plasma lactate levels were similar, but the parasite clearance time was much shorter among artesunate-treated patients (P=.019). Fewer patients became hypoglycemic during artesunate therapy (10%) than during quinine therapy (28%) (P=.03). Artesunate is at least as effective as quinine in the treatment of adults with severe malaria. Larger trials are required to determine whether mortality is reduced among patients treated with artesunate.", "Sixty-six children presenting to Singa hospital, Sudan with different manifestations of severe Plasmodium falciparum malaria were randomly divided into two well-matched groups (33 in each arm) to receive either intravenous artesunate 2·4 mg/kg at 0, 12, and 24 hours, then daily, or intravenous quinine 20mg/kg initially then 10mg/kg three times a day. There was no significant difference in the fever, parasite clearance, and coma resolution times. Three patients died, one in the artesunate and two in the quinine groups. One patient developed hypoglycaemia following quinine infusion. Thus, artesunate can be used for the treatment of severe falciparum malaria.\n Copyright © 2010 Royal Society of Tropical Medicine and Hygiene.", "Seventy-nine comatose cerebral malaria patients given standard supportive treatment were randomized to receive specific antimalarial chemotherapy of intravenous quinine, intravenous artesunate, or artemisinin suppositories. Artesunate and artemisinin reduced peripheral asexual parasitaemia significantly more rapidly than quinine (90% clearance time 16 h, 18.9 h and 34.5 h respectively), but did not significantly reduce the duration of coma or mortality. The rapid lowering of peripheral parasitaemia may not ameliorate complications already present. These results demonstrate that artemisinin suppositories are as effective as artesunate and quinine given intravenously, and have economic and practical advantages for the treatment of severe malaria in areas remote from major medical centres. However, large numbers of patients will need to be studied if differences in mortality between the 3 treatment groups are to be demonstrated.", "Severe malaria remains a major cause of mortality and morbidity for children living in many tropical regions. With the emergence of strains of Plasmodium falciparum resistant to both chloroquine and quinine, alternative antimalarial agents are required. The artemisinin group of compounds are rapidly effective in severe disease when given by intramuscular or intravenous injection. However, these routes of administration are not always available in rural areas. In an open, randomized comparison 109 Vietnamese children, aged between 3 months and 14 years, with severe P.falciparum malaria, were allocated at random to receive artemisinin suppositories followed by mefloquine (n = 37), intramuscular artesunate followed by mefloquine (n = 37), or intravenous quinine followed by pyrimethamine/sulfadoxine (n = 35). There were 9 deaths: 2 artemisinin, 4 artesunate and 5 quinine-treated children. There was no difference in fever clearance time, coma recovery, or length of hospital stay among the 3 groups. However, parasite clearance times were significantly faster in artemisinin and artesunate-treated patients than in those who received quinine (P < 0.0001). Both artemisinin and artesunate were very well tolerated, but children receiving these drugs had lower peripheral reticulocyte counts by day 5 of treatment than those in the quinine group (P = 0.011). No other adverse effect or toxicity was found. There was no treatment failure in these 2 groups, but 4 patients in the quinine group failed to clear their parasites within 7 d of starting treatment and required alternative antimalarial therapy. Artemisinin suppositories are easy to administer, cheap, and very effective for treating children with severe malaria. In rural areas where medical facilities are lacking these drugs will allow antimalarial therapy to be instituted earlier in the course of the disease and may therefore save lives." ]

[ "9722821", "1445500", "3358237", "9339968", "8836022", "2465581", "9487169", "2249964" ]

[ "The outreach-assisted model of partner notification with IDUs.", "Results of a randomized trial of partner notification in cases of HIV infection in North Carolina.", "Efficiency and cost-effectiveness of field follow-up for patients with Chlamydia trachomatis infection in a sexually transmitted diseases clinic.", "Partner notification for syphilis: a randomized, controlled trial of three approaches.", "Individual counseling of patients with sexually transmitted diseases. A way to improve partner notification in a Zambian setting?", "The impact of a clinic-based educational videotape on knowledge and treatment behavior of men with gonorrhea.", "Home sampling versus conventional contact tracing for detecting Chlamydia trachomatis infection in male partners of infected women: randomised study.", "An analysis of and intervention in the sexual transmission of disease." ]

[ "This analysis describes the Outreach-Assisted Model of Partner Notification, an innovative strategy for encouraging seropositive injecting drug users (IDUs) to inform their partners of shared human immunodeficiency virus (HIV) exposure. The analysis focuses on two core components of the notification process: the identification of at-risk partners and preferences for self-tell vs. outreach assistance in informing partners of possible exposure to the virus.\n Using community outreach techniques, 386 IDUs were recruited for HIV pretest counseling, testing, and partner notification over a 12-month period. Of these, 63 tested HIV seropositive, and all but three returned for their test results. The 60 who were informed of their serostatus were randomly assigned to either a minimal or an enhanced intervention condition. Participants assigned to the minimal (self-tell) group were strongly encouraged to inform their partners of possible exposure. Those assigned to the enhanced (outreach-assisted) group had the option of either informing one or more of their partner(s) themselves or choosing to have the project's outreach team do so.\n Together, the 60 index persons who received their results provided names or at least one piece of locating information for a total of 142 partners with whom they perceived having shared possible exposure to the virus within the past five years. By itself, drug use accounted for half of all partners named. Sexual behavior alone accounted for 25% of named partners. Eighty-two percent of the enhanced group preferred to have the outreach team tell at least one partner; the team was requested to notify 71% of the total number of partners whom this group named.\n Findings suggest that IDUs want to notify their partners of shared HIV exposure. Outreach assistance was the preferred mode in the majority of cases. Expanding traditional community-based HIV outreach activities to include delivering street-based counseling, test, a partner notification appears to be a positive and workable prevention strategy.", "We sought to compare two methods of notifying sex partners of subjects infected with the human immunodeficiency virus (HIV) or persons who had shared needles with them (needle-sharing partners): \"patient referral,\" in which the responsibility for notifying partners was left to the patient, and \"provider referral,\" in which providers attempted to notify partners.\n Names of sex partners and needle-sharing partners and information on how to locate them were obtained from consenting HIV-infected subjects identified in the HIV-testing programs at three public health departments in North Carolina. The subjects were randomly assigned to a patient-referral group (in which patients had the initial responsibility for notifying their partners) or a provider-referral group (in which the study counselor notified the partners). The success of attempts to notify partners was monitored by means of interviews with counselors conducted both in the field and at the health department.\n Of 534 HIV-positive persons identified at the health departments, 247 (46 percent) did not return for counseling after the test, 8 were counseled outside the study, and 117 (22 percent) were ineligible. Of the 162 invited to participate, 88 (54 percent) declined and 74 (46 percent) agreed. The subjects were mostly male (69 percent), black (87 percent), homosexual or bisexual (76 percent of the men), and had a median age of 30 years. Thirty-nine were assigned to the provider-referral group and 35 to the patient-referral group. In the provider-referral group 78 of 157 partners (50 percent) were successfully notified, whereas in the patient-referral group only 10 of 153 (7 percent) were notified. Of the partners notified by the counselors, 94 percent were not aware that they had been exposed to HIV. Overall, 23 percent of the partners notified and tested were HIV-positive.\n In this trial, leaving the notification of partners up to the subjects (patient referral) was quite ineffective, despite the North Carolina law requiring that partners be notified. Partner notification by public health counselors (provider referral) was significantly more effective. Although the effectiveness of notification procedures is constrained by the accuracy of the information provided by HIV-infected patients, counselors who notify the partners of an infected patient can refer them to educational, medical, and support services targeted to persons at high risk for HIV infection and may encourage the adoption of less risky behavior.", "Unlike contact-tracing procedures for syphilis and gonorrhea, field follow-up to locate and treat patients with Chlamydia trachomatis infections has not been extensively applied in the United States. We implemented two studies to assess the efficiency and cost-effectiveness of using field follow-up for contact of two groups: patients with chlamydial infection detected as part of a screening program and women who were sexual partners of men with nongonococcal urethritis (NGU). Of the 142 patients with chlamydial infection who had not been treated empirically, 112 (79%) returned for treatment when a reminder system was used, as compared with a return rate of 97% (259/266) achieved by field follow-up (P less than 0.0001). Among the 678 men with NGU enrolled in a randomized trial of field follow-up vs. two self-referral methods, field follow-up yielded over three times as many partners returning to the clinic for treatment as did either of the other two methods (P less than 0.001). Analyses using the estimated costs of the intervention strategies and the medical costs associated with an untreated chlamydial infection showed that field follow-up by trained investigators proved to be not only the most efficient method for locating patients with chlamydial infection and/or patients who were at risk for it, but also the most cost-effective in terms of total health-care dollars spent.", "To determine the cost and effectiveness of three approaches to partner notification for infectious syphilis.\n People with syphilis were randomly assigned to: (1) notification of partners by patients themselves within 2 days or disease intervention specialists would notify them; (2) immediate notification by intervention specialist; or (3) immediate notification by intervention specialists, who had the option of drawing blood in the field. Costs of intervention specialists' time, travel, and overhead were measured. Intention-to-treat analysis measured outcomes per randomized index patient.\n From December, 1990 through March, 1993, 1,966 index patients with syphilis (primary 9%; secondary 18%; and early latent 73%) were randomized in Broward County (Ft. Lauderdale), Florida (1,191); Tampa, Florida (569); and Paterson, New Jersey (206). Index patients reported 11,272 potentially exposed partners and sufficient information to initiate investigations for 2,761. Of these, 2,236 were located, 367 had newly identified infections, and 870 others received preventive treatment. The three partner notification approaches had similar success locating partners (1.1-1.2 per index patient) and treating partners (0.61-0.67 per index). The cost was $317 to $362 per partner treated; the optimal strategy differed by study site.\n Partner notification identified many infected and potentially infected people. The cost and effectiveness of the three types of provider notification were similar. Alternative approaches are needed to reach infected partners who could not be notified.", "Sexually transmitted diseases (STD) are a major health problem in Zambia. Partner notification, which is a recommended strategy to decrease STD, must be improved.\n To assess whether individual counseling of patients with STD, combined with contact slip(s), had any impact on the proportion of sex partners traced in an urban setting in Zambia.\n A randomized trial comprised of 94 women and 302 men with STD.\n Women and men in the intervention group informed more partners than did those in the control group. In the intervention group, 1.8 partners per man was treated compared to 1.2 in the control group (P < 0.001). There was no difference between the two groups of women. There was a gradual decline from numbers of partners informed to numbers of partners treated according to the patient to number of contact slips filed.\n Individual counseling of men with STD improved partner notification.", "The impact of a ten-minute, soap opera-style videotape on knowledge and treatment behavior of black men with gonorrhea was tested in randomized clinical trials. The videotape, shown to individual patients after diagnosis, produced a sizeable increase in the percentage of patients who returned for their test-of-cure examination: while only 43.3% of control group patients returned, 53.5% of those in the videotape group did so; chi 2(1) = 9.0; P less than 0.003. In a follow-up study, similar results were found: videotape group (59.0%), control group (39.1%); chi 2(1) = 6.2; P less than 0.015. The videotape also produced large, significant increases in patient knowledge, as measured by a test administered during patients' clinic visit (P less than 0.0001). No measureable effect of the videotape was detected on patients' willingness to refer sexual contacts for treatment. The findings suggest that clinic-based educational materials, particularly soap opera-style videotapes that engender audience identification, create emotional significance for the viewer, and model requisite communication skills, may have a significant role to play in control of sexually transmitted diseases.", "nan", "Sexually transmitted diseases are a serious threat to the public health. Indeed, when an individual seeks medical treatment for a sexually transmitted disease, health authorities frequently attempt to identify, procure, and treat that individual's sexual contact(s). We conducted a comparative analysis of three alternative approaches to tracing the sexual partners of individuals diagnosed as having a sexually transmitted disease. The first approach involved counseling individuals (n = 27) infected with either gonorrhea or nongonococcal urethritis and exhorting them to procure their sexual partners for treatment. In addition to counseling, the second and third approaches involved distributing \"occasion cards\" for patients to use when informing sexual contacts of the need for treatment. Moreover, in the second approach, the counselor (a nurse or physician) informed infected patients (n = 19) that they and their partners could waive the $3 clinic fee contingent upon the partners seeking treatment within 1 week. In the third approach, the counselor asked infected persons (n = 19) to accept a follow-up telephone contact if their sexual partners failed to seek treatment within 1 week. The third approach was most effective. Ninety percent of the partners identified through this approach sought treatment, versus only about 60% of the partners in the other two conditions. The third approach was also the least expensive, costing about $2.95 to procure each partner for treatment." ]

[ "3309236", "6408619" ]

[ "Efficacy of inhaled amikacin as adjunct to intravenous combination therapy (ceftazidime and amikacin) in cystic fibrosis.", "Efficacy of inhaled tobramycin in the treatment of pulmonary exacerbations in children with cystic fibrosis." ]

[ "Eighty-seven patients with cystic fibrosis were admitted to hospital with an acute exacerbation of pulmonary symptoms associated with isolation of Pseudomonas aeruginosa from sputum. The patients were randomly allocated to receive intravenously administered ceftazidime (250 mg/kg/day) and amikacin (33 mg/kg/day) alone or with inhaled amikacin (100 mg twice a day). Other aspects of the 2-week treatment were constant. The two therapy groups were comparable in all aspects. At the completion of therapy, the addition of aerosolized amikacin produced temporary eradication of P. aeruginosa in 70% of the patients, compared with 41% in the intravenous therapy only group (P less than 0.02). Suppression of P. aeruginosa in sputum cultures was correlated with the amikacin sputum concentrations. However, both regimens resulted in similar improvements in clinical, radiologic, laboratory, and pulmonary function measurements, and within 4 to 6 weeks most patients were recolonized with P. aeruginosa. There was no serious toxicity or adverse effect. In patients with cystic fibrosis, the addition of aerosol aminoglycoside to systemic antipseudomonal combination therapy is not clinically beneficial.", "Two forms of treatment of acute pulmonary exacerbations in patients with cystic fibrosis were compared: intravenous ticarcillin (300 mg drug per kg per day) and tobramycin (10 mg drug per kg per day) versus the same intravenous antibiotic therapy plus inhaled tobramycin (80 mg three times per day). The 16 patients in the intravenous plus inhaled tobramycin group were similar to the 12 control patients in age, sex, Schwachman scores, pulmonary function and pretreatment colony counts of Pseudomonas aeruginosa in sputum. Treatment resulted in significant improvement in clinical status and pulmonary function without any apparent differences in the two groups. However, intravenous plus inhaled tobramycin resulted in temporary eradication of P. aeruginosa in 63% of the patients compared to 25% in the intravenous only group (P = 0.03). Suppression of P. aeruginosa in sputum cultures did not correlate with clinical response to treatment. No renal toxicity or elevations of serum tobramycin were observed in the intravenous plus inhaled tobramycin group." ]

[ "6452842", "9299652", "2855297", "8678385", "1460211", "17283559", "7751531" ]

[ "Ipratropium nasal spray: a new treatment for rhinorrhea in the common cold.", "Common cold and high-dose ipratropium bromide: use of anticholinergic medication as an indicator of reflex-mediated hypersecretion.", "Ipratropium bromide treatment of experimental rhinovirus infection.", "Effectiveness and safety of intranasal ipratropium bromide in common colds. A randomized, double-blind, placebo-controlled trial.", "A double-blind, placebo-controlled study of the safety and efficacy of ipratropium bromide nasal spray versus placebo in patients with the common cold.", "Efficacy and safety of topical combinations of ipratropium and xylometazoline for the treatment of symptoms of runny nose and nasal congestion associated with acute upper respiratory tract infection.", "A dose-response study of the efficacy and safety of ipratropium bromide nasal spray in the treatment of the common cold." ]

[ "A need is often present for symptomatic treatment of the common cold. A blocked nose can be opened by a vasoconstrictor, but no effective therapy is known today for rhinorrhea. The aim of the present trial was to study the effect of the topically active parasympatholytic, ipratropium, on rhinorrhea. In a placebo-controlled group comparative trial, 80 micrograms of ipratropium were taken as a nasal spray 4 times daily for 1 wk by 40 adults with spontaneously occurring common colds. All subjects administered an intranasal vasoconstrictor (xylomethazoline, 0.1%) 5 min before administering placebo or ipratropium. Ipratropium treatment resulted in a significant reduction in nasal discharge compared with that of placebo treatment during the whole treatment period (p less than 0.001), but the drug was especially effective the first 3 days, when the watery secretion was predominant. It was concluded that this new spray can be of value in the first days of a cold, when nasal discharge is a nuisance.", "It was our aim to study the role played by parasympathetic reflexes for the amount and physical characteristics of nasal discharge during a common cold, and to define the maximum anti-rhinorrhoea effect obtainable with anticholinergic medication. Fifty adults with naturally acquired colds were treated with a very high dose of the topically active cholinoceptor-antagonists ipratropium bromide in a randomized, double-blind, placebo-controlled study of parallel groups. A dosage of 400 micrograms was given 4 times daily for 3 days, using a specially manufactured high-dosed pressurized aerosol. This treatment resulted in a 56% reduction in the number of nose blowings (p < 0.01) and a 58% reduction in the weight of blown secretions (p < 0.01). Assessment of the \"pourability\" of the nasal discharge indicated that ipratropium bromide mainly reduces the watery secretions but not the mucopurulent secretions. The high dose of ipratropium bromide caused nose- and mouth-dryness in a considerable number of the patients. In conclusion: (1) during the first days of a common cold about 60% of the nasal discharge is a reflex-mediated product from nasal glands; (2) this type of secretion is predominantly watery; and (3) ipratropium bromide can reduce watery rhinorrhoea in the common cold, but a lower dose is required in order to avoid side effects.", "The importance of parasympathetic-cholinergic mechanisms in the production of common cold symptoms is not clear. The quaternary ammonium anticholinergic antagonist ipratropium bromide was intranasally administered under double-blind, randomized, placebo-controlled conditions to assess its tolerance and efficacy in reducing nasal hypersecretion in adult volunteers with experimental rhinovirus colds. Ipratropium was sprayed intranasally three times daily (80 micrograms per treatment) for 5 days beginning 24 h after intranasal inoculation of rhinovirus type 39. Clinical colds occurred in 50% of 30 infected ipratropium recipients and in 76% of 33 infected placebo recipients (P = 0.04). The nasal mucus weights tended to be lower for ipratropium-treated persons (mean +/- standard deviation, 14.7 +/- 15.1 g/5 days) than for placebo-treated recipients (24.7 +/- 28.0 g/5 days; P = 0.076). Whereas total nasal symptom scores were similar between the two groups, the rhinorrhea score analyzed for each day of treatment showed nonsignificant trends favoring the ipratropium group over the last 4 days of treatment. Ipratropium was generally well tolerated. The results suggest that cholinergic mechanisms are at least partially responsible for nasal mucus production in rhinovirus colds but that the effect of anticholinergic compounds alone is insufficient to be of practical use in treatment, although they may have value as components of multi-ingredient preparations.", "To determine the tolerability and clinical effectiveness of intranasal ipratropium bromide for the treatment of symptoms of common colds.\n Multicenter, double-blind, randomized trial.\n 3 university student health services.\n 411 previously healthy persons 14 to 56 years of age who had cold symptoms that had lasted for no more than 36 hours, rhinorrhea subjectively judged to be of at least moderate severity, and documented nasal discharge of at least 1.5 g over a 1-hour observation period.\n Either 1) ipratropium bromide nasal spray 0.06% in buffered salt solution, two 42-micrograms sprays per nostril administered by metered pump spray; 2) control nasal spray, which consisted of buffered salt solution; or 3) no treatment. Treatments were self-administered three or four times daily during waking hours for 4 days. After receiving their morning dose, patients stayed at the study center for 6 hours on study day 1 and 3 hours on study day 2; symptom severity was recorded and nasal mucus discharges were collected and weighed hourly during these periods.\n Ipratropium recipients had 26% less nasal discharge than controls (P = 0.0024) and 34% less nasal discharge than untreated patients (P = 0.0001). Severity of rhinorrhea as judged subjectively was reduced in ipratropium recipients by 31% compared with controls and by 78% compared with untreated patients (P = 0.0001 for both comparisons). In addition to being associated with reductions in daily assessments of the severity of rhinorrhea (P < or = 0.003), ipratropium was associated with reduced sneezing on study days 2 (20% difference; P = 0.03) and 4 (30% difference; P = 0.02) but not with reduced nasal congestion compared with the control spray. Ipratropium was generally well tolerated but was associated with higher rates of blood-tinged mucus (16.8% in the ipratropium group compared with 3.6% in the control group; P = 0.01) and nasal dryness (11.7% in the ipratropium group compared with 3.6% in the control group; P = 0.021) than the control spray. Patient assessments of the overall effectiveness of treatment were more favorable for ipratropium than for the control spray (P < or = 0.026) or for no treatment (P < or = 0.002) on each day of inquiry (study days 1, 2, and 5).\n Intranasal ipratropium bromide provides specific relief of rhinorrhea and sneezing associated with common colds.", "Ipratropium bromide (IB) has been found to reduce secretions in the upper respiratory tract; this is accomplished through competitive inhibition of acetylcholine at muscarinic receptors that control rhinorrhea production. This study compared the safety and efficacy of IB with placebo in the symptomatic relief of rhinorrhea in patients with the common cold. Human subjects with symptoms of a common cold, primarily rhinorrhea, were enrolled and treated with either IB (84 micrograms/nostril) or placebo; each was administered as two sprays per nostril, four times a day, for 4 days. Primary efficacy analyses were in-clinic measurements of nasal discharge weights over a 3-hour period after administration on days 1 and 2 and assessment of rhinorrhea symptoms by use of a subjective patient-completed visual analog rating scale. IB significantly reduced rhinorrhea an average of 18% over placebo for days 1 and 2 (p = 0.01). Visual analog scale scores showed an average improvement in rhinorrhea of 22% over placebo (p = 0.001). When patients with relatively minor rhinorrhea (baseline weight of nasal discharge < or = 1.0 gm) were excluded, IB produced an average reduction in nasal discharge of 23% over placebo for days 1 and 2 (p = 0.003).", "Rhinorrhea and nasal congestion are simultaneous symptoms associated with the common cold. This study investigated the efficacy and safety of a combination nasal spray of ipratropium and xylometazoline for simultaneous treatment of these symptoms.\n The trial was a multicenter double-blind, parallel-group, randomized design on patients with common cold symptoms. Patients scored symptoms of runny nose and nasal congestion and recorded adverse events in a diary for up to 7 days. Patients also recorded tissue use. The five test treatments consisted of ipratropium, 0.6 mg/mL, and xylometazoline, 1.0 mg/mL; ipratropium, 0.6 mg/mL, and xylometazoline, 0.5 mg/mL; ipratropium, 0.6 mg/mL; xylometazoline, 1.0 mg/mL; and placebo solution.\n Eight hundred sixty-four patients were screened and 786 patients received treatment. One day after treatment there was a clear separation between the scores for the placebo and ipratropium treatment groups for rhinorrhea and between the placebo and xylometazoline treatment groups for congestion. Both ipratropium/xylometazoline 1.0 and ipratropium/xylometazoline 0.5 treatments were superior to xylometazoline with respect to rhinorrhea (p < 0.0001) and superior to ipratropium with respect to nasal congestion scores (p < 0.001). Both the ipratropium combination treatments had significantly lower tissue use than the xylometazoline treatment group (p < 0.0001). Adverse events were distributed equally between the treatments, except mucus tinged with blood, epistaxis, nasal passage irritation, and nasal dryness, which had a higher incidence in the three groups that received medicines containing ipratropium.\n The results indicate that a combination medicine of ipratropium and xylometazoline is safe and effective for treatment of rhinorrhea and nasal congestion associated with common cold.", "Rhinorrhea is an annoying symptom of the common cold for which effective therapy is not currently available. Ipratropium bromide (IB) is an anticholinergic drug that has been shown to decrease glandular secretion when applied topically to the nasal mucosa. The purpose of this study was to compare the efficacy and safety of three doses of IB nasal spray versus either vehicle or no treatment in relieving rhinorrhea in patients with naturally acquired colds. Rhinorrhea severity was measured objectively by determining nasal discharge weights and subjectively by means of visual analog scale scores. Compared with either vehicle or no treatment, IB nasal spray produced a significant decrease in the severity of rhinorrhea. A dose of 84 micrograms (two sprays of a 0.06% solution in buffered saline solution) in each nostril was more efficacious than a 42 microgram per nostril dose and only marginally less efficacious than a 168 micrograms per nostril dose. The 84 micrograms per nostril dose also was associated with fewer adverse events than was the higher dose. None of the adverse events related to intranasal IB therapy was of a serious nature. The use of IB nasal spray appears to be a rational and safe approach to relieving rhinorrhea associated with the common cold." ]

[ "8688398", "790961", "6552999", "5232199", "6708033", "2872429", "6383045", "446106" ]

[ "Randomised comparison between a loading and incremental dose model for ritodrine administration in preterm labour.", "Effect of terbutaline on premature labor. A double-blind placebo-controlled study.", "[Tocolysis with hexoprenalin and salbutamol in a clinical comparison].", "Isoxuprine and premature labour.", "Comparison of magnesium sulfate, terbutaline and a placebo for inhibition of preterm labor. A randomized study.", "Single-centre randomised trial of ritodrine hydrochloride for preterm labour.", "A double-blind study comparing ritodrine and terbutaline in the treatment of preterm labor.", "A Danish multicenter study on ritodrine in the treatment of pre-term labour." ]

[ "To compare a new loading dose regimen for intravenous ritodrine administration in preterm labour with the conventional dose regimen.\n Multicentre randomised trial using numbered opaque sealed envelopes.\n Five teaching hospitals in the Netherlands.\n Women (n = 203) in preterm labour at less than 34 weeks of gestation.\n Women received either a loading dose ritodrine infusion followed, as soon as tocolysis was reached, by a decrease in infusion rate or the conventional schedule of increasing doses until uterine quiescence was achieved.\n Frequency of successful tocolysis (71%) and duration of treatment (55 h) were similar in both groups, but the loading dose schedule was better tolerated with fewer adverse events. Also the number of dose adjustments was smaller than in the incremental dose group (P < 0.001). Overall, the differences between the two regimens were unexpectedly small.\n Despite the small differences, the loading model is easier to apply, requires fewer dose adjustments, is better tolerated with less side effects, and reduces the likelihood of clinical error.", "The effect of terbutaline, a \"selective\" beta2-receptor stimulator, was compared with that of placebo in 30 patients in premature labor. Treatment consisted of an intravenous infusion for at least 8 hours, and then of subcutaneous injections four times daily for 3 days together with peroral treatment, which was continued until the end of week 36 of pregnancy. In 12 of 15 terbutaline-treated patients (80 per cent) premature labor was arrested beyond the treatment period, compared with three of 15 in the placebo group (20 per cent). This difference is statistically significant (p less than 0.01). No serious side effects were observed. During infusion, there was an increase in maternal heart rate. This was more pronounced in the terbutaline group (30 per cent) than in the placebo group (9 per cent). There were no adverse effects on blood pressure, but fetal tachycardia was observed more frequently in the terbutaline than in the placebo group. The results suggest that terbutaline is a safe, potent, and well-tolerated inhibitor of premature labor.", "140 patients with a threatening premature birth at the greater than or equal to 24-less than 37 week of gestation were in this study randomly treated with hexoprenalin or salbutamol. In 77% in the hexoprenalin and in 74% in the salbutamol group the weight of the newborn was greater than or equal to 2500 g. In 66% in both study groups the birth occurred after the completed 37 weeks of gestation. During infusion of hexoprenalin tachycardia in mothers occurred statistically highly significantly less than during salbutamol. 11% of the mothers in the hexoprenalin group had side-effects during infusion compared to 30% in the salbutamol group. The correlation between the tocolysis-index (Baumgarten) and the prolongation-index (Richter) given by the regression lines facilitates in some measure the comparison of different tocolytic drugs concerning its tocolytic effect.", "nan", "Magnesium sulfate has been recommended as a safe and effective agent for inhibiting preterm labor. Its reported adequacy as a tocolytic agent, however, has not been substantiated by randomized, controlled trials. To assess the efficacy of magnesium sulfate, we initiated a prospective, randomized study comparing the capabilities of magnesium sulfate, terbutaline and a placebo (5% dextrose in lactated Ringer's solution) for labor inhibition. The study population consisted of 54 patients between 26 and 34 weeks of gestation and in preterm labor. The diagnosis of labor was made if, following hydration, persistent uterine contractions occurred at a frequency of at least three in a ten-minute period and cervical examination suggested active labor. Success was defined as postponement of delivery for at least 48 hours after initiation of therapy. Despite a trend toward increased efficacy in the terbutaline group there were no significant differences between the three treatment groups with regard to capability of delaying delivery at least 48 hours. Also, there were no significant differences between the groups with regard to gestational age at delivery, birth weight and neonatal survival. The fact that delivery occurred in less than 48 hours of approximately one-half the patients under the best of circumstances emphasizes the need for more effective techniques for the inhibition of preterm labor and the need for a better understanding of the mechanisms involved in the initiation of preterm labor.", "106 women between 24 and 33 weeks' gestation and in preterm labour, rigidly defined to include cervical dilatation plus regular uterine contractions, were randomly allocated to receive either intravenous ritodrine hydrochloride or no tocolytic treatment. Ritodrine treatment significantly delayed delivery for 24 hours or less but did not significantly modify the ultimate perinatal consequences of preterm labour.", "One hundred women in preterm labor were randomly treated with ritodrine or terbutaline in a double-blind fashion. The drugs were comparably effective during intravenous therapy but, in women with intact membranes, an oral dose of terbutaline, 30 mg daily, was significantly more effective than ritodrine, 120 mg daily, in preventing recurrent labor during a 5-day course of oral therapy (one of 19 versus 12 of 23, p less than 0.001). In women with intact membranes, pregnancy was prolonged 40 +/- 25 days (mean +/- SD) in women receiving terbutaline orally and only 22 +/- 24 days in women receiving ritodrine orally (p less than 0.01). In women with intact membranes, a heart rate greater than or equal to 130 bpm occurred in in a higher proportion of women receiving intravenous treatment with ritodrine than among those receiving terbutaline (20 of 31 versus 8 of 27, p less than 0.05). Terbutaline-treated women, however, were significantly more likely to have a serum glucose level in excess of 140 mg/dl than were women treated with ritodrine (13 of 26 versus 6 of 29, p less than 0.05). Side effects commonly observed during intravenous therapy included nausea (22%), chest pain (15%), and shortness of breath (15%). Side effects were significantly (p less than 0.025) more likely to occur during periods when the infusion rate was being increased rather than during periods when the infusion rate was constant.", "nan" ]

[ "19577277", "8088611", "11146078", "11181662", "8960474", "16394300", "10343192", "3760480" ]

[ "Importance of delivered cycles and nomogram for intraperitoneal chemotherapy in ovarian cancer.", "A comparison of intravenous versus intraperitoneal chemotherapy for the initial treatment of ovarian cancer.", "Intraperitoneal cisplatin-based chemotherapy vs. intravenous cisplatin-based chemotherapy for stage III optimally cytoreduced epithelial ovarian cancer.", "Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group.", "Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer.", "Intraperitoneal cisplatin and paclitaxel in ovarian cancer.", "A comparative study of intraperitoneal carboplatin versus intravenous carboplatin with intravenous cyclophosphamide in both arms as initial chemotherapy for stage III ovarian cancer.", "[Polychemotherapy of ovarian cancer via combined intravenous and intraperitoneal routes. Technic and preliminary results]." ]

[ "Intraperitoneal (IP) chemotherapy has gained enthusiasm in the treatment of ovarian cancer. Despite having a better survival advantage than intravenous (IV) chemotherapy, IP chemotherapy still poses significant morbidity and complications. Identifying the subset of patients who could best benefit from IP chemotherapy, and those who would least benefit from this treatment, thus avoiding potential complications, is critical.\n Between January 2001 and December 2007, 367 patients with stage III epithelial ovarian cancer underwent randomized trial for IP/IV chemotherapy were recruited to construct a nomogram, which is a graphical representation of Cox proportional hazards model adopting six weighted risk factors including age, CA125, IP/IV delivery, stage, histology, and upper abdominal metastases. The nomogram was internally validated for discrimination and calibration. The concordance index was used for quantifying the predictive ability of overall survival with bootstrapping to correct for bias.\n The cycles of completed IP chemotherapy had an impact on overall survival (> or =5 vs. < or =4 cycles, P=0.02). A nomogram for predicting median survival and 5-year survival probability was constructed with a concordance index of 0.72. Upper abdominal tumor metastases (P<0.001) and colon resection (P=0.02) predicted increased chances for early discontinuation of IP chemotherapy.\n At least five IP cycles are needed to achieve better survival. Nomogram can help to identify the subset of patients who can least benefit from IP chemotherapy, thus avoiding potential IP complications and help to facilitate discussion between patient and physician, risk stratification, and help to guide clinical care.", "A phase III study was conducted comparing intraperitoneal (ip) versus intravenous (iv) cisplatin-based therapy for patients with newly diagnosed ovarian cancer to determine if the pharmacologic advantage of ip delivery could be translated into an improved response and survival rate. Twenty-nine patients were randomized to receive six cycles of ip cisplatin 200 mg/m2 plus ip etoposide 350 mg/m2 with iv thiosulfate protection given every 4 weeks; thirty-three patients were randomized to receive six cycles of iv cisplatin 100 mg/m2 plus iv cyclophosphamide 600 mg/m2 administered every 3 weeks. Patients were stratified by stage (IIC-IV) and size of residual disease (> or < or = 1 cm). The study was conducted in a community-wide setting. The complete response in evaluable patients was 48% in the ip group and 52% in the iv group. The surgical complete response rate for all patients on study, underestimated because not all patients in complete clinical remission had a second-look laparotomy, was 31% in the ip group and 33% in the iv group. There was no difference in the response rates between the treatment arms as a function of residual disease < or = or > 1 cm. With a median follow-up of 46 months (range 21-70 months) there is no difference in response duration or survival. Both regimens were well tolerated with comparable hematologic and nonhematologic toxicity.", "To compare the survival between intraperitoneal cisplatin-based chemotherapy (IPCT) and intravenous cisplatin-based chemotherapy (IVCT) in stage III epithelial ovarian cancer with minimal residual disease (<1 cm) after primary debulking surgery.\n One hundred and thirty-two patients with stage III epithelial ovarian cancer after optimal primary debulking surgery with minimal residual disease between April 1990 and March 1995 were entered into a randomized clinical trial in which IPCT or IVCT was administered at 3-week intervals. Patients in the IPCT arm received cisplatin-based (100 mg/m(2)) intraperitoneal chemotherapy. Patients in the IVCT arm received cisplatin-based (50 mg/m(2)) intravenous chemotherapy. The tumor response was assessed every 3 months. The hematological toxicity using the South West Oncology Group (SWOG) toxicity criteria was assessed. Catheter complications associated with intraperitoneal chemotherapy were also analyzed.\n The estimated median survival in the IPCT group was 43 months (95% confidence interval, 34-54) and IVCT group was 48 months (95% confidence interval, 37-59). The hazard ratio of death was not statistically significant between IPCT and IVCT (hazard ratio, 1.13; 95% CI, 0.69-1.86; P=0.317). The frequencies of hematological toxic effects were significantly lower in the IPCT group than in the IVCT group.\n Intravenous and intraperitoneal chemotherapy are associated with equivalent survival in patients with minimal residual stage III epithelial ovarian cancer after optimal cytoreductive surgery.", "To compare the progression-free and overall survival in small-volume residual ovarian cancer after treatment with intravenous (IV) cisplatin and paclitaxel or an experimental regimen of IV carboplatin followed by IV paclitaxel and intraperitoneal cisplatin.\n Patients were randomized to receive either IV paclitaxel 135 mg/m(2) over 24 hours followed by IV cisplatin 75 mg/m(2) every 3 weeks for six courses or IV carboplatin (area under curve 9) every 28 days for two courses, then IV paclitaxel 135 mg/m(2) over 24 hours followed by intraperitoneal (IP) cisplatin 100 mg/m(2) every 3 weeks for six courses.\n Of the 523 patients who entered this trial, 462 were determined to be assessable, with prognostic factors well balanced between the treatments. Neutropenia, thrombocytopenia, and gastrointestinal and metabolic toxicities were greater in the experimental arm. As a result, 18% of the patients received < or = two courses of IP therapy. Progression-free survival was superior for patients randomized to the experimental treatment arm (median, 28 v 22 months; relative risk, 0.78; log-rank P =.01, one-tail). There was a borderline improvement in overall survival associated with this regimen (median, 63 v 52 months; relative risk, 0.81; P =.05, one-tail).\n An experimental regimen including moderately high-dose IV carboplatin followed by IP paclitaxel and IV cisplatin yielded a significant improvement in progression-free survival when compared with a standard regimen of IV cisplatin and paclitaxel. Because the improvement in overall survival was of borderline statistical significance and toxicity was greater, the experimental arm is not recommended for routine use. However, the results provide direction for further clinical investigation in small-volume ovarian cancer.", "Intravenous platinum-based chemotherapy is the standard primary therapy for advanced ovarian cancer. We conducted a phase 3 trial to compare the effects of intraperitoneal and intravenous cisplatin on the survival of women with previously untreated, stage III, epithelial ovarian cancer.\n The patients underwent an initial exploratory laparotomy and resection of all tumor masses larger than 2 cm. Within four weeks after surgery, six courses of intravenous cyclophosphamide (600 mg per square meter of body-surface area per course) plus either intraperitoneal cisplatin (100 mg per square meter) or intravenous cisplatin (100 mg per square meter) were administered at three-week intervals.\n Of 654 randomized patients, 546 were eligible for the study. The estimated median survival was significantly longer in the group receiving intraperitoneal cisplatin (49 months; 95 percent confidence interval, 42 to 56) than in the group receiving intravenous cisplatin (41 months; 95 percent confidence interval, 34 to 47). The risk of death was lower in the intraperitoneal group than in the intravenous group (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Moderate-to-severe tinnitus, clinical hearing loss, and neuromuscular toxic effects were significantly more frequent in the intravenous group.\n As compared with intravenous cisplatin, intraperitoneal cisplatin significantly improves survival and has significantly fewer toxic effects in patients with stage III ovarian cancer and residual tumor masses of 2 cm or less.", "Standard chemotherapy for newly diagnosed ovarian cancer is a platinum-taxane combination. The Gynecologic Oncology Group conducted a randomized, phase 3 trial that compared intravenous paclitaxel plus cisplatin with intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel in patients with stage III ovarian cancer.\n We randomly assigned patients with stage III ovarian carcinoma or primary peritoneal carcinoma with no residual mass greater than 1.0 cm to receive 135 mg of intravenous paclitaxel per square meter of body-surface area over a 24-hour period followed by either 75 mg of intravenous cisplatin per square meter on day 2 (intravenous-therapy group) or 100 mg of intraperitoneal cisplatin per square meter on day 2 and 60 mg of intraperitoneal paclitaxel per square meter on day 8 (intraperitoneal-therapy group). Treatment was given every three weeks for six cycles. Quality of life was assessed.\n Of 429 patients who underwent randomization, 415 were eligible. Grade 3 and 4 pain, fatigue, and hematologic, gastrointestinal, metabolic, and neurologic toxic effects were more common in the intraperitoneal-therapy group than in the intravenous-therapy group (P< or =0.001). Only 42 percent of the patients in the intraperitoneal-therapy group completed six cycles of the assigned therapy, but the median duration of progression-free survival in the intravenous-therapy and intraperitoneal-therapy groups was 18.3 and 23.8 months, respectively (P=0.05 by the log-rank test). The median duration of overall survival in the intravenous-therapy and intraperitoneal-therapy groups was 49.7 and 65.6 months, respectively (P=0.03 by the log-rank test). Quality of life was significantly worse in the intraperitoneal-therapy group before cycle 4 and three to six weeks after treatment but not one year after treatment.\n As compared with intravenous paclitaxel plus cisplatin, intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel improves survival in patients with optimally debulked stage III ovarian cancer.\n Copyright 2006 Massachusetts Medical Society.", "Cisplatin (C) or carboplatin (CBP) plus cyclophosphamide (CTX) was until recently considered standard chemotherapy for advanced ovarian cancer (OC). Attempts to maximize platinum and its analog activity against OC include its administration directly into the peritoneal cavity. In the past we have shown that intraperitoneal (IP) CBP administration is a safe and effective treatment for OC [Polyzos et al: Proc Am Assoc Cancer Res 1990;31: 1120]. In the present study we aimed to compare the effectiveness and toxicity of CBP administration either intravenously (IV) or IP plus CTX IV. Since 1990, 90 evaluable patients with stage III OC were prospectively randomized to receive CBP 350 mg/m2 IV or IP plus CTX 600 mg/m2 IV (in both groups) every 3-4 weeks for six courses. The randomization incorporated stratification according to performance status and the amount of residual tumor (maximum diameter </=2 or >2 cm). Clinical assessment was performed with abdominal CT and serum CA-125. Responses were observed in 33/46 = 72% (95/CI 56.5-84.0) of the IV group and in 33/44 = 75% (95/CI 59.7-86.8) of the IP group with 48 and 45% clinical complete responses, respectively. Times to progression were 19 months (8-62+) for the IV group and 18 (6-72+) for the IP group. Median survivals were: 25 months (6-80+) and 26 months (6-72+), respectively. Significantly more patients in the IV group than in the IP group had grade 3 or higher leukopenia (p < 0. 01) and grade 3 thrombocytopenia (p < 0.09). Morbidity due to infectious complications in the IP group was minimal. It seems that IP CBP is equally effective to IV administration in terms of response and survival with less myelotoxicity. The favorable results on survival demonstrated in studies with IP C administration in patients with small volume disease [Alberts et al: N Engl J Med 1996;335:1950-1965] could not be repeated in the present study applying CBP in patients with variable tumor size and a relatively small number of patients. The likelihood that patients with large volume disease would benefit from a regional approach compared to systemic administration is small and this explains the inability to detect a difference between the two arms.", "20 patients with F.I.G.O. stages III ovarian cancer were entered into a randomised trial between January 1980 and March 1984. After a surgical resection as complete as possible, 10 of these patients received an intravenous chemotherapy with Adriamycin, Vincaleucoblastin Bleomycin, Fluorouracil and Ifosfamid monthly for 10 months. The other 10 patients received the same combined chemotherapy but by a double route: Intravenously and intraperitoneally. The results were judged at \"second look surgery\". 1 Of the 10 patients who were treated intravenously, 2 who had had a complete surgical resection had no recurrence. Of the remaining 8 patients who had had an incomplete resection, 4 still had residual lesions that could not be removed completely." ]

[ "9349677", "11570931", "15839735", "11900758", "17426347" ]

[ "Rhythmic facilitation of gait training in hemiparetic stroke rehabilitation.", "The effects of live, taped, and no music on people experiencing posttraumatic amnesia.", "The effects of music on pain perception of stroke patients during upper extremity joint exercises.", "Kinematic optimization of spatiotemporal patterns in paretic arm training with stroke patients.", "Rhythmic auditory stimulation improves gait more than NDT/Bobath training in near-ambulatory patients early poststroke: a single-blind, randomized trial." ]

[ "Experimental and control groups of 10 hemiparetic stroke patients each underwent a 6 week, twice daily gait training program. The control group participated in a conventional physical therapy gait program. The experimental group trained in the same basic program with the addition of rhythmic auditory stimulation (RAS). Patients entered the study as soon as they could complete 5 strides with hand-held assistance. The training program had to be completed within 3 months of the patients' stroke. In the experimental group RAS was used as a timekeeper to synchronize step patterns and gradually entrain higher stride frequencies. Study groups were equated by gender, lesion site, and age. Motor function was assessed at pretest using Barthel, Fugl-Meyer, and Berg Scales. Walking patterns were assessed during pre- and post-test without RAS present. Pre- vs post-test measures revealed a statistically significant (P<0.05) increase in velocity (164% vs 107%), stride length (88% vs 34%), and reduction in EMG amplitude variability of the gastrocnemius muscle (69% vs 33%) for the RAS-training group compared to the control group. The difference in stride symmetry improvement (32% in the RAS-group vs 16% in the control group) was statistically not significant. The data offer evidence that RAS is an efficient tool to enhance efforts in gait rehabilitation with acute stroke patients.", "This study compared the effects of live, taped, and no music, on agitation and orientation levels of people experiencing posttraumatic amnesia (PTA). Participants (N = 22) were exposed to all 3 conditions, twice over 6 consecutive days. Songs used in the live and taped music conditions were identical and were selected based on participants' own preferred music. Pre and posttesting was conducted for each condition using the Agitated Behavior Scale (Corrigan, 1989) and the Westmead PTA Scale (Shores, Marosszeky, Sandanam, Batchelor, 1986). Participants' memory for the music used was also tested and compared with their memory for pictorial material presented in the Westmead PTA Scale. Results indicate that music significantly reduced agitation (p <.0001) and enhanced orientation (p <.001) however, the difference between live and taped music was not significant (p =.7). The mean number of pictures in the Westmead PTA scale recalled was 0.84 and the mean number of music selections recalled was 1.22 but this difference was not significant (p =.7). However, the trend suggests that music selections are more easily encoded in memory and then retrieved on request, than that of pictures. Analysis of responses in a follow-up assessment questionnaire showed that 77% of participants recalled the music program while in PTA, indicating that it reached the memory threshold. Sixty-four percent recalled the live music and 55% recalled the taped music condition however this difference was not significant (p =.7). Results suggest that music therapy programs have an important role to play in the management of people in PTA.", "The purpose of this study was to determine the effects of music therapy on pain perception of stroke patients during upper extremity joint exercises. Ten stroke patients (1 male and 9 females) ranging in age from 61 to 73 participated in the study. Music conditions used in the study consisted of: (a) song, (b) karaoke accompaniment (same music to condition A except singers' voices), and (c) no music. Exercise movements in this study included hand, wrist, and shoulder joints. During the 8-week period music therapy sessions, subjects repeated 3 conditions according to the randomized orders and subjects rated their perceived pain on a scale immediately after each condition. The General Linear Model (GLM) Repeated Measures ANOVA revealed that there were no significant differences in pain rating across the three music conditions. However, positive affects and verbal responses, while performing upper extremity exercises with both music and karaoke accompaniment music, were observed using video observations.", "The effect of rhythmic cueing on spatiotemporal control of sequential reaching movements of the paretic arm was studied in 21 hemispheric stroke patients. Reaching movements were studied with and without rhythmic metronome cuing in a counterbalanced design. Metronome frequencies were entrained to the naturally selected frequency of the patient. Results indicate statistically significant (P<0.05) improvements of spatiotemporal arm control during rhythmic entrainment. Variability of timing and reaching trajectories were reduced significantly. Time series analysis of sequential movement repetitions showed an immediate reduction in variability of arm kinematics during rhythmic entrainment within the first two to three repetitions of each trial. Rhythm also produced significant increases in angle ranges of elbow motion (P<0.05). Analysis of acceleration and velocity profiles of the wrist joint showed significant kinematic smoothing during rhythmic cuing. The link between rhythmic sensory timing and spatiotemporal motor control was investigated using a mathematical optimization model with minimization of peak acceleration as criterion. Rhythmically cued acceleration profiles fit the predicted model data significantly closer (P<0.01) than the self-paced profiles. Since velocity and acceleration are mathematical derivatives of position-time trajectories, the model data suggest that enhanced timing precision via temporal phase and period coupling of the motor pattern to the rhythmic time timekeeper enhances the brain's computational ability to optimally scale movement parameters across time.", "The effectiveness of 2 different types of gait training in stroke rehabilitation, rhythmic auditory stimulation (RAS) versus neurodevelopmental therapy (NDT)/Bobath- based training, was compared in 2 groups of hemiparetic stroke patients over a 3-week period of daily training (RAS group, n = 43; NDT/Bobath group =35).\n Mean entry date into the study was 21.3 days poststroke for the RAS group and 22.3 days for the control group. Patients entered the study as soon as they were able to complete 5 stride cycles with handheld assistance. Patients were closely equated by age, gender, and lesion site. Motor function in both groups was pre-assessed by the Barthel Index and the Fugl-Meyer Scales.\n Pre- to posttest measures showed a significant improvement in the RAS group for velocity (P = .006), stride length (P = .0001), cadence (P = .0001) and symmetry (P = .0049) over the NDT/Bobath group. Effect sizes for RAS over NDT/Bobath training were 13.1 m/min for velocity, 0.18 m for stride length, and 19 steps/min for cadence.\n The data show that after 3 weeks of gait training, RAS is an effective therapeutic method to enhance gait training in hemiparetic stroke rehabilitation. Gains were significantly higher for RAS compared to NDT/Bobath training." ]

[ "12020141", "16696748", "8078528", "11563205", "12521968", "16183652", "12588572", "9596598", "12588573", "12130606", "15173480", "11772188", "17397425", "17510847", "18662214", "10195971", "10591231", "19392952", "11953541", "17416878", "15805440", "16203842", "10023893", "15604156", "11890582", "1392755", "18808597", "11039967" ]

[ "Fall and injury prevention in older people living in residential care facilities. A cluster randomized trial.", "A randomized trial of a multicomponent home intervention to reduce functional difficulties in older adults.", "A multifactorial intervention to reduce the risk of falling among elderly people living in the community.", "A randomized controlled trial of a community-based consultation service to prevent falls.", "Multifactorial intervention after a fall in older people with cognitive impairment and dementia presenting to the accident and emergency department: randomised controlled trial.", "Randomised controlled trial of prevention of falls in people aged > or =75 with severe visual impairment: the VIP trial.", "Preventing falls in community-dwelling frail older people using a home intervention team (HIT): results from the randomized Falls-HIT trial.", "A randomised controlled trial of general practitioner safety advice for families with children under 5 years.", "Effectiveness of a multifaceted intervention on falls in nursing home residents.", "Randomised factorial trial of falls prevention among older people living in their own homes.", "A randomized, clinical trial of a home safety intervention based in an emergency department setting.", "Effects of improved access to safety counseling, products, and home visits on parents' safety practices: results of a randomized trial.", "Kenosha County falls prevention study: a randomized, controlled trial of an intermediate-intensity, community-based multifactorial falls intervention.", "A randomized trial to assess the effectiveness of an infant home safety programme.", "Lack of effectiveness of a multidisciplinary fall-prevention program in elderly people at risk: a randomized, controlled trial.", "Preventing injuries in children: cluster randomised controlled trial in primary care.", "Home visits by an occupational therapist for assessment and modification of environmental hazards: a randomized trial of falls prevention.", "Effect of a risk-based multifactorial fall prevention program on the incidence of falls.", "Benefits of home visits for falls and autonomy in the elderly: a randomized trial study.", "Studying injury prevention: practices, problems, and pitfalls in implementation.", "Long term effects of a home visit to prevent childhood injury: three year follow up of a randomized trial.", "Reaching an underserved population with a randomly assigned home safety intervention.", "Prevention of falls in the elderly trial (PROFET): a randomised controlled trial.", "Providing child safety equipment to prevent injuries: randomised controlled trial.", "Preventing falls in older people: outcome evaluation of a randomized controlled trial.", "Can health visitors prevent fractures in elderly people?", "Effectiveness of a falls-and-fracture nurse coordinator to reduce falls: a randomized, controlled trial of at-risk older adults.", "Effects of a programme of multifactorial home visits on falls and mobility impairments in elderly people at risk: randomised controlled trial." ]

[ "Falls and resulting injuries are particularly common in older people living in residential care facilities, but knowledge about the prevention of falls is limited.\n To investigate whether a multifactorial intervention program would reduce falls and fall-related injuries.\n A cluster randomized, controlled, nonblinded trial.\n 9 residential care facilities located in a northern Swedish city.\n 439 residents 65 years of age or older.\n An 11-week multidisciplinary program that included both general and resident-specific, tailored strategies. The strategies comprised educating staff, modifying the environment, implementing exercise programs, supplying and repairing aids, reviewing drug regimens, providing free hip protectors, having post-fall problem-solving conferences, and guiding staff.\n The primary outcomes were the number of residents sustaining a fall, the number of falls, and the time to occurrence of the first fall. A secondary outcome was the number of injuries resulting from falls.\n During the 34-week follow-up period, 82 residents (44%) in the intervention program sustained a fall compared with 109 residents (56%) in the control group (risk ratio, 0.78 [95% CI, 0.64 to 0.96]). The adjusted odds ratio was 0.49 (CI, 0.37 to 0.65), and the adjusted incidence rate ratio of falls was 0.60 (CI, 0.50 to 0.73). Each of 3 residents in the intervention group and 12 in the control group had 1 femoral fracture (adjusted odds ratio, 0.23 [CI, 0.06 to 0.94]). Clustering was considered in all regression models.\n An interdisciplinary and multifactorial prevention program targeting residents, staff, and the environment may reduce falls and femoral fractures.", "To test the efficacy of a multicomponent intervention to reduce functional difficulties, fear of falling, and home hazards and enhance self-efficacy and adaptive coping in older adults with chronic conditions.\n A prospective, two-group, randomized trial. Participants were randomized to a treatment group or no-treatment group.\n Urban community-living older people.\n Three hundred nineteen community-living adults aged 70 and older who reported difficulty with one or more activities of daily living.\n Occupational and physical therapy sessions involving home modifications and training in their use; instruction in strategies of problem-solving, energy conservation, safe performance, and fall recovery techniques; and balance and muscle strength training.\n Outcome measures included self-rated functional difficulties with ambulation, instrumental activities of daily living, activities of daily living, fear of falling, confidence performing daily tasks, and use of adaptive strategies. Observations of home hazards were also conducted.\n At 6 months, intervention participants had less difficulty than controls with instrumental activities of daily living (P=.04, 95% confidence interval (CI)=-0.28-0.00) and activities of daily living (P=.03, 95% CI=-0.24 to -0.01), with largest reductions in bathing (P=.02, 95% CI=-0.52 to -0.06) and toileting (P=.049, 95% CI=-0.35-0.00). They also had greater self-efficacy (P=.03, 95% CI=0.02-0.27), less fear of falling (P=.001, 95% CI=0.26-0.96), fewer home hazards (P=.05, 95% CI=-3.06-0.00), and greater use of adaptive strategies (P=.009, 95% CI=0.03-0.22). Benefits were sustained at 12 months for most outcomes.\n A multicomponent intervention targeting modifiable environmental and behavioral factors results in life quality improvements in community-dwelling older people who had functional difficulties, with most benefits retained over a year.", "Since falling is associated with serious morbidity among elderly people, we investigated whether the risk of falling could be reduced by modifying known risk factors.\n We studied 301 men and women living in the community who were at least 70 years of age and who had at least one of the following risk factors for falling: postural hypotension; use of sedatives; use of at least four prescription medications; and impairment in arm or leg strength or range of motion, balance, ability to move safely from bed to chair or to the bathtub or toilet (transfer skills), or gait. These subjects were given either a combination of adjustment in their medications, behavioral instructions, and exercise programs aimed at modifying their risk factors (intervention group, 153 subjects) or usual health care plus social visits (control group, 148 subjects).\n During one year of follow-up, 35 percent of the intervention group fell, as compared with 47 percent of the control group (P = 0.04). The adjusted incidence-rate ratio for falling in the intervention group as compared with the control group was 0.69 (95 percent confidence interval, 0.52 to 0.90). Among the subjects who had a particular risk factor at base line, a smaller percentage of those in the intervention group than of those in the control group still had the risk factor at the time of reassessment, as follows: at least four prescription medications, 63 percent versus 86 percent, P = 0.009; balance impairment, 21 percent versus 46 percent, P = 0.001; impairment in toilet-transfer skills, 49 percent versus 65 percent, P = 0.05; and gait impairment, 45 percent versus 62 percent, P = 0.07.\n The multiple-risk-factor intervention strategy resulted in a significant reduction in the risk of falling among elderly persons in the community. In addition, the proportion of persons who had the targeted risk factors for falling was reduced in the intervention group, as compared with the control group. Thus, risk-factor modification may partially explain the reduction in the risk of falling.", "Multifaceted programs that combine assessment with interventions have been shown to reduce subsequent falls in some clinical trials. We tested this approach to see whether it would be effective if offered as a consultation service using existing health care resources.\n The subjects of this randomized controlled trial had to be aged 65 years or more and had to have fallen within the previous 3 months. They were randomly assigned to receive either usual care or the intervention, which consisted of in-home assessment in conjunction with the development of an individualized treatment plan, including an exercise program for those deemed likely to benefit. The primary outcomes were the proportion of participants who fell and the rate of falling during the following year. Visits to the emergency department and admissions to hospital were secondary outcomes.\n One hundred and sixty-three subjects were randomly assigned to either the control or the intervention group, and 152 provided data about their falls. There were no significant differences between the control and intervention groups in the cumulative number of falls (311 v. 241, p = 0.34), having one or more falls (79.2% v. 72.0%, p = 0.30) or in the mean number of falls (4.0 v. 3.2, p = 0.43). Analysis of secondary outcomes (health care use) also showed no significant differences between the intervention group and the control group. In the Cox regression analysis, there was no significant difference between the groups in the proportion of subjects having one or more falls (p = 0.55), but there was a significantly (p < 0.001) longer time between falls in the intervention group. In a post hoc subgroup analysis, subjects with more than 2 falls in the 3 months preceding study entry who had been assigned to the intervention group were less likely to fall (p = 0.046) and had a significantly longer time between falls (p < 0.001), when compared with the group who received usual care.\n The intervention did not decrease significantly the cumulative number of falls, the likelihood of participants having at least one fall over the next year or the mean number of falls. It did increase significantly the time between falls in a survival analysis when age, sex and history of falling were used as covariates.", "To determine the effectiveness of multifactorial intervention after a fall in older patients with cognitive impairment and dementia attending the accident and emergency department.\n Randomised controlled trial.\n 274 cognitively impaired older people (aged 65 or over) presenting to the accident and emergency department after a fall: 130 were randomised to assessment and intervention and 144 were randomised to assessment followed by conventional care (control group).\n Two accident and emergency departments, Newcastle upon Tyne.\n Primary outcome was number of participants who fell in year after intervention. Secondary outcomes were number of falls (corrected for diary returns), time to first fall, injury rates, fall related attendances at accident and emergency department, fall related hospital admissions, and mortality.\n Intention to treat analysis showed no significant difference between intervention and control groups in proportion of patients who fell during 1 year's follow up (74% (96/130) and 80% (115/144), relative risk ratio 0.92, 95% confidence interval 0.81 to 1.05). No significant differences were found between groups for secondary outcome measures.\n Multifactorial intervention was not effective in preventing falls in older people with cognitive impairment and dementia presenting to the accident and emergency department after a fall.", "To assess the efficacy and cost effectiveness of a home safety programme and a home exercise programme to reduce falls and injuries in older people with low vision.\n Randomised controlled trial.\n Dunedin and Auckland, New Zealand.\n 391 women and men aged > or =75 with visual acuity of 6/24 or worse who were living in the community; 92% (361 of 391) completed one year of follow-up.\n Participants received a home safety assessment and modification programme delivered by an occupational therapist (n = 100), an exercise programme prescribed at home by a physiotherapist plus vitamin D supplementation (n = 97), both interventions (n = 98), or social visits (n = 96).\n Numbers of falls and injuries resulting from falls, costs of implementing the home safety programme.\n Fewer falls occurred in the group randomised to the home safety programme but not in the exercise programme (incidence rate ratios 0.59 (95% confidence interval 0.42 to 0.83) and 1.15 (0.82 to 1.61), respectively). However, within the exercise programme, stricter adherence was associated with fewer falls (P = 0.001). A conservative analysis showed neither intervention was effective in reducing injuries from falls. Delivering the home safety programme cost NZ650 dollars (234 pounds sterling, 344 euros, US432 dollars) (at 2004 prices) per fall prevented.\n The home safety programme reduced falls and was more cost effective than an exercise programme in this group of elderly people with poor vision. The Otago exercise programme with vitamin D supplementation was not effective in reducing falls or injuries in this group, possibly due to low levels of adherence. Trial registration number ISRCTN15342873.", "To evaluate the effect of an intervention by a multidisciplinary team to reduce falls in older people's homes.\n Randomized, controlled trial with follow-up of subjects for 1 year.\n University-affiliated geriatric hospital and older patients' homes.\n Three hundred sixty subjects (mean age +/- standard deviation = 81.5 +/- 6.4) admitted from home to a geriatric hospital and showing functional decline, especially in mobility.\n The participants were randomly assigned to receive a comprehensive geriatric assessment followed by a diagnostic home visit and home intervention or a comprehensive geriatric assessment with recommendations and usual care at home. The home intervention included a diagnostic home visit, assessing the home for environmental hazards, advice about possible changes, offer of facilities for any necessary home modifications, and training in the use of technical and mobility aids. An additional home visit was made after 3 months to reinforce the recommendations. After 12 months of follow-up, a home visit was made to all study participants.\n Number of falls, type of recommended home modifications, and compliance with recommendations.\n After 1 year, there were 163 falls in the intervention group and 204 falls in the control group. The intervention group had 31% fewer falls than the control group (incidence rate ratio (IRR) = 0.69, 95% confidence interval (CI) = 0.51-0.97). The intervention was most effective in a subgroup of participants who reported having had two or more falls during the year before recruitment into the study. In this subgroup, the proportion of frequent fallers and the rate of falls was significantly reduced for the intervention group compared with the control group (21 vs 36 subjects with recurrent falls, P =.009; IRR = 0.63, 95% CI = 0.43-0.94). The compliance rate varied with the type of change recommended from 83% to 33% after 12 months of follow-up.\n Home intervention based on home visits to assess the home for environmental hazards, providing information about possible changes, facilitating any necessary modifications, and training in the use of technical and mobility aids was effective in a selected group of frail older subjects with a history of recurrent falling.", "To assess effectiveness of general practitioner advice about child safety, and provision of low cost safety equipment to low income families, on use of safety equipment and safe practices at home.\n Randomised, unblinded, controlled trial with initial assessment and six week follow up by telephone survey. Twenty families from intervention and control groups were randomly selected for a home visit to assess validity of responses to second survey.\n A general practice in Nottingham.\n 98% (165/169) of families with children aged under 5 years registered with the practice.\n General practitioner safety advice plus, for families receiving means tested state benefits, access to safety equipment at low cost. Control families received usual care.\n Possession and use of safety equipment and safe practices at home.\n Before intervention, the two groups differed only in possession of fireguards. After intervention, significantly more families in intervention group used fireguards (relative risk 1.89, 95% confidence interval 1.18 to 2.94), smoke alarms (1.14, 1.04 to 1.25), socket covers (1.27, 1.10 to 1.48), locks on cupboards for storing cleaning materials (1.38, 1.02 to 1.88), and door slam devices (3.60, 2.17 to 5.97). Also, significantly more families in intervention group showed very safe practice in storage of sharp objects (1.98, 1.38 to 2.83), storage of medicines (1.15, 1.03 to 1.28), window safety (1.30, 1.06 to 1.58), fireplace safety (1.84, 1.34 to 2.54), socket safety (1.77, 1.37 to 2.28), smoke alarm safety (1.11, 1.01 to 1.22), and door slam safety (7.00, 3.15 to 15.6). Stratifying results by receipt of state benefits showed that intervention was at least as effective in families receiving benefits as others.\n General practitioner advice, coupled with access to low cost equipment for low income families, increased use of safety equipment and other safe practices. These findings are encouraging for provision of injury prevention in primary care.", "To evaluate the effectiveness of a multifaceted, nonpharmaceutical intervention on incidence of falls and fallers.\n Prospective, cluster-randomized, controlled 12-month trial.\n Six community nursing homes in Germany.\n Long-stay residents (n = 981) aged 60 and older; mean age 85; 79% female.\n Staff and resident education on fall prevention, advice on environmental adaptations, progressive balance and resistance training, and hip protectors.\n Falls, fallers, and fractures.\n The incidence density rate of falls per 1,000 resident years (RY) was 2,558 for the control group (CG) and 1,399 for the intervention group (IG) (relative risk (RR) = 0.55, 95% confidence interval (CI) = 0.41-0.73). Two hundred forty-seven (52.3%) fallers were detected in the CG and 188 (36.9%) in the IG (RR = 0.75, 95% CI = 0.57-0.98). The incidence density rate of frequent fallers (>2/year) was 115 (24.4%) for the CG and 66 (13.0%) for the IG (RR = 0.56, 95% CI = 0.35-0.89). The incidence density rate of hip fractures per 1,000 RY was 39 for the CG and 43 for the IG (RR = 1.11, 95% CI = 0.49-2.51). Other fractures were diagnosed with an incidence density rate of 52 per 1,000 RY for CG and 41 per 1,000 RY for IG (RR = 0.78, 95% CI = 0.57-1.07).\n The incidence density rate of falls and fallers differed considerably between the control and intervention groups. The study was underpowered to demonstrate a significant difference of hip or nonhip fractures. Because of a low fracture rate in both groups, the investigation of fracture rates would have required a larger sample size to detect an effect of the intervention.", "To test the effectiveness of, and explore interactions between, three interventions to prevent falls among older people.\n A randomised controlled trial with a full factorial design.\n Urban community in Melbourne, Australia.\n 1090 aged 70 years and over and living at home. Most were Australian born and rated their health as good to excellent; just over half lived alone.\n Three interventions (group based exercise, home hazard management, and vision improvement) delivered to eight groups defined by the presence or absence of each intervention.\n Time to first fall ascertained by an 18 month falls calendar and analysed with survival analysis techniques. Changes to targeted risk factors were assessed by using measures of quadriceps strength, balance, vision, and number of hazards in the home.\n The rate ratio for exercise was 0.82 (95% confidence interval 0.70 to 0.97, P=0.02), and a significant effect (P<0.05) was observed for the combinations of interventions that involved exercise. Balance measures improved significantly among the exercise group. Neither home hazard management nor treatment of poor vision showed a significant effect. The strongest effect was observed for all three interventions combined (rate ratio 0.67 (0.51 to 0.88, P=0.004)), producing an estimated 14.0% reduction in the annual fall rate. The number of people needed to be treated to prevent one fall a year ranged from 32 for home hazard management to 7 for all three interventions combined.\n Group based exercise was the most potent single intervention tested, and the reduction in falls among this group seems to have been associated with improved balance. Falls were further reduced by the addition of home hazard management or reduced vision management, or both of these. Cost effectiveness is yet to be examined. These findings are most applicable to Australian born adults aged 70-84 years living at home who rate their health as good.", "To assess the effectiveness of an emergency department (ED)-based home safety intervention on caregivers' behaviors and practices related to home safety.\n We conducted a randomized, clinical trial of 96 consecutive caregivers of children who were younger than 5 years and presented to an urban pediatric ED for evaluation of an acute unintentional injury sustained in the home. After completing a structured home safety questionnaire via face-to-face interview, caregivers were randomly assigned to receive either comprehensive home safety education and free safety devices or focused, injury-specific ED discharge instructions. Participants were contacted by telephone 2 months after the initial ED visit for repeat administration of the safety questionnaire. The pretest and posttest questionnaires were scored such that the accrual of points correlated with reporting of safer practices. Scores were then normalized to a 100-point scale. The overall safety score reflected performance on the entire questionnaire, and the 8 category safety scores reflected performance in single areas of home injury prevention (fire, burn, poison, near-drowning, aspiration, cuts/piercings, falls, and safety device use). The main outcome was degree of improvement in safety practices as assessed by improvement in safety scores.\n The intervention group demonstrated a significantly higher average overall safety score at follow-up than the control group (73.3% +/- 8.4% vs 66.8% +/-11.1) and significant improvements in poison, cut/piercing, and burns category scores. Caregivers in the intervention group also demonstrated greater improvement in reported use of the distributed safety devices.\n This educational and device disbursement intervention was effective in improving the home safety practices of caregivers of young children. Moreover, the ED was used effectively to disseminate home injury prevention information.", "To present the results of an intervention trial to enhance parents' home-safety practices through pediatric safety counseling, home visits, and an on-site children's safety center where parents receive personalized education and can purchase reduced-cost products.\n Pediatricians were randomized to a standard- or an enhanced-intervention group. Parents of their patients were enrolled when the patient was 6 months or younger and observed until 12 to 18 months of age.\n A hospital-based pediatric resident continuity clinic that serves families living in low-income, inner-city neighborhoods.\n First- and second-year pediatric residents and their patient-parent dyads.\n Parents in the standard-intervention group received safety counseling and referral to the children's safety center from their pediatrician. Parents in the enhanced-intervention group received the standard services plus a home-safety visit by a community health worker.\n Home observers assessed the following safety practices: reduction of hot-water temperature, poison storage, and presence of smoke alarms, safety gates for stairs, and ipecac syrup.\n The prevalence of safety practices ranged from 11% of parents who stored poisons safely to 82% who had a working smoke alarm. No significant differences in safety practices were found between study groups. However, families who visited the children's safety center compared with those who did not had a significantly greater number of safety practices (34% vs 17% had > or 3).\n Home visiting was not effective in improving parents' safety practices. Counseling coupled with convenient access to reduced-cost products appears to be an effective strategy for promoting children's home safety.", "To decrease the rate of falls in high-risk community-dwelling older adults.\n Randomized, controlled trial.\n Community-based.\n Three hundred forty-nine adults aged 65 and older with two falls in the previous year or one fall in the previous 2 years with injury or balance problems.\n Subjects received two in-home visits from a trained nurse or physical therapist who assessed falls risk factors using an algorithm. The intervention consisted of recommendations to the subject and their primary physician, referrals to physical therapy and other providers, 11 monthly telephone calls, and a balance exercise plan. Control subjects received a home safety assessment.\n The primary outcome was rate of falls per year in the community. Secondary outcomes included all-cause hospitalizations and nursing home admissions per year.\n There was no difference in rate of falls between the intervention and control groups (rate ratio (RR)=0.81, P=.27). Nursing home days were fewer in the intervention group (10.3 vs 20.5 days, P=.04). Intervention subjects with a Mini-Mental State Examination (MMSE) score of 27 or less had a lower rate of falls (RR=0.55; P=.05) and, if they lived with someone, had fewer hospitalizations (RR=0.44, P=.05), nursing home admissions (RR=0.15, P=.003), and nursing home days (7.5 vs 58.2, P=.008).\n This multifactorial intervention did not decrease falls in at-risk community-living adults but did decrease nursing home utilization. There was evidence of efficacy in the subgroup who had an MMSE score of 27 or less and lived with a caregiver, but validation is required.", "The aim of this study was to test an intervention aimed at addressing the risk of injury in infants 2 - 12 months of age. A non-blinded, randomized controlled trial was conducted, whereby parents were randomly assigned to either a control or one of two intervention groups. Parents completed questionnaires regarding safety behaviours and injuries at the 2 (baseline), 6 and 12 month immunization visit at the community health unit. During the 2 month visit to the health unit, the two intervention groups received a home safety kit containing nine items, an instructional brochure and a risk assessment checklist. Subjects randomized to the safety kit plus home visit group also received a standardized home visit from a community health nurse. Two of the 14 parental safety behaviours showed a significant increase in use among parents in the intervention groups. Neither of the interventions was associated with a reduction in parent-reported injuries among children. It was concluded that home visitation may provide a beneficial adjunct to the provision of safety devices and may increase use by parents.", "To assess whether a pragmatic multidisciplinary fall-prevention program was more effective than usual care in preventing new falls and functional decline in elderly people.\n A two-group, randomized, controlled trial with 12 months of follow-up.\n University hospital and home-based intervention, the Netherlands.\n Three hundred thirty-three community-dwelling Dutch people aged 65 and over who were seen in an emergency department after a fall.\n Participants in the intervention group underwent a detailed medical and occupational-therapy assessment to evaluate and address risk factors for recurrent falls, followed by recommendations and referral if indicated. People in the control group received usual care.\n Number of people sustaining a fall (fall calendar) and daily functioning (Frenchay Activity Index).\n Results showed no statistically significantly favorable effects on falls (odds ratio=0.86, 95% confidence interval (CI)=0.50-1.49) or daily functioning (regression coefficient=0.37, CI=-0.90 to 1.63) after 12 months of follow-up.\n The multidisciplinary fall-prevention program was not effective in preventing falls and functional decline in this Dutch healthcare setting. Implementing the program in its present form in the Netherlands is not recommended. This trial shows that there can be considerable discrepancy between the \"ideal\" (experimental) version of a program and the implemented version of the same program. The importance of implementation research in assessing feasibility and effectiveness of such a program in a specific healthcare setting is therefore stressed.", "To assess the effectiveness of safety advice at child health surveillance consultations, provision of low cost safety equipment to families receiving means tested state benefits, home safety checks, and first aid training on frequency and severity of unintentional injuries in children at home.\n Cluster randomised controlled trial.\n 36 general practices in Nottingham.\n All children aged 3-12 months registered with participating practices.\n A package of safety advice at child health surveillance consultations at 6-9, 12-15, and 18-24 months; provision of low cost safety equipment to families on means tested state benefits; and home safety checks and first aid training by health visitors.\n Primary outcomes measures were frequency and severity of medically attended injuries. Secondary outcome measures were self reported safety practices, possession and use of safety equipment, knowledge and confidence in dealing with first aid, and perceptions of risk of injury and risk of hazards assessed by postal questionnaire at baseline and follow up at 25 months.\n At baseline, both groups had similar risk factors for injury, sociodemographic characteristics, safety practices, possession and use of safety equipment, knowledge and confidence in dealing with first aid, and perceptions of risk. No significant difference was found in frequency of at least one medically attended injury (odds ratio 0.97, 95% confidence interval 0.72 to 1.30), at least one attendance at an accident and emergency department for injury (1.02, 0.76 to 1.37), at least one primary care attendance for injury (0.75, 0.48 to 1.17), or at least one hospital admission for injury (0.69, 0.42 to 1.12). No significant difference in the secondary outcome measures was found between the intervention and control groups.\n The intervention package was not effective in reducing the frequency of minor unintentional injuries in children at home, and larger trials are required to assess the effect on more severe injuries.", "To determine whether occupational therapist home visits targeted at environmental hazards reduce the risk of falls.\n A randomized controlled trial.\n Private dwellings in the community in Sydney, Australia.\n A total of 530 subjects (mean age 77 years), recruited primarily before discharge from selected hospital wards.\n A home visit by an experienced occupational therapist, who assessed the home for environmental hazards and facilitated any necessary home modifications.\n The primary study outcome was falls, ascertained over a 12-month follow-up period using a monthly falls calendar.\n Thirty six percent of subjects in the intervention group had at least one fall during follow-up, compared with 45% of controls (P = .050). The intervention was effective only among subjects (n = 206) who reported having had one or more falls during the year before recruitment into the study; in this group, the relative risk of at least one fall during follow-up was 0.64 (95% confidence interval, 0.50-0.83). Similar results were obtained when falls data were analyzed using survival analysis techniques (proportional and multiplicative hazards models) and fall rates (mean number of falls per person per year). About 50% of the recommended home modifications were in place at a 12-month follow-up visit.\n Home visits by occupational therapists can prevent falls among older people who are at increased risk of falling. However, the effect may not be caused by home modifications alone. Home visits by occupational therapists may also lead to changes in behavior that enable older people to live more safely in both the home and the external environment.", "To evaluate the effects of a multifactorial fall prevention program on falls and to identify the subgroups that benefit the most.\n Randomized controlled trial.\n Community-dwelling subjects who had fallen at least once during the previous 12 months.\n Five hundred ninety-one subjects randomized into intervention (IG) (n=293) and control (CG) (n=298) groups.\n A multifactorial 12-month fall prevention program.\n Incidence of falls.\n The intervention did not reduce the incidence of falls overall (incidence rate ratio (IRR) for IG vs CG=0.92, 95% confidence interval (CI)=0.72-1.19). In subgroup analyses, significant interactions between subgroups and groups (IG and CG) were found for depressive symptoms (P=.006), number of falls during the previous 12 months (P=.003), and self-perceived risk of falling (P=.045). The incidence of falls decreased in subjects with a higher number of depressive symptoms (IRR=0.50, 95% CI=0.28-0.88), whereas it increased in those with a lower number of depressive symptoms (IRR=1.20, 95% CI=0.92-1.57). The incidence of falls decreased also in those with at least three previous falls (IRR=0.59, 95% CI=0.38-0.91) compared to those with one or two previous falls (IRR=1.28, 95% CI=0.95-1.72). The intervention was also more effective in subjects with high self-perceived risk of falling (IRR=0.77, 95% CI=0.55-1.06) than in those with low self-perceived risk (IRR=1.28, 95% CI=0.88-1.86).\n The program was not effective in reducing falls in the total sample of community-dwelling subjects with a history of falling, but the incidence of falls decreased in participants with a higher number of depressive symptoms and in those with at least three falls.", "To investigate whether home visits by a occupational therapist reduces the risk of falling and improves the autonomy of older patients hospitalized for falling.\n In this randomized, controlled trial set in a geriatric hospital, 60 patients (mean age, 83.5 yr) who were hospitalized for falling were recruited from the acute medicine department. A home visit from an occupational therapist and an ergotherapist assessed patients' homes for environmental hazards and recommended modifications. The outcomes measured were falls, autonomy, hospitalization for falling, institutionalization, and death.\n During the follow-up period, the rate of falls, hospitalization for falls, institutionalization, and death were not significantly different between the two groups. Both groups had a loss of dependence at 12 mo. This loss of dependence was significant in the control group but not in the intervention group.\n Home visits from occupational therapists during hospitalization of older patients at risk for falling can help to preserve the patient's autonomy.", "This prospective, randomized, controlled trial was conducted to determine feasibility and effectiveness of a chronic care model approach to injury prevention compared with standard anticipatory guidance. Enrolled caregivers of children aged 0 to 5 years received focused counseling from a physician and health assistant, educational handouts, phone follow-up, and access to free safety devices and automobile restraint evaluations. Only 35.1% of eligible parents participated. Home visits were completed at 6 months to observe safety practices. Injuries were gleaned from parent report and medical record review. Safety practices were evaluated in 27 households. Chart review showed no significant difference in the number of medically attended injuries between groups (P = 0.6). The impact of the chronic care model on injury prevention in primary care could not be determined with certainty. Evaluating effectiveness of injury prevention strategies on actual safety practices with direct observation is challenging.", "To assess the long term effect of a home safety visit on the rate of home injury.\n Telephone survey conducted 36 months after participation in a randomized controlled trial of a home safety intervention. A structured interview assessed participant knowledge, beliefs, or practices around injury prevention and the number of injuries requiring medical attention.\n Five pediatric teaching hospitals in four Canadian urban centres.\n Children less than 8 years of age presenting to an emergency department with a targeted home injury (fall, scald, burn, poisoning or ingestion, choking, or head injury while riding a bicycle), a non-targeted injury, or a medical illness.\n We contacted 774 (66%) of the 1172 original participants. A higher proportion of participants in the intervention group (63%) reported that home visits changed their knowledge, beliefs, or practices around the prevention of home injuries compared with those in the non-intervention group (43%; p<0.001). Over the 36 month follow up period the rate of injury visits to the doctor was significantly less for the intervention group (rate ratio = 0.74; 95% CI 0.63 to 0.87), consistent with the original (12 month) study results (rate ratio = 0.69; 95% CI 0.54 to 0.88). However, the effectiveness of the intervention appears to be diminishing with time (rate ratio for the 12-36 month study interval = 0.80; 95% CI 0.64 to 1.00).\n A home safety visit was able to demonstrate sustained, but modest, effectiveness of an intervention aimed at improving home safety and reducing injury. This study reinforces the need of home safety programs to focus on passive intervention and a simple well defined message.", "To access an underserved, mobile segment of a monolingual Spanish speaking population and to improve maternal self efficacy for home safety behaviors using a culturally appropriate intervention.\n A pre- and post-test experimental design tested differences in maternal childhood injury health beliefs (MCIHB) and controllable safety hazards (CHS). Participants were randomly assigned to experimental and control groups. Baseline data assessed demographic and study variables comparability. The intervention included counseling, assessment of maternal safety practices, and provision of safety items.\n A non-urban area in Texas where low income, largely migrant Hispanics represent the majority of residents.\n Eighty two mothers of 1--4 year old children.\n The 95% retention rate of an itinerant, hard to reach population suggests that minority participants may be receptive to culturally appropriate home visits. The intervention group demonstrated improved self efficacy for home safety behaviors (F (2, 77)=7.50, p=0.01). Mothers with stronger self efficacy and fewer perceived barriers had fewer accessible in-home hazards. Observed home hazard predictors were: (a) never being married; (b) poor home repair, (c) lower self efficacy for safety behaviors; and (d) control group status.\n Safety items coupled with a home visit tailored to child age and maternal culture was an effective intervention in a hard to reach population. This study contributes to designing research for a monolingual population with limited local language proficiency and community residency. Injuries represent a major source of health disparities in these neglected populations.", "Falls in elderly people are a common presenting complaint to accident and emergency departments. Current practice commonly focuses on the injury, with little systematic assessment of the underlying cause, functional consequences, and possibilities for future prevention. We undertook a randomised controlled study to assess the benefit of a structured inderdisciplinary assessment of people who have fallen in terms of further falls.\n Eligible patients were aged 65 years and older, lived in the community, and presented to an accident and emergency department with a fall. Patients assigned to the intervention group (n=184) underwent a detailed medical and occupational-therapy assessment with referral to relevant services if indicated; those assigned to the control group (n=213) received usual care only. The analyses were by intention to treat. Follow-up data were collected every 4 months for 1 year.\n At 12-month follow-up, 77% of both groups remained in the study. The total reported number of falls during this period was 183 in the intervention group compared with 510 in the control group (p=0.0002). The risk of falling was significantly reduced in the intervention group (odds ratio 0.39 [95% CI 0.23-0.66]) as was the risk of recurrent falls (0.33 [0.16-0.68]). In addition, the odds of admission to hospital were lower in the intervention group (0.61 [0.35-1.05]) whereas the decline in Barthel score with time was greater in the control group (p<0.00001).\n The study shows that an interdisciplinary approach to this high-risk population can significantly decrease the risk of further falls and limit functional impairment.", "To assess the effectiveness of safety advice and safety equipment in reducing unintentional injuries for families with children aged under 5 years and living in deprived areas.\n Randomised controlled trial.\n 47 general practices in Nottingham.\n 3428 families with children under 5.\n A standardised safety consultation and provision of free and fitted stair gates, fire guards, smoke alarms, cupboard locks, and window locks.\n Primary outcome measures were whether a child in the family had at least one injury that required medical attendance and rates of attendance in primary and secondary care and of hospital admission for injury over a two year period. Secondary outcome measures included possession of safety equipment and safety practices.\n No significant difference was found in the proportion of families in which a child had a medically attended injury (odds ratio 1.14, 95% confidence interval 0.98 to 1.50) or in the rates of attendance in secondary care (incidence rate ratio 1.02, 0.90 to 1.13) or admission to hospital (1.02, 0.70 to 1.48). However, children in the intervention arm had a significantly higher attendance rate for injuries in primary care (1.37, 1.11 to 1.70, P = 0.003). At both one and two years' follow up, families in the intervention arm were significantly more likely to have a range of safety practices, but absolute differences in the percentages were relatively small.\n The intervention resulted in significant improvements in safety practices for up to two years but did not reduce injuries that necessitated medical attendance. Although equipment was provided and fitted free of charge, the observed changes in safety practices may not have been large enough to affect injury rates.", "To evaluate the outcome of an intervention to reduce hazards in the home on the rate of falls in seniors.\n Randomized controlled trial, with follow-up of subjects for 1 year.\n Community-based study in Perth, Western Australia.\n People age 70 and older.\n One thousand eight hundred seventy-nine subjects were recruited and randomly allocated by household to the intervention and control groups in the ratio 1:2. Because of early withdrawals, 1,737 subjects commenced the study. All members of both groups received a single home visit from a research nurse. Intervention subjects (n = 570) were offered a home hazard assessment, information on hazard reduction, and the installation of safety devices, whereas control subjects (n = 1,167) received no safety devices or information on home hazard reduction.\n Both groups recorded falls on a daily calendar. Reported falls were confirmed by a semistructured telephone interview and were assigned to one of three overlapping categories: all falls, falls inside the home, and falls involving environmental hazards in the home. Analysis was by multivariate modelling of rate ratios and odds ratios for falls, corrected for household clustering, using Poisson regression and logistic regression with robust variance estimation.\n Overall, 86% of study subjects completed the 1 year of follow-up. The intervention was not associated with any significant reduction in falls or fall-related injuries. There was no significant reduction in the intervention group in the incidence rate of falls involving environmental hazards inside the home (adjusted rate ratio, 1.11; 95% CI = 0.82-1.50), or the proportion of the intervention group who fell because of hazards inside the home (adjusted odds ratio, 0.97; 95% CI = 0.74-1.28). No reduction was seen in the rate of all falls (adjusted rate ratio, 1.02; 95% CI = 0.83-1.27) or the rate of falls inside the home (adjusted rate ratio, 1.17; 95% CI = 0.85-1.60). There was no significant reduction in the rate of injurious falls in intervention subjects (adjusted rate ratio, 0.92; 95% CI = 0.73-1.14).\n The intervention failed to achieve a reduction in the occurrence of falls. This was most likely because the intervention strategies had a limited effect on the number of hazards in the homes of intervention subjects. The study provides evidence that a one-time intervention program of education, hazard assessment, and home modification to reduce fall hazards in the homes of healthy older people is not an effective strategy for the prevention of falls in seniors.", "To assess whether intervention by a health visitor could reduce the number of fractures, over a four year period, in those aged 70 and over.\n Randomised, controlled trial; randomisation by household.\n General practice in a market town.\n Of 863 patients aged 70 and over on the practice records, 674 were traced and successfully interviewed; 350 were assigned to the intervention group, 324 as controls.\n The people in the intervention group were allocated to the care of a health visitor. The approach was four pronged: assessment and correction of nutritional deficiencies, including reducing smoking and alcohol intake; assessment and referral of medical conditions such as heart block or inappropriate medication; assessment and correction of environmental hazards in the home such as poor lighting; assessment and improvement of fitness--for example, exercise classes for the moderately fit. The intervention continued for four years.\n Fracture rate over four years.\n The incidence of fractures was 5% (16/350) in the intervention group and 4% (14/324) in the control group (difference not significant).\n A health visitor visiting a group of people aged 70 and over and using simple preventive measures had no effect on the incidence of fractures.", "To assess the effectiveness of a community-based falls-and-fracture nurse coordinator and multifactorial intervention in reducing falls in older people.\n Randomized, controlled trial.\n Screening for previous falls in family practice followed by community-based intervention.\n Three hundred twelve community-living people aged 75 and older who had fallen in the previous year.\n Home-based nurse assessment of falls-and-fracture risk factors and home hazards, referral to appropriate community interventions, and strength and balance exercise program. Control group received usual care and social visits.\n Primary outcome was rate of falls over 12 months. Secondary outcomes were muscle strength and balance, falls efficacy, activities of daily living, self-reported physical activity level, and quality of life (Medical Outcomes Study 36-item Short Form Questionnaire).\n Of the 3,434 older adults screened for falls, 312 (9%) from 19 family practices were enrolled and randomized. The average age was 81+/-5, and 69% (215/312) were women. The incidence rate ratio for falls for the intervention group compared with the control group was 0.96 (95% confidence interval=0.70-1.34). There were no significant differences in secondary outcomes between the two groups.\n This nurse-led intervention was not effective in reducing falls in older people who had fallen previously. Implementation and adherence to the fall-prevention measures was dependent on referral to other health professionals working in their usual clinical practice. This may have limited the effectiveness of the interventions.", "To evaluate whether a programme of multifactorial home visits reduces falls and impairments in mobility in elderly people living in the community.\n Randomised controlled trial with 18 months of follow up.\n Six general practices in Hoensbroek, the Netherlands.\n 316 people aged 70 and over living in the community, with moderate impairments in mobility or a history of recent falls.\n Five home visits by a community nurse over a period of one year. Visits consisted of screening for medical, environmental, and behavioural factors causing falls and impairments in mobility, followed by specific advice, referrals, and other actions aimed at dealing with the observed hazards.\n Falls and impairments in mobility.\n No differences were found in falls and mobility outcomes between the intervention and usual care groups.\n Multifactorial home visits had no effects on falls and impairments in mobility in elderly people at risk who were living in the community. Because falls and impairments in mobility remain a serious problem among elderly people, alternative strategies should be developed and evaluated." ]

[ "795498", "6209832", "1699308", "6171491", "2436359", "1561645", "12097849", "2885946", "9550505", "2466351", "4764994", "1709311" ]

[ "Combined dexamethasone and low-molecular-weight dextran in acute brain infarction: double-blind study.", "A randomized controlled trial of hemodilution therapy in acute ischemic stroke.", "Adjusted hypervolemic hemodilution in acute ischemic stroke.", "[Dextran-40 in nonhemorrhagic cerebrovascular accidents].", "Glycerol and dextran combined in the therapy of acute stroke. A placebo-controlled, double-blind trial with a planned interim analysis.", "Custom-tailored hemodilution with albumin and crystalloids in acute ischemic stroke.", "Hydroxyethyl starch for hypervolemic hemodilution in patients with acute ischemic stroke: a randomized, placebo-controlled phase II safety study.", "Multicenter trial of hemodilution in acute ischemic stroke. I. Results in the total patient population. Scandinavian Stroke Study Group.", "Hypervolemic hemodilution in acute ischemic stroke: the Multicenter Austrian Hemodilution Stroke Trial (MAHST).", "Hypervolemic hemodilution treatment of acute stroke. Results of a randomized multicenter trial using pentastarch. The Hemodilution in Stroke Study Group.", "Management of completed strokes with dextran 40. A community hospital failure.", "Neurological deterioration under isovolemic hemodilution with hydroxyethyl starch in acute cerebral ischemia." ]

[ "Intramuscular dexamethasone combined with intravenous low-molecular-weight dextran (dextran 40) was compared with placebo in 40 patients with acute ischaemic cerebral infarction. A double-blind procedure was used. Dexamethasone was given for up to 14 days and dextran 40 for up to three days after the infarction. A weighted scoring system was used to evaluate neurological state and mobility. There were no differences in mortality or in improvement of the neurological or mobility scores between the two groups.", "Rapid hemodilution in the early phase of ischemic stroke by the combination of venesection (250-650 ml during the first 2 days) and administration of low-molecular weight dextran was evaluated in a prospective controlled trial. Fifty-two patients were randomized to hemodilution therapy and 50 to a control group; the two groups were comparable in important prognostic variables. Mean hemoglobin was reduced from 147 to 127 g/l, hematocrit from 43 to 37% and, in a subsample of patients, whole-blood viscosity at a shear rate of 23 sec-1 from 7.0 to 4.3 cps over the first 2 days. Hemodilution was then maintained by repeated dextran infusions. Of the hemodiluted patients, 85% improved in neurological scoring over the first 10 days as compared to 64% of the control patients (p less than 0.025). The case fatality rate during the first 3 months was little affected by hemodilution. Among the survivors, 8% of the hemodiluted and 31% of the non-hemodiluted patients were unable to walk at 3 months. The proportion of surviving patients still hospitalized at the 3-month follow-up was 13% in the hemodilution group and 39% in the control group (p less than 0.01). The combination of venesection and dextran 40 administration is thus an unsophisticated but effective way to achieve rapid hemodilution in patients with acute cerebral infarction, and it improves the overall clinical outcome over the first 3 months.", "We prospectively randomized 47 patients with acute ischemic stroke of the middle cerebral artery of less than 24 hours' duration to either adjusted hypervolemic hemodilution or control treatment and followed them up for 90 days. Rapid hemodilution to a target hematocrit of 30-35% as monitored with bedside determinations was achieved by using infusions of dextran 40, venesections, and infusions of additional crystalloid solution when necessary. There was no difference in the death rate between the two treatment groups. Of these 47 patients, 37 (19 in the hemodilution group and 18 in the control group) could be followed up for the entire study period of 3 months. The relative improvement in neurologic function from day 1 to days 8, 21, and 90 was significantly better in the hemodilution group than in the control group. In accordance, special tests for fine motor control of the paretic arm disclosed better performance in the hemodilution group. The frequency of patients with severe disability was significantly lower in the hemodilution group on days 8 and 21. Plasma viscosity (measured in 11 patients) was not affected by infusions of dextran 40. Vigorous hypervolemic hemodilution in patients with acute ischemic stroke is well tolerated and improves early neurologic outcome with an effect lasting at least 3 months.", "nan", "The results of clinical trials investigating various therapies in acute ischemic stroke have been inconsistent. The effect of glycerol therapy and a combination therapy of glycerol and dextran was evaluated in a double-blind, placebo-controlled study. Repeated neurologic examinations (Day 0, Weeks 1, 6, 12, and 24) according to a modified Mathew score were performed on 62 patients. Statistical analysis showed no superiority of either treatment compared with placebo in acute ischemic stroke. A retrospective estimation of the Type II error of the study yielded approximately p = 0.25. A major side effect was hemolysis in 98% of patients treated with glycerol.", "Hemodilution in the acute phase of ischemic stroke is still controversial. Multicenter studies have failed to demonstrate any benefit. The present study focuses attention on analysis of circulation in stroke and on individual restabilization of circulation.\n The Amsterdam Stroke Study is a prospective, single-center, randomized clinical trial (n = 300). Normovolemic hemodilution is accomplished in a customized procedure by administration of 20% albumin plus crystalloids under hemodynamic and rheological monitoring in the acute phase of stroke. All patients receive general intensive care treatment and monitoring with a pulmonary artery catheter. This custom-tailored fluid therapy is guided on the basis of a target pulmonary capillary wedge pressure (12 +/- 3 mm Hg) and hematocrit (0.32 +/- 0.02). The control group receives only customized rehydration by infusion of crystalloids.\n We obtained significant (p less than 0.05) reduction in mortality at 3 months (from 27% to 16%) and an increase in independence at home (from 35% to 48%) after viscosity reduction by means of hemodilution with albumin in the subgroup with a hematocrit less than 0.45 (n = 201) (specific viscosity effect). We also obtained a significant (p less than 0.005) reduction in mortality at 3 months (from 27% to 8%) and an increase in independence (from 35% to 59%) after only rehydration with crystalloids in the subgroup with overt dehydration (hematocrit greater than or equal to 0.45; n = 51) as compared with the normal-hematocrit group without signs of dehydration (hematocrit less than 0.45; n = 103) (specific rehydration effect).\n This study may provide an explanation for the failures in former hemodilution trials and may re-establish proper hemodilution and rehydration as a valuable therapy in the acute phase of stroke, thus reducing mortality and improving independence after 3 months.", "Hypervolemic hemodilution (HH) with hydroxyethyl starch (HES) significantly increases cerebral blood flow and thus may reduce ischemic tissue damage in the penumbra zones when given within the therapeutic time window. The objective of this study was to investigate the safety of a 10% solution of HES 130/0.4 versus 0.9% saline solution in acute ischemic stroke by the incidence of adverse events (AEs).\n In a controlled, double-blind, randomized, multicenter, phase II, parallel-group study, 106 patients with acute ischemic stroke received high-dose HH with HES 130/0.4 or placebo within 6 h of symptom onset with a randomization ratio of 2:1 in favor of HES therapy.\n There were no significant differences between the groups with regard to the incidence of the specific AEs (cardiovascular events, bleeding complications, allergic reactions) assessed over days 1-30, or mortality over days 1-8. In addition, global tests of efficacy showed a trend towards a better functional outcome with HES therapy; however, the study was not designed to prove efficacy.\n High-dose HH with HES or NaCl was generally safe and well tolerated. Safety profiles were similar for the two treatment groups, and there was a nonsignificant trend towards a better functional outcome with HES therapy.\n Copyright 2002 S. Karger AG, Basel", "Hemodilution by the combination of venesection and dextran 40 administration has previously been reported to enhance neurologic recovery in the acute phase of ischemic stroke. To study this therapeutic principle in its \"natural habitat,\" a stratified and randomized multicenter trial involving 15 large and small hospitals was performed. Patients with acute ischemic stroke of less than 48 hours' duration and with hematocrits of 38-50% on admission were randomized to a hemodilution (183 patients, mean age 72.0 years) or a control group (190 patients, mean age 71.6 years). The two groups did not differ in sex distribution or medical history. Hematocrit, blood pressure, and neurologic score were closely similar at entry. By graded venesection (250-1000 ml) during the first 2 days and dextran 40 infusions (500 ml daily) during 5 days, the mean hematocrit was reduced from 44.2 to 37.1%. Three-month survival expressed as life table product was 0.84 in hemodilution and 0.88 in control patients. In survivors, neurologic score and activities of daily living performance during 3 months of follow-up were not improved by hemodilution. Length of stay in an acute-care hospital and the need for long-term institutional care was not reduced among patients in the hemodilution group. Major cardiovascular events occurred somewhat more often and there was an apparent increase in mortality during the first few days of hemodilution therapy. However, the differences were not significant. We conclude that the present standardized treatment with moderate hemodilution has no overall beneficial effects in general patients with acute ischemic stroke.", "Experimental studies suggest a beneficial effect of hemodilution on acute ischemic stroke. This was not proven by previous multicenter trials in the clinical setting. Various reasons have been suggested for the failure of these studies, which we attempted to consider in the Multicenter Austrian Hemodilution Stroke Trial (MAHST).\n MAHST is a randomized, double-blind, placebo-controlled study of hypervolemic hemodilution (HHD) within 6 hours of a clinically first ischemic stroke localized in the middle cerebral artery territory. The treatment consisted of 10% hydroxyethyl starch 200/0.5 (HES) and was tested against pure rehydration with Ringer's lactate over a period of 5 days. Our primary outcome measure was clinical improvement within 7 days as measured by the Graded Neurologic Scale (GNS). We performed an adaptive interim analysis to reevaluate the study goal after entering half of the projected number of patients (n = 200). At least 600 patients per group would have been required for significant results, and therefore we decided to terminate the trial.\n Ninety-eight patients received HHD and 102 patients placebo. The baseline characteristics were comparable between both groups. In the HHD group the absolute reduction of the hematocrit was 2.5% on day 2 with a maximum of 3.7% on day 5, which compares with a reduction in the placebo group of 1% and 1.9%, respectively. Intention-to-treat analysis showed no significant difference of the change of the GNS scores between HHD-treated (median, -8.5; 95% confidence interval, -14.2 to -4.0) and placebo-treated patients (median, -6.0; 95% confidence interval, -11.0 to 0.0) on day 7, and GNS scores remained similar in both treatment groups throughout the trial. At 3 months, slightly more HHD patients showed complete independence on the Barthel Index (28 versus 24), and fewer HHD than placebo patients had died (13 versus 17), but these differences were not statistically significant. HHD treatment was not associated with any specific adverse event.\n Mild HHD is safe but failed to demonstrate a significant beneficial effect over the pure rehydration regimen in patients with acute ischemic stroke.", "Patients with acute ischemic stroke were randomized less than 24 hours after onset to standard (S) therapy (n = 43) or to hypervolemic hemodilution (HH) with pentastarch (n = 45). The therapeutic goal of hypervolemic hemodilution was to rapidly reduce hematocrit to 33%, to raise cardiac output, and to continue hypervolemic hemodilution for 3 days. A graded neurologic examination was scored by a blinded observer at randomization (baseline), at the end of treatment or after 72 hours, and at a 3-month follow-up; each patient was also rated using Barthel's disability scale at the 3-month follow-up. Group demographics and results of the graded neurologic examination were similar at baseline, except that the HH group contained twice the number of patients with severe strokes and fewer patients randomized within 12 hours compared with the S group. The HH group improved an average of 7 points in neurologic score from baseline to the end of treatment (the S group deteriorated 1 point) and 24 points by the 3-month follow-up (the S group improved 16 points; p = 0.11). The HH group reached an average Barthel disability scale index of 85 while the S group averaged 70 (p = 0.8). Deaths associated with cerebral edema occurred in five patients with severe stroke (four in the HH group vs. one in the S group, p = 0.36). The following subgroups of HH patients showed better overall improvement in neurologic scores: patients entered within 12 hours after stroke onset, patients with a 15% decrease in hematocrit, and patients with a 10% increase in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)", "nan", "In a prospective study, we randomly allocated 70 patients with acute ischemic stroke to two therapy groups. Up to interim analysis, 33 patients underwent bloodletting, with simultaneous infusion of an identical volume of hydroxyethyl starch (10%, 200/0.5). The target hematocrit was 35%. A control group of 37 patients did not receive hemodilution. Apart from an unequal sex distribution, the two groups were comparable with regard to age, cardiovascular risk factors, and medical history. In the hemodilution group, the mean hematocrit fell from 44.4% to 37.7%. After 14 days, improvement on the neurological score scale was 3.3 points in the hemodilution group compared with 6.5 points in the control group (p = 0.12). Subgroups with early inclusion (less than 12 hours) or pronounced lowering of hematocrit (greater than 15% of initial hematocrit) also did not profit from hemodilution. Clinical deterioration observed in eight hemodilution group patients (p less than 0.01) led to discontinuation of the study for ethical reasons." ]

[ "15905297", "8825162", "8400729", "8981127", "15665025", "15266762", "1639990", "7890071", "9557848", "15823228", "9513842", "18793768", "11212860", "19782973", "19268926", "20113961", "20467801", "17094975", "16613888", "18413070", "10911572", "15284215" ]

[ "Impact of assisted hatching on ART outcome in women with endometriosis.", "Does assisted hatching improve implantation rates after in vitro fertilization or intracytoplasmic sperm injection in all patients? A prospective randomized study.", "Chemical removal of the outside of the zona pellucida of day 3 human embryos has no impact on implantation rate.", "Enhancement of outcome from intracytoplasmic sperm injection: does co-culture or assisted hatching improve implantation rates?", "A randomized double-blind controlled study of the efficacy of laser-assisted hatching on implantation and pregnancy rates of frozen-thawed embryo transfer at the cleavage stage.", "Is assisted hatching beneficial in patients with recurrent implantation failures?", "Implantation enhancement by selective assisted hatching using zona drilling of human embryos with poor prognosis.", "Assisted hatching by partial zona dissection of human pre-embryos in patients with recurrent implantation failure after in vitro fertilization.", "A prospective, randomized, double-blind study for the evaluation of assisted hatching in patients with advanced maternal age.", "Implantation failures: success of assisted hatching with quarter-laser zona thinning.", "Assisted hatching does not enhance IVF success in good-prognosis patients.", "Laser zona thinning in women aged <or=37 years: a randomized study.", "Zona thinning with noncontact diode laser in patients aged < or = 37 years with no previous failure of implantation: a prospective randomized study.", "Mechanically expanding the zona pellucida of human frozen thawed embryos: a new method of assisted hatching.", "A prospective, randomized, double-blinded study of assisted hatching in women younger than 38 years undergoing in vitro fertilization.", "Effect of laser zona thinning on vitrified-warmed embryo transfer at the cleavage stage: a prospective, randomized study.", "Laser assisted zona thinning technique has no beneficial effect on the ART outcomes of two different maternal age groups.", "Laser assisted hatching in good prognosis patients undergoing in vitro fertilization-embryo transfer: a randomized controlled trial.", "Laser-assisted hatching increases pregnancy and implantation rates in cryopreserved embryos that were allowed to cleave in vitro after thawing: a prospective randomized study.", "Impact of assisted hatching on fresh and frozen-thawed embryo transfer cycles: a prospective, randomized study.", "Comparison of zona manipulated and zona intact blastocyst transfers: a prospective randomized trial.", "A European multicentre prospective randomized study to assess the use of assisted hatching with a diode laser and the benefit of an immunosuppressive/antibiotic treatment in different patient populations." ]

[ "Assisted hatching can improve the implantation rate in cycles with poor outcome. The impact of assisted hatching in embryos from women with endometriosis is not known. Therefore, the hypothesis that the implantation potential of embryos obtained from women with endometriosis can be improved with assisted hatching was tested.\n In a prospective randomized study, transfer embryos obtained from 60 women with endometriosis were hatched using a laser system and compared to embryos obtained from patients with the same diagnosis which were left intact (n = 30).\n The characteristics of cycles were similar between groups. The pregnancy (40% zona intact, 28.3% assisted hatching), and implantation rates (19.4% zona intact, 17.8% assisted hatching) did not differ in endometriosis cycles regardless of assisted hatching.\n Assisted hatching does not improve outcome in women with endometriosis undergoing assisted reproduction.", "Preliminary data from some research centers indicate that assisted hatching might be of value to increase embryo implantation rate in the human, at least in selected cases. It is not clear, however, whether this technique would be of benefit for all patients undergoing an embryo transfer. We therefore performed a prospective randomized study to evaluate the effect of assisted hatching on the implantation rate in our in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) program.\n In total, 120 couples undergoing an embryo transfer were randomized between two groups: in one group no assisted hatching was performed (AH-), whereas in the other group the embryos selected for transfer were subjected to partial zona dissection (PZD) immediately prior to the transfer (AH+). Using a computer-generated minimization procedure, patients were allocated to one of the two groups according to four pre-selected criteria: the number of embryos transferred, the cumulative score of transferred embryos, the age of the patient, and the use of ICSI.\n Pregnancy and implantation rates in the AH+ and AH- groups were, respectively, 42.1 versus 38.1% and 17.9 versus 17.1%.\n From our data we conclude that assisted hatching through partial zona dissection prior to embryo transfer does not improve pregnancy and embryo implantation rates in unselected patients undergoing IVF or ICSI.", "Two hundred eighteen consenting patients entered a randomized study of the application of chemical zona pellucida thinning on their day 3 embryos, prior to uterine transfer. Of those control patients (n = 108), whose embryos remained unmanipulated, 40 (37.0%) have ongoing/delivered pregnancies, while in the experimental group (n = 110), whose embryos had their zonae pellucidae chemically thinned, there are 49 patients (44.6%) who have ongoing/delivered pregnancies. Although this difference is not significant, clearly the application of this micromanipulative intervention has not been detrimental, and this bodes well for routine application of embryonic micromanipulation procedures in general. Certain patient subgroups were studied including older women, those with elevated basal follicle stimulating hormone levels, patients with embryos of differing zona thickness, and patients with embryos of differing uniformity of zona thickness. No significant influence of chemical removal of the outside of the zona on the implantation rate of embryos in any of these subgroups was observed other than a marginally significant (P = 0.095) improvement of implantation of embryos with less than 4.0 microns variation in zona thickness when chemical zona thinning was applied. Failure of chemical zona thinning to enhance human embryo implantation significantly, compared to assisted hatching by complete zona drilling, strongly suggests that the bilayered human zona pellucida needs to be fully breached, unlike that of the mouse.", "In two separate prospectively randomized trials, intracytoplasmic sperm injection (ICSI) cycles were studied in a controlled manner to monitor the effects of either bovine oviductal epithelial cell co-culture (n = 119) or assisted hatching by zona drilling (n = 100). In the first study, immediately following ICSI, all eggs were placed directly either onto partial monolayers of bovine oviductal cells or into regular culture medium. Although the embryo developmental rate was apparently compromised in part by the presence of the co-culture cells, ultimately there were no significant differences in either the viable pregnancy rate (31.6% co-culture versus 29.0% control) or the embryonic implantation rate (11.4% co-culture versus 13.6% control). Assisted hatching also had no significant impact on ICSI cycle outcome in terms of either the viable pregnancy rate (30.0% assisted hatching versus 32.0% control) or the embryonic implantation rate (8.5% assisted hatching versus 13.5% control). However, in female patients aged > or = 35 years, assisted hatching appeared to convey a marginally significant benefit in terms of both the viable pregnancy rate (35.5% assisted hatching versus 11.1% control) and the embryonic implantation rate (10.3% assisted hatching versus 3.1% control). It seems that the overall improvement of ICSI cycle outcome cannot be achieved by the general application of either co-culture or assisted hatching. Nevertheless, it is possible that there remain specific patient groups that might benefit from selected use of either of these modalities.", "Assisted hatching (AH) in fresh embryo transfer (ET) cycles increases the implantation and pregnancy rates, especially in women with a poor prognosis, repeated implantation failures and in older women. Little information exists in the literature regarding the role of AH in frozen-thawed embryo transfer (FET) cycles.\n Embryos were cryopreserved at the cleavage stage. On the day of FET, 160 patients were randomized according to a computer-generated randomization list in sealed envelopes into the AH group and the control group. The patients and the clinicians were blinded to the group assigned. In the AH group, the outer half of the zona pellucida over a quarter of the diameter of zona was removed using a 1480 nm non-contact laser.\n The two groups were comparable in terms of demographic characteristics, ovarian response of the stimulated cycle and quality of fresh and frozen-thawed embryos. No differences in implantation, pregnancy and multiple pregnancy rates were found between the two groups. There was a non-significant trend of a higher implantation rate in the AH group when the zona thickness was > or = 16 mm.\n Laser AH did not improve the implantation rate of FET cycles and should not be performed routinely in all frozen-thawed embryos at the cleavage stage.", "To assess the possible role of assisted hatching in patients with recurrent implantation failure during IVF cycles.\n Prospective randomized study.\n IVF unit of an academic medical center.\n Women who underwent IVF after at least three failed IVF-ET attempts.\n Patients were prospectively randomized to undergo assisted hatching of their embryos prior to their replacement by mechanical partial zona dissection.\n The study (assisted hatching) and control groups included 104 and 103 patients, respectively. There were no significant between-group differences in patient age, cause of infertility, mean number of previous IVF trials, number of oocytes retrieved, fertilization rate, or number of embryos transferred. No difference in pregnancy rate was noted on comparison of the whole study group, to the whole control group (21% and 27%, respectively). However, when the results were re-analyzed by age groups, assisted hatching was found to be harmful in the youngest group (< 34 years), significantly decreasing pregnancy rates (15% vs 35%, p < 0.05).\n Repeated implantation failure alone is not an indication for assisted hatching. Although assisted hatching appears to be effective in a selected group of older patients, in younger patients it may further hamper implantation and should be avoided.", "Assisted hatching by zona drilling using acidic Tyrode's solution was performed during three randomized trials in 330 in-vitro fertilization patients. The trials were designed in order to study the overall effect of the procedure and whether characteristic patient [i.e. maternal age and basal levels of follicle stimulating hormone (FSH)] and embryonic features (i.e. zona pellucida thickness) are important for the decision to perform assisted hatching routinely. Couples (n = 137; Trial 1) in whom the female partner had normal basal FSH levels were randomized in a control group (without micromanipulation) and a zona drilling group (all embryos micromanipulated). The incidence of implantation (67/239; 28%) of zona-drilled embryos compared favourably with that of control embryos (49/229; 21%), but the difference was not significant. Retrospective analysis revealed that those embryos whose zonae were thicker than 15 microns were rescued. In order to test the validity of this finding, selective assisted hatching was performed on embryos with a poor prognosis in 163 other patients (Trial 2). The couples were randomized into a control group and a group in which embryos were selectively zona-drilled, based on zona thickness and other embryonic features. The rate of embryonic implantation in the selectively zona-drilled group was 25% (70/278), significantly (P less than 0.05) higher than that of control embryos (51/285; 18%). Although it was demonstrated retrospectively and prospectively that assisted hatching by zona drilling is effective in embryos with thick zonae (greater than or equal to 15 microns), patients whose embryos have thin (less than 13 microns) zonae may be jeopardized by the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)", "To examine the potential of the partial zona dissection technique to promote successful implantation by assisting embryo hatching after IVF.\n The study and the control group included 72 and 82 patients, respectively, each had undergone at least three failed IVF-ET attempts. Assisted hatching was performed on four- to six-cell stage embryos by creating a slit in the zona pellucida using the partial zona dissection technique. After 90 minutes incubation (5% CO2, 37 degrees C), the embryos were transferred to the uterus.\n Infertility and IVF Unit of an academic tertiary referral medical center.\n In the assisted hatching group, 230 micromanipulated embryos were replaced (3 or 4 treated embryos per patient) compared with 295 nonmanipulated embryos in the control group. Clinical pregnancy rates (PRs) were similar in the assisted hatching and control groups (n = 15; 20.8% and n = 12; 14.6%, respectively). However, the contribution of assisted hatching by partial zona dissection to successful implantation was related to the patients's age: patients older than 38 years showed a markedly higher PR after assisted hatching: 23.9% in the study group compared with only 7% of the controls.\n These results demonstrate that assisted hatching by partial zona dissection is a quick and efficient method that does not induce any visible damage to the embryos replaced. In a selected group of patients (aged over 38 years, who have failed to conceive in at least three previous IVF attempts) it significantly increases the chances for pregnancy after ET.", "The objective of this study was to determine if assisted hatching improved the rates of implantation, clinical pregnancy and ongoing pregnancy for in-vitro fertilization (IVF) patients aged > or =36 years. On the day of oocyte aspiration, consenting patients were randomized according to whether all embryos underwent the hatching procedure (hatched; n = 41) or all embryos remained unhatched (controls; n = 48). Patients in both groups were treated with methylprednisolone and doxycycline starting on the day of oocyte retrieval and continuing for 4 days. The hatching procedure was performed approximately 55 h after insemination on all potential embryos for transfer and employed the release of acidified acid Tyrode's medium against the zona pellucida to create an opening approximately 20 microm in diameter. No significant differences were noted in the mean age, number of oocytes aspirated and number of embryos transferred between the hatched and control groups. In addition, no significant differences were observed in the rates of implantation (11.1 versus 11.3%), clinical pregnancy (39.0 versus 41.7%) and ongoing pregnancy (29.3 versus 35.4%) between the hatched and control groups respectively. These results suggest that assisted hatching may have no significant impact on IVF success rates in the patient population studied.", "Implantation failure after IVF is one of the factors associated with a reduced chance of pregnancy for some patients. Assisted hatching methodologies are designed to facilitate the embryo's escape from the zona pellucida, and this strategy has been suggested as a means of improving pregnancy rates in patients with previous implantation failure. The aim of this prospective and randomized study was to evaluate the efficacy of quarter-laser zona thinning assisted hatching (qLZT-AH) in improving the implantation of embryos in patients with previous implantation failure. A total of 150 patients with a history of previous implantation failure were treated with intracytoplasmic sperm injection, and allocated into two groups: group 1, only one previous implantation failure, and group 2, repeated implantation failures. The patients in each group were randomized at the time of embryo transfer into a control group (no qLZT-AH) or experimental group where qLZT-AH was performed. For patients with repeated implantation failures, the implantation rate in those who received laser-thinned embryos was significantly higher (P = 0.02) than in those whose embryos were not laser-thinned (10.9 and 2.6% respectively). However, this difference was not observed in patients who presented with only one previous implantation failure. The data demonstrate that qLZT-AH is an effective strategy for improving the implantation of embryos in patients with repeated implantation failures.", "The role of assisted hatching in good-prognosis IVF patients was evaluated in a prospective, randomized, controlled pilot study, which was followed by a retrospective observational series.\n After assisted hatching was proved successful in a mouse embryo study, 20 good-prognosis IVF patients were randomly assigned to either assisted hatching (13) or no assisted hatching (7; the controls). Following this series, 27 good-prognosis IVF patients were retrospectively evaluated to determine the outcome with assisted hatching.\n In the prospective study, clinical pregnancies resulted from 3 (23%) of 13 patients in the hatching group, compared to 3 (43%) of 7 in the control group. Implantation rates were similar: 9.6% in the hatching group and 10.7% in the controls. In the retrospective series, the 11.1% implantation rate with assisted hatching was significantly less than the 42.9% implantation rate seen with traditional IVF.\n Implantation and pregnancy rates are high in young women undergoing traditional IVF. Assisted hatching is not beneficial in these patients.", "The objective of this prospective randomized double-blind clinical trial was to evaluate whether laser zona pellucida thinning of human embryos improves clinical outcomes in women <or=37 years old undergoing IVF-ET treatment. The study did not reveal any significant beneficial effect of laser zona thinning on clinical pregnancy (16 out of 45 vs. 18 out of 39) and live birth rates (13 out of 45 vs. 16 out of 39) between the laser-treated and nontreated groups of patients, although there was a trend toward an increased incidence of dichorionic multiple pregnancies in the study group compared with the control group (7 out of 13 vs. 4 out of 16).", "Zona thinning (ZT) is a technique used to improve pregnancy rates among patients > or = 38 years old and/or patients presenting previous implantation failure. The objective of the study was to determine whether ZT has a beneficial effect on patients younger than 37 years who are undergoing the first ICSI attempt.\n A total of 103 patients submitted to ICSI for the first time and those aged < or = 37 years were divided in a prospective and randomized manner into two groups: group I, patients submitted to ZT (n = 51) (a laser diode with 1.48-micron wavelength (Fertilaser) was used for the procedure); group II, patients with no ZT (n = 52). In both groups, embryo transfer was performed on the second day.\n The age of group I patients (31.8 +/- 3.6) did not differ (P = 0.53) from that of group II patients (31.4 +/- 3.6). The number of metaphase II oocytes was similar (P = 0.76) for the two groups (group I = 9.12 +/- 5.27; group II = 8.67 +/- 5.02). The average number of embryos available per transfer of group I (6.14 +/- 4.02) did not differ (P = 0.69) from that of group II (5.75 +/- 3.83). The number of embryos transferred was similar (P = 0.61) for the two groups (group I = 2.76 +/- 0.9; group II = 2.87 +/- 0.79). The thickness of the zona pellucida of group I embryos (16.6 +/- 2.2 microns) did not differ (P = 0.08) from that of group II embryos (17.1 +/- 1.7 microns). The rate of embryo implantation (20.8%) and the rate of clinical pregnancy per embryo transfer (40.3%) were higher for group II than for group I (17.7% and 33.3%, respectively), but the difference was not significant (P = 0.55 and P = 0.54).\n These results suggest that ZT in the population aged < or = 37 years and with no previous failure of implantation may have no impact on intracytoplasmic sperm injection success rates.", "To determine whether a new assisted hatching (AH) method increases the implantation and clinical pregnancy rates of frozen-thawed day-3 (D3) embryos.\n Prospective study.\n A university hospital in vitro fertilization (IVF) program.\n Patients who had their first IVF/intracytoplasmic sperm injection (ICSI) cycles between June 1, 2006, and December 31, 2008, with fresh IVF-embryo transfer failures or without fresh embryo transfer.\n The couples were randomized into thawed embryo transfer after AH versus no AH. In the AH group, the zona pellucida (ZP) of D3 frozen-thawed embryos was expanded by injected hydrostatic pressure after thawing. In the control group, embryos were pierced by ICSI needles without expanding the ZP.\n Clinical pregnancy and implantation rates.\n The morphologic features of the blastomeres were carefully monitored and recorded. In the AH group, 244 embryos were thawed, and 178 (73.0%) survived; in the control group, 259 embryos were thawed, and 190 (73.4%) survived. Despite the transfer of a similar number of embryos, the AH group resulted in statistically significantly higher implantation and clinical pregnancy rates compared with the no AH group.\n Mechanically expanding the ZP of frozen-thawed D3 embryos with injected hydrostatic pressure after thawing increases the implantation rate compared with control embryos.\n Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.", "To determine whether assisted hatching is beneficial to IVF patients younger than 38 years whose embryos have a thickened zona pellucida (ZP).\n Prospective, randomized, double-blinded, crossover study.\n University-based infertility center.\n One hundred twenty-one women less than 38 years of age, undergoing IVF at Washington University between April 2004 and February 2007, with ZP thickness > or =13 microm for any embryos.\n Measurement of ZP thickness in embryos undergoing IVF; randomization of women with embryos with ZP thickness > or =13 microm to no procedure or assisted hatching performed by acidic Tyrode's solution.\n Clinical intrauterine pregnancy rate, implantation rate, spontaneous pregnancy loss, and live birth rate.\n Baseline characteristics and ZP thickness were not significantly different between the two study arms (hatched and unhatched). No significant differences were observed between hatched and unhatched patients in the rates of clinical pregnancy (47% vs. 50% respectively) or live birth (46% vs. 45% respectively). Further, no significant differences were noted between hatched and unhatched groups in rates of spontaneous abortions, monozygotic twinning, dizygotic twinning, chromosomal abnormalities, or ectopic gestations. In addition, mean ZP thickness did not have a significant effect on pregnancy.\n In patients younger than 38 years with embryos with ZP thickness of > or =13 microm, assisted hatching does not improve the rates of implantation, clinical pregnancy, or live birth, and thus does not appear to offer any benefit to patients in this age group undergoing IVF.\n Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.", "The aim of this study was to determine if laser zona thinning could improve the rates of pregnancy and implantation for vitrified-warmed embryo transfer at the cleavage stage. A total of 400 vitrified-warmed embryo transfer cycles were randomly assigned to either the test group or the control group. The zona pellucida of vitrified-warmed embryos in the patients of the control group was untreated, whereas in the test group it was partially thinned by laser just before embryo transfer. In the test group, the clinical pregnancy and implantation rates were significantly lower as compared with that of the control group (28.5 versus 43.0, P=0.002, and 11.2 versus 16.7, P=0.004, respectively). Therefore the results of this investigation show that laser zona thinning may have an unexpected adverse effect on the rates of clinical pregnancy and implantation of vitrified-warmed embryos at the cleavage stage.\n 2009 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.", "Laser assisted zona thinning is a technique used for facilitating embryo's hatching process and is commonly used for the embryos of poor prognosis patients with advanced maternal age, repeated implantation failures, poor embryo quality or thick zona pellucida. The aim of this study was to investigate the effect of zona thinning on both good or poor prognosis patients of two different age groups.\n We investigated two different age groups (group 1: <35 years and group 2: ≥35 years ) and compared the effect of assisted zona thinning (groups 1A and 2A) versus not-thinned controls (groups 1B and 2B) in both groups.\n The clinical pregnancy rates were 57% and 56% in groups 1A and 1B (p = 0.86), 43% and 38% in groups 2A and 2B (p = 0.59) respectively.\n Our results suggest that laser assisted zona thinning of day 3 embryos has no beneficial effect on clinical pregnancy and implantation outcomes.", "To evaluate whether assisted hatching improves clinical outcomes of embryo transfers to good prognosis patients, defined as patients < or =39 years with normal follicle-stimulating hormone (FSH) and E(2) levels, no more than one previous unsuccessful cycle of in vitro fertilization (IVF)-embryo transfer, and good embryo quality.\n Prospective randomized controlled trial.\n Private assisted reproductive technology (ART) center.\n One hundred ninety-nine good prognosis patients undergoing IVF-embryo transfer.\n In vitro fertilization followed by embryo transfer on day 3 after oocyte retrieval with or without assisted hatching using a 1,480-nm wavelength infrared laser.\n Clinical intrauterine pregnancy, spontaneous pregnancy loss, and live birth.\n Rates of clinical intrauterine pregnancy with fetal cardiac activity (53% vs. 54% per cycle), spontaneous pregnancy loss (13% vs. 16% per pregnancy), and live birth (47% vs. 46% per cycle) were very similar between treatment cycles with laser-assisted hatching and control cycles in which embryos were transferred without assisted hatching. There were no significant differences between treatment and control groups in any measured clinical outcome parameters.\n Assisted hatching does not improve clinical outcomes among good prognosis patients.", "Cryopreservation of embryos may lead to zona hardening that may compromise in vivo hatching and implantation following thawing and transfer. Assisted hatching (AH) has been advocated as a means of assisting the natural hatching process and enhancing implantation.\n The aim of this study was to assess in a prospective randomized manner the effect of laser-assisted hatching (LAH) on implantation as well as clinical and multiple pregnancy rates (the primary outcome) after the transfer of frozen-thawed embryos. All embryos were thawed the day before transfer, and LAH was performed the next day on embryos that cleaved. Control group consisted of embryos that were transferred without AH.\n The performance of LAH significantly increased implantation (9.9 versus 20.1%, P < 0.01), clinical pregnancy (27.3 versus 40.9, P < 0.05) and multiple pregnancy rates (16 versus 40.3%, P < 0.07). In the LAH group, significantly more excess embryos that were left in culture hatched in vitro.\n LAH improves the outcome of frozen-thawed embryo transfer when performed before transfer on embryos that were allowed to cleave.", "The aim of this study was to determine if assisted hatching (AH) could improve the rates of pregnancy and implantation for both fresh and frozen-thawed embryo transfer cycles. A total of 760 fresh embryo transfer cycles and 200 frozen-thawed embryo transfer cycles were randomly assigned to either the treatment group (AH) or the control group (no AH). Zona thinning by laser was performed just before embryo transfer. In fresh embryo transfer cycles, the AH group and control group results were comparable. There were no significant differences in the rates of positive human chorionic gonadotrophin (HCG; 47.5 versus 48.8%), clinical pregnancy (42.4 versus 42.6%), or implantation (26.3 versus 25.2%) between the two groups. However, in frozen-thawed embryo transfer cycles, the rates of positive HCG (32.0 versus 17.0%), clinical pregnancy (25.0 versus 14.0%) and implantation (16.7 versus 7.3%) were significantly greater in the AH group than in the control group (P &lt: 0.05). The results of this investigation show that in the fresh embryo transfer cycles, laser-assisted hatching by zona thinning has no impact on the rates of positive HCG, clinical pregnancy and implantation, whereas in frozen-thawed cycles, assisted hatching by zona thinning significantly increases all three of these rates.", "In this prospective randomized study the effects of enzymatic treatment of zona pellucida of blastocysts on implantation and pregnancy rates were evaluated in a group of patients who had more than five embryos on day 3.\n Forty-six patients with a mean age of 29.8 +/- 4.5 years and mean duration of infertility of 6.72 +/- 0.63 years had blastocyst stage transfers, with a mean number of 2.9 +/- 0.1 embryos replaced per patient. Patients were randomly divided into two groups. The first group consisted of patients (n = 22) who had zona intact blastocyst stage transfers and the second group consisted of patients (n = 24) who had zona manipulated (enzymatic treatment) blastocyst stage transfers. Patient and cycle characteristics were similar in both groups. A commercial cell and serum-free sequential culture system was used for all embryos.\n Overall blastocyst formation rate was 50.3%. Transfer could be done in all patients. The positive beta-human chorionic gonadotropin rate in the zona intact group was 50% (11/22) and in the zona-manipulated group was 70.8% (17/24). Clinical pregnancy, ongoing pregnancy, and implantation rates in zona intact and manipulated groups were 45.5%, 27.3%, and 19%, and 62.5%, 45.8%, and 24% respectively. Although implantation and pregnancy rates in the zona-manipulated group were higher, there were no statistically significant differences in terms of these variables between two groups. No triplet pregnancy was obtained in either group, and the twin pregnancy rate was 20% (2/10) in the zona intact group and 13.3% (2/15) in the zona-manipulated group.\n With further improvements in the embryo culture systems it will become possible in the near future to achieve high implantation rates even with single blastocyst transfers. Enzymatic treatment of the zona pellucida seems that it does not alter the pregnancy and implantation rates, but further studies with larger group of patients are needed to clarify the real effect of this zona manipulation on pregnancy outcome.", "Assisted hatching (AH) techniques, designed for facilitating the embryo escape out of the zona pellucida (ZP) have been used in IVF centres since 1992. The initial indications for AH were patient's age, ZP thickness, high basal FSH and repeated IVF failures. Several retrospective and prospective studies assessing AH in these indications have given disparate results. Our aims were to evaluate the benefits of AH and immunosuppressive/antibiotic treatment (IA) in patients with either a poor prognosis of success, previous implantation failures or transfers of cryopreserved embryos.\n Four IVF centres allocated 426 patients, randomized for AH and IA, into four groups of AH indications between 1997 and 1999. AH was performed with a diode laser. ZP thickness, opening size and embryo score were recorded. Outcome measures were implantation and delivery rates.\n Patients coming for a first or third transfer of cryopreserved embryos and poor prognosis patients admitted for a first trial did not benefit from AH. Even patients with repeated implantation failures of fresh embryos did not gain significantly from AH.\n Among AH indications, absence of implantation after several transfers of good quality embryos remains the strongest patient selection criterion. Prescription of an immunosuppressive/antibiotic treatment is essential." ]

[ "15582060", "15333725", "15173147" ]

[ "Monetary incentives in primary health care and effects on use and coverage of preventive health care interventions in rural Honduras: cluster randomised trial.", "Conditional cash transfers are associated with a small reduction in the rate of weight gain of preschool children in northeast Brazil.", "Impact of the Mexican program for education, health, and nutrition (Progresa) on rates of growth and anemia in infants and young children: a randomized effectiveness study." ]

[ "Scaling-up of effective preventive interventions in child and maternal health is constrained in many developing countries by lack of demand. In Latin America, some governments have been trying to increase demand for health interventions by making direct payments to poor households contingent on them keeping up-to-date with preventive health services. We undertook a public health programme effectiveness trial in Honduras to assess this approach, contrasting it with a direct transfer of resources to local health teams.\n 70 municipalities were selected because they had the country's highest prevalence of malnutrition. They were allocated at random to four groups: money to households; resources to local health teams combined with a community-based nutrition intervention; both packages; and neither. Evaluation surveys of about 5600 households were undertaken at baseline and roughly 2 years later. Pregnant women and mothers of children younger than 3 years old were asked about use of health services (primary outcome) and coverage of interventions such as immunisation and growth monitoring (secondary outcome). Reports were supplemented with data from children's health cards and government service utilisation data. Analysis was by mixed effects regression, accounting for the municipality-level randomisation.\n The household-level intervention had a large impact (15-20 percentage points; p<0.01) on the reported coverage of antenatal care and well-child check-ups. Childhood immunisation series could thus be started more opportunely, and the coverage of growth monitoring was markedly increased (15-21 percentage points; p<0.01. Measles and tetanus toxoid immunisation were not affected. The transfer of resources to local health teams could not be implemented properly because of legal complications.\n Conditional payments to households increase the use and coverage of preventive health care interventions.", "Programs providing cash transfers to poor families, conditioned upon uptake of preventive health services, are common in Latin America. Because of the consistent association between undernutrition and poverty, and the role of health services in providing growth promotion, these programs are supposed to improve children's growth. The impact of such a program was assessed in 4 municipalities in northeast Brazil by comparing 1387 children under 7 y of age from program beneficiary households with 502 matched nonbeneficiaries who were selected to receive the program but who subsequently were excluded as a result of quasi-random administrative errors. Anthropometric status was assessed 6 mo after benefits began to be distributed, and beneficiary children were 0.13 Z-scores lighter (weight-for-age) than excluded children, after adjusting for confounders (P = 0.024). The children's growth trajectories were reconstructed by copying up to 10 recorded weights from their Ministry of Health growth monitoring cards and by relating each weight to the child's age, gender, and duration of receipt of the program benefit in a random effects regression model. Totals of 472 beneficiary and 158 excluded children under 3 y of age were included in this analysis. Each additional month of exposure to the program was associated with a rate of weight gain 31 g lower than that observed in excluded children of the same age (P < 0.001). This failure to respond positively to the program may have been due to a perception that benefits would be discontinued if the child started to grow well. Nutrition programs should guard against giving the impression that poor growth will be rewarded.", "Malnutrition causes death and impaired health in millions of children. Existing interventions are effective under controlled conditions; however, little information is available on their effectiveness in large-scale programs.\n To document the short-term nutritional impact of a large-scale, incentive-based development program in Mexico (Progresa), which included a nutritional component.\n A randomized effectiveness study of 347 communities randomly assigned to immediate incorporation to the program in 1998 (intervention group; n = 205) or to incorporation in 1999 (crossover intervention group; n = 142). A random sample of children in those communities was surveyed at baseline and at 1 and 2 years afterward. Participants were from low-income households in poor rural communities in 6 central Mexican states. Children (N = 650) 12 months of age or younger (n = 373 intervention group; n = 277 crossover intervention group) were included in the analyses.\n Children and pregnant and lactating women in participating households received fortified nutrition supplements, and the families received nutrition education, health care, and cash transfers.\n Two-year height increments and anemia rates as measured by blood hemoglobin levels in participating children.\n Progresa was associated with better growth in height among the poorest and younger infants. Age- and length-adjusted height was greater by 1.1 cm (26.4 cm in the intervention group vs 25.3 cm in the crossover intervention group) among infants younger than 6 months at baseline and who lived in the poorest households. After 1 year, mean hemoglobin values were higher in the intervention group (11.12 g/dL; 95% confidence interval [CI], 10.9-11.3 g/dL) than in the crossover intervention group (10.75 g/dL; 95% CI, 10.5-11.0 g/dL) who had not yet received the benefits of the intervention (P =.01). There were no differences in hemoglobin levels between the 2 groups at year 2 after both groups were receiving the intervention. The age-adjusted rate of anemia (hemoglobin level <11 g/dL) in 1999 was higher in the crossover intervention group than in the intervention group (54.9% vs 44.3%; P =.03), whereas in 2000 the difference was not significant (23.0% vs 25.8%, respectively; P =.40).\n Progresa, a large-scale, incentive-based development program with a nutritional intervention, is associated with better growth and lower rates of anemia in low-income, rural infants and children in Mexico." ]

[ "11844897", "1317294", "12010380", "11128825", "15240983", "15482357", "15836564", "7564725", "7899379", "9885327", "8062355", "7954760" ]

[ "Zolmitriptan versus a combination of acetylsalicylic acid and metoclopramide in the acute oral treatment of migraine: a double-blind, randomised, three-attack study.", "A study to compare oral sumatriptan with oral aspirin plus oral metoclopramide in the acute treatment of migraine. The Oral Sumatriptan and Aspirin plus Metoclopramide Comparative Study Group.", "Mouth-dispersible aspirin in the treatment of migraine: a placebo-controlled study.", "Acetylsalicylic acid effervescent 1000 mg (Aspirin) in acute migraine attacks; a multicentre, randomized, double-blind, single-dose, placebo-controlled parallel group study.", "Efficacy of 1,000 mg effervescent acetylsalicylic acid and sumatriptan in treating associated migraine symptoms.", "Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks.", "Aspirin is efficacious for the treatment of acute migraine.", "The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine.", "[Efficacy and tolerance of an effervescent aspirin-metoclopramide combination in the treatment of a migraine attack. Randomized double-blind study using a placebo].", "Comparative efficacy and safety of calcium carbasalate plus metoclopramide versus ergotamine tartrate plus caffeine in the treatment of acute migraine attacks.", "Double-blind comparison of an acetaminophen 400 mg-codeine 25 mg combination versus aspirin 1000 mg and placebo in acute migraine attack.", "Combined oral lysine acetylsalicylate and metoclopramide in the acute treatment of migraine: a multicentre double-blind placebo-controlled study." ]

[ "This multicentre, randomised, double-blind study compared oral zolmitriptan 2.5 mg with a combination of oral acetylsalicylic acid 900 mg and metoclopramide 10 mg as acute anti-migraine therapy for 3 migraine attacks. In total, 666 patients took at least one dose of study medication (326 took zolmitriptan and 340 took acetylsalicylic acid plus metoclopramide). The percentage of patients with a 2-hour headache response after the first dose for all 3 attacks (the primary end point) was 33.4% with zolmitriptan and 32.9% with acetylsalicylic acid plus metoclopramide [odds ratio 1.06, 95% confidence interval (CI) 0.77-1.47; p = 0.7228]. For the majority of secondary end points, the two treatments demonstrated comparable efficacy. However, post hoc analysis showed that significantly more patients receiving zolmitriptan were free of pain 2 h after the first dose in all 3 attacks compared with patients receiving acetylsalicylic acid plus metoclopramide (10.7 vs. 5.3%; odds ratio 2.19, 95% CI 1.23-4.03; p = 0.0095). In addition, post hoc analysis showed that the overall 2-hour pain-free response rate was consistently higher with zolmitriptan (34.6%) than with acetylsalicylic acid plus metoclopramide (27.9%) (odds ratio 1.40, 95% CI 1.09-1.78; p = 0.007). Both treatments reduced migraine-associated nausea, vomiting, phonophobia and photophobia. There were no important inter-group differences with respect to the onset of meaningful migraine relief, the frequency of headache recurrence, the usage or efficacy of a second dose of medication or the use of escape medication. However, at the last attack, the proportion of patients who expressed overall satisfaction with the treatment was significantly higher in the zolmitriptan group, i.e. 83.7%, versus 75.0% with acetylsalicylic acid plus metoclopramide (p = 0.0346). Both agents were well tolerated. Adverse events were reported by 40.8% (133/326) of zolmitriptan-treated patients and 29.1% (99/340) of those treated with acetylsalicylic acid plus metoclopramide. The incidence of withdrawals due to adverse events was very low with both zolmitriptan (0.9%) and the combination regimen (1.5%); the latter percentage included 1 patient who withdrew from the study due to phlebitis, which was classified as a serious adverse event. This study showed that zolmitriptan is effective and well tolerated for the acute treatment of moderate to severe migraine. Zolmitriptan was at least as effective as acetylsalicylic acid plus metoclopramide in achieving a 2-hour headache response, but significantly more effective than the combination therapy for other end points, including the 2-hour pain-free response.\n Copyright 2002 S. Karger AG, Basel", "In a double-blind, placebo-controlled study, the efficacy, safety and tolerability of 100 mg oral sumatriptan, given as a dispersible tablet, was compared with that of 900 mg oral aspirin plus 10 mg oral metoclopramide in the acute treatment of migraine. A total of 358 patients treated up to three migraine attacks within 3 months, recording clinical information on a diary card. In attack 1, headache relief after 2 h, defined as a reduction in severity from severe or moderate pain to mild or no pain, was recorded in 56% (74/133) of patients who took sumatriptan and 45% (62/138) of patients who took aspirin plus metoclopramide (p = 0.078). This analysis of the primary efficacy end point was not statistically significant. However, for attacks 2 and 3 (secondary end points), headache relief was achieved in 58 versus 36% of patients (p = 0.001) and 65 versus 34% of patients (p less than 0.001), respectively. Relief from nausea, vomiting, photophobia and phonophobia was similar in both treatment groups. Rescue medication was required by fewer patients treated with sumatriptan than by those who received aspirin plus metoclopramide (attack 1, 34 versus 56%, p less than 0.001; attack 2, 32 versus 51%, p = 0.001, and attack 3, 35 versus 54%, p = 0.001). Sumatriptan also produced a faster improvement and resolution of migraine attacks. Comparing the sumatriptan and aspirin plus metoclopramide treatment groups, complete resolution of the attack occurred within 6 h in 32 versus 19% (attack 1), 35 versus 23% (attack 2) and 32 versus 20% of patients (attack 3).(ABSTRACT TRUNCATED AT 250 WORDS)", "To compare the efficacy of mouth-dispersible aspirin 900 mg and placebo in the treatment of migraine.\n Aspirin is widely accepted as an effective therapy for migraine. Previous studies have indicated that gastric stasis and delayed gastric emptying, which occur during migraine attacks, delay aspirin absorption. Mouth-dispersible formulations are considered to be more quickly absorbed than solid formulations and, therefore, may be more effective in treating migraine.\n Randomized, double-blind, placebo-controlled, crossover study in four specialized migraine clinics in the United Kingdom.\n One hundred one patients diagnosed with migraine (according to the International Headache Society diagnostic criteria) participated in the study. Patients received either single doses of mouth-dispersible aspirin (3 x 300 mg) or placebo for moderate pain in the treatment of two migraine attacks. Rescue medication could be taken after 2 hours, if required. The primary efficacy parameter was response to therapy at 2 hours posttreatment. Other efficacy parameters were response to treatment, pain-free, and pain intensity at all other time points. Functional disability, nausea, vomiting, photophobia, phonophobia, symptom relief, patient and investigator global evaluation, use of rescue medication, headache recurrence, and palatability and convenience were also recorded.\n Of 101 patients, 73 took both treatments. At 2 hours, 48% of patients taking mouth-dispersible aspirin responded, compared to only 19% taking placebo (P =.0005). Mouth-dispersible aspirin was significantly better than placebo for response to treatment (P<.05) and pain intensity difference (P<.01) at all time points from 30 minutes posttreatment; for pain-free (P<.05) and use of rescue medication (P<.01) from 3 hours posttreatment; for headache recurrence (P<.05); and for patients' and investigators' global evaluations of efficacy (P =.0001 in both cases).\n Mouth-dispersible aspirin 900 mg is effective compared with placebo for the treatment of moderate migraine head pain, with relief seen from as early as 30 minutes after taking medication.", "In this multicentre, randomized, double-blind, single-dose study a total of 374 patients generally suffering from migraine attacks suitable for treatment with non-prescription drugs, received either oral acetylsalicylic acid effervescent 1000 mg (ASAE) or effervescent placebo for the treatment of an acute migraine attack. Of the 343 patients fulfilling the criteria for efficacy analysis 169 patients took acetylsalicylic acid and 174 placebo. Response rates (reduction of headache severity from severe or moderate to mild or no pain at 2 h after administration) were 55.0% for acetylsalicylic acid and 36.8% for placebo (P < 0.001). Twenty-nine percent of patients in the active treatment group were pain-free after 2 h compared with 16.7% in the placebo group (P = 0.007). No headache recurred within 24 h post-dose in 84.6% of patients in the active group and in 85.1% of patients in the placebo group. Effervescent placebo reduced nausea and vomiting to the same degree as the active drug. Adverse events of acetylsalicylic acid (8.3%) were generally mild or moderate and comparable to those of placebo (2.9%). This study shows that oral ASAE is safe and effective for the treatment of acute migraine attacks.", "Recently a new effervescent acetylsalicylic acid (ASA) tablet with high buffering capacity has been developed. In this double-blind, 3-arm, multicenter, parallel-group study, 433 patients were treated either with 1,000 mg effervescent ASA or 50 mg encapsulated sumatriptan or placebo. The primary endpoint was the percentage of patients with complete remission of the 3 accompanying symptoms nausea, photophobia and phonophobia within 2 h after intake of the study drug. 43.8% of patients treated with ASA, 43.7% of patients treated with sumatriptan and 30.9% of patients treated with placebo showed complete remission of all 3 accompanying symptoms (p < 0.05 for ASA and sumatriptan vs. placebo). Both active treatments were superior to placebo regarding the individual symptoms photophobia and phonophobia, but not for nausea. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (secondary objective) was 49.3% for ASA, 48.8% for sumatriptan and 32.9% for placebo. All active treatments were superior to placebo (p < 0.05). 25.3, 24.4 and 14.5% of patients treated with ASA, sumatriptan or placebo were pain free at 2 h. Drug-related adverse events were reported in 3.9, 4.7 and 6.7% of patients treated with placebo, ASA or sumatriptan. The study showed that administration of effervescent ASA leads to remission of the migraine symptoms nausea, photophobia and phonophobia, reduces migraine headache and is comparable to sumatriptan.\n Copyright 2004 S. Karger AG, Basel", "Acetylsalicylic acid (ASA) in combination with metoclopramide has been frequently used in clinical trials in the acute treatment of migraine attacks. Recently the efficacy of a new high buffered formulation of 1000 mg effervescent ASA without metoclopramide compared to placebo has been shown. To further confirm the efficacy of this new formulation in comparison with a triptan and a nonsteroidal anti-inflammatory drug (ibuprofen) a three-fold crossover, double-blind, randomized trial with 312 patients was conducted in Germany, Italy and Spain. Effervescent ASA (1000 mg) was compared to encapsulated sumatriptan (50 mg), ibuprofen (400 mg) and placebo. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (primary endpoint) was 52.5% for ASA, 60.2% for ibuprofen, 55.8% for sumatriptan and 30.6% for placebo. All active treatments were superior to placebo (P < 0.0001), whereas active treatments were not statistically different. The number of patients who were pain-free at 2 h was 27.1%, 33.2%, 37.1% and 12.6% for those treated with ASA, ibuprofen, sumatriptan or placebo, respectively. The difference between ASA and sumatriptan was statistically significant (P = 0.025). With respect to other secondary efficacy criteria and accompanying symptoms no statistically significant differences between ASA and ibuprofen or sumatriptan were found. Drug-related adverse events were reported in 4.1%, 5.7%, 6.6% and 4.5% of patients treated with ASA, ibuprofen sumatriptan or placebo. This study showed that 1000 mg effervescent ASA is as effective as 50 mg sumatriptan and 400 mg ibuprofen in the treatment of migraine attacks regarding headache relief from moderate/severe to mild/no pain at 2 h. Regarding pain-free at 2 h sumatriptan was most effective.", "More than 50% of migraine sufferers rely on over-the-counter medications for the treatment of migraine. Along with other over-the-counter products, aspirin is considered by the US Headache Consortium to be an option for first-line migraine treatment. This study assessed the efficacy and tolerability of aspirin versus placebo for the acute treatment of a single acute attack of migraine.\n This prospective, randomized, double-blind, parallel-group, placebo-controlled study evaluated the efficacy of a single, 1000-mg dose of aspirin for the treatment of acute moderate to severe migraine, with or without aura. Subjects recorded all study evaluations in a diary at baseline and at .5, 1, 2, 3, 4, 5, 6, and 24 hours after treatment. Pain was rated on a 4-point ordinal scale from no pain to severe pain. The primary efficacy end point was headache response at 2 hours. Secondary efficacy parameters included reduction of nausea, photophobia and phonophobia, pain intensity difference, and headache recurrence at 24 hours.\n Of 485 subjects enrolled, 409 took study medication and 401 treated a confirmed migraine attack (201 with aspirin and 200 with placebo). Baseline demographic and migraine characteristics were not significantly different between groups. The 2-hour headache response rate was 52% with aspirin versus 34% with placebo (P<.001). Aspirin was significantly more effective than placebo for pain reduction beginning 1 hour after dosing (P<.001) and continuing throughout the 6-hour evaluation period. Significantly (P<.05), more subjects were pain free from the 1-hour evaluation through the 6-hour evaluation. Of the aspirin-treated subjects, 20% were pain free at 2 hours versus only 6% of placebo-treated subjects. At 24 hours, the headache recurrence rate was 21.8% for aspirin (23 of 105 subjects) and 27.7% for placebo (19 of 68 subjects). Only 34% of aspirin-treated subjects needed rescue medication at 24 hours compared with 52% of placebo-treated subjects (P<.001). Aspirin was well tolerated, and adverse events were not significantly different between groups.\n This study demonstrates that aspirin is safe and effective for treatment of acute migraine in appropriately selected patients.", "Aspirin is commonly used to treat migraine attacks, although sumatriptan, a much more expensive treatment, is also effective. We compared a combination of lysine acetylsalicylate (equivalent to 900 mg aspirin) and 10 mg metoclopramide (LAS+MTC) with oral sumatriptan (100 mg) and placebo in 421 patients with migraine. LAS+MTC was as effective as sumatriptan with a decrease of headache from severe or moderate to mild or none of 57% and 53%, respectively, for the first migraine attack treated. Both treatments were better than placebo (success rate 24%, p < 0.0001). LAS+MTC was significantly more effective in the treatment of nausea than sumatriptan (p < 0.0001) and was better tolerated (adverse events in 18% and 28%, respectively, p < 0.05). LAS+MTC is as effective as sumatriptan in the treatment of migraine attacks. It is also much cheaper.", "A double blind, randomized, multicenter, parallel group study was carried out to compare the efficacy and tolerance of aspirin 900 mg-metoclopramide 10 mg effervescent association (AAM) with those of placebo in the treatment of acute migraine attack. All patients were selected according to the International Headache Society criteria.\n A total of 303 out-patients with an acute migraine attack were treated orally with either AAM (n = 152) or placebo (n = 151).\n The aspirin-metoclopramide association was significantly more effective than placebo at relieving headache (principal criterion) within 2 h of treatment (54.3% versus 25.9% : p < 0.001), producing entire resolution of acute migraine attack (14.2% versus 5.3% : p = 0.017), reducing the percentage of patients requiring rescue medication (44.3% versus 63.2% : p = 0.001) and increasing the percentage of patients able to resume their usual activities (44.1% versus 22.1% : p = 0.003). AAM also provided more frequent relief from associated symptoms as compared with placebo (37.4% versus 22.1% : p = 0.006). The therapeutic efficacy was rated as good or excellent by 39.7% of patients in the AAM group compared with 20.7% in the placebo group (p < 0.001). Moreover 64.2% of AAM treated patients said they would be prepared to take the treatment again compared with 46.4% who received placebo (p < 0.001). The percentage of patients reporting adverse events was not different between the two treatments (20.4% AAM versus 18.5% placebo : p = 0.684). The most commonly reported symptoms were gastro-intestinal disorders. Similar number of gastralgia occurred with AAM (n = 4) and placebo (n = 3).\n It is concluded that the aspirin-metoclopramide association may be used as a first intention treatment of acute migraine attack in out-patients.", "This randomized, double-blind, double-dummy, multicenter, parallel-group study aimed at comparing the efficacy and safety of calcium carbasalate (equivalent to 900 mg aspirin) plus metoclopramide 10 mg (CM) with ergotamine tartrate 1 mg plus caffeine 100 mg (EC) administered in the treatment of 2 acute migraine attacks. A total of 296 patients fulfilling the International Headache Society diagnostic criteria for migraine were enrolled. In total, one or two migraine attacks were treated in 268 and 235 patients, respectively. The primary endpoint for the first treated attack was headache relief, with intensity decreasing from moderate or severe to mild or absent 2 h after drug intake. Usual secondary efficacy endpoints were assessed. A superiority of CM over EC was observed for both treated attacks for the main endpoint: success in 54 versus 36%, p = 0.003 for the first attack and 60 versus 44%, p = 0.02 for the second attack. CM was also significantly superior to EC during the first attack for complete headache relief (20 vs. 8%, p = 0.006), nausea (42 vs. 63%, p = 0. 007) and willingness to take the drug again (90 vs. 80%, p = 0.043). The global efficacy evaluation, rated by the investigators, was significantly more favorable to CM for both attacks (p = 0.001 for the first attack and p = 0.02 for the second). The patients' evaluation was significant for the first attack (p = 0.002). The global incidence of adverse events was 45% higher with EC, though not significant (32 vs. 22%, p = 0.075). They were most often unspecific and mild to moderate in intensity. Gastrointestinal side effects were significantly less frequent with CM than EC (7 vs. 21%, p = 0.001). Thus, CM is more effective and has a better gastrointestinal safety than EC in the acute treatment of migraine attacks.", "The purpose of this study was to compare the efficacy and tolerance of a single dose of the acetaminophen 400 mg-codeine 25 mg combination (ACC) aspirin 1000 mg (A) and a placebo (P) for the treatment of acute migraine attack. The study design was randomized, multicentre, double-blind and double dummy with cross-over on three periods. Of the 198 patients who had three attacks 29.8%, 52.3% and 49.7% had recorded the complete or almost complete disappearance of the pain at 2 h after P, A and ACC respectively. When compared with the placebo, the difference was significant for the A and ACC. When complete disappearance of pain at 2 h was used as a criterion, no significant difference was observed. These results enabled the sensitivity of the evaluation criteria suggested for clinical trials of migraine attack to be discussed.", "This multicentre, double-blind, randomized, placebo-controlled, parallel study was designed to evaluate the efficacy of combined oral lysine acetylsalicylate and metoclopramide (LAS-MCP) in the acute treatment of migraine attacks. A total of 266 patients, 18-65 years old, with two to six attacks of migraine with or without aura (IHS criteria) per month were included. The patients had to treat two migraine attacks with LAS-MCP (1620 mg lysine acetylsalicylate--the equivalent of 900 mg aspirin--combined with 10 mg metoclopramide) or placebo. The main outcome measure was headache relief (reduction in headache severity from grade 3 or 2--severe or moderate--to grade 1 or 0--mild or none) 2 h after treatment. LAS-MCP was superior to placebo for headache relief (56% vs 28%) and for the following secondary outcome measures: complete headache relief (18% vs 7%; p < 0.001), nausea (28% vs 44%; p < 0.001), vomiting (3% vs 11%; p = 0.001), use of rescue medication (47% vs 68%; p < 0.001), global efficacy judged as good or excellent (32% vs 14%; p < 0.001). The tolerability was considered as good in 94% of treated attacks in both groups. Combined oral lysine acetylsalicylate and metoclopramide is an effective and well-tolerated acute treatment of migraine attacks." ]

[ "11727838", "15290737", "12422010" ]

[ "Clinical investigation of methotrexate in the treatment of ankylosing spondylitis.", "Efficacy of methotrexate in ankylosing spondylitis: a randomized, double blind, placebo controlled trial.", "Is methotrexate effective in ankylosing spondylitis?" ]

[ "To investigate the efficacy and possible side effects of Methotrexate (MTX) treatment in patients with ankylosing spondylitis.\n A total of 51 patients with a diagnosis of AS according to NewYork criteria were randomly distributed into 2 groups. In Group I (n = 25) only Naproxen (1000 mg/day) and in Group II (n = 26) oral MTX (7.5 mg/week) combined with Naproxen were given for 12 months. The patients were evaluated at 3, 6, and 12 months after the start of the treatment according to a number of clinical parameters using objective and subjective variables. Data were analysed using ki-square and Mann-Whitney U tests.\n The comparison of the values using the percent changes and difference scores with respect to pretreatment values showed significant improvement in the \"global evaluation of the physician\" in Group II compared to Group I while no other parameter was found to be significantly different between the two groups. Those results have led us to conclude that a combination of MTX with Naproxen did not prove to be superior to Naproxen-alone treatment in terms of statistical significance. Further trials with MTX employing larger doses and different patient populations, mainly comprised of peripheral arthritis are necessary for delineation of the role of MTX in AS treatment.", "To evaluate the efficacy and safety of methotrexate (MTX) compared with placebo in patients with active ankylosing spondylitis (AS).\n This 24 week, double bind, randomized, placebo controlled trial compared the response between MTX 7.5 mg/week or placebo in patients with active AS. The primary outcome measure was a composite index of improvement in 5 of the following scales: severity of morning stiffness, physical well being, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S), and physician and patient global assessment of disease activity.\n Seventeen patients received MTX and 18 placebo. In the intention-to-treat analysis at 24 weeks, 53% of patients in the MTX group had a treatment response, compared with 17% in the placebo group (p = 0.03). We observed significant improvements with MTX in physical well being (p = 0.009), BASDAI (p = 0.02), BASFI (p = 0.02), physician global assessment (p < 0.001), patient global assessment (p = 0.03), and HAQ-S (p = 0.02). In the adjusted analysis only MTX determined the improvement in the primary outcome. At the end of the trial, one patient with MTX withdrew due to a lack of compliance, and one with placebo due to a lack of efficacy. We did not observe significant differences in rates of side effects between the 2 groups.\n MTX is safe and effective for patients with AS. Longterm studies are needed to evaluate the permanence of its benefit.", "nan" ]

[ "1913022", "2404204", "3044474", "2566048", "3381269", "1390495", "7586783", "6778795", "1771312" ]

[ "Inefficacy of topical alpha interferon in the treatment of oral ulcers of Behçet's syndrome: a randomized, double blind trial.", "A controlled trial of azathioprine in Behçet's syndrome.", "Treatment with acyclovir does not affect orogenital ulcers in Behçet's syndrome: a randomized double-blind trial.", "Double-masked trial of cyclosporin versus colchicine and long-term open study of cyclosporin in Behçet's disease.", "Evaluation of conventional therapy versus cyclosporine A in Behçet's syndrome.", "Low dose cyclosporin A versus pulsed cyclophosphamide in Behçet's syndrome: a single masked trial.", "Inefficacy of azapropazone in the acute arthritis of Behçet's syndrome: a randomized, double blind, placebo controlled study.", "A double blind study of colchicine in Behçet's disease.", "[Desensitization by autologous saliva and Behçet's disease]." ]

[ "nan", "Cytotoxic agents have long been used in Behçet's syndrome, especially for eye involvement, but their effectiveness has been uncertain. We conducted a two-year randomized, placebo-controlled, double-blind trial of azathioprine (2.5 mg per kilogram of body weight per day) in Turkish men with Behçet's syndrome without eye disease (group 1; n = 25) or with eye disease (group 2; n = 48). Corticosteroid treatment remained available to all the patients. All six patients withdrawn from the study because of severe eye disease were receiving placebo (P less than 0.001). Azathioprine was superior to placebo in the prevention of new eye disease in group 1 (1 vs. 8 patients; P less than 0.01) and in group 2 among the 14 patients who at entry had disease in only one eye (P less than 0.001). There were fewer episodes of hypopyon uveitis (1 vs. 15; P less than 0.001) among the group 2 patients who took azathioprine. The patients taking azathioprine also had less frequent oral ulcers, genital ulcers, and arthritis. There were no serious side effects attributable to azathioprine. We conclude that azathioprine is effective in controlling the progression of Behçet's syndrome, especially its most serious manifestation, eye disease.", "Acyclovir is a potent antiviral drug, of proven efficacy in the treatment of herpes simplex virus infection. Since this virus has been implicated in the aetiology of Behçet's syndrome, the effect of acyclovir on orogenital ulceration in this condition was determined in a randomized, double-blind, placebo-controlled, crossover trial. Eighteen of 22 patients entering the study completed the trial. Treatment with acyclovir failed to alleviate the frequency and severity of orogenital ulceration or other disease features.", "The efficacy and safety of oral cyclosporin 10 mg/kg per day in Behçet's disease were compared in a randomised double-masked study with those of colchicine, 1 mg orally per day, and were also investigated in a long-term open study. The double-masked study showed that cyclosporin was effective in treating not only the ocular manifestations of Behçet's disease but also oral aphthous ulcer, dermal lesions, and genital ulceration. Efficacy did not weaken during long-term treatment.", "When ocular structures are affected in Behçet's syndrome, a rapid loss of vision has been the rule regardless of the type of treatment--corticosteroids, Leukeran, Imuran, colchicine. The objectives of the present study were to compare, in a masked manner, conventional treatment (corticosteroids/Leukeran) to treatment with CsA. Forty patients suffering from Behçet's syndrome with active ocular inflammatory reactions were included in the study. These were randomly assigned to conventional or CsA regimens and were regularly examined by a multidisciplinary group of physicians. The unmasked internist modulated the treatment and recorded systemic manifestations. The masked ophthalmologists recorded the ocular findings without knowledge of the assigned type of treatment. An analysis of the results 3 years after initiation of the study shows that CsA is more effective than conventional therapy in decreasing the active ocular inflammatory processes and arresting the deterioration of visual acuity. Regarding the extraocular symptoms, however, conventional therapy is superior to CsA, especially for the control of skin lesions and arthritis. Side effects were recorded in a much higher incidence among patients receiving CsA. However, tight and constant control of the CsA dosage as performed in this study has, so far, prevented clinical and biochemical nephrotoxic manifestations in patients assigned to this treatment.", "A single masked trial of cyclosporin A 5 mg/kg/day versus monthly 1 g intravenous boluses of cyclophosphamide was conducted among 23 patients with Behçet's syndrome and active, potentially reversible uveitis. The trial was unmasked after a mean of 12 (SD 2) months for the cyclosporin A group (n = 12) and a mean of 10 (SD 3) months for the cyclophosphamide group (n = 11). During the initial 6 months the visual acuity significantly improved (p < 0.001) in the cyclosporin A group whereas this was not observed in the cyclophosphamide group. The subsequent follow-up of patients up to 24 months suggested that the initial improvement in visual acuity with cyclosporin A was not sustained. More extensive and especially long-term studies of cyclosporin A in the uveitis of Behçet's syndrome are warranted.", "Sixty-three consecutive Behçet's syndrome patients with an acute arthritis of up to 10 days duration were treated either with azapropazone (APZ) 300 mg t.i.d. or placebo for three weeks. Twenty-eight patients (14 males, 14 females: mean age 36.2 +/- 8.1 SD years) from the APZ group and 29 patients (18 males, 11 females; mean age 34.2 +/- 8.4 SD years) from the placebo group completed the trial. At the end of the trial the arthritis persisted in 53.5% (15/28) of the APZ patients and in 41.3% (12/29) of the placebo patients (chi 2 = 0.85; NS). Six patients (6/28; 21%) from the APZ group and 9 patients (9/29; 31%) from the placebo group developed new joint involvement (chi 2 = 0.7; NS). There was no difference in the duration of arthritis between the two groups (19.9 +/- 8.3 SD days in the APZ groups vs. 19.7 +/- 8.2 SD days in the placebo group; NS). The degree of joint swelling, the tender joint score and the visual analogue score for pain significantly improved in both groups, but there was no difference in any of these parameters between the groups except for a significant difference in the visual analogue score for less pain at the first week in the azapropazone group (t = 2.23; p < 0.05). There were also no differences in the mean numbers of acetaminophen tablets used or in the CRP and ESR levels between the two groups. We conclude that azapropazone is not effective in controlling the arthritis of Behçet's syndrome.", "nan", "Among 240 patients with Behçet's disease seen in the Internal Medicine Department of the Ibnou Rochd University Hospital, Casablanca, between January 1981 and April 1988, 44 were selected to study the effects of desensitization by autologous saliva on oral and genital aphthae and on articular manifestations. Thirty of these 44 patients received gradually decreasing dilutions of their own saliva, and 14 control patients received physiological saline. Injections were administered intradermally twice a week during 15 weeks, then once a week during one year, so that the study lasted one and a half year, from October 1986 to April 1988. No improvement of the arthritis was observed, whereas the oral aphthae were improved in 50% of the patients desensitized by their own saliva. This percentage would have raised some hopes for the treatment of these sometimes disabling lesions were it not for the fact that 50% of the controls were similarly improved. This suggests that desensitization by saliva has a placebo effect." ]

[ "15284736", "9070140", "15228994", "15343260" ]

[ "A randomized clinical trial of the intrapartum assessment of amniotic fluid volume: amniotic fluid index versus the single deepest pocket technique.", "A randomised comparison between amniotic fluid index and maximum pool depth in the monitoring of post-term pregnancy.", "Biophysical profile with amniotic fluid volume assessments.", "Amniotic fluid index vs single deepest pocket technique during modified biophysical profile: a randomized clinical trial." ]

[ "The purpose of this study was to determine whether an intrapartum assessment of amniotic fluid identifies a pregnancy that is at risk for an adverse outcome.\n Parturients who were admitted for delivery were assigned randomly to have the amniotic fluid assessed either by amniotic fluid index or by the presence of a 2 x 1 pocket.\n The amniotic fluid index was obtained in 499 pregnancies, and the 2 x 1 technique was performed in 501. Oligohydramnios was diagnosed in 25% of amniotic fluid index pregnancies versus 8% with the use of the 2 x 1 pocket technique (P <.001). Both techniques failed to identify patients who underwent an amnioinfusion for fetal distress (P=.864) or who experienced variable (P=.208) or late decelerations (P=.210) that influenced delivery, fetal distress in labor (P=.220), caesarean delivery for fetal distress (P=.133), and admission to neonatal intensive care unit (P=.686).\n Neither the amniotic fluid index nor the 2 x 1 pocket technique that was undertaken as a fetal admission test identifies a pregnancy that is at risk for an adverse outcome.", "To compare the impact of two different ultrasound methods for assessing amniotic fluid volume on the incidence of obstetric interventions in post-term pregnancies.\n A prospective randomised controlled trial.\n Liverpool Women's Hospital.\n Five hundred women with singleton, uncomplicated pregnancies with gestational age > or = 290 days.\n Random allocation to fetal monitoring by either: 1. amniotic fluid index and computerised cardiotocography, or 2. maximum pool depth and computerised cardiotocography.\n Primary: caesarean section. Secondary: the number of abnormal monitoring tests, induction of labour, intrapartum management and neonatal outcome.\n The number of abnormal amniotic fluid indices was significantly higher than the number of abnormal maximum pool depths (10% vs 2.4%; OR 4.51, 95% CI 1.82-11.21; P = 0.0008) which resulted in more inductions for abnormal post-term monitoring in the amniotic fluid index group (14.8% vs 8.4%; OR 1.89; 95% CI 1.07-3.33; P = 0.0362) and more intrapartum electronic fetal monitoring (94.4% vs 88.4%; OR 2.21; 95% CI 1.13-4.29; P = 0.0255). There were no other statistically significant differences in outcomes related to labour and delivery, but there was a trend towards more caesarean sections in the amniotic fluid index group (18.8% vs 13.2%), in particular caesarean sections for fetal distress (8% vs 4%). There were no perinatal deaths and no statistically significant differences in perinatal outcome between the two groups.\n Published reference ranges for amniotic fluid index overestimate the number of abnormal results in post-term pregnancies. Their use, when compared with maximum pool depth, is likely to increase the number of obstetric interventions with, as yet, an uncertain impact on perinatal mortality and morbidity. It is possible that antepartum fetal assessment in pregnancies where the risk of adverse perinatal outcome is very low may cause, rather than prevent morbidity.", "To compare the amniotic fluid index (AFI) with the single deepest pocket technique along with the other components of the biophysical profile (BPP) in predicting an adverse pregnancy outcome.\n Prospective, randomized trial of amniotic fluid assessment by AFI or single deepest pocket during a BPP. Cesarean delivery for fetal distress was the primary outcome evaluated.\n The AFI was used in 273 pregnancies and the single deepest pocket in 264. The AFI significantly increased the number of pregnancies labeled as oligohydramnios, 102 women (38%) compared with 46 women (17%; P <.001), odds ratio (OR) = 2.84, 95% confidence interval 1.90-4.25 in the single deepest pocket group. There was no difference in the number of women with oligohydramnios in the AFI group, 16 of 102 (16%), undergoing a cesarean delivery for fetal intolerance of labor compared with the single deepest pocket group, 6 of 46 (13%; P =.676). More women with normal fluid by the AFI method (AFI > 5), 20 of 170 (12%), underwent a cesarean delivery for fetal distress than the women with normal fluid by the single deepest pocket technique (2 cm x 1 cm pocket present) group, 12 of 218 (6%; P =.037, OR = 2.22, 95% confidence interval 1.05-4.70).\n The AFI offers no advantage in detecting adverse outcomes compared with the single deepest pocket when performed with the BPP. The AFI may cause more interventions by labeling twice as many at-risk pregnancies as having oligohydramnios than with the single deepest pocket technique.", "The purpose of this study was to determine the superior technique, if either, of the amniotic fluid index (AFI) vs the single deepest pocket technique in predicting an adverse pregnancy outcome among high-risk patients undergoing antenatal testing.\n Patients having modified biophysical profile (nonstress test plus sonographic estimation of amniotic fluid) were randomized to either have AFI or determination of the presence or absence of a 2 x 1-cm single deepest pocket.\n Between January of 1997 and December of 2001, 1080 women were randomized with 530 women in the AFI arm, and 558 in the 2 x 1 pocket arm. The maternal demographics and prenatal complications were similar between groups. Significantly more patients were identified as having oligohydramnios using AFI (17%) compared with using 2 x 1 pocket (10%) ( P =.002). The overall rate of cesarean section for nonreassuring fetal heart rate (FHR) tracing was 3.8% (30 cases, with 16 cases in the AFI-monitored, and 14 cases in the 2 x 1 pocket-monitored groups, respectively, P =.608). Logistic regression analysis showed no difference between the groups with respect to the ability to identify patients who underwent cesarean section for nonreassuring FHR tracing during labor ( P =.999). The umbilical artery pH <7.1 ( P =.688) and admission to the newborn intensive care unit were also comparable between groups.\n During antepartum fetal surveillance, use of single deepest pocket compared with amniotic fluid index is associated with a significantly lower rate of suspected oligohydramnios." ]

[ "8636779", "8177627", "2149017", "8826606", "10815320", "11136839", "8579082", "7540696", "7520676", "10071455", "9060560", "9615797" ]

[ "Randomized placebo-controlled trial of granulocyte-macrophage colony-stimulating factor in patients with chemotherapy-related febrile neutropenia.", "Recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of febrile neutropenia: a double blind placebo-controlled study in children.", "Efficacy and tolerability of recombinant human granulocyte-macrophage colony-stimulating factor in patients with chemotherapy-related leukopenia and fever.", "Results of a randomized trial of granulocyte colony-stimulating factor in patients with infection and severe granulocytopenia.", "[Granulocyte colony-stimulating factor in the treatment of febrile neutropenia].", "Granulocyte colony-stimulating factor in the treatment of high-risk febrile neutropenia: a multicenter randomized trial.", "Randomized comparison between antibiotics alone and antibiotics plus granulocyte-macrophage colony-stimulating factor (Escherichia coli-derived in cancer patients with fever and neutropenia.", "Improving treatment of chemotherapy-induced neutropenic fever by administration of colony-stimulating factors.", "Filgrastim in patients with chemotherapy-induced febrile neutropenia. A double-blind, placebo-controlled trial.", "Effect of granulocyte-colony stimulating factor on empiric therapy with flomoxef sodium and tobramycin in febrile neutropenic patients with hematological malignancies. Kan-etsu Hematological Disease and Infection Study Group.", "Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients.", "GM-CSF in chemotherapy-induced febrile neutropenia--a double-blind randomized study." ]

[ "To determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) used in addition to standard inpatient antibiotic therapy shortens the period of hospitalization due to chemotherapy-induced neutropenic fever.\n One hundred thirty-four patients with a hematologic (n = 47) or solid tumor (n = 87) who had severe neutropenia (< 0.5 x 10(9)/L) and fever (> 38.5 degrees C once or > 38 degrees C twice over a 12-hour observation period) were randomly assigned to receive GM-CSF 5 micrograms/kg/d (n = 65) or placebo (n = 69) in conjunction with broad-spectrum antibiotics for a minimum of 4 days and a maximum of 14 days. GM-CSF/placebo and antibiotics were stopped if the neutrophil count was greater than 1.0 x 10(9)/L and temperature less than 37.5 degrees C during 2 consecutive days, or for a leukocyte count > or = 10 x 10(9)/L, both followed by a 24-hour observation period (hospitalization period).\n Compared with placebo, GM-CSF enhanced neutrophil recovery. Median neutrophil counts at day 4 were 2.5 x 10(9)/L (range, 0 to 25) in the GM-CSF arm and 1.3 x 10(9)/L (range, 0 to 9) in the placebo arm (P < .001). No significant difference was observed with regard to median number of days with less than 1.0 x 10(9)/L neutrophils (4 v 4) or days of fever (3 v 3). The median number of days patients were hospitalized while on study was comparable in the GM-CSF and placebo groups at 6 (range, 3 to 14) versus 7 (range, 4 to 14), respectively, according to an intention-to-treat analysis (P = .27). Quality-of-life scores in 90 patients demonstrated significant differences in favor of the placebo group. Hospital costs were significantly higher for GM-CSF-treated patients if GM-CSF was included in the price (median costs, $4,140 [US] for GM-CSF v $590 for placebo; P < .05).\n These results indicate that GM-CSF does not affect the number of days for resolution of fever or the hospitalization period for this patient group, although a significant effect of GM-CSF was observed on neutrophil recovery.", "In a double blind study of 58 episodes of fever and profound neutropenia, children with cancer received either recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or placebo, combined with identical antimicrobial therapy, i.e. imipenem, on admission. The criteria for discontinuation of therapy were identical. A difference was demonstrated both in the number of hospital days, totaling 252 days in the rhGM-CSF group and 354 in the placebo group, days receiving antibiotics (220 vs. 322), and in the resolution of neutropenia (4.5 days vs. 6.0 days; P < 0.05). The number of episodes requiring antimicrobial therapy for longer than 10 days was 5 of 28 (12%) in the rhGM-CSF group as opposed to 15 of 30 (50%) in the placebo group (P = 0.01). rhGM-CSF was well-tolerated. We conclude that rhGM-CSF was efficacious in accelerating myeloid recovery and reducing the length of hospitalization in febrile neutropenia.", "30 patients with chemotherapy-related leukopenia (white cells 1.0 x 10(9)/l or lower) and fever (temperature 38.5 degrees C or higher) were treated in a double-blind randomised trial with standard antibiotics and 7 days of intravenously administered recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF, 2.8 micrograms/kg per day) or placebo. GM-CSF administration resulted in a faster percentage increase of peripheral neutrophil count after 2 and 3 days of treatment, except in patients treated with ablative chemotherapy and autologous bone-marrow transplantation. However, GM-CSF did not shorten the period of fever or antibiotic administration. No side-effects were observed; in particular tumour necrosis factor alpha and interleukin-6 did not increase in the 5 GM-CSF patients tested. These data suggest that a subgroup of patients with chemotherapy-related leukopenia and fever may benefit from GM-CSF treatment in view of the observed effects on neutrophil count.", "A study was carried out to investigate the efficacy and toxicity of granulocyte colony-stimulating factor (G-CSF) in the treatment of infection in 119 severely granulocytopenic patients with hematological malignancies after intensive chemotherapy. Patients were assigned randomly to receive either antibiotics alone (ceftazidime, 2 g, i.v., every 8 h + amikacin 7.5 mg/kg, i.v., every 12 h) or the same antimicrobial regimen plus G-CSF (5 micrograms/kg/day, s.c.). Measurements were clinical improvement, eradication of infection and toxicity. Patients who received antibiotics plus G-CSF had more clinical responses (82 versus 60%), less superinfections (6 versus 20%), less mortality (5 versus 15 patients), less days in hospital (median 10 versus 27) and reduced antibiotic usage compared to patients who received only antibiotics. Hematological recovery (granulocytes > 1.0 x 10(9)/l) was also shorter in these patients (12 versus 23 days). Fungal infections occurred only in the group treated with antibiotics alone. Toxicity secondary to G-CSF was absent. We conclude that the addition of G-CSF to broad spectrum antibiotics is useful in selected patients with severe granulocyctopenia after intensive chemotherapy and infection, because if may prove the outcome in these patients.", "To determine whether granulocyte colony-stimulating factor (G-CSF) used in addition to antibiotic therapy, in patients with chemotherapy-induced febrile neutropenia shortens the period of fever, neutropenia and hospitalization.\n The study was prospective. Patients with lymphoblastic acute leukemia (LAL) were included. They received intensive chemotherapy of induction, intensification, or consolidation. At random, a group received amikacin-ceftriaxone; if no had response after 3 days, we added vancomicin and, after 7 days, amphotericin. The other group received in addition these antibiotics, granulocyte colony-stimulating factor.\n The groups were comparable in the magnitude of the initial neutropenia (< 0.5 x 10(9)/L), site of the infection, chemotherapy received germs isolated, age, and sex. The patients of the group that received FEC-G were cured in the course of 3.1 days; in the group without FEC-G, this occurred in 7.2 days (p = 0.0001). At the end of the infectious episode, the number of neutrophils, in the group with FEC-G, was of 1.9 x 10(9)/L versus 0.7 x 10(9)/L (p = 0.0009). The mortality was of one and two cases (p = 0.46). The global mortality was 7.5%.\n The addition of FEC-G to the treatment with antibiotics, in febrile neutropenia, decreases duration of days with fever, hospitalization and neutropenia. However, the frequency of cure is not augmented.", "Granulocyte colony-stimulating factors (G-CSFs) have been shown to help prevent febrile neutropenia in certain subgroups of cancer patients undergoing chemotherapy, but their role in treating febrile neutropenia is controversial. The purpose of our study was to evaluate-in a prospective multicenter randomized clinical trial-the efficacy of adding G-CSF to broad-spectrum antibiotic treatment of patients with solid tumors and high-risk febrile neutropenia.\n A total of 210 patients with solid tumors treated with conventional-dose chemotherapy who presented with fever and grade IV neutropenia were considered to be eligible for the trial. They met at least one of the following high-risk criteria: profound neutropenia (absolute neutrophil count <100/mm(3)), short latency from previous chemotherapy cycle (<10 days), sepsis or clinically documented infection at presentation, severe comorbidity, performance status of 3-4 (Eastern Cooperative Oncology Group scale), or prior inpatient status. Eligible patients were randomly assigned to receive the antibiotics ceftazidime and amikacin, with or without G-CSF (5 microg/kg per day). The primary study end point was the duration of hospitalization. All P values were two-sided.\n Patients randomly assigned to receive G-CSF had a significantly shorter duration of grade IV neutropenia (median, 2 days versus 3 days; P = 0.0004), antibiotic therapy (median, 5 days versus 6 days; P = 0.013), and hospital stay (median, 5 days versus 7 days; P = 0.015) than patients in the control arm. The incidence of serious medical complications not present at the initial clinical evaluation was 10% in the G-CSF group and 17% in the control group (P = 0.12), including five deaths in each study arm. The median cost of hospital stay and the median overall cost per patient admission were reduced by 17% (P = 0.01) and by 11% (P = 0.07), respectively, in the G-CSF arm compared with the control arm.\n Adding G-CSF to antibiotic therapy shortens the duration of neutropenia, reduces the duration of antibiotic therapy and hospitalization, and decreases hospital costs in patients with high-risk febrile neutropenia.", "A prospective, randomized study was conducted to determine if recombinant human granulocyte-macrophage colony-stimulating factor (rh-GMCSF) (Escherichia coli-derived) could improve response rates to antibiotic therapy and shorten the duration of neutropenia in cancer patients. PATIENTS and\n A total of 107 febrile neutropenic cancer patients were randomly assigned to empiric therapy with ticarcillin-clavulanate (4 g ticarcillin + 0.1 g clavulanate i.v. every 4 hours) plus netilmicin (2 mg/kg i.v. every 8 hours) with or without rh-GMCSF (3 micrograms/kg per day i.v.). Clinical improvement, duration of neutropenia, and toxicity were monitored.\n Addition of rh-GMCSF to the antibiotics significantly improved the response rate (96% versus 82%, P = 0.03), but not the survival rate (93% versus 93%), in the evaluable patients. This difference in response rate was not significant when considering all patients in an intent-to-treat analysis. The number of patients who recovered from severe neutropenia ( < 100 cells/microliter) during the period of observation in the study was significantly greater among patients receiving the colony-stimulating factor, although the median duration of neutropenia was not affected. Superinfections and subsequent infections were not significantly different among the two treatment regimens. Side effects were more common among patients treated with the colony-stimulating factor.\n Our data do not support the routine administration of rh-GMCSF with antibiotics for patients with fever and neutropenia. Further studies should be conducted to identify those patients most likely to benefit from rh-GMCSF therapy, such as patients with persistent profound neutropenia and refractory infections.", "Several randomized trials have tested the use of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in relieving chemotherapy-induced bone marrow suppression. However, the use of CSFs in the treatment of neutropenic fever remains virtually unexplored.\n This study evaluated the benefits of adding CSF therapy to the standard antibiotic treatments given to cancer patients for chemotherapy-induced neutropenic fever. The usefulness of CSFs was quantified in terms of reducing the following: (a) the duration of neutropenia, (b) the length of hospitalization, and (c) the overall cost of the treatment.\n A randomized trial was conducted to test whether the administration of either G-CSF or GM-CSF improved the outcome of standard antibiotic therapy (ceftazidime plus amikacin) in nonleukemic cancer patients with fever (> 38 degrees C) and grade IV neutropenia (absolute neutrophil count [ANC] < 500/mm3) induced by standard-dose chemotherapy. Of 121 patients who entered the trial, 39 received G-CSF (5 micrograms/kg body weight per day), 39 received GM-CSF (5 micrograms/kg body weight per day), and 43 received a placebo beginning just after the first dose of antibiotics. Treatments were continued for at least 5 days (7 days with clinically or microbiologically documented infections) or until 2 days after fever subsided and ANCs rose above 1000/mm3.\n The median duration of grade IV neutropenia (ANC of < 500/mm3) was 2 days in both CSF arms and 3 days in the placebo arm (P < .001). The median duration of neutropenia with an ANC of less than 1000/mm3 was also significantly shorter in patients receiving G-CSF or GM-CSF (P < .001). The median duration of fever was similar in the three arms. The median hospital stay was 5 days (range, 5-14 days) in the G-CSF arm, 5 days (range, 5-10 days) in the GM-CSF arm, and 7 days (range, 5-34 days) in the placebo arm (P < .001). The median time on CSF was 4 days in both treatment arms. The mean cost of overall treatment was reduced by $1300-$1400 in the CSF arms compared with the placebo arm (P = .11 for G-CSF versus placebo; P = .06 for GM-CSF versus placebo; P = .7 for G-CSF versus GM-CSF).\n Adding G-CSF or GM-CSF therapy to antibiotic treatment shortens the duration of neutropenia and the duration of hospitalization in patients with neutropenic fever. A statistically nonsignificant trend toward lower cost was observed in the CSF arms as compared with the placebo arm.\n The benefits of CSFs to cancer patients with chemotherapy-induced neutropenic fever merit further evaluation in large randomized trials.", "To determine if filgrastim (recombinant human methionyl granulocyte colony-stimulating factor) used in addition to standard inpatient antibiotic therapy accelerated recovery from infection associated with chemotherapy-induced neutropenia.\n Randomized, double-blind, placebo-controlled trial.\n Hematology and oncology wards of four teaching hospitals.\n 218 patients with cancer who had fever (temperature > 38.2 degrees C) and neutropenia (neutrophil count < 1.0 x 10(9)/L) after chemotherapy.\n Patients were randomly assigned to receive filgrastim (12 micrograms/kg of body weight per day) (n = 109) or placebo (n = 107) beginning within 12 hours of empiric therapy with tobramycin and piperacillin. Patients received treatment and remained in the study until the neutrophil count was greater than 0.5 x 10(9)/L and until 4 days without fever (temperature < 37.5 degrees C) had elapsed.\n Days of neutropenia and fever and days in the study (hospitalization); time to resolution of fever and febrile neutropenia; and frequency of the use of alternative antibiotics.\n Compared with placebo, filgrastim reduced the median number of days of neutropenia (3.0 compared with 4.0 days of a neutrophil count of < 0.5 x 10(9)/L; P = 0.005) and the time to resolution of febrile neutropenia (5.0 compared with 6.0 days; P = 0.01) but not days of fever (3.0 days for both groups). The frequency of the use of alternative antibiotics was similar in the two groups (46% compared with 41%; P = 0.48). The median number of days patients were hospitalized while on study was the same (8.0 days; P = 0.09); however, filgrastim decreased the risk for prolonged hospitalization (> 11 days, 4th quartile) by half (relative risk, 2.1 [95% CI, 1.1 to 4.1]; P = 0.02). In exploratory subset analyses, filgrastim appeared to provide the greatest benefit in patients with documented infection and in patients presenting with neutrophil counts of less than 0.1 x 10(9)/L.\n Filgrastim treatment used with antibiotics at the onset of febrile neutropenia in patients with cancer who have received chemotherapy accelerated neutrophil recovery and shortened the duration of febrile neutropenia.", "The clinical effects of concomitant use of granulocyte-colony stimulating factor (G-CSF) on empiric antibiotic therapy in febrile neutropenic patients were evaluated in a randomized fashion. Two hundred and fourteen neutropenic febrile episodes (neutrophil counts < 1.0 x 10(9)/l) were treated with flomoxef sodium and tobramycin with or without G-CSF. The resolution of fever at day 4 (excellent response) or at day 7 (good response) was deemed effective. Among 157 evaluable episodes, the observed excellent responses were 31 (38.8%) and the good responses were 20 (25.0%) in the G-CSF group; those in the control group were 26 (33.8%) and 25 (32.5%), respectively. The overall efficacy rate was 63.8% (51/80) in the G-CSF group and 66.2% (51/77) in the control group (not significant). The initial neutrophil count was 0.186 +/- 0.249 x 10(9)/l in the G-CSF group and 0.235 +/- 0.290 x 10(9)/l in the control group, and rose to 2.889 +/- 4.198 x 10(9)/l and 0.522 +/- 0.844 x 10(9)/l, respectively, at day 7. These results indicate that G-CSF does not affect the rate of response to empiric antibiotic therapy in febrile neutropenic patients, although a significant effect of G-CSF was observed on neutrophil recovery.", "Infection in neutropenic patients is potentially life-threatening and carries important implications for hospital resource use. Prophylactic administration of cytokines may reduce the severity of neutropenia, but involves the treatment of all patients for the possible benefit of a minority. This study evaluates whether treatment with cytokines in the setting of established febrile neutropenia will influence outcome and be potentially more cost-effective.\n In a double-blind study, pediatric patients with fever and severe neutropenia were randomized to receive granulocyte colony-stimulating factor ([G-CSF] filgrastim; 5 microg/kg/d) or placebo, in addition to antibiotics. The study protocol required a resolution of fever and a neutrophil count > or = 0.2 x 10(9)/L for hospital discharge. Patients could be randomized for up to four independent febrile episodes. A total of 186 episodes of febrile neutropenia were investigated.\n Patients randomized to G-CSF had a shorter hospital stay (median, 5 v 7 days; P = .04) and fewer days of antibiotic use (median, 5 v 6 days; P = .02). G-CSF-treated patients also had more rapid neutrophil recovery and higher neutrophil levels at discharge. The 2-day reduction in hospital stay reduced the median bed cost by 29% per patient admission (P = .04).\n Under the clinical guidelines of our institution, the use of G-CSF in the treatment of established febrile neutropenia produced a small but significant reduction in the time that children required antibiotics and hospital admission, with possible cost savings.", "Modern chemotherapy programmes render patients susceptible to bacterial and fungal infections, and the risk of developing febrile neutropenia after a chemotherapy course is in proportion to the severity and duration of the neutropenia thus caused. This double-blind randomized study presents details of 29 patients who developed febrile neutropenia an average of 10 days after their course of chemotherapy for different types and stages of malignancy. Fourteen received granulocyte/macrophage colony stimulating factor (GM-CSF) and 15 placebo during 7 consecutive days as subcutaneous injections. The GM-CSF group demonstrated significant increases in total white blood cell count (TWBC) and absolute neutrophil count (ANC) from the morning of the third day of the study. The study concludes that GM-CSF has an important therapeutic role in the treatment of febrile neutropenia that arises during intensive chemotherapy programmes but further studies of dosage and therapy duration are required, as is the development of methods of assessing bone marrow vitality." ]

[ "9475328", "11389575", "1531677", "12205570", "15978535", "2142293", "10023791", "2019162", "8680672", "12112791", "17426226", "1534166", "8365299" ]

[ "A placebo-controlled, double-blind trial of the long-term effects of albuterol administration in patients with cystic fibrosis.", "Bronchodilatory effects of salbutamol, ipratropium bromide, and their combination: double-blind, placebo-controlled crossover study in cystic fibrosis.", "Acute bronchodilator response to a combination of beta-adrenergic and anticholinergic agents in patients with cystic fibrosis.", "Effectiveness and tolerability of high-dose salmeterol in cystic fibrosis.", "Inhaled beta-agonists improve lung function but not maximal exercise capacity in cystic fibrosis.", "[The effect of ipratropium bromide on lung function in patients with cystic fibrosis].", "Effects of standard and high doses of salmeterol on lung function of hospitalized patients with cystic fibrosis.", "A controlled trial of long-term bronchodilator therapy in cystic fibrosis.", "The effects of albuterol on the lung function of hospitalized patients with cystic fibrosis.", "Effects of salmeterol on arterial oxyhemoglobin saturations in patients with cystic fibrosis.", "Effect of albuterol on maximal exercise capacity in cystic fibrosis.", "Efficacy of salbutamol and ipratropium bromide in decreasing bronchial hyperreactivity in children with cystic fibrosis.", "The effect of high doses of inhaled salbutamol and ipratropium bromide in patients with stable cystic fibrosis." ]

[ "This placebo-controlled study was designed to confirm a previously performed open label study that showed significant improvement in spirometry on maintenance therapy with albuterol for 1 year. In a double-blind, cross-over trial, albuterol (by metered dose inhaler) 180 microg b.i.d. or placebo were given for 6 months each. Spirometry was monitored at the start, and 3 and 6 months following initiation of each arm of the study. Peak expiratory flow rate (PEFR) was measured twice daily at home before and after study drug administration. Only patients with clinically detectable lung disease were enrolled. Twenty-one patients finished the study. All spirometric tests showed a significant improvement from start to end of the 6 month treatment with albuterol; there was no significant change on placebo. Forced vital capacity improved by 8.2% and forced expiratory volume in 1 s by 12.1% on albuterol therapy. Nevertheless, there was no significant difference between change on albuterol and change on placebo. Home measurements of PEFR showed a significant improvement of 4.7% on albuterol and a non-significant change of 2.0% on placebo from the first to the last week of treatment. None of the long-term improvements (spirometry or home PEFR) correlated with mean daily bronchodilation. For albuterol, the number of days of hospitalization was less than half that for patients on placebo (1.0/patient on albuterol versus 2.6 on placebo), but this did not reach statistical significance. These results suggest a beneficial effect from maintenance therapy with albuterol. Bronchodilation alone probably cannot explain the long-term benefits of albuterol, and other mechanisms may play a role. The lack of significant difference between change on albuterol and change on placebo is probably due to too small a number of patients in this study and lack of statistical power.", "The efficacy of inhaled sympathomimetic and anticholinergic agents on airway obstruction in cystic fibrosis (CF) has been proven in several studies. However, studies comparing combined therapy with monotherapy led to divergent results, probably due to different study designs, different dosages, and the small numbers of patients investigated. Therefore, we wanted to answer the question which inhalation has the best short term effect: a sympathomimetic or an anticholinergic agent, or the combination of both. We investigated 17 patients with CF on 4 successive days in the morning, using pulmonary function testing before and 30 min after inhalation. Each patient received aerosolized salbutamol (SB, maximum dose (max.) 2.5 mg), ipratropium bromide (IB, max. 0.5 mg), the combination of both, or placebo (normal saline) in a randomized, double-blind crossover design. The mean forced expiratory volume in the first second improved significantly (adjusted P-value < 0.017) after each treatment compared to placebo. Analysis of variance showed that SB and combination therapy with SB and IB were superior to IB alone, without significant difference between SB and combination therapy. Response of a patient to combined therapy was usually associated with response to SB. Long-term efficacy and side effects of treatment with bronchodilators still remain to be investigated after this short term study. We conclude that in CF patients bronchodilator therapy with sympathomimetic agents is usually sufficient. Only in cases with proven additional benefit from inhalation by anticholinergics should combination therapy be recommended.", "Patients with cystic fibrosis had a better acute bronchodilator response to albuterol and ipratropium bromide than to either drug alone. Further studies of long-term efficacy and safety seem justified.", "The efficacy and tolerability of high-dose salmeterol (100 mcg, BID) and albuterol (2.5 mg, BID) were compared with those of albuterol (2.5 mg, BID) in outpatients with cystic fibrosis in a randomized, double-blind, double-dummy, placebo-controlled, crossover study with both short- (4 weeks of each) and long-term (24 weeks of each) treatment periods. The primary outcome measure was the difference in mean change in forced expired volume in 1 sec (FEV(1)) from baseline to the end of each treatment, and secondary measures included changes in forced vital capacity (FVC), forced expiratory flow between 25-75% of FVC (FEF(25-75)), patient-rated weekly symptom scores, number of extra (rescue) albuterol treatments, and number of antibiotic treatments. Tolerability was evaluated by changes in vital signs and adverse events.Thirty-six out of 44 patients enrolled finished the short-term treatment period, and 19 out of 23 who continued the study also finished the long-term treatment period. There was no significant difference in the mean % change in FEV(1) from baseline to completion of 4 weeks with each drug in the short-term treatment period (0.1% vs. 0.06%, albuterol vs. salmeterol; respectively). In the long-term treatment period, there was a significant decrease from baseline in FEV(1) with albuterol vs. salmeterol, as measured after both 12 and 24 weeks of each treatment (-6.2% vs. 1.8%, P = 0.013 after 12 weeks, and -6.5% vs. 1.7%, P = 0.002, after 24 weeks, respectively). In both treatment periods, salmeterol was well-tolerated. While there were more rescue treatments per patient per week with albuterol than with salmeterol treatment in both the short- and long-term periods (0.67 vs. 0.40 and 1.76 vs. 0.74, respectively), rescue treatments were needed significantly more often for only the long-term period with albuterol compared to salmeterol (P = 0.022). Also, there were more antibiotic interventions with albuterol than with salmeterol treatment in both the short- and long-term periods (25 vs. 10 and 56 vs. 42, respectively); however, antibiotics were needed significantly more often for only the short-term period (P = 0.011). In addition, there was a significantly higher symptom score with albuterol vs. salmeterol treatment during the second half of the long-term period (1.24 vs. 0.89, P = 0.001).In conclusion, long-term high-dose salmeterol was equally safe and was associated with better pulmonary function, fewer interventions, and fewer respiratory symptoms compared to standard therapy with albuterol in a population of outpatients with mild to moderate CF.\n Copyright 2002 Wiley-Liss, Inc.", "To investigate the effects of inhaled beta-agonists on sub-maximal and maximal exercise capacity, breathing pattern, dyspnoea, leg-discomfort and spirometry in patients with cystic fibrosis (CF).\n Eight patients performed two maximal incremental cycle-ergometry tests on separate days with inhaled placebo or salbutamol (600 microg) administered before each test in a randomized, double-blind, placebo-controlled crossover trial. Primary outcomes were exercise duration (Exdur) in seconds (s) and maximal oxygen uptake (VO2max) in litres/minute (L/min). Forced expiratory volume in 1 s (FEV1) was measured immediately pre-inhaler, post-inhaler and post-exercise. Dyspnoea and leg-discomfort were assessed post-exercise.\n Within-day FEV1 comparisons demonstrated that the placebo test day FEV1 improved significantly post-exercise (0.11 L, p<0.05) and the salbutamol test day FEV1 improved significantly post-inhaler (0.22 L, p<0.001) and post-exercise (0.07 L, p<0.01). Between-day FEV1 comparisons demonstrated significant improvements in post-inhaler (0.17 L, p<0.05) and post-exercise (0.13 L, p<0.05) FEV1 following salbutamol. Sub-maximal and maximal exercise showed no significant difference as shown by Exdur (547+/-154 s vs. 529+/-127 s) and VO2max (1.9+/-0.5 L/min vs. 1.9+/-0.6 L/min). No significant change in breathing pattern, dyspnoea or leg-discomfort was detected. The study had a power of 92% to detect a 10% improvement in Exdur.\n In adults with CF, salbutamol improves post-exercise FEV1 and is safe when administered immediately before exercise but does not improve exercise capacity, exercise-induced dyspnoea or leg-discomfort.", "The main manifestation of cystic fibrosis (CF) of the lungs is an obstructive ventilation disturbance. The fact that the administration of atropine improves pulmonary function in patients with CF suggests a vagal mechanism for the development of bronchal obstruction. In a single-blind, placebo-controlled study, we investigated the effect of 250 micrograms of an inhalation solution of the anticholinergic substance ipatropium bromide (IB) on the pulmonary function of 11 patients with CF (age range: 8 to 29 years). The mean figures for the changes in FEV1.0, FEF25-75%, RV and TLC after inhalation of IB and placebo did not differ significantly. However, FEV1.0 and FEF25-75% after administration of IB increased in 4 out of 11 patients, and decreased in one. The lung volumes changed significantly in only a single case. This variable effect of inhaled IB in CF patients is in agreement with findings that have been observed for other substances with a \"bronchodilatory\" effect in patients with CF.", "In a recent investigation we found that hospitalized patients with cystic fibrosis who received 0.5 cc of 0.5% albuterol nebulizer solution TID significantly increased their pulmonary function across the day, but fell back to baseline overnight. To determine whether this fall could be prevented by the long-acting beta-2 agonist salmeterol at both standard (2 puffs: 42 mcg BID) and high (4 puffs, 84 mcg BID) doses, we evaluated the effects of salmeterol vs. albuterol (2 puffs, 180 mcg QID, and 4 puffs, 360 mcg BID) in a placebo-controlled three-way random crossover, double-blind trial. Eighteen patients in the low-dose group and 10 of the same 18 patients in the high-dose group completed the 3 consecutive days of testing and received either salmeterol, albuterol, or placebo with each of four chest physiotherapy sessions given at 7 AM, 11 AM, 3 PM, and 7 PM. At standard doses (2 puffs), the mean percent changes in FEV1 pre- to post-7 AM therapy for salmeterol (5.5%) and albuterol (9.9%) were significantly greater than with placebo (-1.2%) (P < 0.05 and 0.01, respectively). The mean percent changes in FEV1 from morning baseline with salmeterol were also significantly greater than placebo before 3 PM (12.1% vs. 5.4%, P < 0.01), and neither albuterol nor salmeterol were significantly greater than placebo after 3 PM. At standard doses there was a significant carryover effect with salmeterol to the next morning for the FEV1 (7.3%) when compared to placebo (1.5%) and albuterol (-0.7%) (P < 0.05 and 0.05, respectively). At high doses (4 puffs), the mean percent change in FEV1 with pre- to post-7 AM therapy increased to 22.7% and remained significantly greater than with placebo until pretherapy at 7 PM. The carryover effect the next morning was 14.7%. Salmeterol at 4 puffs compared favorably to albuterol nebulizer therapy given TID in both the incidence of responders for the FEV1 (70% vs. 71%) and the mean changes after therapy at 7 AM (22.7% vs. 14.9%), and provided greater carryover effects to the next morning (14.7% vs. -0.7%), thus preventing the fall in pulmonary function back to baseline overnight. We recommend the use of high-dose salmeterol in hospitalized patients with FVC values of 40% of predicted or greater, starting with 2 and increasing to 4 puffs BID as tolerated.", "To evaluate the effect of long-term bronchodilator therapy in CF patients with demonstrated bronchial hyperresponsiveness, we first performed methacholine challenges to determine responsiveness, then entered 27 patients (16 methacholine responders and 11 nonresponders) into a two-month double-blind crossover trial of albuterol, 90 micrograms by inhalation four times a day vs placebo. Among the responders, daily PEFR measures improved significantly more during treatment with albuterol (12 +/- 32 L/min) than with placebo (-0.4 +/- 19 L/min; p less than 0.05). In addition, a clinically important level of improvement in PEFR (15 percent increase) was reached significantly more frequently in the responders. Methacholine nonresponders had no change in PEFR on either albuterol or placebo. Daily symptom scores as well as spirometry measurements at biweekly visits did not show significant changes. We conclude that long-term therapy with inhaled albuterol improves lung function in CF patients, but only in those with bronchial hyperresponsiveness as demonstrated by methacholine challenge.", "Twenty-four hospitalized patients with cystic fibrosis were enrolled into a 2-d, double-blind, placebo-controlled, randomized crossover trial comparing albuterol inhalation aerosol with a saline placebo. Aerosols were administered with the first three of four chest physiotherapy sessions given 4 h apart. Spirometry was measured before and 45 min after 7:00 A.M. and 3:00 P.M. therapy and before therapy at 7:00 P.M. and 7:00 A.M. the next morning. The mean percent change in FVC, FEV1, and FEF25-75% at 7:00 A.M. was 10.7, 14.8, and 19.6% with albuterol versus 2.4, 1.0, and -0.8% with placebo (p = 0.0012, < 0.0001, and = 0.003, respectively). A greater than 8% change in FEV1 separated changes with albuterol versus placebo with 96% specificity and occurred in 75% of all patients with albuterol; 71% at 7:00 A.M. versus 24% at 3:00 P.M. The reduction in response at 3:00 P.M. (p < 0.01) was presumably due to prolonged effects of morning therapy ( > 4 h). Individual changes in spirometry were significantly more positive and homogeneous with albuterol versus placebo at both 7:00 A.M. and 3:00 P.M. The mean percent change for the FVC, FEV1, and FEF25-75 across the day (7:00 A.M. pretherapy to 7:00 P.M. pretherapy) was 8.1, 10.1, and 9.7% with albuterol versus 3.9, 3.5 and 2.6% with placebo (p = 0.029, 0.036, and 0.232, respectively). The more positive and homogeneous changes in spirometry with albuterol, along with greater changes in these measures across the day when compared with placebo, suggest that albuterol improves pulmonary function in a majority of hospitalized patients with cystic fibrosis.", "Sleep-related oxygen desaturation has been described in patients with cystic fibrosis (CF). Thus we studied the effects of inhaled Salmeterol xinafoate, a long-acting beta-2 agonist, on transcutaneous oxyhemoglobin saturation in sleeping, stable CF patients. Patients with stable CF (n = 23) were divided into responders and nonresponders to beta-2 agonists, based on an albuterol challenge during daytime testing, and then they received salmeterol before sleep, in a double-blind crossover design. Overnight oxyhemoglobin saturation measurements and spirometry on awakening were performed. Salmeterol administration before sleep resulted in statistically significant increases in mean arterial oxyhemoglobin saturation and in FEV(1) and FEF(25-75) on awakening compared to placebo values, but only in patients responding to daytime albuterol inhalation by showing improvement in lung function. We conclude that salmeterol inhalation at bedtime could prevent or reduce nocturnal hypoxemia in daytime albuterol-responsive CF patients, thus improving the long-term clinical outcome of CF lung disease.\n Copyright 2002 Wiley-Liss, Inc.", "Inhaled, short-acting beta-adrenergic agonists (SAbetaAs) are widely prescribed in cystic fibrosis (CF) subjects, despite a lack of convincing data for efficacy and the potential for these agents to result in airway instability. We tested the hypothesis that inhaled albuterol would improve maximal exercise performance in CF subjects with airflow obstruction, as a result of acute bronchodilation.\n Randomized, double-blind, placebo-controlled crossover study of the effect of inhaled albuterol on maximal exercise performance in 20 stable adult CF patients (mean +/- SD age, 23.3 +/- 6.1 years; FEV(1), 57.65 +/- 17.13% of predicted).\n Ventilatory limitation to exercise was demonstrated in 16 subjects (80%). Significant bronchodilation occurred with exercise alone (end-exercise FEV(1), 2.24 +/- 0.8 L; vs preexercise FEV(1), 2.09 +/- 0.77 L; p < 0.0001), but albuterol resulted in significantly greater exercise-induced bronchodilation than placebo (change in FEV(1), 0.3 +/- 0.15 L vs 0.15 +/- 0.11 L; 95% confidence interval [CI], + 0.07 to + 0.23; p < 0.001). However, there was no difference in maximal workload achieved (albuterol, 158 +/- 46 W; vs placebo, 158 +/- 45 W; 95% CI, - 4.41 to + 4.71; p = 0.95), nor any other measure of exercise performance including maximal oxygen uptake.\n Despite causing significant acute bronchodilation, inhaled albuterol did not improve maximal exercise performance in ventilatory-limited CF adults, adding to the body of literature that fails to show any clinical benefit of SAbetaAs in CF subjects. The current results provide further evidence to question the widespread use of these agents, although the potential for adrenergic beta-agonists to instead improve submaximal exercise performance merits further investigation.", "A proportion of patients with cystic fibrosis (CF) suffer from increased airway hyperreactivity but their response to bronchodilators is variable. Adrenergic agents may produce an increase, no change or a decrease in forced expiratory volume in 1 second (FEV1). We hypothesized that the variable response might be related to poor aerosol distribution caused by the presence of secretions. Therefore, in 11 children with CF and airway hyperreactivity the influence of pretreatment with either 0.9% saline, salbutamol, or ipratropium bromide on the methacholine challenge test was evaluated in a double-blind, randomized, cross-over study. FEV1 (mean +/- S.E.) did not change following pretreatment with saline, salbutamol, or ipratropium (1.64 +/- 0.22, 1.63 +/- 0.16 and 1.67 +/- 0.19, respectively). All patients demonstrated airway hyperreactivity with a PC20 below 8 mg/mL (geometric mean, 0.41 mg/mL) after saline pretreatment. Salbutamol inhalation significantly increased the PC20 to 1.24 mg/mL (P less than 0.01), but ipratropium bromide was found to be even more effective than salbutamol (PC20 = 7.37 mg/mL) (P less than 0.0001). We conclude that the variable response to bronchodilator is not secondary to impaired aerosol distribution since ipratropium bromide effectively blocked the response to methacholine. The improvement in PC20 without a change in baseline FEV1 following salbutamol suggests that the adrenergic agent altered the contractile mechanism of smooth muscle.", "The effect of large doses of salbutamol (S) and ipratropium bromide (IB) were tested in a double-blind, randomized, crossover study. Nine patients with cystic fibrosis (CF), aged 12.8 +/- 2 years (mean +/- SE), were studied for 8 h on 2 separate days. Pulmonary function tests (PFTs) included spirometry (FEV1), lung volumes (FRC), and airway resistance (Raw) measured by body plethysmography. Heart rate (HR) and oxygen saturation (SaO2) were measured before each test. On 1 day patients received S 200 micrograms, S 400 micrograms, and IB 80 micrograms, by inhalation at 45-min interval (sequence A). On the other day, the sequence was IB 80 micrograms, S 200 micrograms, and S 400 micrograms (sequence B). The PFTs were obtained at baseline, 45 min after each inhalation, and 4 and 8 h after baseline measurements. Baseline PFTs (mean +/- SE) were not significantly different on the 2 study days (FEV1, 1.48 +/- 0.1 vs 1.42 +/- 0.1 L; FRC, 2.77 +/- 0.6 vs 2.87 +/- 0.6 L; Raw, 4.04 +/- 0.2 vs 4.00 +/- 0.3 cm H2O/L/s). The FEV1 and Raw improved from baseline after each inhalation, and at 4 and 8 h during both days (p < 0.05). Forty-five minutes after S 200 micrograms, plus S 400 micrograms, FEV1, FRC, and Raw were not significantly different compared with the values 45 min after IB 80 micrograms, plus S 200 micrograms (1.67 +/- 0.1 vs 1.63 +/- 0.1 L; 2.81 +/- 0.6 vs 2.65 +/- 0.5 L; and 2.98 +/- 0.2 vs 2.66 +/- 0.1 cm H2O/L/s, respectively). The PFTs were not significantly different after maximal doses of IB (80 micrograms) compared with S (600 micrograms). The HR and SaO2 were not significantly different from baseline throughout the study period. These results indicate that both single and sequential therapy have a similar acute bronchodilator effect provided that large doses are used. We speculate that adrenergic and muscarinic pathways are equally important in airflow obstruction in patients with CF." ]

[ "9284774" ]

[ "Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer." ]

[ "Stage Ib and IIa cervical carcinoma can be cured by radical surgery or radiotherapy. These two procedures are equally effective, but differ in associated morbidity and type of complications. In this prospective randomised trial of radiotherapy versus surgery, our aim was to assess the 5-year survival and the rate and pattern of complications and recurrences associated with each treatment.\n Between September, 1986, and December, 1991, 469 women with newly diagnosed stage Ib and IIa cervical carcinoma were referred to our institute. 343 eligible patients were randomised: 172 to surgery and 171 to radical radiotherapy. Adjuvant radiotherapy was delivered after surgery for women with surgical stage pT2b or greater, less than 3 mm of safe cervical stroma, cut-through, or positive nodes. The primary outcome measures were 5-year survival and the rate of complications. The analysis of survival and recurrence was by intention to treat and analysis of complications was by treatment delivered.\n 170 patients in the surgery group and 167 in the radiotherapy group were included in the intention-to-treat analysis; scheduled treatment was delivered to 169 and 158 women, respectively, 62 of 114 women with cervical diameters of 4 cm or smaller and 46 of 55 with diameters larger than 4 cm received adjuvant therapy. After a median follow-up of 87 (range 57-120) months, 5-year overall and disease-free survival were identical in the surgery and radiotherapy groups (83% and 74%, respectively, for both groups), 86 women developed recurrent disease: 42 (25%) in the surgery group and 44 (26%) in the radiotherapy group. Significant factors for survival in univariate and multivariate analyses were: cervical diameter, positive lymphangiography, and adeno-carcinomatous histotype. 48 (28%) surgery-group patients had severe morbidity compared with 19 (12%) radiotherapy-group patients (p = 0.0004).\n There is no treatment of choice for early-stage cervical carcinoma in terms of overall or disease-free survival. The combination of surgery and radiotherapy has the worst morbidity, especially urological complications. The optimum therapy for each patient should take account of clinical factors such as menopausal status, age, medical illness, histological type, and cervical diameter to yield the best cure with minimum complications." ]

[ "21667366", "16095436", "22768793", "3661282", "1506933", "20484492", "20840874", "19524389", "17204318", "11818305", "2189772", "12959796", "16954124", "19213683" ]

[ "A novel recruitment message to increase enrollment into a smoking cessation treatment program: preliminary results from a randomized trial.", "Recruiting health plan members receiving pharmacotherapy into smoking cessation counseling.", "Reaching out, inviting back: using Interactive voice response (IVR) technology to recycle relapsed smokers back to Quitline treatment--a randomized controlled trial.", "Effectiveness of impersonal versus interpersonal methods to recruit employees into a worksite quit smoking program.", "Using a low-cost, prize-drawing incentive to improve recruitment rate at a work-site smoking cessation clinic.", "Three controlled trials of interventions to increase recruitment to a randomized controlled trial of mobile phone based smoking cessation support.", "Do messages of scarcity increase trial recruitment?", "Impact of a brief motivational smoking cessation intervention the Get PHIT randomized controlled trial.", "Recruiting pregnant smokers into a clinical trial: using a network-model managed care organization versus community-based practices.", "The SUCCESS project: the effect of program format and incentives on participation and cessation in worksite smoking cessation programs.", "Recruitment in a primary care trial on smoking cessation.", "Successful recruitment of minorities into clinical trials: The Kick It at Swope project.", "Interest in an online smoking cessation program and effective recruitment strategies: results from Project Quit.", "A randomized, controlled trial of financial incentives for smoking cessation." ]

[ "Most smokers do not utilize approved interventions for nicotine dependence, reducing the probability of cessation. Smoking cessation programs typically use recruitment messages emphasizing the health threats of smoking. Augmenting this threat message by describing the genetic aspects of nicotine addiction may enhance enrollment into a cessation program. During telephone recruitment, 125 treatment-seeking smokers were randomized to receive by phone either a standard threat message or a threat plus genetic prime message and were offered open-label varenicline and counseling. There was a greater rate of enrollment into the cessation program for the threat plus genetic prime participants (51.7%) versus the threat-only participants (37.7%; p = .03). Smokers who self-identified from racial/ethnic minority groups were less likely to enroll in the cessation program (p = .01) versus smokers who self-identified as Caucasian. These preliminary data suggest that a simple, affordable, and transportable communication approach enhances enrollment of smokers into a smoking cessation program. A larger clinical trial to evaluate a genetic prime message for improving recruitment into smoking cessation programs is warranted.", "Smokers receiving pharmacotherapy and individualized smoking cessation counseling through telephone quitlines have been found to have higher quit rates than smokers receiving pharmacotherapy alone. Health plans are often positioned to encourage their members to use quitline services in addition to pharmacotherapy.\n To determine if healthcare members who were receiving pharmacotherapy increased their participation in smoking quitline services after receiving proactive telephone calls or postcards.\n Randomized controlled trial.\n Health plan members filing pharmacotherapy claims were identified weekly from health plan pharmacy claims data and randomized to 1 of the following 3 conditions: control, recruitment postcard, or recruitment telephone call by a nurse quitline counselor. Enrollment of study members into the quitline program was tracked for 1 month after randomization.\n During 5 months, 625 individuals were identified for participation in the study, with the following enrollment into the program: 0% to the control group, 1.3% to the postcard group, and 20.6% to the telephone call group (P < .001 for significance by group). Although costs for the telephone intervention were the most expensive, it was also the most cost effective, given its success in enrolling members into the program.\n Proactive telephone calling by smoking cessation nurse counselors to smokers receiving pharmacotherapy may be an effective method of enrolling smokers into a cessation quitline. Health plans should consider proactive telephone recruitment to improve use of quitline services.", "Tobacco dependence is a chronic, relapsing condition that typically requires multiple quit attempts and extended treatment. When offered the opportunity, relapsed smokers are interested in recycling back into treatment for a new, assisted quit attempt. This manuscript presents the results of a randomized controlled trial testing the efficacy of interactive voice response (IVR) in recycling low income smokers who had previously used quitline (QL) support back to QL support for a new quit attempt.\n A sample of 2985 previous QL callers were randomized to either receive IVR screening for current smoking (control group) or IVR screening plus an IVR intervention. The IVR intervention consists of automated questions to identify and address barriers to re-cycling in QL support, followed by an offer to be transferred to the QL and reinitiate treatment. Re-enrollment in QL services for both groups was documented.\n The IVR system successfully reached 715 (23.9%) former QL participants. Of those, 27% (194/715) reported to the IVR system that they had quit smoking and were therefore excluded from the study and analysis. The trial's final sample was composed of 521 current smokers. The re-enrollment rate was 3.3% for the control group and 28.2% for the intervention group (p < .001). Logistic regression results indicated an 11.2 times higher odds for re-enrollment of the intervention group than the control group (p < .001). Results did not vary by gender, race, ethnicity, or level of education, however recycled smokers were older (Mean = 45.2; SD = 11.7) than smokers who declined a new treatment cycle (Mean = 41.8; SD = 13.2); (p = 0.013). The main barriers reported for not engaging in a new treatment cycle were low self-efficacy and lack of interest in quitting. After delivering IVR messages targeting these reported barriers, 32% of the smokers reporting low self-efficacy and 4.8% of those reporting lack of interest in quitting re-engaged in a new QL treatment cycle.\n Proactive IVR outreach is a promising tool to engage low income, relapsed smokers back into a new cycle of treatment. Integration of IVR intervention for recycling smokers with previous QL treatment has the potential to decrease tobacco-related disparities.\n ClinicalTrials.gov Identifier: NCT01260597.", "One of the first salient issues a worksite quit smoking program must face is how to motivate employees to enroll and participate. The purpose of this study was to determine the effectiveness of impersonal versus interpersonal recruitment strategies used by an ongoing worksite quit smoking program. One hundred and nineteen smokers who stated on a questionnaire that they would be either \"strongly yes\" or \"yes\" interested in participating in a quit smoking program were randomized into two groups. One group was sent letters by employee mail from the director of the quit smoking program. This letter briefly described the program and invited employees to participate. The other group received a personal phone call from the staff health educator inviting them to participate. Results indicate that of the 46 individuals randomly assigned to Group 1 who were sent letters, none responded to the invitation; while 37 of the 44 employees who received a personal phone call, 19 scheduled an appointment, 7 kept their appointments. These results indicate the possible increased effectiveness of an impersonal versus interpersonal communications in recruiting full-time smoking employees.", "A major obstacle in promoting smoking cessation programs through work sites is recruiting adequate numbers of smokers. We used a quasi-experimental design to evaluate the effect of a low-cost incentive (a prize drawing) for attracting participants to a smoking cessation clinic offered at multiple work sites. Sixty-eight automobile dealerships were randomized to either a \"prize\" or control group. Smokers employed at work sites in the prize group were offered a chance to win a dinner for two for participating in a smoking cessation clinic. In November 1986, a questionnaire assessing tobacco use habits was sent to 3432 employees of the 68 work sites. A cohort of 844 smokers was identified from a total of 1986 employees who returned surveys. All smokers received registration materials to participate, free of charge, in one of three smoking cessation programs held in June 1987. The overall employee participation rate in the smoking cessation program was 6.6% (n = 56) with an overall work-site participation rate of 37.3% (n = 25). The rate was nearly identical in the \"prize\" and control groups (employee rate: 6.3% versus 6.7%; work-site rate: 39.4% versus 35.3%, respectively).", "Recruitment is a major challenge for trials but there is little evidence regarding interventions to increase trial recruitment. We report three controlled trials of interventions to increase recruitment to the Txt2stop trial.\n To evaluate: Trial 1. The impact on registrations of a text message regarding an online registration facility; Trial 2. The impact on randomizations of sending pound5 with a covering letter to those eligible to join the trial; Trial 3. The impact on randomizations of text messages containing quotes from existing participants.\n Single blind controlled trials with allocation concealment. Interventions: Trial 1: A text message regarding our new online registration facility; Trial 2: A letter with pound5 enclosed; Trial 3: A series of four text messages containing quotes from participants. The control group in each trial received standard Txt2stop procedures.\n Trial 1: 3.6% (17/470) of the intervention group and 1.1% (5/467) of the control group registered for the trial, risk difference 2.5% (95% CI 0.6-4.5). 0% (0/ 470) of the intervention group and 0.2% (1/467) of the control group registered successfully online, risk difference -0.2 (95% CI -0.6-0.2); Trial 2: 4.5% (11/246) of the intervention group and 0.4% (1/245) of the control group were randomized into the Txt2stop trial, risk difference 4.0% (95% CI 1.4-6.7); Trial 3: 3.5% (14/405) of the intervention group and 0% (0/406) of the control group were randomized into the Txt2stop trial, risk difference 3.5 (95% CI 1.7-5.2).\n There were no baseline data available for trial 1. Allocation of participant IDs in trials 2 and 3 were systematic.\n Sending a text message about an online registration facility increased registrations to Txt2stop, but did not increase online registrations. Sending a pound5 reimbursement for participants' time and sending text messages containing quotes from existing participants increased randomizations into the Txt2stop trial. Clinical Trials 2010; 7: 265-273. http://ctj.sagepub.com.", "Psychological theory suggests that participants may be more likely to volunteer to join a clinical trial if they perceive places in the trial are a scarce commodity.\n We conducted a single blind, randomized controlled trial to test recruitment strategies within the larger txt2stop smoking cessation trial. 1862 people who were eligible for the txt2stop trial but had not yet consented to join were randomized to receive either A) a reminder about the txt2stop trial plus a message that there were only 300 places left, or B) a reminder about the trial only. The outcome was the participant's consent to join the txt2stop trial 3days after messages were sent.\n Of 895 participants randomized to the intervention group, 90 (10.1%) had consented to join the txt2stop trial. Of the 967 participants randomized to the control group, 67 (6.9%) had consented to join the txt2stop trial (OR=1.50, 95% CI 1.07-2.12).\n Scarcity messages were an effective way to increase recruitment into the txt2stop trial and could be relevant to other trials.\n Communicating scarcity is an effective way to increase trial recruitment.\n Copyright © 2010 Elsevier Inc. All rights reserved.", "Few studies have rigorously evaluated whether providing biologically based health-risk feedback is more effective than standard interventions in increasing smokers' motivation to quit and their long-term abstinence.\n An RCT was conducted from 2005 to 2008. Data were analyzed in 2008.\n Smokers (N=536) were recruited from the community, regardless of their interest in quitting smoking.\n Smokers either received brief ( approximately 20 minutes), personally tailored counseling sessions based on their lung functioning, carbon monoxide (CO) exposure, and smoking-related health conditions, or they received generic smoking-risk information and personalized counseling about their diet, BMI, and physical activity. All were advised to quit smoking and were offered access to a free phone-counseling program.\n Treatment utilization and abstinence at 6 and 12 months post-intervention.\n Participants who received the experimental treatment demonstrated no greater motivation to quit, use of treatment services, or abstinence compared to controls at either follow-up assessment. In fact, controls reported greater motivation to quit at 12 months (M 3.42 vs 3.20, p=0.03), greater use of pharmacotherapy at 6 months (37.8% vs 28.0%, p=0.02), and greater 30-day point prevalent abstinence at 6 months, after controlling for relevant covariates (10.8% vs 6.4%, adjusted p=0.04).\n The present study found no support for adding a personalized health-risk assessment emphasizing lung health and CO exposure to generic cessation advice and counseling for community-based smokers not otherwise seeking treatment.\n NCT00169260.", "Recruiting pregnant smokers into smoking cessation intervention trials is challenging. Changes in health care systems offer new opportunities to overcome many of the obstacles encountered by researchers attempting to address the significant harm from maternal smoking. Investigators could facilitate smoking cessation study recruitment by collaborating with health care systems that systematically collect patient smoking status and record it in a centralized, retrievable fashion. This paper reports the results of utilizing this novel approach and compares it with a typical decentralized practice-based recruitment strategy.\n The study was conducted at Massachusetts General Hospital, in Boston, Massachusetts, from 2000 to 2005. Four hundred forty-two pregnant smokers were recruited for a randomized controlled trial of telephone-delivered smoking counseling from two sources: a network-model managed care health plan and community-based practices (CBP). At the health plan, study recruitment was built on an existing system that permitted pregnant smokers to be identified centrally. At the CBPs, identification and referral systems had to be developed at each practice specifically for the study. The two strategies were compared on the efficiency of recruitment, characteristics of enrollees, and study outcome and process measures.\n The health plan strategy generated referrals nearly twice as fast as the CBP strategy (30.4 vs. 17.0 per month), but because referrals were not timely, a large proportion of women from the plan were too advanced in pregnancy to be eligible to enroll in the study. As a result, the two strategies yielded a comparable enrollment rate. Participants from the health plan were older, better educated, less racially diverse, more likely to be living with the baby's father, and less likely to have smokers in their environment. These differences were largely explained by the socioeconomic diversity of women recruited from the CBPs. Smoking cessation outcomes did not differ by recruitment source.\n A recruitment strategy using a health plan's centralized system was more efficient than a practice-based recruitment strategy at identifying potential study participants, but less efficient at generating study participants from the referrals received. Importantly, participants recruited by the two strategies differed by socioeconomic, but not cessation-related, characteristics. To date, recruiting pregnant smokers into intervention studies remains resource intensive and time consuming. Participant identification and recruitment will be greatly enhanced by health system innovations such as implementation of electronic medical records.", "This study examined the effect of program format and incentives on participation and cessation in worksite smoking cessation programs.\n Twenty-four worksites were randomized to 6 conditions that differed in cessation program format and the use of incentives. Programs were offered for 18 months in each worksite. A total of 2402 cigarette smokers identified at baseline were surveyed 12 and 24 months later to assess participation in programs and cessation.\n A total of 407 (16.9%) of the smoker cohort registered for programs; on the 12- and 24-month surveys, 15.4% and 19.4% of the cohort, respectively, reported that they had not smoked in the previous 7 days. Registration for programs in incentive sites was almost double that of no-incentive sites (22.4% vs 11.9%), but increased registration did not translate into significantly greater cessation rates. Program type did not affect registration or cessation rates.\n Although incentives increase rates of registration in worksite smoking cessation programs, they do not appear to increase cessation rates. Phone counseling seems to be at least as effective as group programs for promoting smoking cessation in worksites.", "The purpose of this study was to describe and compare the rates of recruitment during a randomized clinical trial on smoking cessation in two primary care practices. One site was a five-physician private family practice setting with about 15,000 patients. During 34 days, 576 patients were screened, of whom 22% were smokers. Among the smokers screened, 54% consented, 33% refused consent, and 13% were called in too early to consent. The other site was a six-physician academic medical practice with about 16,000 patients. During 53 days, 1,692 subjects were screened, of whom 16.2% were smokers. Among the smokers, 19% consented, 81% refused consent, and none were called in early. The enrollment of smokers was 3.3 times greater in the private practice than the academic practice. At the first site, study personnel screened 26.6 subjects per day, whereas the practice receptionist screened only 13.4 subjects per day (P less than .01). A randomized trial of having subjects read the informed consent versus having study personnel read it to them showed no differences in recruitment. The data suggest that private practices may have greater potential for subject recruitment than academic sites, that using study personnel improves recruitment, and that having study personnel actively involved in informed consent does not improve recruitment.", "Ethnic minorities are often underrepresented in clinical trials, and their recruitment can challenge researchers. Developing and communicating effective and efficient recruitment strategies may help researchers enroll more minorities into research studies. Kick It at Swope was a double-blind, randomized trial that evaluated bupropion for smoking cessation among 600 adult African Americans who smoked 10 or more cigarettes a day. Proactive recruitment strategies (in-person appeals by study staff and health care providers) and reactive recruitment strategies (disseminating information that asked people to call a study hotline) were implemented sequentially in an additive fashion over 16 months. Resulting patterns of recruitment are described and the two phases are compared based on their relative effectiveness, efficiency, and cost. More enrollees were recruited in the reactive phase (n=534) than in the proactive phase (n=66). Those recruited in the reactive phase were more likely to be eligible (OR=4.8) and more likely to be enrolled (OR=4.2) than those recruited in the proactive phase. Participants recruited in the reactive phase reported significantly higher levels of education and income, better health, and significantly lower indicators of depression and life hassles, compared with those recruited in the proactive phase. The reactive recruitment phase was less expensive than the proactive recruitment phase (22 US Dollars/enrollee vs. 159 US Dollars/enrollee). Reactive recruitment strategies added to multiple proactive clinic-based recruitment strategies were more effective, more efficient, and less costly than proactive recruitment alone. Close monitoring combined with the use of multiple recruitment methods and flexible recruitment plans can lead to successful, efficient, and low-cost recruitment of minorities into clinical trials.", "The Internet is a promising venue for delivering smoking cessation treatment, either as a stand-alone program or as an adjunct to pharmacotherapy. However, there is little data to indicate what percent of smokers are interested in receiving online smoking cessation services or how best to recruit smokers to Internet-based programs.\n Using a defined recruitment sample, this study aimed to identify the percentage of smokers who expressed interest in or enrolled in Project Quit, a tailored, online, cognitive-behavioral support program offered with adjunctive nicotine replacement therapy patches. In addition, we examined the effectiveness of several individual-level versus population-level recruitment strategies.\n Members from two large health care organizations in the United States were invited to participate in Project Quit. Recruitment efforts included proactive invitation letters mailed to 34533 likely smokers and reactive population-level study advertisements targeted to all health plan members (> 560000 adults, including an estimated 98000 smokers across both health care organizations).\n An estimated 1.6% and 2.5% of adult smokers from each health care organization enrolled in Project Quit. Among likely smokers who received proactive study invitations, 7% visited the Project Quit website (n = 2260) and 4% (n = 1273) were eligible and enrolled. Response rates were similar across sites, despite using different sources to assemble the invitation mailing list. Proactive individual-level recruitment was more effective than other forms of recruitment, accounting for 69% of website visitors and 68% of enrollees.\n Smokers were interested in receiving online smoking cessation support, even though they had access to other forms of treatment through their health insurance. Uptake rates for this program were comparable to those seen when smokers are advised to quit and are referred to other forms of smoking cessation treatment. In this sample, proactive mailings were the best method for recruiting smokers to Project Quit.", "Smoking is the leading preventable cause of premature death in the United States. Previous studies of financial incentives for smoking cessation in work settings have not shown that such incentives have significant effects on cessation rates, but these studies have had limited power, and the incentives used may have been insufficient.\n We randomly assigned 878 employees of a multinational company based in the United States to receive information about smoking-cessation programs (442 employees) or to receive information about programs plus financial incentives (436 employees). The financial incentives were $100 for completion of a smoking-cessation program, $250 for cessation of smoking within 6 months after study enrollment, as confirmed by a biochemical test, and $400 for abstinence for an additional 6 months after the initial cessation, as confirmed by a biochemical test. Individual participants were stratified according to work site, heavy or nonheavy smoking, and income. The primary end point was smoking cessation 9 or 12 months after enrollment, depending on whether initial cessation was reported at 3 or 6 months. Secondary end points were smoking cessation within the first 6 months after enrollment and rates of participation in and completion of smoking-cessation programs.\n The incentive group had significantly higher rates of smoking cessation than did the information-only group 9 or 12 months after enrollment (14.7% vs. 5.0%, P<0.001) and 15 or 18 months after enrollment (9.4% vs. 3.6%, P<0.001). Incentive-group participants also had significantly higher rates of enrollment in a smoking-cessation program (15.4% vs. 5.4%, P<0.001), completion of a smoking-cessation program (10.8% vs. 2.5%, P<0.001), and smoking cessation within the first 6 months after enrollment (20.9% vs. 11.8%, P<0.001).\n In this study of employees of one large company, financial incentives for smoking cessation significantly increased the rates of smoking cessation. (ClinicalTrials.gov number, NCT00128375.)\n 2009 Massachusetts Medical Society" ]

[ "9860108", "9690695", "10192829" ]

[ "Ziprasidone 40 and 120 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 4-week placebo-controlled trial.", "An exploratory haloperidol-controlled dose-finding study of ziprasidone in hospitalized patients with schizophrenia or schizoaffective disorder.", "Ziprasidone 80 mg/day and 160 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 6-week placebo-controlled trial. Ziprasidone Study Group." ]

[ "A double-blind, placebo-controlled, multicenter study, was performed to evaluate the efficacy and safety of ziprasidone in 139 patients with an acute exacerbation of schizophrenia or schizoaffective disorder. Patients were randomized to receive ziprasidone 40 mg/day, 120 mg/day or placebo for 28 days. Ziprasidone 120 mg/day was significantly more effective than placebo in improving the BPRS total, CGI-S. BPRS depression cluster and BPRS anergia cluster scores (all P < 0.05). Similarly, the percentages of patients classified as responders on the BPRS (> or = 30% reduction) and the CGI improvement (score < or = 2) were significantly greater with ziprasidone 120 mg/day compared with placebo (P < 0.05). The number of patients who experienced an adverse event was similar in all three treatment groups, and discontinuation due to adverse events was rare (five of 91 ziprasidone-treated patients). The most frequently reported adverse events, that were more common in either ziprasidone group than in the placebo group, were dyspepsia, constipation, nausea and abdominal pain. There was a notably low incidence extrapyramidal side-effects (including akathisia) and postural hypotension and no pattern of laboratory abnormalities or apparent weight gain. Ziprasidone-treated patients were not clinically different from placebo-treated patients on the Simpson-Angus Rating scale, Barnes Akathisia scale and AIMS assessments. These results indicate that ziprasidone 120 mg/day is effective in the treatment of the positive, negative and affective symptoms of schizophrenia and schizoaffective disorder with a very low side-effect burden.", "Ninety patients with schizophrenia or schizoaffective disorder according to DSM-III-R criteria participated in this double-blind, exploratory, dose-ranging trial. After a single-blind washout period of 4 to 7 days, patients were randomly assigned to receive one of four fixed doses of the new antipsychotic, ziprasidone 4 (N = 19), 10 (N = 17), 40 (N = 17), or 160 (N = 20) mg/day or haloperidol 15 mg/day (N = 17) for 4 weeks. A dose-response relationship among ziprasidone groups was established for improvements in Clinical Global Impression Severity (CGI-S) score (p = 0.002) but not in Brief Psychiatric Rating Scale (BPRS) total score (p = 0.08). The intent-to-treat analysis of mean changes from baseline in the BPRS total, BPRS Psychosis core, and CGI-S scores demonstrated that ziprasidone 160 mg/day was comparable with haloperidol in reducing overall psychopathology and positive symptoms and was superior to ziprasidone 4 mg/day. Despite the small sample size and short duration of the trial, the improvement in CGI-S with both ziprasidone 160 mg/day and haloperidol 15 mg/day was statistically significantly greater than with ziprasidone 4 mg/day (p = 0.001 andp = 0.005, respectively). The percentage of patients classified as responders on both the BPRS total (> or = 30% improvement) and CGI-Improvement (score of 1 or 2) scales in the ziprasidone 160 mg/day group was similar to that in the haloperidol group and nonsignificantly greater than that in the ziprasidone 4 mg/day group. On all assessments of clinical efficacy, the improvements associated with ziprasidone 4 mg/day, 10 mg/day, and 40 mg/day were similar. Concomitant benztropine use at any time during the study was less frequent with ziprasidone 160 mg/day (15%) than with haloperidol (53%). Haloperidol was associated with a sustained hyperprolactinemia, unlike ziprasidone, where only transient elevations in prolactin that returned to normal within the dosing interval were observed. Ziprasidone was well tolerated, and the incidence of adverse events was similar in all groups. The results of this study suggest that ziprasidone 160 mg/day is as effective as haloperidol 15 mg/day in reducing overall psychopathology and positive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder but has a lower potential to induce extrapyramidal symptoms.", "In this double-blind study, patients with an acute exacerbation of schizophrenia or schizoaffective disorder were randomized to receive either ziprasidone 80 mg/day (n = 106) or 160 mg/day (n = 104) or placebo (n = 92), for 6 weeks. Both doses of ziprasidone were statistically significantly more effective than placebo in improving the PANSS total, BPRS total, BPRS core items, CGI-S, and PANSS negative subscale scores (p < .05). Ziprasidone 160 mg/day significantly improved depressive symptoms in patients with clinically significant depression at baseline (MADRS > or = 14, over-all mean 23.5) (p < .05) as compared with placebo. The percentage of patients experiencing adverse events was similar in each treatment group, and resultant discontinuation was rare. The most frequent adverse events associated with ziprasidone were generally mild dyspepsia, nausea, dizziness, and transient somnolence. Ziprasidone was shown to have a very low liability for inducing movement disorders and weight gain. The results indicate that ziprasidone is effective and well tolerated in the treatment of the positive, negative, and depressive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder." ]

[ "22170366", "19225128", "20332221", "22952175" ]

[ "A novel fortified blended flour, corn-soy blend \"plus-plus,\" is not inferior to lipid-based ready-to-use supplementary foods for the treatment of moderate acute malnutrition in Malawian children.", "Supplementary feeding with fortified spreads results in higher recovery rates than with a corn/soy blend in moderately wasted children.", "Effectiveness of ready-to-use therapeutic food compared to a corn/soy-blend-based pre-mix for the treatment of childhood moderate acute malnutrition in Niger.", "Treatment of moderate acute malnutrition with ready-to-use supplementary food results in higher overall recovery rates compared with a corn-soya blend in children in southern Ethiopia: an operations research trial." ]

[ "Children with moderate acute malnutrition (MAM) are often treated with fortified blended flours, most commonly a corn-soy blend (CSB). However, recovery rates remain <75%, lower than the rate achieved with peanut paste-based ready-to-use supplementary foods (RUSFs). To bridge this gap, a novel CSB recipe fortified with oil and dry skim milk, \"CSB++,\" has been developed.\n In this trial we compared CSB++ with 2 RUSF products for the treatment of MAM to test the hypothesis that the recovery rate achieved with CSB++ will not be >5% worse than that achieved with either RUSF.\n We conducted a prospective, randomized, investigator-blinded, controlled noninferiority trial involving rural Malawian children aged 6-59 mo with MAM. Children received 75 kcal CSB++ · kg(-1) · d(-1), locally produced soy RUSF, or an imported soy/whey RUSF for ≤12 wk.\n The recovery rate for CSB++ (n = 763 of 888; 85.9%) was similar to that for soy RUSF (795 of 806, 87.7%; risk difference: -1.82%; 95% CI: -4.95%, 1.30%) and soy/whey RUSF (807 of 918, 87.9%; risk difference: -1.99%; 95% CI: -5.10%, 1.13%). On average, children who received CSB++ required 2 d longer to recover, and the rate of weight gain was less than that with either RUSF, although height gain was the same among all 3 foods studied.\n A novel, locally produced, fortified blended flour (CSB++) was not inferior to a locally produced soy RUSF and an imported soy/whey RUSF in facilitating recovery from MAM. The recovery rate observed for CSB++ was higher than that for any other fortified blended flour tested previously. This trial is registered at clinicaltrials.gov as NCT00998517.", "Moderate childhood wasting is defined as having a weight-for-height Z-score (WHZ) < -2, but > or = -3. These children are typically given fortified corn/soy blended flour (CSB), but this intervention has shown limited effectiveness. Fortified spreads (FS) can be used as supplementary foods instead; they are energy-dense, lipid-based pastes with added powdered micronutrients. In this randomized clinical effectiveness trial, the recovery rates were compared among children with moderate wasting who received either milk/peanut FS, soy/peanut FS, or CSB. Children received isoenergetic quantities of food, 314 kJ x kg(-1) x d(-1), for up to 8 wk with biweekly follow-up. The primary outcome was recovery, defined as having a WHZ > -2. Time-event analysis was used to compare the recovery rate. A total of 1362 children were enrolled in the study. Children receiving soy/peanut FS had a similar recovery rate to those receiving milk/peanut FS and children in either FS group were more likely to recover than those receiving CSB (80% in both FS groups vs. 72% in the CSB group; P < 0.01). The rate of weight gain in the first 2 wk was greater among children receiving milk/peanut FS (2.6 g x kg(-1) x d(-1), n = 465) or children receiving soy/peanut FS (2.4 g x kg(-1) x d(-1), n = 450) than among children receiving CSB (2.0 g x kg(-1) x d(-1), n = 447; P < 0.05). Rates of length gain did not differ among the 3 groups. A total of 8% of children in each feeding group developed edema, indicative of severe malnutrition, while receiving supplemental feeding. We conclude that FS are superior supplementary foods to CSB for moderately wasted Malawian children.", "Standard nutritional treatment of moderate acute malnutrition (MAM) relies on fortified blended flours though their importance to treat this condition is a matter of discussion. With the newly introduced World Health Organization growth standards, more children at an early stage of malnutrition will be treated following the dietary protocols as for severe acute malnutrition, including ready-to-use therapeutic food (RUTF). We compared the effectiveness of RUTF and a corn/soy-blend (CSB)-based pre-mix for the treatment of MAM in the supplementary feeding programmes (SFPs) supported by Médecins Sans Frontières, located in the Zinder region (south of Niger). Children measuring 65 to <110 cm, newly admitted with MAM [weight-for-height (WHM%) between 70% and <80% of the NCHS median] were randomly allocated to receive either RUTF (Plumpy'Nut®, 1000 kcal day(-1)) or a CSB pre-mix (1231 kcal day(-1)). Other interventions were similar in both groups (e.g. weekly family ration and ration at discharge). Children were followed weekly up to recovery (WHM% ≥ 85% for 2 consecutive weeks). In total, 215 children were recruited in the RUTF group and 236 children in the CSB pre-mix group with an overall recovery rate of 79.1 and 64.4%, respectively (p < 0.001). There was no evidence for a difference between death, defaulter and non-responder rates. More transfers to the inpatient Therapeutic Feeding Centre (I-TFC) were observed in the CSB pre-mix group (19.1%) compared to the RUTF group (9.3%) (p = 0.003). The average weight gain up to discharge was 1.08 g kg(-1) day(-1) higher in the RUTF group [95% confidence interval: 0.46-1.70] and the length of stay was 2 weeks shorter in the RUTF group (p < 0.001). For the treatment of childhood MAM in Niger, RUTF resulted in a higher weight gain, a higher recovery rate, a shorter length of stay and a lower transfer rate to the I-TFC compared to a CSB pre-mix. This might have important implications on the efficacy and the quality of SFPs.", "Moderate and severe acute malnutrition affects 13% of children <5 y of age worldwide. Severe acute malnutrition affects fewer children but is associated with higher rates of mortality and morbidity. Supplementary feeding programs aim to treat moderate acute malnutrition and prevent the deterioration to severe acute malnutrition.\n The aim was to compare recovery rates of children with moderate acute malnutrition in supplementary feeding programs by using the newly recommended ration of ready-to-use supplementary food (RUSF) and the more conventional ration of corn-soya blend (CSB) in Ethiopia.\n A total of 1125 children aged 6-60 mo with moderate acute malnutrition received 16 wk of CSB or RUSF. Children were randomly assigned to receive one or the other food. The daily rations were purposely based on the conventional treatment rations distributed at the time of the study in Ethiopia: 300 g CSB and 32 g vegetable oil in the control group (1413 kcal) and 92 g RUSF in the intervention group (500 kcal). The higher ration size of CSB was provided because of expected food sharing.\n The HR for children in the CSB group was 0.85 (95% CI: 0.73, 0.99), which indicated that they had 15% lower recovery (P = 0.039). Recovery rates of children at the end of the 16-wk treatment period trended higher in the RUSF group (73%) than in the CSB group (67%) (P = 0.056).\n In comparison with CSB, the treatment of moderate acute malnutrition with RUSF resulted in higher recovery rates in children, despite the large ration size and higher energy content of the conventional CSB ration." ]

[ "7625915", "11075743", "8982557", "7914959", "9527402", "11841067", "10533862", "11843761", "10648669" ]

[ "Is the choice of membrane important for patients with acute renal failure requiring hemodialysis?", "Patient survival and renal recovery in acute renal failure: randomized comparison of cellulose acetate and polysulfone membrane dialyzers.", "Biocompatible dialysis membranes and acute renal failure: a study in post-operative acute tubular necrosis in cadaveric renal transplant recipients.", "Biocompatible membranes in acute renal failure: prospective case-controlled study.", "A multicenter comparison of dialysis membranes in the treatment of acute renal failure requiring dialysis.", "Biocompatible membranes do not promote graft recovery following cadaveric renal transplantation.", "Haemodialysis-membrane biocompatibility and mortality of patients with dialysis-dependent acute renal failure: a prospective randomised multicentre trial. International Multicentre Study Group.", "Low-flux versus high-flux synthetic dialysis membrane in acute renal failure: prospective randomized study.", "Comparison of cellulose diacetate and polysulfone membranes in the outcome of acute renal failure. A prospective randomized study." ]

[ "It has recently been reported that patients with acute renal failure requiring hemodialysis have an improved recovery of renal function and a higher survival rate when the dialysis treatments are performed with a biocompatible membrane rather than a bioincompatible membrane. Our data, obtained in 57 patients with acute renal failure, do not support these findings since neither the mortality nor the required number of dialysis sessions could be influenced by using a biocompatible membrane. The survival rate was similar in both groups (64 versus 72%), and renal function was regained in both groups after 6 dialysis sessions. We conclude that when reviewing the literature as well as other factors, the underlying clinical condition or the skill of the physicians is probably more important than the theoretical superiority of biocompatible membranes.", "To investigate survival and renal recovery after dialysis in patients with acute renal failure with use of synthetic membranes compared with substituted cellulose membranes.\n We prospectively studied survival and recovery of renal function of 66 patients with acute renal failure who required intermittent hemodialysis. Patients were randomized to exclusive treatment with either cellulose acetate (CA) or polysulfone (PS) hemodialysis membranes. Additionally, markers of biocompatibility (complement, leukocyte counts, cytokine concentration) were measured at initiation and 1 hour after initiation of dialysis among 10 patients equally distributed between the CA and PS groups.\n The cohorts were indistinguishable with respect to age, sex, presence of diabetes mellitus, Acute Physiology and Chronic Health Evaluation II scores, percentage in the intensive care unit (ICU), and adequacy of dialysis. Survival (76% CA, 73% PS; P=.78) and recovery of renal function at 30 days (58% CA, 39% PS; P=.14) were not statistically different in the 2 groups. Among 26 CA patients and 27 PS patients treated in the ICU, survival was not statistically different (73% CA, 67% PS; P=.61); however, the proportion of patients recovering renal function suggested a benefit favoring CA membranes (65% CA, 37% PS; P=.04). Additionally, markers of biocompatibility were not significantly different between groups among the 10 patients equally distributed between the CA and PS groups.\n Overall clinical outcomes among patients with acute renal failure treated with CA hemodialysis membranes and those treated with PS membranes were not significantly different. The observed advantage favoring renal recovery among this ICU population treated with CA hemodialysis membranes warrants further investigation.", "Previous experimental and human data suggests a detrimental effect on the course of acute renal failure related to exposure of blood to artificial dialysis membranes of poor biocompatibility. We performed a 2.5-year prospective randomized trial to compare the clinical course of acute renal failure (post-operative ischemic acute tubular necrosis, ATN) in patients receiving a cadaveric renal transplant requiring supportive hemodialysis in the immediate post-transplant setting. Patients were randomized to either a cuprophane or polymethylmethacrylate (PMMA) conventional hollow fiber dialyzer. All patients received a standard immunosuppressive regimen which included induction therapy with either horse anti-thymocyte gamma globulin (ATGAM) or the murine anti-CD3 monoclonal antibody (OKT3). Of 53 patients randomized, 17 were excluded (2 for intervening biopsy-proven rejection prior to recovery from ATN, 10 for primary graft nonfunction and 5 for other reasons), leaving 36 evaluable cases of uncomplicated ATN, 18 in each group. There was no difference by age, race, gender, cause of ESRD, immunosuppressive regimen, cold or warm ischemia time, use of pre-transplant dialysis, percent oliguria or the incidence of intra-dialytic hypotension between the 2 groups. There was no difference in the mean time to recovery from ATN posttransplant (8.9 days in the cuprophane group vs 9.5 days in the PMMA group, p = NS) or in the average number of hemodialysis treatments required (3.6 in both groups, p = NS). There was also no difference in long term allograft outcome in terms of the nadir serum creatinine, the number of episodes of subsequent acute rejection or in the development of chronic rejection. An intent-to-treat analysis of all 53 originally randomized patients similarly yielded no significant differences. A subsequent, non-randomized study using a membrane of intermediate biocompatibility (Hemophan) also showed no difference in recovery time from ATN. Bioincompatible membranes do not seem to have a significant clinical impact on the course of recovery of this form of acute renal failure. The striking benefits of biocompatibility in the course of ARF seen in other human trials may relate more to the non-renal systemic toxic effects of bioincompatibility.", "The mortality of critically ill patients with acute renal failure has been halved through intervention by haemodialysis. However, several reports suggest that the course of the disorder may be prolonged by this procedure. Our prospective randomised study was done to see whether the generation of inflammatory mediators by bio-compatible membranes has an adverse effect on the outcome of acute renal failure. 52 patients, similar in age, severity of acute renal failure, general disease status (APACHE II), and management of acute renal failure or its related conditions, were divided into two groups. Haemodialysis was done with cuprophane or polyacrylonitrile membranes. Cuprophane membranes induced intense activation of the complement system (as judged by measurement of C3a) and lipooxygenase pathway (leukotriene B4) resulting in alterations of neutrophil kinetics and function. The cuprophane group had a lower survival rate (38 vs 65%), a higher proportion of patients dying from sepsis (71 vs 40%), required more haemodialysis sessions (12 vs 9), and demonstrated delayed resolution and recovery from acute renal failure than the polyacrylonitrile group. The difference in mortality regarding lethal sepsis as cause of death was statistically significant. Our observations indicate that the outcome of critically ill patients with acute renal failure may be influenced by bio-incompatibility reactions to the dialysis membrane. These results have direct implications for such patients on haemodialysis.", "The mortality of patients with acute renal failure (ARF) remains high, and in several large studies approaches 60%. This mortality is particularly high in patients with ARF who require dialysis and has not changed substantially over several years, despite the introduction of major advances in monitoring and treatment. Increasing prevalence of comorbidities has been suggested as the major factor in this persistently high mortality. This study investigates the potential role of the dialysis membrane on patient outcome in a prospective multicenter study of 153 patients with ARF requiring dialysis. The membrane assignment was made in alternating order and was limited to membranes with low complement activation (Biocompatible [BCM]) and cellulosic, high complement activation (Bioincompatible [BICM]). Both types of membranes were low-flux membranes. Patients were dialyzed with the assigned membrane until recovery, discharge from hospital, or death. The severity of illness of each patient was assessed using the APACHE II score at the time of initiation of dialysis. A logistic regression analysis was used to adjust for the APACHE II score. The results of the study showed a statistically significant difference in survival (57% in patients on BCM, 46% in patients on BICM; P = 0.03) and in recovery of renal function (64% in patients on BICM and 43% in patients on BICM; P = 0.001). These differences were particularly marked in the patients who were nonoliguric (>400 ml/d of urine output) at initiation of the study. In the subset of patients who were nonoliguric at the start of dialysis, a larger fraction (70%) became oliguric after initiating dialysis on a BICM membrane, in contrast to 44% who were initiated on a BCM membrane (P = 0.03). It is concluded that the biocompatibility of the dialysis membrane plays a role in the outcome of patients with ARF, particularly those who are nonoliguric at the time of initiation of dialysis.", "Controversy surrounds the role of biocompatible membrane dialyzers in treatment of acute renal failure. Studies that have shown a benefit have involved critically ill patients where renal recovery and patient mortality are influenced by other comorbid disease. The aim of the present work is to clarify this issue in a more homogeneous population of patients with acute renal failure following cadaveric renal transplantation.\n All patients with delayed graft function between January 1996 and February 1998 were randomized to receive either a biocompatible (BCM, polysulfone) membrane or bioincompatible (BICM, cuprophane) membrane for dialysis until onset of graft function.\n Forty-one patients were randomized, 23 to receive BCM and 18 BICM. Five patients (2 BCM, 3 BICM; p = NS) with primary non-function of graft were excluded from analysis, leaving 36 cases of acute tubular necrosis (ATN). Patient and donor characteristics were similar in both groups. The BCM group had significantly longer periods of dialysis dependency compared to the BICM group (14 vs 10 days; p = 0.03). There was a tendency towards higher serum creatinine levels in the short term in the BCM group (318 vs 164 micromol/l at 1 month (p = 0.1), 190 vs 169 micromol/l at latest visit (p = 0.07)) and a greater number of acute rejection episodes in the BCM group (3.7 vs 1.7 episodes per 100 days of dialysis dependency, p = 0.1). With an intention-to-treat analysis of all 41 patients originally randomized, there was no significant difference in time to graft recovery between the 2 groups (p = 0.18).\n In the setting of ARF posttransplantation, we have found no evidence to support the use of biocompatible membranes for dialysis. Rather, our study provides argument against a large benefit for the use of BCM in the recovery of ARF, as suggested by earlier studies.", "There is controversy as to whether haemodialysis-membrane biocompatibility (ie, the potential to activate complement and neutrophils) influences mortality of patients with acute renal failure. We did a prospective randomised multicentre trial in patients with dialysis-dependent acute renal failure treated with two different types of low-flux membrane.\n 180 patients with acute renal failure were randomly assigned bioincompatible Cuprophan (n=90) or polymethyl-methacrylate (n=90) membranes. The main outcome was survival 14 days after the end of therapy (treatment success). Odds ratios for survival were calculated and the two groups were compared by Fisher's exact test. Analyses were based on patients treated according to protocol (76 Cuprophan, 84 polymethyl methacrylate).\n At the start of dialysis, the groups did not differ significantly in age, sex, severity of illness (as calculated by APACHE II scores), prevalence of oliguria, or biochemical measures of acute renal failure. 44 patients (58% [95% CI 46-69]) assigned Cuprophan membranes and 50 patients (60% [48-70]) assigned polymethyl-methacrylate membranes survived. The odds ratio for treatment failure on Cuprophan compared with polymethyl-methacrylate membranes was 1.07 (0.54-2.11; p=0.87). No difference between Cuprophan and polymethyl-methacrylate membranes was detected when the analysis was adjusted for age and APACHE II score. 18 patients in the Cuprophan group and 20 in the polymethyl-methacrylate group had clinical complications of therapy (mainly hypotension).\n There were no differences in outcome for patients with dialysis-dependent acute renal failure between those treated with Cuprophan membranes and those treated with polymethyl-methacrylate membranes.", "The influence of dialyzer membrane on the morbidity and mortality of patients with acute renal failure remains a matter of debate. The aim of the prospective randomized clinical study was to assess the influence of the flux of a synthetic dialyzer membrane on patients' survival rate, restitution of renal function, and duration of hemodialysis treatment of patients with acute renal failure as a part of multiorgan failure. Seventy-two patients treated in intensive care units of the University Medical Center Ljubljana were randomized according to the dialyzer used throughout the duration of hemodialysis treatment. There were 38 patients in the low-flux group (dialyzer F6, low-flux polysuphone, Fresenius, Bad Homburg, Germany) and 34 patients in the high-flux group (dialyzer Filtral 12, sulphonated high-flux polyacrylonitrile, Hospal, Industrie Meyzieu, France). Both groups were balanced in terms of sex, age, APACHE II score, oliguria before dialysis, cause of acute renal failure, inotropic support, mechanical ventilation, and the number of failing organs. The patients' survival rate was 18.7% in the low-flux group and 20.6% in the high-flux group. Ten patients (26.3%) recovered their renal function in the low-flux group and 8 (23.5%) in the high-flux group. Hemodialysis treatment lasted 11.2 days in the low-flux and 10.7 days in the high-flux group. An analysis of subgroups with a lower mortality rate (subgroup of patients without oliguria and subgroup of patients with less than 4 failed organ systems) did not show significant differences between the low-flux and high-flux groups in terms of survival rate, recovery of renal function, and duration of hemodialysis treatment. In conclusion, no significant differences were found in the results of low-flux versus high-flux synthetic membrane dialyzer treatment in patients with acute renal failure as a part of multiorgan failure in terms of survival rate, recovery of renal function, incidence of oliguria during hemodialysis, and duration of hemodialysis treatment. The number of failing organs seems to be the most important single factor determining the survival of patients with acute renal failure as a part of multiorgan failure.", "Whether the nature of haemodialysis (HD) membranes can influence the outcome of acute renal failure (ARF) remains debatable. Recent studies have suggested that dialysis with bioincompatible unsubstituted cellulosic membranes is associated with a less favourable patient outcome than dialysis with biocompatible synthetic membranes. Since we generally use a modified cellulosic membrane with substantially lower complement- and leukocyte-activating potential than cuprophane, for dialysis of patients with ARF, and because there are no data in the literature regarding the influence of modified cellulosic membranes on the outcome of patients with ARF, we compared the outcome of ARF patients dialysed either with cellulose diacetate or with a synthetic polysulfone membrane. We also investigated the potential role of permeability by comparing membranes with high-flux versus low-flux characteristics.\n This prospective, randomized, single centre study included 159 patients with ARF requiring HD. Patients were stratified according to age, gender, and APACHE II score and then randomized in chronological order to one of three dialysis membranes: low-flux polysulfone, high-flux polysulfone and meltspun cellulose diacetate.\n Aetiologies of ARF and the prevalence of oliguria were similarly distributed among the three groups. There was no significant difference between the three groups for survival (multivariate Cox's proportional hazards model, P=0.57), time necessary to recover renal function (P=0.82), and number of dialysis sessions required before recovery (P=0.86). Multivariate analysis showed that survival was significantly influenced only by the severity of the disease state (APACHE III score, P<0.0001), but not by the nature of the dialysis membrane (P=0.57) or the presence of oliguria (P=0.24).\n Among patients with ARF requiring HD survival and recovery time are not significantly influenced by the use of either meltspun cellulose diacetate or the more biocompatible high-flux or low-flux polysulfone. Dialysis using modified cellulose membranes is just as effective as dialysis using synthetic polysulfone membranes, but at a lower cost. In addition, the flux of the membrane did not influence patient outcome." ]

[ "3083919", "2558202", "15249521", "1739798" ]

[ "The \"five minute\" consultation: effect of time constraint on clinical content and patient satisfaction.", "Study of the effect of time availability on the consultation.", "Patient-based outcome results from a cluster randomized trial of shared decision making skill development and use of risk communication aids in general practice.", "Health promotion in the general practice consultation: a minute makes a difference." ]

[ "An experiment was carried out in which patients who were seeking appointments for a consultation in a general practice in south London attended consulting sessions booked at 5, 7.5, or 10 minute intervals. The particular session that the patient attended was determined non-systematically. The clinical content of the consultation was recorded on an encounter sheet and on audio-tape. At the end of each consultation patients were invited to complete a questionnaire designed to measure satisfaction with the consultation. The stress engendered in doctors carrying out surgery sessions booked at different intervals of time was also measured. At surgery sessions booked at 5 minute intervals, compared with 7.5 and 10 minute intervals, the doctors spent less time with the patients and identified fewer problems, and the patients were less satisfied with the consultation. Blood pressure was recorded twice as often in surgery sessions that were booked at 10 minute intervals compared with those booked at 5 minute intervals. There was no evidence that patients who attended sessions booked at shorter intervals received more prescriptions, were investigated or referred more often to hospital specialists, or returned more often for further consultations within four weeks. There was no evidence that the doctors experienced more stress in dealing with consultations that were booked at 5 minute intervals than at consultations booked at 7.5 and 10 minute intervals, though they complained of shortage of time more often in surgery sessions that were booked at shorter intervals.", "This study looked at the effect of different appointment time intervals on process and outcome measures in the consultation. Over a five-month period patients attending a two-partner surgery were non-systematically allocated to appointments at five, 10 or 15 minute intervals. Consultations were audiotaped and analysed. When appointments were scheduled at longer intervals, doctors asked significantly more questions and made significantly more statements explaining the problem and its management, while patients asked significantly more questions and made significantly more statements of their own ideas about the problem. In consultations booked at shorter intervals patients were significantly more likely to report in satisfaction questionnaires that they had little or far too little time available. The implications of the results for future planning are discussed.", "Shared decision-making (SDM) between professionals and patients is increasingly advocated from ethical principles. Some data are accruing about the effects of such approaches on health or other patient-based outcomes. These effects often vary substantially between studies.\n Our aim was to evaluate the effects of training GPs in SDM, and the use of simple risk communication aids in general practice, on patient-based outcomes.\n A cluster randomized trial with crossover was carried out with the participation of 20 recently qualified GPs in urban and rural general practices in Gwent, South Wales. A total of 747 patients with known atrial fibrillation, prostatism, menorrhagia or menopausal symptoms were invited to a consultation to review their condition or treatments. After baseline, participating doctors were randomized to receive training in (i) SDM skills; or (ii) the use of simple risk communication aids, using simulated patients. The alternative training was then provided for the final study phase. Patients were randomly allocated to a consultation during baseline or intervention 1 (SDM or risk communication aids) or intervention 2 phases. A randomly selected half of the consultations took place in 'research clinics' to evaluate the effects of more time for consultations, compared with usual surgery time. Patient-based outcomes were assessed at exit from consultation and 1 month follow-up. These were: COMRADE instrument (principal measures; subscales of risk communication and confidence in decision), and a range of secondary measures (anxiety, patient enablement, intention to adhere to chosen treatment, satisfaction with decision, support in decision making and SF-12 health status measure). Multilevel modelling was carried out with outcome score as the dependent variable, and follow-up point (i.e. exit or 1 month later for each patient), patient and doctor levels of explanatory variables.\n No statistically significant changes in patient-based outcomes due to the training interventions were found: COMRADE risk communication score increased 0.7 [95% confidence interval (CI) -0.92 to 2.32] after risk communication training and 0.9 (95% CI -0.89 to 2.35) after SDM training; and COMRADE satisfaction with communication score increased by 1.0 (95% CI -1.1 to 3.1) after risk communication, and decreased by 0.6 (95% CI 2.7 to -1.5) after SDM training. Patients' confidence in the decision (2.1 increase, 95% CI 0.7-3.5, P < 0.01) and expectation to adhere to chosen treatments (0.7 increase, 95% CI 0.04-1.36, P < 0.05) were significantly greater among patients seen in the research clinics (when more time was available) compared with usual surgery time. Most outcomes deteriorated between exit and 1 month later. There was no interaction between intervention effects.\n Patients can be more involved in treatment decisions, and risks and benefits of treatment options can be explained in more detail, without adversely affecting patient-based outcomes. SDM and risk communication may be advocated from values and ethical principles even without evidence of health gain or improvement in patient-based outcomes, but the resources required to enhance these professional skills must also be taken into consideration. These data also indicate the benefits of extra consultation time.", "To see whether extending appointment length from seven and a half minutes or less to 10 minutes per patient would increase health promotion in general practice consultations.\n Controlled trial of 10 minute appointments. Consultations were compared with control surgeries in which the same doctors booked patients at their normal rate (median six minutes per patient).\n 10 general practices in Nottinghamshire.\n 16 general practitioners were recruited. Entry criteria were a booking rate of eight or more patients an hour, a wish for longer consultations, and plans to increase appointment length.\n Duration of consultations; recording of blood pressure, weight, and cervical cytology in the medical record; recording of advice about smoking, alcohol, diet, exercise, and immunisation in the medical record; reporting of the above activities by patients.\n Mean consultation times were 8.25 minutes in the experimental sessions and 7.04 and 7.16 minutes in the control sessions. Recording of blood pressure, smoking, alcohol consumption, and advice about immunisation was significantly more frequent in the experimental sessions, and the proportion of consultations in which one or more items of health education were recorded in the medical notes increased by an average of over 6% in these sessions. Patients more often reported discussion of smoking and alcohol consumption and coverage of previous health problems in the experimental sessions. There was little change in discussion of exercise, diet, and weight or cervical cytology activity.\n Shortage of time is a major factor in general practitioners' failure to realise their potential in health promotion. General practice should be organised so that doctors can run 10 minute appointment sessions." ]

[ "10790464", "12091844" ]

[ "Effect of early versus late administration of human recombinant erythropoietin on transfusion requirements in premature infants: results of a randomized, placebo-controlled, multicenter trial.", "Early treatment with erythropoietin beta ameliorates anemia and reduces transfusion requirements in infants with birth weights below 1000 g." ]

[ "The administration of recombinant human erythropoietin (rHuEPO), started after the first 2 weeks of life, reduces the transfusion requirement in premature infants. However, its use throughout the first 2 weeks of life, when anemia results predominantly from phlebotomy losses, remains controversial. We investigated whether early use of rHuEPO would reduce the total transfusion requirement and/or the number of transfusions throughout the first 2 weeks of life.\n We randomized 114 infants with birth weight (BW) <1250 g to receive rHuEPO (1250 units/kg/week; IV; early group: n = 57) or placebo (late group: n = 57) from day 2 to day 14 of life; subsequently, all the patients received rHuEPO (750 units/kg/week, subcutaneously) for 6 additional weeks. All infants were given oral iron (6 mg/kg/day) and folic acid (2 mg/day).\n The early group showed higher hematocrit and reticulocyte counts than the late group in the first 3 weeks of life, but there was no difference in the total number of transfusions (early: 1.8 +/- 2.3 vs late: 1.8 +/- 2.5 transfusion/patient) or the transfusion requirement throughout the first 2 weeks of life (early:.8 +/- 1.1 vs late:.9 +/- 1.3) could be demonstrated. In infants with BW <800 g and total phlebotomy losses >30 mL/kg (n = 29), a lower number of transfusions was received by infants in the early group, compared with late group, from the second week to the end of the treatment (early: 3.4 +/- 1.1 vs late: 5.4 +/- 3.7 transfusion/patient). No clinical adverse effects were observed. Thrombocytosis was detected during the treatment with rHuEPO in 31% of the infants.\n In the whole population, the early administration of rHuEPO induced a rise of reticulocyte counts, but not enough to reduce the transfusion requirement. The most severely ill infants (BW <800 g and phlebotomy losses >30 mL/kg) seemed to benefit from early use of rHuEPO, and this deserves additional study.", "To investigate whether recombinant erythropoietin (rhEPO) reduces the need for transfusion in extremely low birth weight (ELBW) infants (birth weight 500-999 g) and to determine the optimal time for treatment.\n In a blinded multicenter trial, 219 ELBW infants were randomized on day 3 to one of 3 groups: early rhEPO group (rhEPO from the first week for 9 weeks, n = 74), late rhEPO group (rhEPO from the fourth week for 6 weeks, n = 74), or control group (no rhEPO, n = 71). All infants received enteral iron (3-9 mg/kg/day) from the first week. The rhEPO beta dose was 750 IU/kg/week. Success was defined as no transfusion and hematocrit levels never below 30%.\n Success rate was 13% in the early rhEPO group, 11% in the late rhEPO group, and 4% in the control group (P =.026 for early rhEPO versus control group). Median transfusion volume was 0.4 versus 0.5 versus 0.7 mL/kg/day (P =.02) and median donor exposure was 1.0 versus 1.0 versus 2.0 (P =.05) in the early rhEPO group, the late rhEPO group, and the control group, respectively. Infection risk was not increased and weight gain was not delayed with rhEPO beta.\n Early rhEPO beta treatment effectively reduces the need for transfusion in ELBW infants." ]

[ "2909689" ]

[ "Timing of operation for ruptured supratentorial aneurysms: a prospective randomized study." ]

[ "A total of 216 patients with a ruptured aneurysm of the anterior part of the circle of Willis were enrolled into this prospective randomized study of timing of the operation after aneurysmal subarachnoid hemorrhage (SAH). Only patients in clinical Grades I to III (according to the classification of Hunt and Hess) who were admitted and randomly assigned to a treatment group within 72 hours after the SAH were included in the trial. The patients were randomly assigned to one of three operation groups: acute surgery (AS: 0 to 3 days after the SAH; day of SAH = Day 0), intermediate surgery (IS: 4 to 7 days after the SAH), or late surgery (LS: 8 days to an indefinite time after the SAH). Three patients (4.3%) in the IS group and six patients (8.6%) in the LS group died before surgery was undertaken. At 3 months post-SAH, 65 patients (91.5%) from the AS group were classified as independent compared to 55 (78.6%) from the IS group and 56 (80.0%) from the LS group. The management mortality rate in the AS group was 5.6% compared to 12.9% in the LS group. Of the 216 patients enrolled in the timing study, 159 were randomly assigned to an independent double-blind placebo-controlled trial of nimodipine in Grade I to III patients. A total of 79 patients received nimodipine and 80 placebo. When the nimodipine group and the no-nimodipine group (the 80 placebo-treated patients plus the 52 patients who were not entered into the nimodipine trial) were analyzed separately, a significant difference was seen in the outcome of the no-nimodipine group (dependent AS vs. dependent IS, p = 0.01). Nimodipine treatment was associated with a significant reduction of delayed ischemic deterioration (all operation group combined, nimodipine vs. no nimodipine p = 0.01; LS with nimodipine vs. LS with no nimodipine, p = 0.03)." ]

[ "19453040", "20490797", "17375049", "16332600", "1997835", "11914933", "9350242", "11720425", "1900687", "8888803", "16971718", "7596054", "3276900", "2276014", "12827681", "6171898", "18083404", "15108041" ]

[ "Randomized, controlled study of continuous 5-FU infusion starting immediately after curative surgery for advanced colorectal cancer.", "Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC).", "An individual patient data meta-analysis of adjuvant therapy with uracil-tegafur (UFT) in patients with curatively resected rectal cancer.", "Adjuvant chemotherapy in colorectal cancer: a joint analysis of randomised trials by the Nordic Gastrointestinal Tumour Adjuvant Therapy Group.", "Effective surgical adjuvant therapy for high-risk rectal carcinoma.", "Efficacy of oral UFT as adjuvant chemotherapy to curative resection of colorectal cancer: multicenter prospective randomized trial.", "[Prospective controlled study on the usefulness of Carmofur as a postoperative adjuvant chemotherapy for colorectal cancer].", "Adjuvant 5FU plus levamisole in colonic or rectal cancer: improved survival in stage II and III.", "[Cooperative study of surgical adjuvant chemotherapy for colorectal cancer (third report): five-year results. Cooperative Study Group of Surgical Adjuvant Chemotherapy for Colorectal Cancer in Japan].", "Oral adjuvant chemotherapy with carmofur (HCFU) for colorectal cancer: five-year follow-up. Tokai HCFU Study Group--third study on colorectal cancer.", "Chemotherapy with preoperative radiotherapy in rectal cancer.", "Five-year results of a randomized controlled trial of adjuvant chemotherapy for curatively resected colorectal carcinoma. The Colorectal Cancer Chemotherapy Study Group of Japan.", "Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01.", "Adjuvant chemotherapy with 5-fluorouracil, vincristine and CCNU for patients with Dukes' C colorectal cancer. The Swedish Gastrointestinal Tumour Adjuvant Therapy Group.", "Randomised clinical trial of adjuvant postoperative RT vs. sequential postoperative RT plus 5-FU and levamisole in patients with stage II-III resectable rectal cancer: a final report.", "Adjuvant chemotherapy in cancer of the colon and rectum: demonstration of effectiveness of prolonged 5-FU chemotherapy in a prospectively controlled, randomized trial.", "Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study.", "Randomized controlled trial of the efficacy of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil and uracil/tegafur." ]

[ "The usefulness of adjuvant chemotherapy started immediately following surgery was evaluated.\n A randomized clinical trial was performed on 133 patients with advanced colorectal cancer using oral anticancer agents with one-week continuous 5-FU infusion starting immediately after curative surgery. In Group A and Group B, 300 mg/day of HCFU was orally administered for two years starting two weeks after surgery, and in addition, 333 mg/m2/day of 5-FU was drip infused from the central vein for seven days from the day of surgery in Group B.\n For 1919 days after surgery, there were no significant intergroup differences in overall survival (OS) and disease-free survival (DFS), but OS and DFS in Group B rectal cancer patients were significantly better when compared to Group A rectal cancer patients. On the other hand, OS tended to be better in Group A colon cancer patients, but no significant intergroup differences were seen, while intergroup differences tended to be smaller when corrected for disease stage.\n Continuous 5-FU infusion starting immediately after curative surgery for colorectal cancer was safe. While further investigation is necessary to elucidate the degree of improvement in postoperative prognosis, the results of the present study suggest that continuous 5-FU infusion improves prognosis in advanced rectal cancer.", "In the latter 1990s, adjuvant chemotherapy for completely resected Stage III colorectal cancer remained controversial in Japan. We conducted two independent randomized controlled trials in patients with Stage III colon and rectal cancer.\n Patients were randomly assigned to receive surgery alone or surgery followed by treatment with UFT (400 mg/m²/day), given for five consecutive days per week for 1 year. The primary endpoint was relapse-free survival (RFS), and the secondary endpoint was overall survival (OS).\n A total of 334 patients with colon cancer and 276 with rectal cancer were enrolled. The patients' characteristics were similar between the UFT group and the Surgery-alone group. There was no significant difference in RFS or OS in colon cancer. In rectal cancer, however, RFS and OS were significantly better in the UFT group than in the Surgery-alone group. The only grade 4 toxicity in the UFT group was diarrhea, occurring in one patient with colon cancer and one patient with rectal cancer.\n Postoperative adjuvant chemotherapy with UFT is successfully tolerated and improves RFS and OS in patients with Stage III rectal cancer. In colon cancer, the expected benefits were not obtained (hazard ratio = 0.89).", "Uracil-Tegafur (UFT), an oral fluorinated pyrimidine chemotherapeutic agent, has been used for adjuvant chemotherapy in curatively resected colorectal cancer patients. Past trials and meta-analyses indicate that it is somewhat effective in extending survival of patients with rectal cancer. The objective of this study was to perform a reappraisal of randomised clinical trials conducted in this field. We designed an individual patient-based meta-analysis of relevant clinical trials to examine the benefit of UFT for curatively resected rectal cancer in terms of overall survival (OS), disease-free survival (DFS), and local relapse-free survival (LRFS). We analysed individual patient data of five adjuvant therapy randomised clinical trials for rectal cancer, which met the predetermined inclusion criteria. These five trials had a combined total of 2091 patients, UFT as adjuvant chemotherapy compared to surgery-alone, 5-year follow-up, intention-to-treat-based analytic strategy, and similar endpoints (OS and DFS). In a pooled analysis, UFT had significant advantage over surgery-alone in terms of both OS (hazard ratio, 0.82; 95% confidence interval (CI), 0.70-0.97; P=0.02) and DFS (hazard ratio, 0.73; 95%CI, 0.63-0.84; P<0.0001). This individual patient-based meta-analysis demonstrated that oral UFT significantly improves both OS and DFS in patients with curatively resected rectal cancer.", "Due to uncertainties regarding clinically meaningful gains from adjuvant chemotherapy after colorectal cancer surgery, several Nordic Groups in the early 1990s initiated randomised trials to prove or reject such gains. This report gives the joint analyses after a minimum 5-year follow-up. Between October 1991 and December 1997, 2 224 patients under 76 years of age with colorectal cancer stages II and III were randomised to surgery alone (n = 1 121) or adjuvant chemotherapy (n = 1 103) which varied between trials (5FU/levamisole for 12 months, n = 444; 5FU/leucovorin for 4-5 months according to either a modified Mayo Clinic schedule (n = 262) or the Nordic schedule (n = 397). Some centres also randomised patients treated with 5FU/leucovorin to+/-levamisole). A total of 812 patients had colon cancer stage II, 708 colon cancer stage III, 323 rectal cancer stage II and 368 rectal cancer stage III. All analyses were according to intention-to-treat. No statistically significant difference in overall survival, stratified for country or region, could be found in any group of patients according to stage or site. In colon cancer stage III, an absolute difference of 7% (p = 0.15), favouring chemotherapy, was seen. The present analyses corroborate a small but clinically meaningful survival gain from adjuvant chemotherapy in colon cancer stage III, but not in the other presentations.", "Radiation therapy as an adjunct to surgery for rectal cancer has been shown to reduce local recurrence but has not improved survival. In a previous study, combined radiation and chemotherapy improved survival significantly as compared with surgery alone, but not as compared with adjuvant radiation, which many regard as standard therapy. We designed a combination regimen to optimize the contribution of chemotherapy, decrease recurrence, and improve survival as compared with adjuvant radiation alone.\n Two hundred four patients with rectal carcinoma that was either deeply invasive or metastatic to regional lymph nodes were randomly assigned to postoperative radiation alone (4500 to 5040 cGy) or to radiation plus fluorouracil, which was both preceded and followed by a cycle of systemic therapy with fluorouracil plus semustine (methyl-CCNU).\n After a median follow-up of more than seven years, the combined therapy had reduced the recurrence of rectal cancer by 34 percent (P = 0.0016; 95 percent confidence interval, 12 to 50 percent). Initial local recurrence was reduced by 46 percent (P = 0.036; 95 percent confidence interval, 2 to 70 percent), and distant metastasis by 37 percent (P = 0.011; 95 percent confidence interval, 9 to 57 percent). In addition, combined therapy reduced the rate of cancer-related deaths by 36 percent (P = 0.0071; 95 percent confidence interval, 14 to 53 percent) and the overall death rate by 29 percent (P = 0.025; 95 percent confidence interval, 7 to 45 percent). Its acute toxic effects included nausea, vomiting, diarrhea, leukopenia, and thrombocytopenia. These effects were seldom severe. Severe, delayed treatment-related reactions, usually small-bowel obstruction requiring surgery, occurred in 6.7 percent of all patients receiving radiation, and the frequencies of these complications were comparable in both treatment groups.\n The combination of postoperative local therapy with radiation plus fluorouracil and systemic therapy with a fluorouracil-based regimen significantly and substantively improves the results of therapy for rectal carcinoma with a poor prognosis, as compared with postoperative radiation alone.", "The purpose of this study is to evaluate the efficacy of postoperative adjuvant chemotherapy using uracil and tegafur (UFT) for colorectal cancer.\n In a multicenter trial among 43 institutions for patients who underwent curative resection of Dukes' B or C colorectal cancer, a surgery alone group (control group) and a treatment group (UFT group) to which UFT was administered at 400 mg/day for 2 years following surgery were compared. A total of 320 patients were registered between March 1991 and April 1994, and 289 of these patients were analyzed as a full-analysis set.\n The 5-year disease-free survival rate was 75.7% in the UFT group and 60.1% in the control group, respectively, and the stratified log-rank test showed the statistical significance ( P=0.0081). This difference was marked in rectal cancer ( P=0.0016) and, in particular, the local recurrence was reduced. No significant difference was observed in the 5-year survival rate. The incidence of adverse reactions on administration of UFT was low, and there was no serious adverse reaction.\n It is suggested that the consecutive administration of UFT at 400 mg/day was an effective and highly safe therapeutic method as postoperative adjuvant chemotherapy for rectal cancer.", "A prospective controlled study, the 7th cooperative study of the Japanese Foundation for Multidisciplinary Treatment, was conducted to evaluate the usefulness of concomitant therapy with MMC + HCFU as a postoperative adjuvant therapy in patients with colorectal cancer who had undergone curative resection for a period of 2 years and 11 months from February, 1986. The Dukes B and C patients with colorectal cancer classified by macroscopic examination who had an intravenous MMC 6 mg/m2 on the day of operation and followed by oral HCFU for 12 months from 2 weeks after operation (Group X) were compared with patients who had operation only (Group Y). Some 978 patients with colon cancer and 713 patients with rectal cancer were enrolled in the study, 85 (5.0%) of whom were not eligible. The 5-year survival rate of Group X in colon cancer was 79.3% and that of Group Y was 76.4%: thus the survival rate of Group X was slightly better than that of Group Y, but no significant difference was found between the two groups. Subset analysis revealed that the survival rate of Group X in advanced cancer of stage III b + IV, according to the General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus in Japan, was 62.4% and that of Group Y was 46.2%. Thus, the survival rate of Group X was significantly better than that of Group Y (logrank test: p = 0.035, generalized Wilcoxon test: p = 0.025). The disease-free survival rate was not significantly different between the groups with colon cancer and rectal cancer. The above results suggest that HCFU is useful for patients with a high risk of recurrence who had advanced colon cancer (stage III b + IV). However, additional prospective studies are required to verify them.", "Based on the first favourable results of adjuvant therapy of 5FU plus levamisole in Dukes C colonic cancer in 1990, we conducted a prospective trial. 1029 patients were randomised to receive one year 5FU plus levamisole or no further treatment following curative surgery for stage II or III colon (n = 730) or rectal cancer (n = 299). 45% were in stage II and 55% in stage III. With a median follow-up of 4 years and 9 months a significant reduction in odds of death (25%, SD 9%, P = 0.007) was observed for those with adjuvant treatment (65% at 5 year) compared to the observation group (55%). Improved relative survival was present in stage III (56% vs 44%), and in stage II patients (78% vs 70%). In rectal cancer a non-significant difference in disease-free or overall survival was observed. Distant metastases developed in 76%, while local recurrence alone occurred in 14%. An early start of adjuvant treatment (< 4 weeks) did not affect results. Compliance to 5FU plus levamisole was 69%. Severe toxicity did not occur. In conclusion, one year 5FU plus levamisole was of benefit in stage II and III colonic cancer; in rectal cancer a significant positive effect could not be demonstrated.", "A randomized controlled study was carried out by the envelope method with 491 institutions in participation across the country in order to find an optimal surgical adjuvant chemotherapy for curatively resected colorectal cancer. The schedules for drug administration were different in four districts: ACNU + Futraful (FT) group and FT alone group in the Hokkaido-Shikoku district; the same schedule groups plus untreated group in the Chubu-Kinki district; MMC+FT group, FT alone group in the Tohoku-Kanto district; and ADM+FT group and FT alone group in the Chugoku-Kyushu district. The numbers of patients admitted to this study were 2,450 cases with colon cancer and 2,456 cases met the evaluation criteria of this study. The 5-year survival rate on the whole did not differ from combination therapy to single drug therapy in either colon cancer or rectal cancer, but in Dukes C rectal cancer the five-year survival rate tended to be higher with the combination therapies. In n2 (+) or a2(s) rectal cancer in particular, combination therapies with MMC and FT and with ADM and FT achieved significantly higher five-year survival rate, and the rate of local recurrence was significantly lower with ADM+FT.", "A joint study was performed by the Tokai HCFU study group, which included seven institutions, to examine the value of oral administration of Carmofur (HCFU), a 5-fluorouracil (5-FU) derivative, for postoperative adjuvant chemotherapy in patients with colorectal cancer undergoing curative resection.\n The patients were divided into two groups, a control group receiving no HCFU and a group administered HCFU for 1 year, using a centralized registration system by telephone. Among 173 patients entered into this study, 159 evaluable cases were analyzed for evaluation of the drug.\n The cumulative 5-year disease-free rate of patients who received HCFU was significantly increased compared with the control group. In particular, the rate was much higher in patients with colon cancer. No severe side effects arose from adjuvant chemotherapy with HCFU.\n Adjuvant chemotherapy with oral HCFU appears to provide a useful and safe postoperative treatment.", "Preoperative radiotherapy is recommended for selected patients with rectal cancer. We evaluated the addition of chemotherapy to preoperative radiotherapy and the use of postoperative chemotherapy in the treatment of rectal cancer.\n We randomly assigned patients with clinical stage T3 or T4 resectable rectal cancer to receive preoperative radiotherapy, preoperative chemoradiotherapy, preoperative radiotherapy and postoperative chemotherapy, or preoperative chemoradiotherapy and postoperative chemotherapy. Radiotherapy consisted of 45 Gy delivered over a period of 5 weeks. One course of chemotherapy consisted of 350 mg of fluorouracil per square meter of body-surface area per day and 20 mg of leucovorin per square meter per day, both given for 5 days. Two courses were combined with preoperative radiotherapy in the group receiving preoperative chemoradiotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy; four courses were planned postoperatively in the group receiving preoperative radiotherapy and postoperative chemotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy. The primary end point was overall survival.\n We enrolled 1011 patients in the trial. There was no significant difference in overall survival between the groups that received chemotherapy preoperatively (P=0.84) and those that received it postoperatively (P=0.12). The combined 5-year overall survival rate for all four groups was 65.2%. The 5-year cumulative incidence rates for local recurrences were 8.7%, 9.6%, and 7.6% in the groups that received chemotherapy preoperatively, postoperatively, or both, respectively, and 17.1% in the group that did not receive chemotherapy (P=0.002). The rate of adherence to preoperative chemotherapy was 82.0%, and to postoperative chemotherapy was 42.9%.\n In patients with rectal cancer who receive preoperative radiotherapy, adding fluorouracil-based chemotherapy preoperatively or postoperatively has no significant effect on survival. Chemotherapy, regardless of whether it is administered before or after surgery, confers a significant benefit with respect to local control. (ClinicalTrials.gov number, NCT00002523 [ClinicalTrials.gov].).\n Copyright 2006 Massachusetts Medical Society.", "In order to evaluate the significance of postoperative adjuvant chemotherapy for colorectal carcinoma, the Colorectal Cancer Chemotherapy Study Group, from 140 leading hospitals in Japan, conducted a prospective, randomized, controlled trial on patients who had undergone curative resections for colorectal carcinomas during the period from February 1984, to December 1985. The regimens for colon cancer were, Arm I: mitomycin C [intraoperative portal vein bolus (12 mg/m2) + postoperative, twice weekly and then three times bimonthly for six months intermittent i.v. bolus (6 mg/m2)] + 5-fluorouracil (5-FU) 200 mg/body/day p.o. for six months; Arm II: postoperative twice weekly and then three times bimonthly intermittent i.v. bolus mitomycin C (6 mg/m2) for six months + 5-FU 200 mg/body/day p.o. for six months; Arm III: surgery alone. The regimens for rectal cancer were, Arm IV: same as Arm I, with superior rectal artery infusion of the same mitomycin C dose instead of portal vein infusion; Arm V: same as Arm II; Arm VI: same as Arm III. Of 2001 collected cases, 1805 eligible cases (899 colon cancers and 906 rectal cancers) were analyzed. Significant differences in five-year survival rates were found between Arms IV and V and Arm VI [Arm IV: 70.7% (95% confidence interval (C.I.): 65.6-75.8%), P = 0.004 vs Arm V: 73.6% (68.5-78.7%), P = 0.000 vs Arm VI (control): 60.2% (54.5-65.9%)]. No significant difference in overall survival rate was found in the colon cancer patients [Arm I: 80.4% (75.7-85.1%), not significant (N.S.) vs Arm II: 82.1% (77.8-86.4%), N.S. vs Arm III (control): 79.5% (74.6-84.4%)]. When stratified into Dukes classes, however, Dukes C patients in Arm II showed a significantly improved survival rate compared with that of those in Arm III [Arm I: 72.6% (64.8-80.4%), N.S. vs Arm II: 75.0% (67.9-82.1%), P = 0.012 vs Arm III (control): 61.0% (51.4-70.6%)]. We conclude the adjuvant use of long term oral 5-FU and intermittent mitomycin C (i.v.) to improve the survival rate of patients with curatively resected rectal cancer. Further comparative study is, however, recommended to confirm the effectiveness of 5-FU alone and the combination of 5-FU and mitomycin C. Regional chemotherapy made no contribution to reducing an hepatic recurrence of colon cancer or a local recurrence of rectal cancer.", "Information is presented from 555 patients with Dukes B and C rectal cancers treated by curative resection who were entered into the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol R-01 between November 1977 and October 1986. Their average time on study was 64.1 months. The patients were randomized to receive no further treatment (184 patients), postoperative adjuvant chemotherapy with 5-fluorouracil, semustine, and vincristine (MOF) (187 patients), or postoperative radiation therapy (184 patients). The chemotherapy group, when compared with the group treated by surgery alone, demonstrated an overall improvement in disease-free survival (P = .006) and in survival (P = .05). Employing the proportional hazards model, a global test was used to determine the presence of treatment interactions. Investigation of stratification variables employed in this study indicated that sex, and to a lesser extent age and Dukes stage, made individual contributions to the disease-free survival and the survival benefit from chemotherapy. When evaluated according to sex, the benefit for chemotherapy at 5 years, both in disease-free survival (29% vs. 47%; P less than .001; relative odds, 2.00) and in survival (37% vs. 60%; P = .001; relative odds, 1.93), was restricted to males. When males were tested for age trend with the use of a logistic regression analysis, chemotherapy was found to be more advantageous in younger patients. When the group receiving post-operative radiation (4,600-4,700 rad in 26-27 fractions; 5,100-5,300 rad maximum at the perineum) was compared to the group treated only by surgery, there was an overall reduction in local-regional recurrence from 25% to 16% (P = .06). No significant benefit in overall disease-free survival (P = .4) or survival (P = .7) from the use of radiation has been demonstrated. The global test for interaction to identify heterogeneity of response to radiation within subsets of patients was not significant. In conclusion, this investigation has demonstrated a benefit from adjuvant chemotherapy (MOF) for the management of rectal cancer. The observed advantage was restricted to males. Postoperative radiation therapy reduced the incidence of local-regional recurrence, but it failed to affect overall disease-free survival and survival.", "A prospective controlled randomized trial testing adjuvant postoperative combination chemotherapy (5-fluorouracil, lomustine (CCNU) and vincristine) versus no adjuvant therapy in patients operated on for Dukes' C colorectal cancer is reported. In total 334 patients aged less than 70 years were recruited: 205 patients with colonic and 99 with rectal cancer, but there were three protocol violations and these cases are excluded from further consideration. Twenty-seven patients had a limited resection of their cancer. After 5 years' follow-up there was no significant difference in the tumour-free survival rate or in the survival rate between the treated and control groups. Twenty-nine of the 147 patients who started chemotherapy discontinued this treatment because of side-effects, mainly from the gastrointestinal tract. In 30 patients treatment was discontinued because of recurrent disease. The conclusion is that systemic administration of combination chemotherapy for colorectal cancer after operation is not worthwhile in routine clinical practice.", "A randomised clinical trial was performed in patients undergoing radical surgery for rectal cancer to compare the efficacy and toxicity of adjuvant postoperative radiation therapy (RT) to sequential RT and chemotherapy (CT) with 5-fluorouracil (5-FU) plus levamisole (LEV). The primary end point was overall survival (OS); secondary end points were disease-free survival (DFS), the rate of loco-regional recurrence, and treatment-related toxicity; the final results of this trial are reported.\n Patients in arm I underwent RT (50 Gy) in daily fractions of 2 Gy, 5 days/week for 5 weeks. Patients in arm II began with 5-FU (450 mg/sqm/day intravenous (i.v.) bolus, days 1-5) plus LEV (150 mg/day orally, days 1-3); postoperative RT was delivered during week 2 at the same dosage and schedule as in arm I. The other five cycles of CT (5-FU every 28 days and LEV every 15 days for the length of 5-FU administration) continued after the end of RT if clinical and hemato-biochemical parameters were in the normal range.\n From May 1992 to December 1998, 218 patients were enrolled into the randomised clinical trial (144 men, 74 women; age range: 28-75, median 64 years). The median follow-up time was 58.1 months (range: 1-3,271 days). No significant difference was observed between the two arms of treatment as regards OS and DFS (P = 0.18 and P = 0.66, respectively). Cox regression analysis for OS confirmed what was observed by univariate analysis for all variables except age. Older age (>60 years) and pathologic lymph-node involvement defined the subgroups with the worst prognosis. Cox regression analysis for DFS confirmed what was observed by univariate analysis for all variables: the only independent variable in predicting DFS was pathologic lymph-node involvement.\n Our findings suggest no difference in OS, loco-regional and distant site progressions of postoperative RT alone compared to sequential postoperative RT and CT; notably, this latter regimen was associated with higher toxicity which seriously impaired the patient's compliance to CT. The low loco-regional recurrence rate (9.2%) observed in our patients undergoing postoperative RT alone compared to similarly treated patients in previously performed clinical trials (20-25%) underline the role of radical surgery (mesorectal excision) coupled with a complete postoperative RT regimen. On the other hand, the similar efficacy of these two adjuvant modalities of treatment might be conditioned by both the low compliance (59%) to the CT regimen as well as the sequential, instead of concurrent, schedule of administration of RT and CT, which may have decreased further the expected efficacy of the combined regimen.\n Copyright 2003 Wiley-Liss, Inc.", "nan", "The aim of the QUASAR trial was to determine the size and duration of any survival benefit from adjuvant chemotherapy for patients with colorectal cancer at low risk of recurrence, for whom the indication for such treatment is unclear.\n After apparently curative resections of colon or rectal cancer, 3239 patients (2963 [91%] with stage II [node negative] disease, 2291 [71%] with colon cancer, median age 63 [IQR 56-68] years) enrolled between May, 1994, and December, 2003, from 150 centres in 19 countries were randomly assigned to receive chemotherapy with fluorouracil and folinic acid (n=1622) or to observation (with chemotherapy considered on recurrence; n=1617). Chemotherapy was delivered as six 5-day courses every 4 weeks or as 30 once-weekly courses of intravenous fluorouracil (370 mg/m2) with high-dose (175 mg) L-folinic acid or low-dose (25 mg) L-folinic acid. Until 1997, levamisole (12 courses of 450 mg over 3 days repeated every 2 weeks) or placebo was added. After 1997, patients who were assigned to receive chemotherapy were given fluorouracil and low-dose folinic acid only. The primary outcome was all-cause mortality. Analyses were done by intention to treat. This trial is registered with the International Clinical Trial Registry, number ISRCTN82375386.\n At the time of analysis, 61 (3.8%) patients in the chemotherapy group and 50 (3.1%) in the observation group had missing follow-up. After a median follow-up of 5.5 (range 0-10.6) years, there were 311 deaths in the chemotherapy group and 370 in the observation group; the relative risk of death from any cause with chemotherapy versus observation alone was 0.82 (95% CI 0.70-0.95; p=0.008). There were 293 recurrences in the chemotherapy group and 359 in the observation group; the relative risk of recurrence with chemotherapy versus observation alone was 0.78 (0.67-0.91; p=0.001). Treatment efficacy did not differ significantly by tumour site, stage, sex, age, or chemotherapy schedule. Eight (0.5%) patients in the chemotherapy group and four (0.25%) in the observation group died from non-colorectal cancer causes within 30 weeks of randomisation; only one of these deaths was deemed to be possibly chemotherapy related.\n Chemotherapy with fluorouracil and folinic acid could improve survival of patients with stage II colorectal cancer, although the absolute improvements are small: assuming 5-year mortality without chemotherapy is 20%, the relative risk of death seen here translates into an absolute improvement in survival of 3.6% (95% CI 1.0-6.0).", "We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT).\n Patients with stage II, III, or IV (Dukes' B, C) colorectal cancer were enrolled and randomly assigned to one of three groups: an immunochemotherapy group (mitomycin C [MMC] + 5-fluorouracil [5-FU] + HCFU + OK-432), a chemotherapy group (MMC + 5-FU + HCFU), and a control group (surgery alone) for those with colon cancer (study 1); and an immunochemotherapy group (MMC + 5-FU + UFT + OK-432), a chemotherapy group (MMC + 5-FU + UFT), and a control group (surgery alone) for those with rectal cancer (study 2).\n A total of 760 patients with colon cancer and 669 patients with rectal cancer were entered into this randomized clinical trial (RCT). The incidence of side-effects was in the order of: immunochemotherapy group > chemotherapy group > control group in both the cohort of patients with colon cancer and the cohort with rectal cancer. In particular, the frequency of leucopenia and skin disorders was significantly higher than control groups. There were no severe adverse events such as death related to the adjuvant therapy. In both the colon cancer and rectal cancer cohorts, no significant difference in the 5-year survival rate and disease-free survival rate was noted among the three groups.\n The results of an RCT demonstrated that the combination of MMC + 5-FU + HCFU + OK-432 for colon cancer and that of MMC + 5-FU + UFT + OK-432 for rectal cancer could not prolong the survival of patients with surgically resected colorectal cancer, but that both combinations were well tolerated as adjuvant therapy. We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT)." ]

[ "16990605" ]

[ "A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study." ]

[ "The development of inhibitory antibodies to factor VIII is a serious complication of hemophilia. FEIBA (factor VIII inhibitor-bypassing activity), an activated prothrombin complex concentrate (aPCC), and NovoSeven, recombinant factor VIIa (rFVIIa), are used as hemostatic bypassing agents in treating patients with inhibitors. The FENOC study was designed to test equivalence of the products in the treatment of ankle, knee, and elbow joint bleeding. A prospective, open-label, randomized, crossover, equivalency design was used. The parameters of interest were the percentage of patients who reported efficacy in response to FEIBA and the percentage that reported efficacy in response to NovoSeven. A difference in these percentages of no more than 15% was determined to be a clinically acceptable magnitude for equivalence of the 2 products. The primary outcome was evaluation 6 hours after treatment. Data for 96 bleeding episodes contributed by 48 participants were analyzed. The criterion for declaring the 2 products equivalent at 6 hours was not met; however, the confidence interval of the difference in percentages of efficacy reported for each product only slightly exceeded the 15% boundary (-11.4%-15.7%), P=.059. FEIBA and NovoSeven appear to exhibit a similar effect on joint bleeds, although the efficacy between products is rated differently by a substantial proportion of patients. This trial was registered at www.clinicaltrials.gov as #NCT00166309." ]

[ "14736444" ]

[ "Effect of rate or rhythm control on quality of life in persistent atrial fibrillation. Results from the Rate Control Versus Electrical Cardioversion (RACE) Study." ]

[ "We studied the influence of rate control or rhythm control in patients with persistent atrial fibrillation (AF) on quality of life (QoL).\n Atrial fibrillation may cause symptoms like fatigue and dyspnea. This can impair QoL. Treatment of AF with either rate or rhythm control may influence QoL.\n Quality of life was assessed in patients included in the Rate Control Versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study (rate vs. rhythm control in persistent AF). Rate control patients (n = 175) were given negative chronotropic drugs and oral anticoagulation. Rhythm control patients (n = 177) received serial electrocardioversion, antiarrhythmic drugs, and oral anticoagulation, as needed. Quality of life was studied using the Short Form (SF)-36 health survey questionnaire at baseline, one year, and the end of the study (after 2 to 3 years of follow-up). At baseline, QoL was compared with that of healthy control subjects. Patient characteristics related to QoL changes were determined.\n Mean follow-up was 2.3 years. At baseline, QoL was lower in patients than in age-matched healthy controls. At study end, under rate control, three subscales of the SF-36 improved. Under rhythm control, no significant changes occurred compared with baseline. At study end, QoL was comparable between both groups. The presence of complaints of AF at baseline, a short duration of AF, and the presence of sinus rhythm (SR) at the end of follow-up, rather than the assigned strategy, were associated with QoL improvement.\n Quality of life is impaired in patients with AF compared with healthy controls. Treatment strategy does not affect QoL. Patients with complaints related to AF, however, may benefit from rhythm control if SR can be maintained." ]

[ "7774735", "7078845" ]

[ "A randomized prospective trial comparing single dose prostaglandin E2 vaginal gel with forewater amniotomy for induction of labour.", "Role of the cervix in the induction of labor." ]

[ "A prospective randomized parallel-group study was carried out to compare the efficacy of a single dose vaginal prostaglandin E2 gel with forewater amniotomy for induction of labour at term in 260 parturients (110 primigravid and 150 parous women) with low risk pregnancy and favourable cervix. In the prostaglandin E2 (PGE2) managed group, the primigravidae were treated with 2 mg PGE2 gel and parous patients with 1 mg PGE2 gel. Forewater amniotomy was performed 4 h later, or sooner if women requested analgesia. In the amniotomy group, artificial forewater amniotomy was carried out and a repeat cervical assessment done 4 h later, or sooner if women requested analgesia. In both groups, intravenous oxytocin was established if there was evidence of disordered uterine activity, 6 h after the start of initial intervention. An assessment of consumers' views was carried out by using a standardized questionnaire completed 48 h after delivery. There was a significant reduction in the requirement for oxytocin augmentation in women treated with PGE2: primigravidae, odds ratio (OR), 0.27 and 95% confidence interval (CI), 0.12-0.61; multiparae, OR, 0.19 and 95% CI, 0.08-0.45. Fewer primigravidae managed with PGE2 gel required epidural analgesia (OR, 0.16; 95% CI, 0.06-1.00). Fewer parous women managed with PGE2 gel required parenteral opiates (OR, 0.44; 95% CI, 0.23-0.85) and more women required inhalation analgesia or no analgesia (OR, 2.22; 95% CI, 1.76-2.79). The intervention to delivery intervals were shortened in PGE2 groups independent of parity but the differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)", "A study on induction of labor was carried out to test the hypothesis that changing the cervix will enhance the effectiveness of induction of labor. Fifty pregnant women near term with Bishop scores of 4 or less were divided into 5 study groups, in which a 12-hour preparation phase procedure was carried out to produce cervical or myometrial changes. All women had continuous measurement of uterine activity by an extraovular catheter. The patients were divided into 1) control subjects, and into groups treated with 2) laminaria, 3) Foley catheter, 4) amniotomy, and 5) oxytocin infusion. These preparation techniques were used for 12 hours, after which rupture of membranes was carried out in all cases. Although all procedures significantly changed the cervix, none but oxytocin affected the induction-to-delivery interval. The authors concluded that when a study design rigidly controls for cervical Bishop score, timing of rupture of membranes, and oxytocin infusion rates, the cervical preparation alone will not enhance inducibility." ]

[ "10086941" ]

[ "Randomised controlled trial of budesonide for the prevention of post-bronchiolitis wheezing." ]

[ "Previous studies suggest that recurrent episodes of coughing and wheezing occur in up to 75% of infants after acute viral bronchiolitis.\n To assess the efficacy of budesonide given by means of a metered dose inhaler, spacer, and face mask in reducing the incidence of coughing and wheezing episodes up to 12 months after acute viral bronchiolitis.\n Children under the age of 12 months admitted to hospital with acute viral bronchiolitis were randomised to receive either budesonide or placebo (200 microg or one puff twice daily) for the next eight weeks. Parents kept a diary card record of all episodes of coughing and wheezing over the next 12 months.\n Full follow up data were collected for 49 infants. There were no significant differences between the two study groups for the number of infants with symptom episodes up to six months after hospital discharge. At 12 months, 21 infants in the budesonide group had symptom episodes compared with 12 of 24 in the placebo group. The median number of symptom episodes was 2 (range, 0-13) in those who received budesonide and 1 (range, 0-11) in those who received placebo. Because there is no pharmacological explanation for these results, they are likely to be caused by a type 1 error, possibly exacerbated by there being more boys in the treatment group.\n Routine administration of budesonide by means of a metered dose inhaler, spacer, and face mask system immediately after acute viral bronchiolitis cannot be recommended." ]

[ "2645569", "6823418", "8241636", "6423796", "3569347", "3627875", "3292250" ]

[ "Randomized trial of taurine supplementation for infants less than or equal to 1,300-gram birth weight: effect on auditory brainstem-evoked responses.", "Feeding the low-birth-weight infant: I. Taurine and cholesterol supplementation of formula does not affect growth and metabolism.", "Influence of dietary taurine on vitamin D absorption.", "Effect of taurine supplementation on hepatic function during short-term parenteral nutrition in the premature infant.", "Fat absorption in preterm infants fed a taurine-enriched formula.", "Taurine supplementation of a premature formula improves fat absorption in preterm infants.", "Development of the nervous and cardiovascular systems in low-birth-weight infants fed a taurine-supplemented formula." ]

[ "Taurine may be important to the developing eye and brain of the small preterm infant. A blinded randomized trial was conducted to determine whether taurine supplementation of healthy infants of less than or equal to 1,300 g birth weight until their discharge from the hospital increases their growth rate, neurobehavioral development, electroretinographic development, or maturation of auditory brainstem-evoked responses. Infants were fed with Similac Special Care as desired, which was prepared to contain less than 5 mg/L of taurine or 45 mg/L of taurine, a concentration similar to that of human milk. Infants who did not receive taurine supplementation (n = 19) and those who did (n = 18) were similar with respect to condition at study entry, caloric intake, and growth rates throughout the study, and electroretinographic findings and scores on the Brazelton Behavioral Assessment Scale at 37 weeks' postmenstrual age. Infants who received taurine supplementation had greater overall plasma taurine concentrations. The group receiving taurine supplementation also had more mature auditory-evoked responses at 37 weeks' postmenstrual age with a modest (0.2 to 0.5 ms) but consistent reduction (P less than .05) in the interval between stimulus and response at two different stimulation rates. Although further study is needed, taurine intake appears to influence auditory system maturation of preterm infants.", "Taurine and cholesterol are constituents of human milk that are present in smaller amounts in infant formulas. Infants fed such formulas have lower plasma and urine concentrations of taurine and of serum total cholesterol. In the present investigation, in infants of 31 to 36 weeks gestational age, the effects of supplementing a 1.5 g/100 mL whey-predominant formula with taurine alone or with taurine plus cholesterol were examined. Infants fed the supplemented formula were compared with infants fed the unsupplemented formula and with infants fed pooled, expressed human milk (185 mL/kg/d). Approximately 45% of the human milk provided to each infant was that of the infant's mother (35% pasteurized and 10% fresh). From the time of reaching a weight of 2,400 g to 4 months of age the last group of infants was fed ad libitum. No consistent statistically significant differences in growth, as measured by rate of gain in crown-rump length, crown-heel length, or head circumference, were observed. There was a tendency, however, for the formula-fed infants to gain weight more slowly before reaching 2,400 g and to gain weight more quickly after a weight of 2,400 g was attained to 4 months of age. No differences in concentrations of BUN, total serum proteins, or acid-base status were observed among the formula-fed groups. The concentration of BUN increased in the formula-fed groups compared with the group fed human milk during the last half of the study. The formula-fed infants tended to have higher total serum proteins and to be slightly more acidotic than the infants fed human milk prior to discharge at a weight of 2,400 g but not thereafter. Thus, infants fed 185 mL/kg/d gained weight at rates comparable to those for fetuses of the same gestational age. Supplementation of formulas with taurine or taurine plus cholesterol did not produce changes in growth or general metabolism discernible under the present experimental conditions.", "To evaluate the influence of dietary taurine supplementation on vitamin D absorption, we studied three groups of infants: 21 (11 preterm) were fed a taurine-free formula, 21 (10 preterm) were fed a taurine-supplemented formula (50 mg/100 g of powder) and 20 (9 preterm) were fed human, not heat-treated milk. Taurine, total bile acids, glyco-(GBA) and tauro-(TBA) conjugated bile acids, 25-hydroxyvitamin D3 (25OHD3) and 1,25-dihydroxyvitamin D3 (1,25OH2D3) were determined in all infants at birth in blood cord and at one and three months of life. In preterm infants fed a taurine-free formula, we found lower plasma taurine levels than in infants of other groups at one and three months of life. In these infants, GBA predominated, with a G/T ratio of 1.1 and 1.4 at one and three months of life, whereas in all other infants TBA predominated with a G/T ratio always < 1. Also, 25OHD3 and 1,25OH2D3 levels were significantly lower in preterm infants fed a taurine-free formula than in infants fed a taurine-enriched formula or human milk. Term infants fed a taurine-free formula did not show differences in the parameters studied in comparison to infants of other groups. Low taurine dietary intake appears to compromise vitamin D absorption in preterm infants, and therefore taurine supplementation of preterm infant formulas should be encouraged.", "To evaluate the potential role of taurine deficiency in the pathogenesis of parenteral nutrition-induced cholestasis, 20 premature (less than 34 weeks AGA) infants were randomized to receive parenteral nutrition with and without taurine (10.8 mg/kg/day) during the first 10 days of life. Birth weight, gestational age, and protein and caloric intake were similar in both groups. Plasma taurine levels and hepatic function were assessed before the study began (3 +/- 1 days of age), at 5 +/- 1 days of age, and at 9 +/- 1 days of age. Although plasma taurine levels were significantly greater at 5 +/- 1 and 9 +/- 1 days of age (p = 0.009) in the group receiving supplementation, no differential effect on hepatocellular function could be detected during this short period of time. A decrease in plasma ammonia (p = 0.001), alanine aminotransferase (ALT) (p = 0.036), gamma-glutamyltranspeptidase (GGTP) (p = 0.05), 5'-nucleotidase (5'N) (p = 0.001), and bile salt concentrations was noted in both groups, indicating the rapid maturation of hepatic function even in the presence of parenteral nutrition during the first 10 days of life.", "An adapted cow's milk infant formula without or with extra taurine (350 mumol/l) was fed to four and five infants, respectively. The infants, born after 28-32 weeks gestation, and initially fed with a starting formula for preterms, were switched to one of the two above-mentioned formulae at approximately the 16th day of life. Each infant was studied during 4 consecutive weeks. The faecal excretion of fat, energy and total bile acids was determined from 3-day stool collections each week. The addition of taurine to the infant formula neither improved the uptake of fat and energy nor changed the faecal bile acid excretion. Growth velocity was similar in both groups of infants. Based on these results there is no rationale for adding taurine to adapted cow's milk infant formula to obtain a better fat absorption.", "The predominance of taurine (Tau) conjugated over glycine conjugated bile acids in infants fed human milk as opposed to those on formulas without added Tau could account for a more complete absorption of fat. Fifteen low birth weight infants were randomized to either Enfamil Premature or to Enfamil Premature added with 40 mumol/dl of Tau and compared to a third group made up of nine low birth weight infants fed their own mother's preterm milk. Formulas and human milk were fed according to tolerance and constituted the sole nutrition for 3 months. A metabolic study was carried out at 3 wk of age and control of growth was done periodically. Urinary Tau excretion (mumol/dl) was very low (p less than 0.001) in the group fed Enfamil Premature (0.3 +/- 0.1) when compared to the values obtained in infants supplemented with Tau (51.6 +/- 12.5) and in those on human milk (36.3 +/- 7.9). Infants supplemented with Tau (92.5 +/- 1.2) had a coefficient of fat absorption which was higher (p less than 0.05) than the unsupplemented group (87.5 +/- 7.9) and comparable to the human milk-fed group (91.6 +/- 1.4). The effect was more pronounced on the saturated fatty acids and varied inversely with their individual water solubility. There was no effect of Tau on nitrogen retention and growth was identical in the three groups. These data show that the addition of Tau to formula had no effect on growth but improved the absorption of fat especially saturated fatty acids which require higher concentrations of bile acids to form mixed micelles.", "An adapted cow's milk formula with or without supplemental taurine (480 mumol/l) was fed for 16 weeks to 20 low-birth-weight infants. In the 2nd and 16th weeks of life, respectively, the following parameters were determined: growth, sonography of heart and brain, ECG, EEG, neurological development and the taurine concentration of plasma and urine. None of the parameters investigated was influenced by taurine supplementation except the urinary taurine excretion. At least according to these data, the addition of taurine to whey-predominant infant formulae seems to be unnecessary for the development of heart and brain function in low-birth-weight infants." ]

[ "20841574" ]

[ "Game-based versus traditional case-based learning: comparing effectiveness in stroke continuing medical education." ]

[ "To evaluate family physicians' enjoyment of and knowledge gained from game-based learning, compared with traditional case-based learning, in a continuing medical education (CME) event on stroke prevention and management.\n An equivalence trial to determine if game-based learning was as effective as case-based learning in terms of attained knowledge levels. Game questions and small group cases were developed. Participants were randomized to either a game-based or a case-based group and took part in the event.\n Ontario provincial family medicine conference.\n Thirty-two family physicians and 3 senior family medicine residents attending the conference.\n Participation in either a game-based or a case-based CME learning group.\n Scores on 40-item immediate and 3-month posttests of knowledge and a satisfaction survey.\n Results from knowledge testing immediately after the event and 3 months later showed no significant difference in scoring between groups. Participants in the game-based group reported higher levels of satisfaction with the learning experience.\n Games provide a novel way of organizing CME events. They might provide more group interaction and discussion, as well as improve recruitment to CME events. They might also provide a forum for interdisciplinary CME. Using games in future CME events appears to be a promising approach to facilitate participant learning." ]

[ "14568795", "7488373", "15679563", "12122630", "9088679", "207210", "2323085", "9339980", "7485860", "11879929", "6257815" ]

[ "Evaluation of topical povidone-iodine in chronic suppurative otitis media.", "Treatment of chronic ear disease. Topical ciprofloxacin vs topical gentamicin.", "Topical quinolone vs. antiseptic for treating chronic suppurative otitis media: a randomized controlled trial.", "[Efficacy of topical ciprofloxacin and tobramycin in combination with dexamethasone in the treatment of chronic suppurative otitis media].", "A double blind, prospective trial of topical ciprofloxacin versus normal saline solution in the treatment of otorrhoea.", "[Double-blind comparative study of trimethroprim-sulphacetamide-polymyxin b and gentamicin in the treatment of otorrhoea (author's transl)].", "A double-blind, randomized, prospective trial of a topical antiseptic versus a topical antibiotic in the treatment of otorrhoea.", "Chronic otitis media treated topically with ciprofloxacin or tobramycin.", "[Multicenter study comparing the efficacy and tolerance of topical ciprofloxacin (0.3%) versus topical gentamicin (0.3%) in the treatment of simple, non-cholesteatomaous chronic otitis media in the suppurative phase].", "Treatment of chronic suppurative otitis media with ofloxacin in hydroxypropyl methylcellulose ear drops: a clinical/bacteriological study in a rural area of Malawi.", "A double-blind comparative study of trimethoprim-polymyxin B versus trimethoprim-sulfacetamide-polymyxin B otic solutions in the treatment of otorrhea." ]

[ "To evaluate if povidone-iodine (PVP-I) can be used topically in the treatment of chronic suppurative otitis media-tubotympanic disease and to compare it with ciprofloxacin hydrochloride ear drops.\n Prospective double-blind randomized study.\n Academic tertiary medical center.\n Forty patients with chronic suppurative otitis media were randomized into 2 groups.\n One group (19 patients) received 5% PVP-I ear drops, while the other group (21 patients) received 0.3% ciprofloxacin ear drops. Both were administered topically, 3 drops 3 times daily for 10 days. These patients were followed up at weekly intervals for up to 4 weeks after commencing therapy.\n Clinical improvement at the end of study was 88% in the PVP-I group and 90% in the ciprofloxacin group. The most commonly isolated organism was Pseudomonas aeruginosa. In vitro resistance to ciprofloxacin was seen in 17% of organisms, while no resistance was seen for PVP-I.\n To our knowledge, this is the first study to evaluate the efficacy of PVP-I as a topical agent in the treatment of chronic suppurative otitis media. The results show that clinically, topical PVP-I is as effective as topical ciprofloxacin, with a superior advantage of having no in vitro drug resistance. Also, there is an added benefit of reduced cost of therapy.", "To determine and compare the therapeutic efficiency of ciprofloxacin hydrochloride and gentamicin sulfate in the treatment of chronic ear disease.\n Prospective randomized study.\n Academic tertiary medical center.\n Consecutive referred sample of 44 patients with chronic suppurative otitis media randomized into two groups.\n Ciprofloxacin hydrochloride (200 mg/mL) was administered to the first group (composed of 24 patients), while the second group (composed of 20 patients) received gentamicin sulfate (5 mg/mL) locally, five drops three times a day for 10 days.\n In the ciprofloxacin group, 21 (88%) of the 24 patients with suppurative chronic otitis media were cured. On the other hand, only six (30%) of the patients in the gentamicin group were cured. The rest of the patients showed no clinical or bacteriological improvement.\n To our knowledge, this is the first study to compare the efficiency of two topical otic preparations in the treatment of chronic ear disease. The results show that topical ciprofloxacin preparation is more efficacious and efficient than topical gentamicin for the treatment of chronic otitis media in the acute stage.", "To compare a topical quinolone antibiotic (ciprofloxacin) with a cheaper topical antiseptic (boric acid) for treating chronic suppurative otitis media in children.\n Randomized controlled trial.\n A total of 427 children with chronic suppurative otitis media enrolled from 141 schools following screening of 39 841 schoolchildren in Kenya. Intervention Topical ciprofloxacin (n = 216) or boric acid in alcohol (n = 211); child-to-child treatment twice daily for 2 weeks.\n Resolution of discharge (at 2 weeks for primary outcome), healing of the tympanic membrane, and change in hearing threshold from baseline, all at 2 and 4 weeks.\n At 2 weeks, discharge was resolved in 123 of 207 (59%) children given ciprofloxacin, and in 65 of 204 (32%) given boric acid (relative risk 1.86; 95% CI 1.48-2.35; P < 0.0001). This effect was also significant at 4 weeks, and ciprofloxacin was associated with better hearing at both visits. No difference with respect to tympanic membrane healing was detected. There were significantly fewer adverse events of ear pain, irritation, and bleeding on mopping with ciprofloxacin than boric acid.\n Ciprofloxacin performed better than boric acid and alcohol for treating chronic suppurative otitis media in children in Kenya.", "To evaluate the efficacy of topical ciprofloxacin and tobramycin with and without topical dexamethasone in the treatment of chronic suppurative otitis media without cholesteatoma.\n The study included 103 ears of 80 patients (49 males, 31 females; mean age 31 years; range 18 to 60 years) with chronic suppurative otitis media without cholesteatoma. The patients were randomly divided into four groups to receive topical applications of either ciprofloxacin and tobramycin alone, or in combination with dexamethasone. Cultures were obtained from the ears preoperatively and 24 hours after treatment.\n Aerobic bacteria were isolated in 94.1% of patients before the treatment, the most common being Pseudomonas aeruginosa (38.9%). With dexamethasone, the clinical response for ciprofloxacin and tobramycin increased from 80% to 90% and from 70% to 75%, respectively, but this improvement was not significant (p > 0.03). Addition of dexamethasone to ciprofloxacin decreased the recovery period from 14 days to seven days, whereas no change (7 days) was observed with tobramycin.\n The efficacy of ciprofloxacin and tobramycin were similar in the treatment of chronic suppurative otitis media. Addition of dexamethasone to ciprofloxacin decreased the treatment period.", "The clinical and bacteriological efficacy of topical ciprofloxacin in saline solution and a saline solution without antibiotics, for the treatment of otorrhoea, was assessed. Fifty affected ears which had an acute exacerbation of chronic otitis media with tympanic membrane perforation were included in this study. Only 35 ears completed the study. Both medications were randomly given to patients. Therapeutic efficacy was evaluated on the seventh day of treatment. A favourable clinical response was observed in 89.5% of the ciprofloxacin-treated group and in 43.8% of the saline-treated group, respectively (P < 0.005). Bacteriological eradication was also observed to be higher in the ciprofloxacin-treated group (P < 0.005). From these preliminary results, topical ciprofloxacin appears to be effective in curing the acute phase of chronic otitis media.", "A double-blind comparative study of the use of Garamycine (gentamicin) ear drops and TSP (trimethroprim-sulphacetamide-polomyxin B) ear drops in the treatment of 100 cases of otorrhoea due to external otitis, a recurrent otitis media accompanied by perforation of the drum, an infection of the mastoid cavity or a postoperative infection, provided evidence of the effectiveness of both medications. TSP ear drops gave positive results in 42 out of 50 cases treated, whilst for gentamicin aural solution results were positive for 46 out of 50 cases. Gentamicin gave a successful result in 5 of the 8 failures with TSP, whilst TSP cured the four original failures with gentamicin. There were no signs of ototoxicity, of excessive fungal proliferation nor of any local sensitivity to the ear drops. It would seem that these aural preparations are complementary, capable of resulting in the disappearance of the majority of bacterial agents responsible for pathogenic otorrhoea.", "The clinical efficacy was assessed of a topical antiseptic (aluminium acetate) and a topical antibiotic (gentamicin sulphate) for the initial treatment of otorrhoea. Evidence of resistant organisms developing to either treatments after 9 and 21 days was also examined. 139 affected ears were entered into the trial and of these, 102 (74%) completed the study. Improvement in the otorrhoea occurred in 68% of ears treated with gentamicin and 67% of ears treated with aluminium acetate, with no significant difference between the two treatments. No resistant organisms to aluminium acetate were encountered. Twelve gentamicin-treated ears had gentamicin-resistant organisms at presentation and one patient developed a gentamicin-resistant Pseudomonas during treatment. We therefore recommend a topical antiseptic such as aluminium acetate rather than a topical antibiotic in the initial treatment of otorrhoea on the grounds of cost, avoidance of resistance and toxicity.", "To evaluate the efficacy of ciprofloxacin compared with tobramycin and placebo ear drops in the treatment of chronic suppurative otitis media without cholesteatoma.\n Sixty ears (in 51 patients) were randomly divided into 3 treatment groups: ciprofloxacin hydrochloride, tobramycin, and placebo interventions.\n The otolaryngology department of a university teaching hospital.\n All ears were treated topically for 3 weeks.\n Each patient received a small, numbered bottle and was instructed to instill 5 drops 3 times daily for 3 weeks. The final clinical and bacteriologic assessment was made after 3 weeks.\n The organism most commonly isolated from the ear discharge was Pseudomonas aeruginosa. Its sensitivity to ciprofloxacin and tobramycin was 94.2% and 70.6%, respectively. The clinical response was 78.9%, 72.2%, and 41.2% in the ciprofloxacin, tobramycin, and placebo groups, respectively. The bacteriologic response rate was 66.7% for the ciprofloxacin and tobramycin groups and 20% for the placebo group. Treatment with ciprofloxacin ear drops seemed to be as effective as treatment with tobramycin.\n While the lack of ototoxicity of ciprofloxacin was not tested in our study, this treatment may be considered as a potential topical therapy for cases of chronic suppurative otitis media.", "A multicentre double-blind randomized study was carried out to compare topical ciprofloxacin and topical gentamicin in the treatment of simple non-cholesteatomatous purulent chronic otitis media. Three hundred and eight patients were included in the study, 159 treated with ciprofloxacin and 149 treated with gentamicin. The percentage of clinical success (elimination of otorrhoea) was 95% with ciprofloxacin and 94% with gentamicin (ns). Likewise, the percentage of bacteriological erradication was 96% with ciprofloxacin and 93% with gentamicin. Both drugs were well tolerated, without changes in the audiometric values. In these patients, topical ciprofloxacin shows the same efficacy as topical gentamicin without any potential ototoxic effect.", "Chronic suppurative otitis media in young children is a major problem in Africa, with socio-economic consequences at a later age. Common treatment regimens with antibiotics are expensive and often not practically feasible. Therefore, a project was started to develop a low-cost and effective treatment in a rural area of Malawi by studying the clinical efficacy of an inexpensive application regimen of ofloxacin (0.075%) in hydroxypropyl methylcellulose (1.5%) ear drops. In earlier studies with this treatment regimen, it was possible to cure approximately 70% of ears. The aim of this study was to find out whether the bacteriological spectrum cultured from wet ears before and after treatment, and patterns of resistance to antibiotics, played a role in the percentage of cures. Patients with long-standing chronic suppurative otitis media were clinically assessed and treated with suction cleaning and instillation of ear drops on days 1, 3, 7 and 10. Bacterial swabs were taken for culture and sensitivity tests for ofloxacin were on days 1 and 10 from the ears that were still discharging. After 21 weeks, the ears were assessed again clinically. Clinical cure was considered to be complete cessation of otorrhea. Ninety of 104 tested patients (124 ears) completed the study. About 73% of the ears had become dry by day 10. This dropped to 42% after 21 weeks. Before treatment, most ears (91%) harbored fecal bacteria, Proteus mirabilis (74%) and enterococci (60%) being the most frequently isolated microbes. The second group of frequently cultured bacteria were water bacteria e.g. Pseudomonas species and other non-fermenters (69%), whereas the classical otitis media pathogens were detected only in 15% of ears. Before treatment, 9.7% of strains were resistant to ofloxacin, most (30/35) of which were cultured from ears that were eventually cured. After treatment, fecal and water bacteria were still the most frequently found, with 36% new strains and an overall sensitivity to ofloxacin of 58%. Bacterial resistance did not appear to play an important role in the outcome of treatment. These data rather suggest a very high risk of infection due to poor hygiene conditions. Medical treatment can only have a longer-lasting effect if accompanied by community-based programs that focus on improvement of hygiene. A public health approach is necessary alongside a medical approach for the management of CSOM.", "This was a double-blind randomized study to compare the safety and efficacy of trimethoprim-polymyxin B (TP) and trimethoprim-sulfacetamide-polymyxin B (TSP) drops in the treatment of otorrhea. The 68 cases treated suffered from external otitis, recurrent otitis media with tympanic membrane perforation, or infected mastoid cavities and post-operative tympanoplasties. The TP ototopical solution was successful in 60.6 per cent of cases compared to 88.6 per cent of cases with TSP. These rates were statistically different using the Chi Square with Yates' correction method. There were no signs of ototoxicity, fungal infection overgrowth or local sensitivity to either of the solutions. The study has shown that both drugs are equally safe and that TSP is significantly more effective in the treatment of otorrhea." ]