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[ "14993491", "9292565", "7640431", "8704114", "1889973", "8887291", "12110028", "7806419", "8821843", "11280496", "7780060", "9631846", "3410567", "1555881", "7554987", "8488820", "7887824", "7546525", "3524607", "8141183", "10620550", "8786174", "10978398", "1745022", "11374763" ]

[ "Enhanced long-term reduction of plasma leptin concentrations by super-flux polysulfone dialysers.", "Biocompatible membranes preserve residual renal function in patients undergoing regular hemodialysis.", "Biocompatibility and performance of a modified cellulosic and a synthetic high flux dialyzer. A randomized crossover comparison between cellulose triacetate and polysulphon.", "The effect of membrane biocompatibility on plasma beta 2-microglobulin levels in chronic hemodialysis patients.", "Removal of silicon, aluminum and beta 2-microglobulin in chronic haemodialysis patients.", "Effects of different membranes and dialysis technologies on patient treatment tolerance and nutritional parameters. The Italian Cooperative Dialysis Study Group.", "Intercurrent clinical events are predictive of plasma C-reactive protein levels in hemodialysis patients.", "Complement activation in dialysis: effects on cytokines, lymphocyte activation and beta 2 microglobulin.", "Effect of the membrane biocompatibility on nutritional parameters in chronic hemodialysis patients.", "Preservation of residual renal function in dialysis patients: effects of dialysis-technique-related factors.", "High-flux dialysis membranes improve lipid profile in chronic hemodialysis patients.", "Postdialysis fatigue: lack of effect of a biocompatible membrane.", "Influence of dialysate and membrane biocompatibility on hemodynamic stability in hemodialysis.", "Phagocyte metabolic activity during hemodialysis with different dialyzers not affecting the number of circulating phagocytes.", "Beta-2-microglobulin removal by different hemodialysis membranes.", "Beta 2-microglobulin generation and removal in long slow and short fast hemodialysis.", "Acute symptoms during and between hemodialysis: the relative role of speed, duration, and biocompatibility of dialysis.", "Systemic cardiovascular response in hemodialysis without and with ultrafiltration with membranes of high and low biocompatibility.", "Patient reactions and granulocyte degranulation during hemodialysis with cuprophane and polycarbonate membranes. A double-blind study.", "Role of bradykinin in anaphylactoid reactions during hemodialysis with AN69 dialyzers.", "Prospective crossover trial of the influence of vitamin E-coated dialyzer membranes on T-cell activation and cytokine induction.", "A new polymethylmethacrylate membrane for hemodialysis.", "Effect of high-flux dialysis on the anaemia of haemodialysis patients.", "Acute intradialytic well-being: results of a clinical trial comparing polysulfone with cuprophan. Bergamo Collaborative Dialysis Study Group.", "Do high-flux dialysis membranes affect renal dyslipidemia?" ]

[ "Hyperleptinaemia in chronic haemodialysis (CHD) patients has been associated with malnutrition, which is an independent predictor of morbidity and mortality in this patient group.\n To assess the influence of HD on plasma leptin, 10 CHD patients were crossover randomized to low-flux polysulfone (PS: F 6HPS), high-flux PS (F 60S), super-flux PS (F 500S) or super-flux cellulose-tri-acetate (CTA: Tricea 150G) for 12 weeks each. Blood samples were collected at the start of the study and each 12-week period. In addition, the relationship between patient characteristics, inflammation and leptin was analysed.\n At baseline, all groups showed similar leptin concentrations (mean 33.6+/-21.7 ng/ml). After a single HD session, a significant (P<0.01) decrease was observed with all three high permeable devices (Tricea 150G -52.7+/-6.4%; F 60S -63.1+/-5.7%; F 500S -68.7+/-8.2%), whereas leptin remained stable with low-flux PS. After 12 weeks, a marked increase was observed with low-flux PS (week 1, 30.4+/-23.0; week 12, 40.5+/-5.4 ng/ml, P = 0.05), no change with super-flux CTA and high-flux PS (Tricea 150G week 1, 29.4+/-23.7; week 12, 32.0+/-27.9 ng/ml, P = ns; F 60S week 1, 36.0+/-31.8; week 12, 33.0+/-31.2 ng/ml, P = ns), and a significant decrease with super-flux PS (week 1, 38.3+/-33.0; week 12, 29.5+/-31.9 ng/ml, P = 0.02). The change in leptin after 12 weeks was significantly different between super-flux PS, and both low-flux PS (P = 0.009) and super-flux CTA (P = 0.01). Besides interleukin-6 (IL-6) at the start of the study (P = 0.006), no correlations were observed between patient characteristics, parameters of inflammation and plasma leptin levels.\n Apart from low-flux PS, plasma leptin decreased considerably with all three high permeable dialysers after a single HD session. In the long run, leptin levels were lower with high-flux PS than with low-flux PS. Moreover, after switching from high-flux PS to super-flux PS (but not super-flux CTA), an additional decrease in leptin was observed. Apart from IL-6 at the start of the study, neither patient characteristics nor inflammatory parameters correlated with plasma leptin levels in this patient group.", "Initiation of hemodialysis causes a further decrease of residual renal function (RRF). To assess the impact of the biocompatibility of the dialysis membrane, we performed a prospective randomized investigation in 20 normotensive patients with tubulointerstitial nephritis. The patients were randomly allocated to treatment with either a high-flux polysulfone or cellulose membrane over a period of 12 months. RRF, defined by creatinine clearance and daily urine volume, was found to decrease in both groups of patients after the initiation of hemodialysis. Of the two membranes used, however, the cellulose membrane caused an accelerated decrease of RRF (P < 0.05). The better maintenance of RRF in patients treated with polysulfone membranes was associated with higher Kt/V values and increased hematocrit values (P < 0.05). The pathophysiologic mechanism underlying the more rapid decline of RRF could not be explained by intradialytic hypotension, but may be related to the nephrotoxic effects of inflammatory mediators due to bioincompatibility. Therefore, the use of polysulfone membranes might be preferable in patients with relevant RRF.", "The biocompatibility and performance of two high flux membranes (modified cellulosic: cellulose-triacetate (CTA), and a synthetic material: polysulphon [PS]) were assessed in 31 stable patients on hemodialysis (HD) in a randomized crossover study. Parameters evaluated included leukocytes, complement activation products C3a and C5a, cytokines, lymphocyte subpopulations, urea, creatinine, phosphate, and beta 2 microglobulin. Considering biocompatibility, the drop in the number of leukocytes was more pronounced during CTA HD compared with PS (p = 0.045), although both were low in comparison with cuprammonium dialysis in the same patients, as observed during a separate study. Both membranes induced a low and transient state of complement activation. Interleukin 1 beta and interleukin 6 could not be detected at all, whereas tumor necrosis factor alpha levels were marginally elevated before and after HD with both membranes. During the first 30 min of HD with either membrane, the numbers of CD8+ cells decreased significantly, resulting in an increase in the CD4/CD8 ratios; in addition, the number of NK cells decreased. Performance, as measured by extraction ratios for small molecular weight solutes and Kt/V urea, was significantly better during CTA dialysis (p < 0.001), but almost similar after correction for membrane surface area. On the basis of these data, it seems justified to conclude that, whereas biocompatibility of the PS dialyzer appeared slightly superior to CTA, performance of both dialyzers was comparable.", "Several studies have shown that patients who have been dialyzed with high-flux biocompatible membranes have a lower plasma level of beta 2-microglobulin and a lower incidence of amyloid disease compared with patients who have been dialyzed with low-flux bioincompatible membranes. However, because high-flux membranes are associated with significant dialytic removal of beta 2-microglobulin, the specific role of membrane biocompatibility in influencing the rate of increase of beta 2-microglobulin has not been previously determined. This study investigated the effect of biocompatibility on the rate of increase of plasma levels of beta 2-microglobulin in 159 new hemodialysis patients from 13 dialysis centers (ten centers affiliated with Dallas Nephrology Associates and three with Vanderbilt University Medical Center) by using two low-flux membranes with widely different biocompatibilities. These patients were prospectively randomized to be dialyzed with either a low-flux biocompatible membrane or a low-flux bioincompatible membrane. Plasma beta 2-microglobulin levels were measured at 0, 3, 6, 9, 12, and 18 months. Sixty-six patients completed the 18-month study. Plasma beta 2-microglobulin increased in all patients; however, the increase was not significantly different from baseline at any time point in the group that used the biocompatible membrane. In this group, beta 2-microglobulin increased from (mean +/- SD) 27.8 +/- 14.8 mg/L to 34.0 +/- 10.0 mg/L at 18 months (P = not significant), and the mean increase at 18 months was 2.6 +/- 14.7 mg/L. In contrast, the increase in plasma beta 2-microglobulin level in the bioincompatible membrane group became significant in Month 6 when the levels had increased from a baseline of 24.8 +/- 9.6 mg/L to 29.5 +/- 12.2 mg/L (P < 0.001); these increases continued to be significant until Month 18, when serum beta 2-microglobulin reached 36.8 +/- 13.9 mg/L with an average increase of 11.8 +/- 11.2 mg/L (P < 0.0001). The higher rate of plasma B2-microglobulin increase in the group that had been dialyzed with the bioincompatible membrane was also evident when only patients who had completed the study were analyzed. There were no significant differences in the actual level of beta 2-microglobulin or in residual renal function between the two groups during the 18 months of the study. It was concluded that over a period of 18 months, the use of biocompatible membranes, even in the low-flux configuration, is associated with a significantly slower increase in plasma beta 2-microglobulin, independent of the influence of residual renal function.", "One hundred outpatients on chronic haemodialysis with polymethylmethacrylate (PMMA) membrane dialyzer were randomly chosen. A control group of 100 likewise randomly chosen outpatients were treated with cuprophane membrane dialyzer. In both groups the treatments lasted for one year. Comparison of the test results revealed that Si, Al and beta 2-M.G levels could be reduced in patients on chronic HD with PMMA.", "There is increasing evidence that the biochemical and cellular phenomena induced by blood/ membrane/dialysate interactions contribute to dialysis-related intradialytic and long-term complications. However, there is a lack of large, prospective, randomized trials comparing biocompatible and bioincompatible membranes, and convective and diffusive treatment modalities. The primary aim of this prospective, randomized trial was to evaluate whether the use of polysulfone membrane with bicarbonate dialysate offers any advantage (in terms of treatment tolerance, nutritional parameters and pre-treatment beta-microglobulin levels) over a traditional membrane (Cuprophan). A secondary aim was to assess whether the use of more sophisticated methods consisting of a biocompatible synthetic membrane with different hydraulic permeability at different ultrafiltration rate (high-flux hemodialysis and hemodiafiltration) offers any further advantages. Seventy-one Centers were involved and stratified according to the availability of only the first two or all four of the following techniques: Cuprophan hemodialysis (Cu-HD), low-flux polysulfone hemodialysis (LfPS-HD), high-flux polysulfone high-flux hemodialysis (HfPS-HD), and high-flux polysulfone hemodiafiltration (HfPS-HDF). The 380 eligible patients were randomized to one of the two or four treatments (132 to Cu-HD, 147 to LfPS-HD, 51 to HfPS-HD and 50 to HfPS-HDF). The follow-up was 24 months. No statistical difference was observed in the algebraic sum of the end points between bicarbonate dialysis with Cuprophan or with low-flux polysulfone, or among the four dialysis methods under evaluation. There was a significant decrease in pre-dialysis plasma beta 2-microglobulin levels in high-flux dialysis of 9.04 +/- 10.46 mg/liter (23%) and in hemodiafiltration of 6.35 +/- 12.28 mg/liter (16%), both using high-flux polysulfone membrane in comparison with Cuprophan and low-flux polysulfone membranes (P = 0.032). The significant decrease in pre-dialysis plasma beta 2-microglobulin levels could have a clinical impact when one considers that beta 2-microglobulin accumulation and amyloidosis are important long-term dialysis-related complications.", "In chronic hemodialysis (HD) patients, the repetitive induction of the acute phase response (APR) may induce a chronic micro-inflammatory state, leading to various long-term complications.\n The present prospective study was designed to assess the alterations in the APR in 74 patients who were randomized to HD with a high-flux polysulfone (PS; F 60S), a super-flux PS (F 500S), or a super-flux cellulosic tri-acetate (CTA and CTA with filtered dialysate, CTA(f)) dialyzer. Blood samples collected at the start of the study and after twelve weeks were analyzed for interleukin-6 (IL-6) and C-reactive protein (CRP). In addition to the microbiological quality of the dialysate, the appearance of a \"clinical event\" was assessed.\n At baseline, mean IL-6 levels were within the reference range whereas mean CRP levels were slightly elevated. Mean values did not change after 12 weeks of HD with either modality. After subdividing the patients in quartiles with increasing change in plasma CRP, 23.0% of the patients showed a change of more than 8.0 mg/L. In a multiple regression analysis, CRP levels appeared to be independent of the degree of dialysate contamination, the material and the flux characteristics of the devices. In fact, the variable \"clinical events\" was the only significant predictor of the plasma CRP levels (P < 0.001).\n Based on these results, both PS and CTA super-flux dialyzers appear safe for clinical use. Whether changes in CRP values, which are associated with intercurrent clinical events, influence the long-term prognosis of chronic HD patients remains to be established.", "Anaphylatoxins generated by complement activation by filter membranes are present in plasma during hemodialysis (HD). In the presence of endotoxins which may contaminate the dialysate, they can trigger monocytes to produce interleukin-1 (IL-1) and tumor necrosis factor (TNF), with detrimental effects for the patients. We have investigated whether or not the use of complement activating (cuprophan) and non- (or less-) activating membranes (polysulfone, polymethylmethacrylate or polyacrylonitrile) per se influences cytokine levels in HD patients. Our results indicate that if a sterile bicarbonate solution is used as dialysate, there are no significant increases in IL-1, TNF, interleukin-2 (IL-2) and soluble IL-2 receptors (sIL-2r) throughout HD, even with cuprophan membranes. Moreover even a prolonged use of this membrane (three months) did not change pre-dialysis levels of cytokines and receptors. Use of complement activating membranes also does not influence beta 2 microglobulin levels.", "Malnutrition is highly prevalent in chronic hemodialysis patients and is an important determinant of their morbidity and mortality. Several recent studies have suggested that the inflammatory response associated with the biocompatibility of the dialysis membranes is a potential contributing factor. In a prospective study of 159 new hemodialysis patients from two centers randomized to either a low-flux biocompatible (BCM) membrane or a low-flux bioincompatible (BICM) membrane, we measured the long-term effects of biocompatibility on several nutritional parameters, including estimated dry weight, serum albumin, insulin-like growth factor-1 (IGF-1), and prealbumin over 18 months. Our results show that the BCM group had a mean (+/- SD) increase in their dry weight of 2.96 +/- 6.88 kg at month 12 and 4.36 +/- 8.57 kg at month 18 (P < 0.05 vs. baseline for both), whereas no change in mean weight was observed in BICM group. Following initiation of hemodialysis, a significant increase was observed in serum albumin levels in both groups of patients. However, the biocompatible group had an earlier and more marked increase in serum albumin levels compared to the BICM group. The average increase in serum albumin compared to baseline was consistently greater than 0.25 g/dl after seven months in the BCM group, but did not reach this level until 12 months after initiation of dialysis in the BICM group. The difference between the groups was statistically significant at months 7, 8, and 10 (P < 0.05, higher in the BCM group). Furthermore, the overall difference in serum albumin concentration between the two groups was larger in the center where the dose of dialysis was equivalent (P < 0.001). A consistently higher value was also observed in IGF-1 levels for BCM patients compared to BICM group (P = NS). In a further analysis, changes in IGF-1 levels, but not prealbumin, predicted the subsequent changes in serum albumin. We conclude that biocompatible hemodialysis membranes favorably impact on the nutritional status of chronic hemodialysis patients, independently of the flux characteristics of the membranes, and that IGF-1 may be an early marker of nutritional status.", "Residual renal function (RRF) is of paramount importance to dialysis adequacy, morbidity, and mortality, particularly for long-term continuous ambulatory peritoneal dialysis (CAPD) patients. Residual renal function seems to be better preserved in patients on CAPD than in hemodialysis (HD) patients. We analyzed RRF in 45 patients with end-stage renal disease (ESRD), commencing either CAPD or HD, to prospectively define the time course of the decline in RRF, and to evaluate dialysis-technique-related factors such as cardiovascular stability and bioincompatibility.\n Single-center prospective investigation in parallel design with matched pairs.\n Fifteen patients starting CAPD and 15 matched pairs of patients commencing HD were matched according to cause of renal failure and RRF. Hemodialysis patients were assigned to two dialyzer membranes differing markedly in their potential to activate complement and cells (bioincompatibility). Fifteen patients were treated exclusively with the cuprophane membrane (bioincompatible) and the other 15 patients received HD with the high-flux polysulfone membrane (biocompatible).\n Residual renal function was determined at initiation of dialytic therapy and after 6, 12, and 24 months. Dry weight (by chest x ray and diameter of the vena cava) was closely recorded throughout the study, and the number of hypotensive episodes counted.\n Residual renal function declined in both CAPD and HD patients, although this decline was faster in HD patients (2.8 mL/minute after 6 months and 3.7 mL/min after 12 months) than in CAPD patients (0.6 mL/min and 1.4 mL/min after 6 and 12 months respectively). It declined faster in patients with bioincompatible than with biocompatible HD membranes (3.6 mL/min vs 1.9 mL/min after 6 months). Eleven percent of the HD sessions were complicated by clinically relevant blood pressure reductions, but there were no differences between the two dialyzer membrane groups. None of the CAPD patients had documented hypotensive episodes. None of the study patients suffered severe illness or received nephrotoxic antibiotics or radiocontrast media.\n The better preservation of RRF in stable CAPD patients corresponded with greater cardiovascular stability compared to HD patients, independently of the membrane used. Furthermore, there was a significantly higher preservation of RRF in HD patients on polysulfone versus cuprophane membranes, indicating an additional effect of biocompatibility, such as less generation of nephrotoxic substances by the membrane. Thus, starting ESRD patients on HD prior to elective CAPD should be avoided for better preservation of RRF.", "In a controlled prospective trial, the effect of a switch from cellulose-based, low-flux dialysis membranes to polysulphone, high-flux membranes on lipid parameters was evaluated. Baseline values of lipid parameters were identical in the study group and the control group in which the dialysis membrane remained unchanged. After 6 wk, total triglyceride, very low-density lipoprotein (VLDL) triglyceride, and VLDL cholesterol decreased, respectively, 28 +/- 17 (P < 0.01), 38 +/- 17 (P < 0.01), and 24 +/- 21% (P < 0.05), and the proportion of total cholesterol that was high-density lipoprotein cholesterol increased from 15 +/- 5 to 18 +/- 5% (P < 0.05) in the high-flux polysulphone group, whereas these variables remained unchanged in the control group. Low-density lipoprotein and total cholesterol as well as Kt/V, protein catabolic rate, parathyroid hormone, albumin, and body weight did not change. No change in lipoprotein lipase activity was found. In a second study, the effects of a single hemodialysis session with high-flux polysulphone and low-flux, cellulose-based membranes on lipid parameters and lipolytic activity were compared in a cross-over fashion. Treatment with both membranes resulted in a significant decrease in plasma triglyceride, VLDL triglyceride, and VLDL cholesterol. Lipoprotein lipase activity increased during hemodialysis. Changes in lipid parameters and lipolytic activity were identical during the two treatments.", "Tumor necrosis factor-alpha (TNF-alpha) has been shown to have somnogenic properties. Plasma levels of this cytokine have been found to increase significantly during dialysis with a bioincompatible (cuprophane) membrane in patients with postdialysis fatigue (PDF). We conducted a crossover study with random assignment to ascertain whether a biocompatible membrane might attenuate the increase of TNF-alpha and severity of PDF. Sixteen patients on maintenance hemodialysis underwent dialysis with either cuprophane (n = 8) or polymethylmethacrylate (PMMA; n = 8) membranes for 1 week and then switched to the opposite membrane during the second week. Predialysis and postdialysis measurements of plasma TNF-alpha levels were performed during the first and last dialysis treatments of each week. A fatigue score was determined from the sum of duration of fatigue and sleep within 6 hours of the completion of dialysis. TNF-alpha levels increased by an average of 18.3% during dialysis with cuprophane membranes but only 2.4% with PMMA membranes (P = 0.04). Despite this, fatigue scores remained unaltered (approximately 4 of 6). Hence, the biocompatible membrane, PMMA, failed to alleviate PDF. This suggests that dialytic stimulation of TNF-alpha plays no substantial role in the pathogenesis of PDF.", "The contributions of membrane biocompatibility, dialysate temperature and sodium concentration to hemodynamic stability during hemodialysis were studied in 8 patients with a high incidence of hemodialysis-induced symptomatic hypotension. Patients were treated during 8 different periods, randomly ordered in each case, resulting from the combination of the following: the membrane, either Cuprophan or Polyacrylonitrile; the dialysate temperature, 37 or 35 degrees C, and the sodium concentration, 133 or 139 mmol/l. The incidence of symptomatic hypotension was lower at 35 degrees C in the entire study with either membrane and either sodium concentration. It was also lower with a sodium concentration of 139 mmol/l with either temperature and either membrane. There was a lower incidence of symptomatic hypotension when using Polyacrylonitrile, but this difference was not significant. We conclude that changes in physicochemical parameters of dialysate lead to worth-while improvement of symptomatic hypotension in hemodialysis patients, but membrane biocompatibility seems to play a minor role.", "Overall leukocyte counts decrease during certain forms of hemodialysis, but little information is available on the intradialytic evolution of phagocytic metabolic function, especially during dialysis with dialyzers not affecting the number of circulating phagocytes. This study evaluated the phagocytic capacity of granulocytes and monocytes to generate CO2 out of glucose under basic unchallenged conditions and after stimulation with latex or zymosan, before and after 15, 60 and 240 minutes of dialysis with reused cuprophan, AN69S, polysulphone, polymethylmethacrylate and hemophan hemodialyzers. Phagocytic metabolic function was assessed in whole blood on the basis of 14CO2-production from labelled glucose during the phagocytic process. There were no changes in basic unchallenged CO2-production with any of the dialyzers. Reactivity to latex and zymosan, expressed per number of phagocytes, showed no decrease, irrespective of the membrane type. For polymethylmethacrylate and reused cuprophan, a slight but significant increase in metabolic reactivity was observed in response to latex and zymosan. The test employed may give a screening picture of the phagocytic reaction to contact with dialyzers and membranes and thus of their degree of biocompatibility towards the phagocyte system.", "nan", "We studied the influence of different modes of hemodialysis (HD) on plasma levels of beta 2-microglobulin (P-beta 2-m) and its correlation to changes in leukocyte count, complement activation (C3a), and elastase generation. The influence of dialyzer membrane, membrane surface area, duration of treatment, and blood flow was analyzed with respect to post-HD levels of P-beta 2-m. Twenty patients underwent 12 modes of bicarbonate hemodialysis in random order (n = 252) using three different membranes (Cuprophan [CU], hemophan [HE], or polyamide [PA], two dialyzer areas, and fast (400 mL/min) or slow (200 mL/min) blood flow (Qb) for 2 or 4 hours, respectively. All dialysate was collected and beta 2-m was analyzed (D-beta 2-m). After correction for hemoconcentration, P-beta 2-m concentrations were found to have decreased significantly during treatment with all three membranes (CU, 0.9 +/- 0.3 mg/L, P = 0.002; HE, 1.2 +/- 0.3 mg/L, P < 0.001; and PA, 8.3 +/- 0.3 mg/L, P < 0.001). Elimination of P-beta 2-m was influenced by type of membrane (P < 0.001) and ultrafiltration volume (P = 0.0019) but not by membrane area or Qb. The largest reduction in P-beta 2-m (-10.4 mg/L) was achieved by the following treatment combination: PA membrane, large dialyzer area, and low Qb for 4 hours. P-beta 2-m decreased more during PA dialysis at low Qb for 4 hours (-9.9 +/- 0.5 mg/L) than during high Qb for 2 hours (-6.8 +/- 0.5 mg/L, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)", "The relationship between hemodialysis (HD) symptoms and dialyzer membrane composition and area, blood-flow, treatment duration, urea removal, ultrafiltration volume, leukocyte activation, and complement generation (C3a) was studied in 20 patients undergoing 234 HD treatments by 12 different modes in random order using Cuprophan, hemophane, or polyamide membranes with small or large membrane areas with high Qb (400 ml/min) and short duration (2 h) or low Qb (200 ml/min) and long duration (4 h). Fewer symptoms occurred during the 2-h HD at high Qb than during the 4-h HD with low Qb (19% vs. 32%, p = 0.0351). No differences were observed between different dialyzer membranes or areas. More intradialytic symptoms occurred when urea elimination was high than it was low (p = 0.0044). Leukocyte activation (leukocyte drop) after 15 min of dialysis and complement generation did not influence symptom incidence. Blood pressure changes were mainly influenced by ultrafiltration volume (p < 0.001). Symptoms between dialyses were determined by urea removal and ultrafiltration. Membrane, area, or Qb were of no importance. Thus, duration of dialysis, urea removal, and demand for ultrafiltration, but not membrane composition, area, or biocompatability, are important for the development of HD-related symptoms.", "In order to test whether dialyzer membrane biocompatibility influences systemic cardiovascular function, we treated 8 hemodialysis patients (4 men and 4 women, aged 24-73 years) with a low-biocompatible (cuprophane) and a high-biocompatible (polyacrylonitrile) membrane in a randomized double-blind crossover protocol using bicarbonate hemodialysis without ultrafiltration for the first 60 min and with ultrafiltration for the remaining treatment time. Left ventricular function and systemic hemodynamics were assessed noninvasively at baseline and during treatment by Doppler echocardiography combined with external subclavian artery pulse trace calibrated with oscillometrically measured brachial artery blood pressures. There was no significant difference in the cardiovascular response to the 2 membranes, neither during isolated hemodialysis nor when ultrafiltration was added. Mean arterial pressure increased 10% (p < 0.001) during isolated hemodialysis and returned to baseline levels with ultrafiltration. The cardiac index decreased 22% (p < 0.001) during ultrafiltration, due to the greater decrease in left ventricular stroke index (30%, p < 0.001) than increase in heart rate (9%, p < 0.05). Total peripheral resistance increased 10% (p < 0.05) during isolated hemodialysis and a further 19% (p < 0.01) when ultrafiltration was added. Hence, profound cardiovascular alterations were observed during hemodialysis treatment; however, these changes were not related to the biocompatibility of the membranes.", "During dialysis with cuprophane or polycarbonate filters, a fall in neutrophil and eosinophil cell counts is observed. Total complement remains unchanged, but C3a increases indicating complement activation. Release of granular granulocyte proteins is observed indicating granulocyte activation. Patient reactions or biochemical findings indicate no significant difference when polycarbonate or cuprophane membranes are used, except perhaps less complement activation with polycarbonate. The biochemical observations may be due to complement activation or cell contact with the membrane.", "In vitro experiments have related anaphylactoid reactions in patients treated with angiotensin-converting enzyme (ACE) inhibitors during dialysis with AN69 membranes to excessive bradykinin generation using this negatively charged dialysis membrane. In the present clinical trial plasma bradykinin levels were followed during the early phase of dialysis in 10 patients, not being treated with ACE inhibitors, using AN69, cuprophane, and polysulfone membranes. Bradykinin was measured after extraction by radioimmunoassay. During this study one episode of anaphylaxis occurred during dialysis with the AN69 membrane. Blood samples were collected during the first 5 min of the adverse reaction and showed a more than 100-fold increase in the venous effluent of the AN69 dialyzer (baseline 40 +/- 3 vs. 4,900 +/- 130 fmol/ml after 5 min). Even though none of the patients received ACE inhibitors, there were 4 more asymptomatic individuals who displayed a more than two-fold increase in their plasma bradykinin concentrations in the venous effluent of the AN69 dialyzer. When these patients were treated either with cuprophane or with polysulfone dialyzers, no significant bradykinin formation was detected, nor were there any adverse events. Taken together, these findings show that anaphylactoid reactions with the AN69 membrane are due to excessive bradykinin generation which even may occur in the absence of ACE inhibitors.", "Cytokine induction by dialyzer membranes has been related to several acute and chronic side effects of hemodialysis treatment, among them being immune dysfunction and progressive atherosclerosis. Surface modification of cuprophane dialyzers with the antioxidant vitamin E is a new approach to enhance biocompatibility and improve cytokine levels, as well as immune function. Twenty-one patients undergoing treatment with hemophane (HE) dialyzers were enrolled onto a crossover study with a vitamin E-coated (VE) dialyzer or a synthetic polyamide (PA) dialyzer. In vitro assays of lymphocyte activation and measurements of cytokine induction were performed to evaluate biocompatibility. Four weeks of treatment with either VE or PA dialyzers enhanced in vitro proliferation of peripheral blood leukocytes in comparison to treatment with HE membranes used before study entry. Enhancement of lymphocyte function was independent of dialysis efficiency, which was kept constant during the study. In the interdialytic interval, preactivation of monocytes for the production of interleukin-6 (IL-6) did not differ between VE or PA dialysis. In contrast, the VE membrane reduced acute production of IL-6 during a dialysis treatment, whereas the PA membrane did not. Unlike IL-6, the regulatory cytokine IL-10 is not inhibited by either membrane. This is important because IL-10 is believed to have a beneficial effect on immune function in dialysis patients. The VE membrane, despite being based on a cuprophane backbone, is similar to the highly biocompatible PA dialyzer in terms of its effect on lymphocyte function, whereas it exerts an additional suppressive effect on the overproduction of proinflammatory cytokines.", "High molecular weight (MW) solutes are not removed during conventional hemodialysis (HD), and their accumulation is thought to play a role in some long-term HD complications (anemia, bone and joint pain, neuropathy, itching). The present trial was conducted to evaluate the removal capacity during in vivo HD of a new polymethylmethacrylate (PMMA) membrane (Filtryzer BK-F, 1.3 m2) compared to conventional PMMA (BK-P, 1.6 m2) and to cellulose acetate (CA, 1.3 m2). BK-F dialyzers, with a pore size of 100 A degrees and 62% porosity, are designed to remove high MW substances. Ten stable anuric RDT patients (53 +/- 13 years) were treated for one week with each membrane in a randomized sequence. Plasma concentrations of creatinine, BUN and beta 2-microglobulin (beta 2-M) were measured before (b) and after (a) HD to determine the reduction rate for these substances (%). Beta 2-M concentration after HD was corrected for changes in distribution volume. Samples of spent dialysate were collected after 3 minutes, 120 minutes and at the end of HD sessions, and appropriately treated and concentrated for HPLC analysis. The reduction rate for BUN and creatinine was similar for the 3 membranes. BK-F showed a higher beta 2-M reduction rate than BK-P (p < 0.005) or CA (p < 0.0001). HPLC analysis of dialysate showed prevalent peaks < 4 kilodaltons (kDa) throughout HD for BK-P and CA. Solutes > 10 kDa were infrequently detected. Peak profile during HD with BK-F was quite different, showing a predominant peak > 50 kDa which also included albumin. However, albumin loss significantly decreased after 120 minutes and at the end of dialysis compared with the 3-minute values, and was lower than that reported in CAPD patients. With BK-F a peak of MW > 500 kDa was also detected which previous studies indicated as a range characterized by the presence of erythropoiesis inhibitors. Use of the BK-F membrane in HD could afford satisfactory removal of high MW substances, thereby preventing or controlling some long-term HD complications such as anemia or beta 2-M amyloid formation.", "Anaemia is one of the major clinical characteristics of patients with chronic renal failure, and has a considerable effect on morbidity and mortality. Adequate dialysis is of paramount importance in correcting anaemia by removing small and medium-sized molecules, which may inhibit erythropoiesis. However, high-molecular-weight inhibitors cleared only by means of highly porous membranes have also been found in uraemic serum and it has been claimed from uncontrolled studies that high-flux dialysis could improve anaemia in haemodialysis patients.\n We therefore planned this multicentre randomized controlled trial with the aim of testing whether the use of a large-pore biocompatible membrane for a fixed 12-week follow-up improves anaemia in haemodialysis patients in comparison with the use of a conventional cellulose membrane. Eighty-four (5.3%) of a total of 1576 adult haemodialysed patients attending 13 Dialysis Units fulfilled the entry criteria and were randomly assigned to the experimental treatment (42 patients) or conventional treatment (42 patients).\n Haemoglobin levels increased non-significantly from 9.5+/-0.8 to 9.8+/-1.3 g/dl (dP=0. 069) in the population as a whole, with no significant difference between the two groups (P:=0.485). Erythropoietin therapy was given to 32/39 patients (82%) in the conventional group, and 26/35 (74%) in the experimental group (P:=0.783) with subcutaneous administration to 26/32 patients in conventional and to 23/26 patients in experimental group, P:=0.495. Dialysis dose (Kt/V) remained constant in both groups (from 1.30+/-0.17 to 1.33+/-0.20 in the conventional group and from 1.28+/-0.26 to 1.26+/-0.21 in the experimental group, P:=0.242). Median pre- and post-dialysis beta(2)-microglobulin levels remained constant in the conventional group (31.9 and 34.1 mg/dl at baseline) and decreased in the experimental group (pre-dialysis values from 31.1 to 24.7 mg/dl, P:=0.004 and post-dialysis values from 24.8 to 20.8 mg/dl, P:=0.002). Median erythropoietin doses were not different at baseline (70 IU/kg/week in conventional treatment and 90 IU/kg/week in experimental treatment, P:=0.628) and remained constant during follow-up (from 70 to 69 IU/kg/week in the conventional group and from 90 to 91 IU/kg/week in the experimental group, P:=0.410). Median erythropoietin plasma levels were in the normal range and remained constant (from 12.1 to 12.9 mU/ml in the conventional group and from 13.2 to 14.0 mU/ml in the experimental group, P:=0.550).\n This study showed no difference in haemoglobin level increase between patients treated for 3 months with a high-flux biocompatible membrane in comparison with those treated with a standard membrane. When patients are highly selected, adequately dialysed, and have no iron or vitamin depletion, the effect of a high-flux membrane is much less than might be expected from the results of uncontrolled studies.", "We conducted a multicenter, randomized, double-blind, controlled clinical trial to compare the effects of a synthetic, high-flux polysulfone membrane with a standard cuprophan one on acute clinical complications during a diffusive dialysis procedure. The principal end-point, that is, the number of hypotensive episodes, was similar in polysulfone (39; 23.8%) and cuprophan (32; 19.5%). Likewise, no significant difference was found between the two membranes as far as the secondary end-point was concerned, that is, the effect on headache, nausea, pruritus and sense of well-being. We conclude that high-flux polysulfone, acutely used in standard diffusive dialysis, has no favorable influence on hypotensive episodes and does not affect some typical dialysis-related symptoms any differently from cuprophan membrane. The need is stressed for well-controlled studies specifically designed to assess the worth of new dialysis techniques and materials that may vastly raise the cost of dialysis treatment.", "High-flux hemodialysis has been reported to attenuate renal dyslipidemia. To evaluate the contribution of dialysis membrane composition per se, we compared the impact on the lipoprotein profile of hemodialysis (HD) with a conventional cellulose dialysis membrane with that of a synthetic high-flux dialysis membrane in standard hemodialysis mode. Forty-two patients (24 men, 18 women; mean age, 69 years; range, 39-85 years) on maintenance HD with cellulosic dialysis membranes were randomized and stratified for diabetes mellitus to 12 weeks of HD treatment with either a cellulose acetate (CA; n = 23) or polyacrylonitrile (AN69; n = 19) membrane. HD was performed in a conventional low-flux standard HD mode 4-6 hours/session. Plasma levels of lipids (TC, TG), apolipoproteins (A-I, B, C-III, E), lipoprotein (a) (Ip(a)), and individual apoA and apoB containing lipoproteins (LP-A-I, LP-A-I:A-II, LP-B, LP-Bc) were determined. At baseline, the AN69 group had slightly higher plasma concentrations of apoC-III and C-III/HS, but there were no other differences at entry in study variables between the treatment groups. Twelve week treatment with an AN69 membrane did not result in any significant changes in lipoprotein profile compared with treatment with a cellulose acetate membrane. HD with AN69 dialysis membranes in the conventional low-flux standard hemodialysis mode does not affect the lipoprotein profile." ]

[ "17548549", "11677004" ]

[ "A randomized controlled trial of resistance exercise in individuals with ALS.", "The value of muscle exercise in patients with amyotrophic lateral sclerosis." ]

[ "To determine the effects of resistance exercise on function, fatigue, and quality of life in individuals with ALS.\n Subjects with a diagnosis of clinically definite, probable, or laboratory-supported ALS, forced vital capacity (FVC) of 90% predicted or greater, and an ALS Functional Rating Scale (ALSFRS) score of 30 or greater were randomly assigned to a resistance exercise group that received a home exercise program consisting of daily stretching and resistance exercises three times weekly or to a usual care group, who performed only the daily stretching exercises. ALSFRS, the Fatigue Severity Scale (FSS), and Short Form-36 (SF-36) were completed at baseline and monthly for 6 months. FVC and maximum voluntary isometric contraction (MVIC) were monitored monthly throughout the study.\n Of 33 subjects screened, 27 were randomly assigned (resistance = 13; usual care = 14). Eight resistance exercise subjects and 10 usual care subjects completed the trial. At 6 months, the resistance exercise group had significantly higher ALSFRS and SF-36 physical function subscale scores. No adverse events related to the intervention occurred, MVIC and FVC indicated no negative effects, and less decline in leg strength measured by MVIC was found in the resistance exercise group.\n Our study, although small, showed that the resistance exercise group had significantly better function, as measured by total ALS Functional Rating Scale and upper and lower extremity subscale scores, and quality of life without adverse effects as compared with subjects receiving usual care.", "The role of physical activity for patients with amyotrophic lateral sclerosis (ALS) is controversial. Twenty-five ALS patients were randomized to receive a moderate daily exercise program (n=14) or not to perform any physical activity beyond their usual daily requirements (n=11). At baseline and after 3, 6, 9 and 12 months, patients were assessed by manual muscle strength testing, the Ashworth spasticity scale, ALS functional rating scale (FRS), fatigue severity scale, a visual analogue scale for musculoskeletal pain and the quality-of-life scale (SF-36). At 3 months, patients who performed regular exercise showed less deterioration on FRS and Ashworth scales, but not on other parameters. At 6 months, there was no significant difference between groups, although a trend towards less deterioration in the treated group on most scales was observed. At 9 and 12 months, there were too few patients in each group for statistical evaluation. Our results show that a regular moderate physical exercise program has a short-lived positive effect on disability in ALS patients and should be recommended." ]

[ "15082724", "12805325", "10025379", "7428142", "11711015", "10721551", "9101682", "4020412", "12033481", "6717508", "10715289" ]

[ "Factors associated with breast cancer clinical trials participation and enrollment at a large academic medical center.", "Barriers to clinical trial participation by older women with breast cancer.", "Accrual to breast cancer clinical trials at a university-affiliated hospital in metropolitan Detroit.", "Recruitment of patients to cooperative group clinical trials.", "Participation and successful patient recruitment in primary care.", "General practitioners' views on patient care research.", "Recruitment of general practitioners and patients in a sore throat study.", "Selection bias in clinical trials.", "Factors affecting general practitioner involvement in a randomised controlled trial in primary care.", "Physicians' reasons for not entering eligible patients in a randomized clinical trial of surgery for breast cancer.", "Factors that predict the referral of breast cancer patients onto clinical trials by their surgeons and medical oncologists." ]

[ "The practice patterns of medical oncologists at a large National Cancer Institute Comprehensive Cancer Center in Detroit, MI were evaluated to better understand factors associated with accrual to breast cancer clinical trials.\n From 1996 to 1997, physicians completed surveys on 319 of 344 newly evaluated female breast cancer patients. The 19-item survey included clinical data, whether patients were offered clinical trial (CT) participation and enrollment, and when applicable, reasons why they were not. Multivariate analyses using logistic regression were performed to evaluate predictors of an offer and enrollment.\n The patients were 57% white, 32% black, and 11% other/unknown race. One hundred six (33%) were offered participation and 36 (34%) were enrolled. In multivariate analysis, CTs were less likely offered to older women (mean age, 52 years for those offered v 57 years for those not offered; P =.0005) and black women (21% of blacks offered v 42% of whites; P =.0009). Women with stage 1 disease, poor performance status, and those who were previously diagnosed were also less likely to be offered trials. None of these factors were significant predictors of enrollment. Women were not offered trials because of ineligibility (57%), lack of available trials (41%), and noncompliance (2%). Reasons for failed enrollment included patient refusal (88%) and failed eligibility (12%).\n It is important for cooperative groups to design studies that will accommodate a broader spectrum of patients. Further work is needed to assess ways to improve communication about breast cancer CT participation to all eligible women.", "Although 48% of breast cancer patients are 65 years old or older, these older patients are severely underrepresented in breast cancer clinical trials. This study tested whether older patients were offered trials significantly less often than younger patients and whether older patients who were offered trials were more likely to refuse participation than younger patients.\n In 10 Cancer and Leukemia Group B institutions, using a retrospective case-control design, breast cancer patients eligible for an open treatment trial were paired: less than 65 years old and > or = 65 years old. Each of the 77 pairs were matched by disease stage and treating physician. Patients were interviewed as to their reasons for participating or refusing to participate in a trial. The treating physicians were also given questionnaires about their reasons for offering or not offering a trial.\n Sixty-eight percent of younger stage II patients were offered a trial compared with 34% of the older patients (P =.0004). In multivariate analyses, disease stage and age remained highly significant in predicting trial offering (P =.0008), when controlling for physical functioning and comorbidity. Of those offered a trial, there was no significant difference in participation between younger (56%) and older (50%) patients (P =.67).\n In a multivariate analysis including comorbid conditions, age and stage were the only predictors of whether a patient was offered a trial. The greatest impediment to enrolling older women onto trials in the setting of this study was the physicians' perceptions about age and tolerance of toxicity.", "Despite the large number of available studies, most women with breast cancer do not participate in clinical trials, and this is especially true among lower income and minority women. In this study the authors surveyed the practice patterns of four medical oncologists who comprised the clinical breast service at a large urban university hospital to develop a better understanding of the clinical trials enrollment process for women with breast cancer. Of 136 new female breast cancer patients seen by the four physicians over a 7-month period, there were 47 women (34%) offered participation in a clinical trial, and 16 women (12%) were eventually enrolled. Women who were offered participation were more likely to be younger (p = 0.068) and to have earlier stage disease then were women not offered participation (p = 0.008). Women enrolled into a trial were also more likely to be younger, although this difference was not statistically significant (p = 0.114). Patient race was not associated with the accrual or enrollment process. Over half of the women were not offered participation in clinical trials because of the lack of available studies. Further work evaluating the process of patient enrollment and physician and patient barriers is necessary to develop effective strategies for recruitment into breast cancer clinical trials.", "One of the prerequisites for a successful clinical trial is the accrual of a sufficient number of patients for study. Because the sample-size requirements for a randomized clinical trial can rarely be met by a single institution in a short period of time, cooperative groups have taken in a major role in conducting clinical trials. In this paper, the recruitment of patients at our institution to a lung cancer clinical trial is evaluated. A total of 653 lung cancer cases were reviewed. Of the 77 cases which were eligible for the trial, 41 were accessioned. The reasons why eligible patients were not accessioned to the trial are discussed.", "The demand for family physicians (FPs) to participate in research is growing. The delicate balance between research participation and the daily practice routine might explain the often-disappointing number of patients recruited. We analyzed practice and physician characteristics associated with successful patient recruitment.\n We used a survey to conduct this study.\n There was a total of 165 FPs who participated in a combined randomized clinical trial/cohort study on drug treatment of dyspepsia in the Netherlands.\n We surveyed FPs about personal and practice characteristics and their motivation for participation in the project. These data were then related to the number of patients recruited. Univariate associations were calculated; relevant factors were entered into a logistic model that predicted patient recruitment.\n Data on 128 FPs could be analyzed (80% response rate); these FPs recruited 793 patients in the cohort study (mean = 6.3 per FP) and 527 in the clinical trial (mean = 4.2 per FP). The main reasons for participation were the research topic (59%) and the participation of an academic research group in the study (63%). Many FPs felt that participation was a professional obligation (39%); the financial incentive played a minor role (15%). The number of recruited patients was only independently associated with the participation of an academic research group.\n Successful patient recruitment in primary care research is determined more by motivation driven by the research group than by financial incentives, the research topic, or research experience.", "Little research has been undertaken into the factors affecting recruitment by Australian general practitioners of patients for clinical trials. Understanding the differences between recruiters and non-recruiters will assist researchers in better supporting general practitioners involved in such research.\n A survey of general practitioners involved in recruiting patients for clinical trials for the RACGP Research Program was undertaken.\n Recruiters were more likely to be interested in learning more about research, to perceive involvement as worthwhile, to desire a good relationship with Research Program staff and to feel the doctor-patient relationship assists recruitment.\n Recruiters in general are average general practitioners, male, middle-aged and work in group practices. Most felt some discomfort in recruiting patients, but believed the strong doctor-patient relationship assisted in the process.\n The Research Program needs to recruit general practitioners interested in research, choose topics of interest, keep recruitment protocols simple and stay in contact.", "nan", "Of 90 patients with intermediate or high-grade sarcoma eligible for a randomized trial of adjuvant doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio), 48 were not entered: 24 (27%) by physician's choice and 24 refused randomization. Sixty-five percent of lower stage patients were randomized compared with 37% of those with higher stage (P = .02). Patients with extremity lesions were more frequently offered participation in the study (P = .07). Patients with lower stage lesions accepted randomization more readily than those with higher stage lesions (P = .01). As predicted by the higher stage and percentage of central lesions, the disease-free survival of nonrandomized patients was inferior to that of randomized patients (P = .15). Thus, patients at high risk appeared to avoid randomization and adjuvant doxorubicin in this trial, resulting in an inferior disease-free survival for the nonrandomized control group. Important questions generally require randomized trials that reliably determine relative treatment differences. If, however, the patients in a clinical trial are not representative of the entire patient population because of patient and physician selection biases, the generalizability of the results to the entire patient population may be compromised. For example, the prognosis of the general population cannot necessarily be inferred from the selected group in the study. In this study, the randomized and nonrandomized series yielded differing conclusions regarding treatment efficacy, even when an adjustment was made for known prognostic facts.", "To investigate factors associated with patient recruitment by general practitioners (GPs) in a randomised controlled trial in primary care.\n Cross sectional survey of 100 GPs who had agreed to recruit patients for a randomised controlled trial. A postal questionnaire was sent to the 100 GPs to collect information on factors associated with recruitment in the randomised controlled trial.\n The response rate to the survey was 97%. GPs who reported that practice nurses were involved in the research project were significantly more likely to recruit patients into the trial. Age, sex, membership of an independent practitioner association (IPA), number of half days worked, and the number of GPs working in a practice were not associated with recruitment.\n Involvement of practice nurses together with GPs may improve recruitment of patients in randomised controlled trials in primary care in New Zealand.", "We studied the reasons surgical principal investigators chose not to enter patients in a large, multicenter trial sponsored by a cooperative group. In 1976 the National Surgical Adjuvant Project for Breast and Bowel Cancers (NSABP) initiated a clinical trial to compare segmental mastectomy and postoperative radiation, or segmental mastectomy alone, with total mastectomy. Because the low rates of accrual were threatening to close the trial prematurely, we mailed a questionnaire to the 94 NSABP principal investigators, asking why they were not entering eligible patients in the trial. A response rate of 97 per cent was achieved. Physicians who did not enter all eligible patients offered the following explanations: (1) concern that the doctor-patient relationship would be affected by a randomized clinical trial (73 per cent), (2) difficulty with informed consent (38 per cent), (3) dislike of open discussions involving uncertainty (22 per cent), (4) perceived conflict between the roles of scientist and clinician (18 per cent), (5) practical difficulties in following procedures (9 per cent), and (6) feelings of personal responsibility if the treatments were found to be unequal (8 per cent). Further investigation into the behavioral aspects of the investigator-patient relationship is particularly pressing, since fear of change in this relationship was the most common reason given for not entering eligible patients in the trial.", "To improve understanding of physicians' reluctance to refer patients to clinical trials.\n This study was conducted in a large metropolitan region from 1993 to 1995 using a two-staged population-based sampling strategy. A total of 147 physicians discussed 245 patient cases and their own knowledge, attitudes, and practices toward clinical trials.\n Ninety-three patients (38. 0%) were offered a trial, and 49 (52.7%) of them agreed to participate. Forty-five patients (18.4%) actually received their adjuvant therapy on trial. Older patients and those with a poorer prognosis were less likely to be referred. Patients who delayed their decision were more than three times as likely to participate in a trial and more than eight times as likely to participate when they were reported to be actively involved in making the decision. Generally, physicians in university settings and who had formal support from a cooperative group were more likely to refer patients to trials. More specifically, surgeons referred more patients to trials when they felt comfortable explaining trials or believed that treatment should not stray from protocol. Oncologists were less likely to make referrals if they perceived the paperwork to be onerous or entry requirements to be too stringent. Surgeons' participation in recommending adjuvant therapy to patients resulted in more trial referrals unless they treated their patients with tamoxifen.\n (1) Physicians still need to overcome attitudinal and practical barriers to trial participation, (2) more support for physicians is needed, (3) surgeons may play a pivotal role in the recruitment of patients to adjuvant therapy trials, and (4) garnering patient enthusiasm for trial participation and involving them in the choice of adjuvant therapy may be key components to increasing trial enrollment." ]

[ "20955402", "8273321", "2835836", "8080985", "333769", "9308570" ]

[ "A randomized phase II trial of Arginine Butyrate with standard local therapy in refractory sickle cell leg ulcers.", "A randomized controlled trial of solcoseryl and duoderm in chronic sickle-cell ulcers.", "Topical antibiotics in chronic sickle cell leg ulcers.", "Accelerated healing of chronic sickle-cell leg ulcers treated with RGD peptide matrix. RGD Study Group.", "Isoxsuprine hydrochloride in the therapy of sickle cell leg ulceration.", "Propionyl-L-carnitine in chronic leg ulcers of homozygous sickle cell disease: a pilot study." ]

[ "Sickle cell leg ulcers are often debilitating, refractory to healing, and prone to recurrence. Healing of leg ulcers was incidentally observed during dose-ranging trials of Arginine Butyrate in beta haemoglobinopathies. Here, a controlled Phase II trial was performed in sickle cell patients who had lower extremity ulcers refractory to standard care for at least 6 months. Patients were randomized to receive standard local care alone (Control Arm) or standard care with Arginine Butyrate administered 5 d/week (Treatment Arm), for 12 weeks. Ulcers were photographed weekly, traced, and ulcer areas were calculated by computerized planimetry and compared between the two study arms. Twenty-seven study courses were evaluated. Control Arm subjects had 25 ulcers with a mean area of 25·7 cm(2) initially and 23·2 cm(2) after 12 weeks; 2/25 (8%) healed completely. Treatment Arm subjects had 37 ulcers with a mean area of 50·6 cm(2) initially and 28·3 cm(2) at 12 weeks; 11/37 of these (30%) healed completely. After 3 months, proportions of ulcers which healed were 6/25 (24%) and 29/37 (78%), in the Control and Treatment Arms respectively (P < 0·001). These findings strongly suggest that Arginine Butyrate merits further evaluation for the treatment of refractory sickle cell leg ulcers in larger trials.\n © 2010 Blackwell Publishing Ltd.", "A randomized controlled trial of Solcoseryl, DuoDerm and conventional conservative therapy with Eusol has been performed in 32 patients with homozygous sickle-cell (SS) disease. After 12 weeks' baseline observation, patients were randomized to one of three therapies and monitored for a further 12 weeks. Of 44 ulcerated legs, 20 received control treatment, 12 Solcoseryl and 12 DuoDerm. DuoDerm was generally unacceptable, and two-thirds of the patients defaulted from this treatment. Solcoseryl increased ulcer healing compared to the controls but the difference was not significant. Solcoseryl was well tolerated and may have a role in the treatment of chronic leg ulcers of sickle-cell disease.", "A randomized, controlled, trial of a topical antibiotic preparation (neomycin, bacitracin, and polymyxin B) was performed in 30 patients with homozygous sickle cell (SS) disease and chronic leg ulceration. Over a period of 8 weeks, the reduction in ulcer size was significantly (P less than 0.05) greater in the treatment group than in the control group. The results suggest that these topical antibiotics may contribute to the therapy of chronic leg ulceration associated with sickle cell disease.", "Leg ulcers are a chronic manifestation of sickle-cell disease (SCD) and are often painful, disabling, and difficult to treat. RGD peptide matrix treatment is a novel therapy designed to provide a topical synthetic extracellular matrix that can act as a temporary substitute for the damaged natural matrix at the ulcer site. In this randomized, placebo-controlled, double-blind, prospective, multicenter investigation, SCD patients with full-thickness leg ulcers were treated with standard therapy plus RGD peptide matrix or saline placebo once weekly for up to 10 weeks. Healing in patients with chronic ulcers (2 months or greater in duration) was significantly accelerated (P = .0085) in RGD peptide matrix recipients compared with the placebo group. In these chronic ulcer cases, the average percent ulcer closure (decrease in ulcer surface area) in the RGD peptide matrix group (54.4% +/- 8.9%) exceeded that in the placebo group (19.0% +/- 24.3%) nearly threefold by study endpoint. Furthermore, RGD peptide matrix was equally effective in promoting healing of long persistent ulcers and ulcers of shorter duration. In contrast, standard therapy plus placebo was significantly less effective (P = .001) in promoting healing for ulcers of progressively greater duration. The results of this study provide preliminary evidence that RGD peptide matrix treatment may significantly accelerate healing of chronic sickle-cell leg ulcers.", "nan", "nan" ]

[ "14601351", "4085708", "9624745", "15826410", "3746764", "3267741", "6428555", "7862598", "2797576", "16675365", "7086742", "9672056", "17359606", "10320488", "9624744", "11037083", "6436855", "9093498", "3556893", "6841071", "11099285", "17014912", "6349737", "6372925", "1780394" ]

[ "PHASE: a randomised, controlled trial of supervised self-help cognitive behavioural therapy in primary care.", "Changes in psychological diagnosis and prescription in a practice employing a counsellor.", "Evaluation of a primary care counselling service in Dorset.", "Thirty-six month outcome data from a trial of counselling with chronically depressed patients in a general practice setting.", "Psychological treatment in general practice: its effect on patients and their families.", "Group therapy in a general practice setting for frequent attenders: a controlled study of mothers with pre-school children.", "Clinical psychologist in primary care: controlled clinical and economic evaluation.", "Evaluation of the short-term impact of counseling in general practice.", "Taking mental health services to the people: the effects of referral to traditional psychiatric facilities.", "Effectiveness of an intervention to reduce sickness absence in patients with emotional distress or minor mental disorders: a randomized controlled effectiveness trial.", "Clinical psychology in general practice: a controlled trial evaluation.", "Cost-effectiveness of treatments for major depression in primary care practice.", "Cluster randomised controlled trial of the effectiveness of primary care mental health workers.", "Dedicated psychiatric care within general practice: health outcome and service providers' views.", "A randomized controlled trial and economic evaluation of counselling in primary care.", "Randomized controlled trial of cognitive behaviour therapy for repeated consultations for medically unexplained complaints: a feasibility study in Sri Lanka.", "Cost-benefit analysis of a controlled trial of nurse therapy for neuroses in primary care.", "A randomised controlled trial and cost analysis of problem-solving treatment for emotional disorders given by community nurses in primary care.", "Assessing the impact of psychological intervention on family practice clinic visits.", "Referrals to the psychiatric services by general practitioners in relation to the introduction of sessions by psychiatrists in Health Centres.", "Randomised controlled trial of non-directive counselling, cognitive-behaviour therapy, and usual general practitioner care for patients with depression. II: cost effectiveness.", "A pragmatic, unblinded randomised controlled trial comparing an occupational therapy-led lifestyle approach and routine GP care for panic disorder treatment in primary care.", "Brief psychotherapy in family practice. A controlled prospective intervention trial.", "Cognitive therapy for major depressive disorder in primary care.", "Evaluation of a brief psychological treatment for emotional disorders in primary care." ]

[ "Common mental health problems account for up to 40% of all general practitioner (GP) consultations. Patients have limited access to evidence-based psychological therapies. Cognitive behavioural therapy self-help strategies offer one potential solution.\n To determine differences in clinical outcome, patient satisfaction and costs, between a cognitive behavioural-based self-help package facilitated by practice nurses compared to ordinary care by GPs for mild to moderate anxiety and depression.\n Randomised controlled trial.\n Seventeen primary healthcare teams.\n Patients presenting to their GP with mild to moderate anxiety and/or depression were recruited to the study and randomised to receive either a self-help intervention facilitated by practice nurses or ordinary care. The self-help intervention consisted of up to three appointments: two 1 week apart and a third 3 months later. There were no restrictions on ordinary care.\n Intention-to-treat analysis showed that patients treated with practice nurse-supported cognitive behavioural therapy self-help attained similar clinical outcomes for similar costs and were more satisfied than patients treated by GPs with ordinary care. On-treatment analysis showed patients receiving the facilitated cognitive behavioural therapy self-help were more likely to be below clinical threshold at 1 month compared to the ordinary care group (odds ratio [OR] = 3.65, 95% confidence interval [CI] = 1.87 to 4.37). This difference was less well marked at 3 months (OR = 1.36, 95% CI = 0.52 to 3.56).\n Facilitated cognitive behavioural self-help may provide a short-term cost-effective clinical benefit for patients with mild to moderate anxiety and depression. This has the potential to help primary care provide a choice of effective psychological as well as pharmacological treatments for mental health problems.", "This study investigated the effect on consultation rates and psychotropic drug prescribing of employing a counsellor in a general practice. No major change was detected in the number of prescriptions for psychotropic drugs or the consultation rates during the years that counselling was available. An increase in the number of psychotropic drug prescriptions in the year after counselling was accounted for by a very small number of patients. Three years after counselling more than three-quarters of the patients who had been counselled were receiving no medical attention for psychiatric problems. This may either reflect the effect of counselling over a longer period or the natural history of the problems.", "Research into the effectiveness of counselling in primary care is rare. This study attempts to provide a thorough evaluation of the effects of a new counselling service introduced throughout Dorset.\n To evaluate the impact of counselling on client symptomatology, self-esteem, and quality of life. The effect of counselling on drug prescribing, referrals to other mental health professionals, and client and general practitioner (GP) satisfaction were also assessed.\n All new clients referred for counselling were asked to complete and return questionnaires before and after counselling. A total of 385 clients took part in the study. The first and second assessments were compared statistically. Clients were ascribed a psychiatric diagnosis using a simplified version of DSM-IIIR (Diagnostic and Statistical Manual of the American Psychiatric Association). GPs' views of the service were determined using a specially designed questionnaire. Drug data were obtained from the Prescription Pricing Authority and referral statistics from Dorset HealthCare National Health Service (NHS) Trust.\n The number of psychiatric symptoms and their severity were significantly reduced by counselling. There were no significant differences in the prescription of anxiolytic/hypnotic and anti-depressant medication between matched practices with and without counsellors. The presence of a counsellor did not affect the rate of referral to other mental health professionals. Clients and GPs valued the service highly.\n The Psychology Managed Counselling Service is an effective method of running a counselling service and is well received by both clients and GPs. Counselled clients improved significantly on several measures.", "Counsellors have been employed in general practice with little evidence of effectiveness in this setting. This randomized controlled trial examined long-term effectiveness of short-term counselling in general practice for patients with chronic depression, either alone or combined with anxiety. Participants were 181 patients recruited from nine general practitioners' (GP) practices in Derbyshire by screening consecutive attenders using the Beck Depression Inventory. Both the experimental and control group received routine GP treatment but the experimental group were also referred to the practice counsellor. Depression and social adjustment were measured at baseline, 6, 12, and 36 months. There was an overall significant improvement in the actual scores over time, but there were no significant differences between the two groups on any of the measures at either 6, 12, or 36 months. Although fewer experimental group patients were still 'cases' on the BDI than controls at 6 and 12 months, this difference disappeared at 36 months. There was no evidence to demonstrate a long-term effect of improved outcomes in those referred to counselling.", "Rates of consultations and prescriptions for patients referred to clinical psychologists, and for these patients' immediate families, were investigated for three-year periods both before and after referral. Patients and their children consulted more and had more medication prescribed before referral than control groups, this tendency being particularly prevalent in the year before referral. After the contact with the psychologist there was a decrease in all these indices in the short term, and there were long-term decreases in psychotropic drug prescriptions for patients and in both consultations and prescriptions for their children.", "The frequent attendance of women suffering from anxiety and depression is a common problem in general practice and the problems are often externalized through the women's children. A small controlled study was carried out in a general practice surgery to see whether demand for medical attention by mothers of pre-school children would decrease after they attended a discussion group. Twenty women who fulfilled the study criteria of more than double the national average consultation rate for their age group and of having at least one pre-school child, were sequentially allocated to a treatment or control group. The group therapy was held over two terms of 10 sessions, each of 90 minutes, and was led by a psychologist and a general practitioner. Consultation rates (including surgery visits, house calls and prescription requests) were recorded for five consecutive six-month periods before and after the intervention. At follow-up six months after the end of the treatment a significant reduction in consultation rate had been achieved and maintained by the treated group compared with the controls (P<0.01). This study shows the value of attending to the cause of frequent consultation as well as to the complaints presented.", "In a controlled, evaluated study of a behaviourally orientated clinical psychology service based in a health centre two randomised groups of patients were compared. Patients in the control group received usual primary care management; subject patients received the same, but in addition were able to consult a clinical psychologist in the health centre. Outcome was assessed by psychosocial and economic measures. These showed changes in favour of the subject condition, many of which were statistically significant.", "This paper describes the findings of a randomised controlled trial of the short-term impact of counseling in the general practice setting. Compared with patients who received usual advice from their general practitioner for acute problems such as relationship difficulties, anxiety and depression, those who received counseling from qualified counselors working within the primary health care context showed greater improvement in psychological health as measured by the General Health Questionnaire. Significantly fewer of those counselled were prescribed anti-depressant drugs by the general practitioners in the study, or were referred to psychiatrists or clinical psychologists for care. In addition those patients who attended sessions with the practice counselor were more likely to report that they were satisfied with their treatment and more expressed feelings of well-being.", "This study investigated the effects of establishing a locally integrated mental health team in a small New Zealand township (Mosgiel), by comparing it with a similar township (Port Chalmers) without such established services. The rate of referral for out-of-district public and private inpatient and outpatient care was taken as an inverse measure of the strength of community resources to cope with psychiatric problems at the local level. In terms of referrals for inpatient care it was found that increased locally available mental health services did not reduce the number of onward referrals. However, length of hospital stay was significantly less. The total number of referrals to Dunedin for outpatient care also showed no significant change over time. The effect in this instance seems to be qualitative in that the proportion of first time referrals decreased while referrals tended to increase. It was also found that the lack of community mental health teams resulted in more self referrals to private health care. The appropriateness of this development needs further investigation. The presence of such a team is associated with a refinement in general practitioner referring practices.", "The purpose of this study was to evaluate the effectiveness of an activating intervention designed to reduce sick leave duration in patients with emotional distress or minor mental disorders.\n In a 1.5-year randomized controlled trial, 194 patients with minor mental disorders received either an experimental intervention by social workers or general practitioners' usual care. The intervention focused on understanding causes, developing and implementing problem-solving strategies and promoting early work resumption. Outcome measures were sick leave duration, mental health and physical health (questionnaires included the Hospital Anxiety and Depression Scale, the Four-Dimensional Symptom Questionnaire and SF-36), all measured at baseline at and 3, 6 and 18 months later. Multilevel analyses were used to evaluate differences between groups.\n The groups did not differ significantly on any of the outcome measures, except that the experimental group reported higher satisfaction with treatment.\n Although the intervention has benefits, it was not successful at its primary goal (i.e., to reduce sick leave duration in patients with emotional distress or minor mental disorders). Programs aimed at the reduction of sick leave duration may yield better results if targeted at patients with more severe emotional problems than at those with exclusively emotional distress or minor mental disorders, or if delivered by caregivers who are closer to the work environment than are social workers, such as occupational physicians.", "A controlled trial study is described in which 50 consecutive potential referrals for psychological treatment from one general practice were randomly allocated either to behavioural treatment or no-treatment conditions. Treatment-group patients received treatment from a clinical psychologist working within the practice; the control-group patients continued to be managed by their general practitioner. The patients' use of NHS resources was assessed during the treatment period (or its equivalent for the control group) and at a follow-up comparison point, when the patients' subjective ratings of their progress were also obtained. Between referral and the end of treatment the treated group received significantly less psychotropic medication than the control group. This difference was not, however, maintained at the longer-term follow-up. No differences in general practice consultation rates, in the subjective ratings of psychological distress, in control orientation or life satisfaction were found between the two groups, but the level of patient satisfaction was high. Implications for the design of future studies and for psychological health care delivery systems are discussed.", "This study augments a randomized controlled trial to analyze the cost-effectiveness of 2 standardized treatments for major depression relative to each other and to the \"usual care\" provided by primary care physicians.\n A randomized controlled trial was conducted in which primary care patients meeting DSM-III-R criteria for current major depression were assigned to pharmacotherapy (where nortriptyline hydrochloride was given) or interpersonal psychotherapy provided in a standardized framework or a primary physician's usual care. Two outcome measures, depression-free days and quality-adjusted days, were developed using information on depressive symptoms over time. The costs of care were calculated. Cost-effectiveness ratios comparing the incremental outcomes with the incremental costs for the different treatments were estimated. Sensitivity analyses were performed.\n In terms of both economic costs and quality-of-life outcomes, patients assigned to the pharmacotherapy group did slightly better than those assigned to interpersonal psychotherapy. Both standardized therapies provided better outcomes than primary physician's usual care, but each consumed more resources. No meaningful cost-offsets were found. The incremental direct cost per additional depression-free day for pharmacotherapy relative to usual care ranges from $12.66 to $16.87 which translates to direct cost per quality-adjusted year gained from $11270 to $19510.\n Standardized treatments for depression lead to better outcomes than usual care but also lead to higher costs. However, the estimates of the cost per quality-of-life year gained for standardized pharmacotherapy are comparable with those found for other treatments provided in routine practice.", "Mental health issues are a core part of the work of primary care and are the second most common reason for consultations. There is some evidence that the quality of primary care mental health provision is variable.\n To evaluate the effectiveness of primary care mental health workers with regards to satisfaction with care, mental health symptoms, use of the voluntary sector, and cost effectiveness of care.\n Cluster randomised controlled trial.\n Practices in the Heart of Birmingham Primary Care Trust, Birmingham, England.\n Nineteen practices and 368 patients (18 to 65 years of age) with a diagnosis of a new or ongoing common mental health problem were recruited. Sixteen practices and 284 patients completed the trial.\n Patients in intervention practices had a higher mean level of general satisfaction than those in control practices (difference between group scores of 8.3, 95% confidence interval = 1.3 to 15.3, P = 0.023). The two groups did not differ in mental health symptom scores or use of the voluntary sector.\n For patients with common mental health problems, primary care mental health workers may be effective at increasing satisfaction with an episode of care.", "Health service reforms have led to relocation of care of the chronic mentally ill from institutions to the community, with subsequent demands on the primary health care team. Few studies have attempted to identify satisfactory models of care for this patient group. This study explores the impact of the employment of a community psychiatric nurse (CPN) by a general practice in Aberdeen city to co-ordinate care of discharged long-stay psychiatric patients resettled in hostels. A similar general practice with a comparable group of registered patients was selected as a control group. Patient health outcome was measured using the Health of the Nation Outcome Scales (HoNOS) and service providers' views on dedicated psychiatric care within general practice were explored using qualitative methods. Improvements in communication, liaison and drug management were reported in the intervention practice. A primary care-based CPN service dedicated to the care of the chronic mentally ill promoted a smooth transfer of care from long-term institutionalized care to the community setting.", "Counselling in primary care settings remains largely unevaluated. Such evaluation has been strongly recommended.\n To determine the relative effectiveness and cost-effectiveness of generic counselling and usual general practitioner (GP) care for patients with minor mental health problems.\n A randomized controlled trial and health economic evaluation were carried out in nine general practices. Access to generic counselling (brief counselling, generally involving up to six 50-minute sessions) was compared with usual GP care. A total of 162 patients aged 16 years and over with diverse mental health problems (excluding phobic conditions and psychoses) were randomized. The Hospital Anxiety and Depression (HAD) scale, COOP/WONCA (World Organization of Family Doctors) functional health assessment charts, and the delighted-terrible faces scale were used to assess outcome four months after randomization.\n The two groups were similar at baseline. There were significant improvements in both groups between randomization and follow-up for most outcome measures, but no significant differences between the study arms. The 95% confidence limits were narrow and excluded clinically significant effects. Under various assumptions concerning the cost of secondary care referrals and of counselling time, no clear cost advantage was associated with either intervention.\n This pragmatic trial demonstrates no difference in functional or mental health outcome at four months between subjects offered access to counselling and those given usual care by their GP. There is no clear difference in the cost-effectiveness of the two interventions. Purchasers should take account of these findings in allocating resources within primary care.", "Research on the management and the outcome of treatment of medically unexplained symptoms is very limited. Development of simple but effective techniques for treatment and demonstration of their effectiveness when applied in primary health care are needed.\n A randomized controlled trial was carried out with follow-up assessments at 3 months after baseline assessments using the Short Explanatory Model Interview (SEMI), General Health Questionnaire (GHQ-30), Bradford Somatic Inventory (BSI) and patient satisfaction on a visual analogue scale. The study was carried out in a general out-patient clinic in Sri Lanka. The intervention group received six, 30 min sessions based on the principles of cognitive behavioural therapy over a period of 3 months. The control group received standard clinical care.\n Eighty patients out of the 110 patients referred, were eligible. Sixty-eight were randomly allocated equally to the control and treatment groups. All 34 in the treatment group accepted the treatment offer and 22 completed between three and six sessions. At 3 months, 24 in the treatment and 21 in the control group completed follow-up assessments. Intention-to-treat analysis revealed significant differences in mean scores of outcome measures (adjusted for baseline scores) between control and intervention groups respectively--complaints 6.1 and 3.8 (P = 0.001), GHQ 10.4 and 6.3 (P = 0.04), BSI score 15.6 and 132 (P < 0-01), visits 7.9 and 3.1 (P = 0.004).\n Intervention based on cognitive behavioural therapy is feasible and acceptable to patients with medically unexplained symptoms from a general out-patients clinic in Sri Lanka. It had a significant effective in reducing symptoms, visits and distress, and in increasing patient satisfaction.", "In a randomized, controlled trial neurotic patients (mainly phobics and obsessive-compulsives) in primary care were assigned to behavioural psychotherapy from a nurse therapist or to routine care from their general practitioner. At the end of one year clinical outcome was significantly better in patients cared for by the nurse therapist. Economic outcome to one year, compared with the year before entering the trial, showed a slight decrease in the use of resources by the nurse therapist group (N = 22), and an increase in resource usage in the GP-treated group (N = 28), mainly due to the latter's increased absence from work and more hospital treatment and drugs. On the reasonable assumptions that nurse therapists treat 46 patients a year and that such patients treated behaviourally maintain their gains for 2 years, the economic benefits to society from nurse therapists treating such patients may outweigh the costs. This excludes any monetary value on the substantial clinical gains such as reduction in fear and anxiety. However, the numbers are small, few economic differences were significant, and many patients either did not complete the trial or waiting-list periods or they failed to return economic data. Conclusions must thus be tempered with caution, even though pre-treatment demographic and clinical data of non-returners were comparable with those of returners, and though the few drop-outs who could be rated at one year had not improved. The findings cannot be extrapolated to other types of clinical problem and treatment.", "We set out to investigate whether community nurses could be trained in problem-solving therapy and, once trained, how effective they would be in treating emotional disorders in primary care.\n Seventy patients with an emotional disorder in primary care were randomly allocated to receive either problem-solving therapy from a trained community nurse or treatment as usual from their general practitioner. Interview and self-rated assessments of clinical and economic outcome were made pretreatment, at eight weeks and at 26 weeks after treatment.\n There was no difference in clinical outcome between patients who received problem-solving treatment and patients who received the general practitioner's usual treatment. However, patients who received problem-solving treatment had fewer disability days and fewer days off work. The health care cost of problem-solving was greater than that of the general practitioner's usual treatment but this was more than offset by savings in the cost of days off work.\n Problem-solving treatment can be given by trained community nurses. The clinical effectiveness and cost-benefit of the treatment will depend on the selection of appropriate patients.", "The effects of brief psychological intervention on rates of medical utilization were investigated in a family practice clinic. Patients referred to the psychology service served as experimental subjects. These subjects underwent psychological assessment and treatment from supervised clinical psychology externs in joint working arrangements with family practice residents. Control subjects were other family practice patients, matching the experimental group in age, sex, and race. The number of medical visits to the family practice clinic, specialty clinics, and the emergency room were the dependent measures. The study period was two years. Results indicated that the experimental subjects were more likely than control subjects to decrease medical utilization of the family practice clinic. The findings are consistent with earlier work showing an association between brief psychosocial intervention and decreases in the frequency of clinic visits. However, this study suggests that preinternship-level clinical psychology trainees can be equally as effective in providing this intervention as mental health professionals who have completed their training.", "nan", "To compare the cost effectiveness of general practitioner care and two general practice based psychological therapies for depressed patients.\n Prospective, controlled trial with randomised and patient preference allocation arms.\n General practices in London and greater Manchester.\n 464 of 627 patients presenting with depression or mixed anxiety and depression were suitable for inclusion.\n Usual general practitioner care or up to 12 sessions of non-directive counselling or cognitive-behaviour therapy provided by therapists.\n Beck depression inventory scores, EuroQol measure of health related quality of life, direct treatment and non-treatment costs, and cost of lost production.\n 197 patients were randomly assigned to treatment, 137 chose their treatment, and 130 were randomised only between the two psychological therapies. At four months, both non-directive counselling and cognitive-behaviour therapy reduced depressive symptoms to a significantly greater extent than usual general practitioner care. There was no significant difference in outcome between treatments at 12 months. There were no significant differences in direct costs, production losses, or societal costs between the three treatments at either four or 12 months. Sensitivity analyses did not suggest that the results depended on particular assumptions in the statistical analysis.\n Within the constraints of available power, the data suggest that both brief psychological therapies may be significantly more cost effective than usual care in the short term, as benefit was gained with no significant difference in cost. There are no significant differences between treatments in either outcomes or costs at 12 months.", "Treated anxiety increased in the UK by over 30% since 1994. Medication and psychological treatment is most common, but outcomes are sometimes poor, with high relapse rates. Lifestyle has a potential role in treatment, but is not considered in clinical guidelines. Panic disorder is potentially influenced by lifestyle factors.\n 16 week unblinded pragmatic randomised controlled trial in 15 East of England primary care practices (2 Primary Care Trusts). Participants met DSM-IV criteria for panic disorder with/without agoraphobia. Follow-up at 20 weeks and 10 months. Control arm, unrestricted routine GP care. Trial Arm, Occupational therapy-led lifestyle treatment comprising: lifestyle review of fluid intake, diet pattern, exercise, caffeine, alcohol and nicotine; negotiation of positive lifestyle changes; monitoring and review of impact of changes. Primary outcome measure: Beck Anxiety Inventory.\n Intention-to-treat analysis provided between-group comparisons using analysis of co-variance. Bonferroni method to adjust p-values.\n From 199 referrals, 36 GP care and 31 lifestyle arm patients completed to final follow-up. Significantly lower lifestyle arm BAI scores at 20 weeks (p<0.001), non-significant (p=0.167) at 10 months after Bonferroni correction. 63.6% lifestyle arm, and 40% GP arm patients (p=0.045) panic-free at 20 weeks; 67.7% and 48.5% (p=0.123) respectively at 10 months.\n Final study size/power calls for caution in interpreting findings.\n A lifestyle approach may provide a clinically effective intervention at least as effective as routine GP care, with significant improvements in anxiety compared with routine GP care at the end of treatment. Further study is required before suggesting practice changes.", "In a prospective (controlled) trial, the result in 18 patients receiving eight, weekly half-hour sessions of brief problem-oriented dynamic psychotherapy was compared with the result in an equal number receiving eight, weekly half-hour sessions of family practitioner therapy and in another 20 receiving no additional therapy. The subjects were drawn from patients at ten suburban family practices in Sydney. They had had psychological complaints for at least six months. No differences between the three treatment groups were found in the final outcome, either in a symptom severity and social dysfunction factor or in a physical disability and medication factor.", "Cognitive therapy for depression is a psychological treatment designed to train patients to identify and correct the negative depressive thinking which, it has been hypothesised, contributes to the maintenance of depression. General practice patients meeting Research Diagnostic Criteria for primary major depressive disorder were randomly allocated either to continue with the treatment they would normally receive (which in the majority of cases included antidepressant medication) or to receive, in addition, sessions of cognitive therapy. At completion of treatment, patients receiving cognitive therapy were significantly less depressed than the comparison group, both on blind ratings of symptom severity made by psychiatric assessors and on a self-report measure of severity of depression. At three-month follow-up cognitive therapy patients no longer differed from patients receiving treatment-as-usual, but this was mainly as a result of continuing improvement in the comparison group.", "A randomized trial in general practice compared: (i) a brief psychological treatment (problem-solving) given by a psychiatrist; (ii) any treatment of the GP's choice, whether psychological or pharmacological. The patients had recent onset emotional disorders of poor prognosis. Patients in the problem-solving group showed significantly greater reductions in symptoms. Problem-solving as given by a psychiatrist was feasible in primary care and acceptable to patients. Problem-solving is now being evaluated as given by general practitioners trained in the method." ]

[ "8239591", "10517189", "2732125", "15551160", "2667903", "16575723", "16798042", "2081722", "1554839", "1596044", "8507759", "15214959", "20215128", "16354469", "4907514", "7695265", "22296864", "3334575", "15578399" ]

[ "Quinolones in treatment of human brucellosis: comparative trial of ofloxacin-rifampin versus doxycycline-rifampin.", "Ciprofloxacin and rifampicin versus doxycycline and rifampicin in the treatment of brucellosis.", "Comparison of three different regimens in the treatment of acute brucellosis: a multicenter multinational study.", "Comparison of the efficacy of two months of treatment with co-trimoxazole plus doxycycline vs. co-trimoxazole plus rifampin in brucellosis.", "Comparative trial of doxycycline plus streptomycin versus doxycycline plus rifampin for the therapy of human brucellosis.", "Efficacy of gentamicin plus doxycycline versus streptomycin plus doxycycline in the treatment of brucellosis in humans.", "Comparison between doxycycline-rifampin-amikacin and doxycycline-rifampin regimens in the treatment of brucellosis.", "Failure of prolonged treatment with ciprofloxacin in acute infections due to Brucella melitensis.", "Failure of ceftriaxone in the treatment of acute brucellosis.", "Treatment of human brucellosis with doxycycline plus rifampin or doxycycline plus streptomycin. A randomized, double-blind study.", "Open, randomized therapeutic trial of six antimicrobial regimens in the treatment of human brucellosis.", "Ofloxacin plus rifampicin versus doxycycline plus rifampicin in the treatment of brucellosis: a randomized clinical trial [ISRCTN11871179].", "Comparison of the efficacy of gentamicin for 5 days plus doxycycline for 8 weeks versus streptomycin for 2 weeks plus doxycycline for 45 days in the treatment of human brucellosis: a randomized clinical trial.", "Comparison of three different combination therapies in the treatment of human brucellosis.", "Ampicillin in the treatment of brucellosis. A controlled therapeutic trial.", "Possible implications of doxycycline-rifampin interaction for treatment of brucellosis.", "Comparison of doxycycline-streptomycin, doxycycline-rifampin, and ofloxacin-rifampin in the treatment of brucellosis: a randomized clinical trial.", "Comparative study of two regimens in the treatment of brucellosis.", "A randomized, double-blind study to assess the optimal duration of doxycycline treatment for human brucellosis." ]

[ "Quinolones have been reported to be active against Brucella species in vitro. In this prospective randomized study, the efficacy and safety of the combination of ofloxacin plus rifampin were compared with the efficacy and safety of doxycycline plus rifampin, both combinations administered for a 6-week period in treatment of brucellosis. Sixty-one patients were enrolled in the study, and 49 had blood or bone marrow cultures positive for Brucella melitensis. Thirty patients received 200 mg of doxycycline plus 600 mg of rifampin once daily, and 31 patients were treated with 400 mg of ofloxacin plus 600 mg of rifampin once daily for 6 weeks. Nine patients in each group had complications of the disease. There was one therapeutic failure in the ofloxacin-rifampin treatment group, and one patient from each group relapsed (3.3% of those in the doxycycline-rifampin treatment group versus 3.2% of those in the ofloxacin-rifampin treatment group). Gastric discomfort was the major side effect observed in 13 patients (43.3%) who received doxycycline plus rifampin, whereas only 2 patients (6.5%) treated with ofloxacin plus rifampin complained of gastric irritation. These results suggest that the combination of ofloxacin plus rifampin administered for 6 weeks is as effective as doxycycline plus rifampin given for the same period, regardless of the presence of complications of the disease.", "The present study was undertaken to evaluate the efficacy, safety, and patient tolerability of two antibiotic regimens for the treatment of brucellosis: rifampicin 600 mg/day and doxycycline 200 mg/day for 45 days (group 1), versus rifampicin 600 mg/day and ciprofloxacin 1 g/day for 30 days (group 2). Forty patients were diagnosed with brucellosis based on clinical and microbiological findings. The two groups were comparable regarding age and sex distribution. The average number of days without fever and symptoms was lower in group 2 patients than in group 1 patients (mean+/-SD: 3.85+/-1.98 for group 1 vs. 2.78+/-1.03 for group 2, P=0.044). During the 1-year follow-up period, three (15%) patients in group 2 and two (10%) patients in group 1 had clinical relapses; these rates were not significantly different. Ciprofloxacin and rifampicin treatment for brucellosis is as effective as the standard regimen of doxycycline and rifampicin and offers the advantage of a shorter duration of treatment.", "The present study was undertaken to evaluate efficacy, safety and patient acceptability of three antibiotic regimens for the treatment of acute brucellosis. Six different centres were involved: three in France, one in Greece and two in Spain. The regimens were: oral rifampicin 900 mg/day plus oral doxycycline 200 mg/day for 45 days (A), oral doxycycline 200 mg/day for 45 days plus im streptomycin 1 g/day for 21 days (regimen B) [corrected] and the WHO regimen (C) combining oral tetracycline 2 g/day for 21 days plus im streptomycin, 1 g/day, for 14 days. Regimens A and B were randomly allocated in all centres, while regimen C was allocated only in two centres. All patients were suffering from acute brucellosis clinically and biologically proven. 143 patients were allocated for treatment and analysed. Their mean age was 41 years (range 13-70), 49 were female and 94 male, and their mean weight was 64 kg (range 35-98). Among these patients, 14% had localized disease (nine orchitis, eight osteo-articular involvement and one pleural effusion), but there was no statistical difference between the three regimens in regard to this localized disease. Forty-five per cent of the patients had positive blood cultures. The cure rate with regimen A was 95%, 96% with regimen B and 59% with regimen C. Thus regimen A presented the same efficacy rate as regimen B, but regimen C cannot be regarded as the treatment of choice for acute brucellosis.", "To compare the efficacy of two different regimens in treatment of brucellosis.\n This randomised clinical trial study was conducted on 280 patients with brucellosis in Babol, Iran, from April 1999 to January 2002. One of the following two regimens was randomly prescribed for two months: co-trimoxazole plus doxycycline (CD group) and co-trimoxazole plus rifampin (CR group).\n 140 patients with the mean age of 35.56 (16.2) years, and 140 patients with the mean age of 31.39 (18) years, were treated with co-trimoxazole plus doxycycline and co-trimoxazole plus rifampin, respectively. Clinical manifestations and laboratory test results were similar in both groups (p >0.05), except in sex and clinical types (p <0.05). Failure of treatment was seen in 10 (7.1%) and 23 (16.4%) cases treated in the CD group and CR group, respectively (95% CI, 0.174 to 0.862; OR = 0.387; p = 0.020). Relapse was seen in 12 cases (8.6%) treated in the CD group and in 14 cases (10%) treated in the CR group (95% CI, 0.365 to 1.87; OR = 0.826; p = 0.646). Failure of treatment plus relapse was seen in 22 (15.7%) and 37 (26.4%) cases treated in the CD group and CR group, respectively (95%CI, 0.278 to 0.929, OR = 0.508; p = 0.028). Risk for developing of failure of treatment and relapse in patients treated with co-trimoxazole plus rifampin was 1.96 times higher than those treated with co-trimoxazole plus doxycycline. Among the relapsed patients, 18 (69.2%) cases occurred within 6 months after completion of therapy, and most of them in uncomplicated patients.\n Using two months of treatment, the efficacy of co-trimoxazole plus doxycycline is better than co-trimoxazole plus rifampin.", "Effectiveness and therapeutic value of the doxycycline plus streptomycin and doxycycline plus rifampin schedules of treatment of human brucellosis have been assessed by carrying out a prospective study on 111 patients randomly distributed into two groups. Patients in group A were treated with doxycycline plus streptomycin sulphate and those in group B with doxycycline plus rifampin. The temperature of all patients reverted to normal, and 54 patients from group A (91.6%) and 45 from group B (86.5%) achieved total recovery with a single therapeutic cycle. Two therapeutic failures and 3 relapses in group A (8.4%) and 7 relapses in group B (13.46%) were observed. The tolerance to both regimens was good. Although the combination doxycycline plus rifampin offers a more convenient oral administration, in the light of these results, until more extensive research is carried out, it should be considered as an alternative rather than a first choice in the treatment of human brucellosis.", "In the treatment of human brucellosis, antibiotic regimens containing an aminoglycoside are reportedly associated with fewer relapses.\n This prospective, randomized study employed doxycycline (100 mg administered orally twice daily for 45 days) in combination with either streptomycin (1 g administered intramuscularly daily for 14 days; the DS regimen) or gentamicin (5 mg/kg per day administered intramuscularly for 7 days; the DG regimen). Efficacy of treatment was determined by rates of failure or relapse with a follow-up period of 1 year.\n Ninety-seven patients with a mean age (+/- standard deviation [SD]) of 33.74+/-15.47 years and 94 patients with the a mean age (+/-SD) of 36.2+/-14.14 years were treated with regimens DG and DS, respectively (P = .277). The clinical manifestations in both groups of patients were similar with the exception of sweating, which was more common in the DG group (P = .04). Three (3.2%) of the patients in the DS group and 3 (3.1%) of patients in the DG group experienced relapse (difference, 0.1%; 95% confidence interval [CI], -4% to 5%; P = 1.0). Overall, 7 (7.4%) of the patients in the DS group and 5 (5.2%) of the patients in the DG group experienced failure of therapy or relapse (difference, 2.2%; 95% CI, -4.5% to 8.9%; P = .563). The actuarial probability for relapse at 12 months after completion of therapy was 4.3% in the DS group and 2.1% in the DG group (difference, 2.2%; 95% CI, -2.8% to 7.2%).\n The combination of oral doxycycline for 45 days plus intramuscular gentamicin for 7 days is equally as effective as traditional therapy using doxycycline for 45 days plus streptomycin for 14 days.", "Combination drug therapy of brucellosis leads to recovery of symptoms, shortening of symptomatic interval, and decrease in morbidity rate, but single drug therapy is associated with more relapse episodes and a higher rate of drug resistance. Different drug combinations have been evaluated in the treatment of brucellosis. Considering the failure of treatment and relatively high rate of relapse of the disease with the World Health Organization's (WHO) recommended therapeutic regimen, we evaluated a new regimen that we assumed would increase the success of treatment and decrease the rate of relapse. In this study we compare the standard regimen of the WHO, doxycycline-rifampin (DR), to triple therapy with doxycycline-rifampin-amikacin (ADR).\n Two hundred and twenty-eight consecutive patients with brucellosis, who attended Hamedan Sina Hospital between 1999 and 2001, whether seen as outpatients or as inpatients, were enrolled in the study. The participants were randomly allocated to the DR group (receiving doxycycline 100 mg twice a day and rifampin 10 mg/kg body weight/day every morning, both taken orally for eight weeks) or the ADR group (receiving doxycycline 100 mg twice a day and rifampin 10 mg/kg body weight/day every morning, both taken orally for eight weeks, plus 7.5 mg/kg amikacin intramuscularly twice a day for seven days). The patients were checked for the relief of symptoms, drug side-effects, and relapse of disease during the treatment and follow-up.\n Of the 228 patients enrolled, eight were withdrawn - four patients from the DR group and four from the ADR group. Of the remaining 220 participants (110 in the ADR group and 110 in the DR group), 107 were male (48.6%) and 113 were female (51.4%). Mean age was 35.7+/-17 years in the ADR group and 37+/-18.4 years in the DR group (p=0.5). In the DR group, 97 (88.2%) and in the ADR group, 106 (96.4%) of the patients had relief of symptoms (a significant difference by Chi-square test (p=0.04)). After completion of treatment, and at the sixth month follow-up, nine (9.3%) patients in the DR group and six (5.7%) in the ADR group experienced a relapse of the disease, with no significant difference (p=0.4). Mild side-effects were found in only 10 patients, and none required discontinuation of the therapeutic regimen. Of these patients, four were from DR group and six from ADR group; no significant difference was observed (p=0.7).\n Given the fact that the ADR regimen had a higher efficacy and more rapid action in terms of relief of symptoms compared to the DR regimen, and that no significant difference in drug side-effects and disease relapse existed in the patients of either group, adding amikacin to the DR standard treatment regimen seems beneficial.", "A randomized prospective, pilot study was performed to compare the efficacy of oral ciprofloxacin (750 mg or 1000 mg bd) with standard oral antimicrobial therapy (rifampicin plus doxycycline) in the treatment of acute infection with Brucella melitensis. All antimicrobial drugs were administered for 42 days. Although all patients responded rapidly, five of the six patients receiving ciprofloxacin relapsed following cessation of therapy. There were no relapses among the patients who received doxycycline/rifampicin. Despite its in-vitro activity against B. melitensis (MIC 0.5 mg/l), ciprofloxacin, administered twice daily, does not appear to constitute adequate therapy for acute brucellosis.", "In an open, multicenter study conducted in Israel in 1989, 18 patients with acute brucellosis were randomized to receive either less than or equal to 2 g of intramuscularly administered ceftriaxone daily for at least 2 weeks or doxycycline for 4 weeks plus streptomycin for 2 weeks. All 10 patients treated with the combination of doxycycline plus streptomycin responded promptly, and their infections did not relapse during 6 months of follow-up. Of eight patients treated with ceftriaxone, six did not respond initially; when ceftriaxone was replaced by the combination of doxycycline and streptomycin, patients responded immediately. No relapses of infection were observed in these patients during follow-up. One patient who received ceftriaxone responded and remained well at the end of 6 months of follow-up, and one patient who initially responded to therapy with this drug experienced relapse of infection within 3 weeks but recovered when the doxycycline/streptomycin regimen was initiated. We conclude that despite encouraging data from in vitro studies and promising clinical studies, 2 g of ceftriaxone administered im daily should not be considered appropriate therapy for brucellosis.", "To compare the effectiveness of doxycycline-rifampin (DR) combination therapy with that of the classic doxycycline-streptomycin (DS) combination in patients with brucellosis.\n A randomized, double-blind study, with a mean follow-up of 15.7 months.\n A 1000-bed teaching hospital in Barcelona, Spain.\n Ninety-five patients (68 men and 27 women; mean age, 39 years) diagnosed with brucellosis on the basis of both clinical and serologic findings; 81 of these patients had blood cultures positive for Brucella melitensis.\n Forty-four patients received doxycycline, 100 mg every 12 hours, and rifampin, 15 mg/kg body weight per day in a single morning dose, for 45 days; 51 patients received the same dose of doxycycline for 45 days plus streptomycin, 1 g/d for 15 days.\n Therapeutic failure and relapse during the follow-up period.\n The mean time to defervescence was 4.2 days for the DR group and 3.2 days for the DS group (P greater than 0.2). The actuarial probability of therapeutic failure or relapse at 12 months of follow-up (Kaplan-Meier) was 14.4% in the DR group and 5.9% in the DS group (difference, 8.5%; 95% Cl, -4.8% to 21.6%; P greater than 0.2). All three patients with spondylitis in the DR group failed therapy compared with one of four patients in the DS group. Excluding patients with spondylitis, the actuarial failure rate was 4.9% and 4.3% in the DR and DS groups, respectively, at 12 months of follow-up (difference, 0.6%; Cl, -8.1% to 9.4%; P greater than 0.2).\n Doxycycline-rifampin combination therapy for 45 days is as effective as the classic DS combination in most patients with brucellosis; however, DR therapy might be less effective in those patients with spondylitis.", "This report describes the results of six antimicrobial regimens used for the treatment of brucellosis in an open, randomized study performed over two periods (1980-1983 and 1984-1987). In the first period, rifampicin and doxycycline were used for 4 weeks, trimethoprim-sulfamethoxazole for 6 months, and doxycycline for 6 weeks. During the second period, we used streptomycin for 2 or 3 weeks together with doxycycline for 6 weeks and rifampicin with doxycycline for 6 weeks. Comparison of the results showed the following: (1) no statistically significant findings were revealed when the different regimens were compared and (2) the regimens containing streptomycin yielded statistically more favorable results than those consisting of rifampicin and monotherapy when the patients treated with rifampicin were compared with those taking streptomycin and those receiving single-agent therapy. No significant differences were observed between monotherapeutic regimens and those including rifampicin.", "The combination therapies recommended by the World Health Organization for treatment of brucellosis are doxycycline plus rifampicin or doxycycline plus streptomycin. Although highly successful results have been obtained with these two regimens, relapse rates as high as 14.4%. The most effective and the least toxic chemotherapy for human brucellosis is still undetermined. The aim of the present study was to investigate the efficacy, adverse effects and cost of ofloxacin plus rifampicin therapy, and doxycycline plus rifampicin therapy and evaluate in the treatment of brucellosis.\n The open trial has been carried out prospectively by the two medical centers from December 1999 to December 2001 in Duzce region Turkey. The diagnosis was based on the presence of signs and symptoms compatible with brucellosis including a positive agglutination titre (>/=1/160) and/or a positive culture. Doxycycline and rifampicin group consisted of 14 patients who were given doxycycline 200 mg/day plus rifampicin 600 mg/day during 45 days and this group Ofloxacin plus rifampicin group was consisted of 15 patients who were given ofloxacin 400 mg/day plus rifampicin 600 mg/day during 30 days.\n Regarding clinical and/or demographic characteristics no significant difference was found between two groups of patients that underwent two different therapeutic regimens. At the end of the therapy, two relapses were seen in both groups (p = 0.695). Although duration of therapy was two weeks shorter in group treated with rifampicin plus ofloxacin, the cure rate was similar in both groups of examinees. Fever dropped more rapidly in the group that treated with rifampicin plus ofloxacin, 74 +/- 30 (ranges 48-216) vs. 106 +/- 26 (ranges 48-262) hours (p = 0.016).\n Ofloxacin plus rifampicin therapy has advantages of shorter treatment duration and provided shorter course of fever with treatment than in doxycycline plus rifampicin therapy. However, cost of ofloxacin plus rifampicin treatment is higher than doxycycline plus rifampicin treatment. Because of the similar effects, adverse effects and relapses rates between two regimens, we still advice doxycycline plus rifampicin for the treatment of brucellosis for countries, which have limited resources.", "To compare the efficacy of gentamicin for 5 days plus doxycycline for 8 weeks with streptomycin for 2 weeks plus doxycycline for 45 days in the treatment of human brucellosis.\n In each arm of the study, 82 patients older than 10 years randomly received 5 mg/kg gentamicin once daily for 5 days plus 100 mg of doxycycline twice daily for 8 weeks or 1 g of streptomycin intramuscularly for 2 weeks plus the same dose of doxycycline for 45 days. Therapeutic failure and relapse in these two treatment groups were compared. This study was registered in the Iranian Registry of Clinical Trials (www.irct.ir) with registration number ID: IRCT138708191441N1.\n The clinical manifestations in these two groups were similar. Therapeutic failure was seen in two (2.4%) patients in the gentamicin/doxycycline group and in four (4.9%) patients in the streptomycin/doxycycline group [relative risk (RR) = 0.5, 95% confidence interval (CI) 0.09-2.66, P = 0.68]. Relapse was seen in two (2.4%) cases in the gentamicin/doxycycline group and in five (6.1%) cases in the streptomycin/doxycycline group (RR = 0.4, 95% CI 0.08-2, P = 0.44). The efficacy with the gentamicin/doxycycline regimen was 95.12% and that with the streptomycin/doxycycline regimen was 89% (RR = 1.07, 95% CI 0.98-1.17, P = 0.25). Cox regression analyses showed no differences among the two treatment groups for patients who had relapse or therapeutic failure and those who had not regarding baseline covariates such as sex, duration of disease before diagnosis, positive blood culture and focal disease.\n The results show that the efficacy of gentamicin for 5 days plus doxycycline for 8 weeks is not superior to that of streptomycin for 2 weeks plus doxycycline for 45 days.", "The efficacy and tolerability of three different combination treatment regimens in human brucellosis were compared in 118 uncomplicated patients enrolled in a prospective study between May 1997 and December 2002. Brucellosis was diagnosed using standard clinical and microbiological findings. Patients with central nervous system involvement, spondylitis, endocarditis or children under 16 years of age were excluded from the study. Patients were randomly assigned to receive 400 mg of ofloxacin plus 600 mg of rifampicin (OR, n = 41), 200 mg of doxycycline plus 600 mg of rifampicin (DR, n = 45) or 1g intramuscularly streptomycin (administered for three weeks) plus 200 mg doxycycline (DS, n = 32) daily for 6 weeks. All patients were followed up at least 6 months after cessation of therapy. There was no statistical difference between the groups on relapse rates and clinical response to the treatment (P>0.05). Five patients in OR (12.8%), six patients in DR (14.3%) and three patients in DS groups (9.7%) suffered relapse. The side-effects were seen in eight (19.5%), 21 (46.7%) and eight (25.0%) patients of OR, DR and DS groups, respectively. The use of combination therapy of ofloxacin plus rifampicin for 6 weeks was found to be as effective as DR and DS. The side-effects of therapy in OR and DS groups was less severe than in the DR group.", "nan", "We studied the possible interaction between rifampin and doxycycline in 20 patients with brucellosis treated randomly with either doxycycline and streptomycin or doxycycline and rifampin. The doxycycline levels in the plasma of patients in the group treated with rifampin were significantly lower than those in the plasma of patients treated with doxycycline and streptomycin. Furthermore, clearance in patients treated with rifampin was significantly higher than that in patients treated with doxycycline and streptomycin, and consequently, the elimination half-life and the area under the concentration-time curve were significantly lower. There was no therapeutic failure or relapse in the group treated with doxycycline and streptomycin, whereas 2 of 10 patients in the group treated with doxycycline and rifampin had a therapeutic failure or relapse. The plasma doxycycline levels had an inverse correlation with plasma rifampin levels. In the group treated with rifampin, those who were rapid acetylators had lower levels of doxycycline. In conclusion, combined treatment with rifampin reduces the levels of doxycycline in plasma. These data suggest that therapeutic failures or relapses may result from this interaction.", "Traditional regimens for the treatment of brucellosis are associated with significant relapse rates. The aim of this study was to compare the efficacy of ofloxacin plus rifampin (OFX-RIF) versus doxycycline plus streptomycin (DOX-STR) and doxycycline plus rifampin (DOX-RIF) regimens in the treatment of brucellosis.\n Two hundred and nineteen patients with brucellosis were enrolled in a randomized clinical trial; 28 cases were withdrawn because they did not attend the follow-up. Out of 191 patients with brucellosis, 64 received OFX-RIF, 62 received DOX-RIF, and 65 patients received DOX-STR regimens. All patients were assessed during the period of therapy in the second, fourth, and sixth weeks by clinical course and were also followed up clinically and serologically for 6 months after the cessation of therapy.\n The highest clinical response (95.4%) was observed in the DOX-STR group (p=0.009). The results of multivariate analysis indicate that treatment with DOX-STR had the least therapeutic failures among the three groups (p=0.033). Adverse reactions were seen in 16.8% of patients, but there was no significant difference among the three groups (p=0.613). The lowest relapse rate (4.6%) was observed in the DOX-STR group (p=0.109).\n We conclude that the DOX-STR combination should remain the first-line regimen for the treatment of brucellosis in our region; we recommend DOX-RIF and OFX-RIF combinations as the second-line regimens.\n Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.", "nan", "Human brucellosis is usually treated with a combination of tetracyclines and aminoglycosides. However, the optimal duration of therapy has not been clearly determined.\n We conducted a prospective, double-blind, randomized, multicenter study comparing treatment with doxycycline (100 mg po b.i.d.) for 30 days (30-day group) with the same dosage of doxycycline for 45 days (45-day group) in patients with brucellosis without endocarditis, spondylitis, or neurobrucellosis. All patients were treated with gentamicin (240 mg im once daily) for the first 7 days. Therapeutic outcome was evaluated by measuring relapse rates and drug safety.\n Seventy-three patients were included in each group. During the first 45 days after treatment, the percentage of patients with relapse was significantly higher in the 30-day group than in the 45-day group (12.3% vs. 1.37%; relative risk, 9.00; 95% confidence interval [CI], 1.17-69.2; P=.017). Between day 45 after treatment and 12 months after treatment, no further significant differences were found in relapse rates between groups (9.38% in the 30-day group vs. 11.11% in the 45-day group; relative risk, 0.84; 95% CI, 0.31-2.30; P=.78). Overall, relapses occurred in 15 (20.55%) of 73 patients in the 30-day group and in 9 (12.33%) of 73 patients in the 45-day group (relative risk, 1.67; 95% CI, 0.78-3.56; P=.264). Compliance and adverse effects were comparable in the 2 groups.\n Doxycycline treatment for 45 days significantly decreased early relapse rates among adults with brucellosis without increasing adverse effects." ]

[ "17469006", "2316590", "16582128", "1769603", "7171513", "15625138", "15511760", "2789542" ]

[ "Management of severe hypertension in the postpartum period with intravenous hydralazine or labetalol: a randomized clinical trial.", "The use of nifedipine during the postpartum period in patients with severe preeclampsia.", "Effect of L-arginine therapy on the glomerular injury of preeclampsia: a randomized controlled trial.", "[Management of severe pre-eclampsia in the puerperium. Comparative study of sublingual nifedipine and hydralazine].", "A randomized study comparing timolol and methyldopa in hospital treatment of puerperal hypertension.", "Postpartum preeclampsia management with furosemide: a randomized clinical trial.", "A randomised placebo controlled trial of loop diuretics in moderate/severe pre-eclampsia, following delivery.", "Utilization of hydralazine or alpha-methyldopa for the management of early puerperal hypertension." ]

[ "To compare the safety and efficacy of intravenous labetalol and intravenous hydralazine for acutely lowering blood pressure in the puerperium.\n Randomized clinical trial.\n Critical care unit of gynecology and obstetrics department in the Complejo hospitalario \"Dr. AAM\" de la Caja de Seguro Social in Panama.\n Eighty-two women with severe hypertension during the postpartum period.\n Patients were randomized to receive hydralazine (5 mg as a slow bolus dose given intravenously, and repeated every 20 minutes to a maximum of five doses) or labetalol (20 mg in an intravenous bolus dose followed by 40 mg if not effective within 20 minutes, followed by 80 mg every 20 minutes to a maximum dose of 300 mg). The primary endpoint was the successful lowering of blood pressure. Secondary endpoints were maternal complications and side-effects.\n Forty-two women were enrolled in the hydralazine group and 40 in the labetalol group. Women were similar with respect to characteristics at randomization. No significant differences were observed for persistent severe hypertension or maternal side-effects. There was only one case of persistent severe hypertension in the labetalol group. There were no maternal deaths in any of the women studied.\n This randomized clinical trial shows that intravenous hydralazine and intravenous labetalol are effective and safe in the management of severe hypertension in the postpartum period.", "Nifedipine is a calcium channel blocker that reduces blood pressure and increases renal blood flow. This double-blind investigation evaluated the effect of nifedipine in postpartum patients with severe preeclampsia. Thirty-one patients were randomized to receive either nifedipine (10 mg) or placebo every 4 hours beginning immediately after delivery. Data analysis revealed a significantly higher urine output in the nifedipine group during the first 24 hours after delivery (3834 versus 2057 ml; p less than 0.05). A significant reduction in mean arterial pressure was also noted in the nifedipine group between 18 and 24 hours postpartum (93.9 versus 100.2 mm Hg; p less than 0.05). There were no significant differences in the systolic or diastolic blood pressures, pulse, laboratory study results, or the need to administer hydralazine to control blood pressure. Nifedipine appears to have a beneficial effect on urinary output and mean arterial pressure during the first 24 hours post partum in patients with severe preeclampsia.", "To assess the benefit of l-arginine, the precursor to nitric oxide, on blood pressure and recovery of the glomerular lesion in preeclampsia.\n Forty-five women with preeclampsia were randomized to receive either l-arginine or placebo until day 10 postpartum. Primary outcome measures including mean arterial pressure, glomerular filtration rate, and proteinuria were assessed on the third and 10th days postpartum by inulin clearance and albumin-to-creatinine ratio. Nitric oxide, cyclic guanosine 3'5' monophosphate, endothelin-1, and asymmetric-dimethyl-arginine and arginine levels were assayed before delivery and on the third and 10th days postpartum. Healthy gravid women provided control values. Assuming a standard deviation of 10 mm Hg, the study was powered to detect a 10-mm Hg difference in mean arterial pressure (alpha .05, beta .20) between the study groups.\n No significant differences existed between the groups with preeclampsia before randomization. Compared with the gravid control group, women with preeclampsia exhibited significantly increased serum levels of endothelin-1, cyclic guanosine 3'5' monophosphate, and asymmetric-dimethyl-arginine before delivery. Despite a significant increase in postpartum serum arginine levels due to treatment, no differences were found in the corresponding levels of nitric oxide, endothelin-1, cyclic guanosine 3'5' monophosphate, or asymmetric-dimethyl-arginine between the two groups with preeclampsia. Further, there were no significant differences in any of the primary outcome measures with both groups demonstrating similar levels in glomerular filtration rate and equivalent improvements in both blood pressure and proteinuria.\n Blood pressure and kidney function improve markedly in preeclampsia by the 10th day postpartum. Supplementation with l-arginine does not hasten this recovery.\n I.", "At random, two therapeutic schemes for severe preeclampsia during the puerperium, were evaluated. Group A (n = 20) was left without antihypertensive medication and sublingual nifedipine was used only in case of diastolic pressure of 110 mmHg or more. Group B (n = 18) receive Hydralazine 40 mlg. per os, every 6 hrs.; in this group also, nifedipine was administered in case of diastolic pressure of 110 mmHg or more. The only differences were that in group B the intervals for the administration of nifedipine were much shorter than in group A; also, in the same group the need for another antihypertensive was more frequent (5 of 18 vs 1 of 20 patients).", "nan", "This investigation was undertaken to estimate whether a brief postpartum course of furosemide for patients with preeclampsia benefits recovery and shortens hospitalization by enhancing diuresis, lessening severe hypertension, and reducing the need for antihypertensive therapy.\n Two hundred sixty-four patients with preeclampsia were enrolled. After spontaneous onset of postpartum diuresis and discontinuation of intravenous magnesium sulfate, patients were randomly assigned to receive either no therapy or 20 mg oral furosemide daily for 5 days with oral potassium supplementation. Patient outcomes were compared between treatment groups with regard to classification of hypertensive disease.\n Only postpartum patients with severe preeclampsia (n = 70) who received furosemide compared with controls had significantly lower systolic blood pressure by postpartum day 2 (142 +/- 13 mm Hg compared with 153 +/- 19 mm Hg, P < .004) and required less antihypertensive therapy during hospitalization (14% compared with 26%, P = .371) and at discharge (6% compared with 26%, P = .045). No benefit was shown for patients with mild preeclampsia (n = 169) or superimposed preeclampsia (n = 25). Neither length of hospitalization nor frequency of delayed postpartum complications was positively affected by the intervention.\n Brief postpartum furosemide therapy for patients with severe preeclampsia seems to enhance recovery by normalizing blood pressure more rapidly and reducing the need for antihypertensive therapy. Shortening of hospitalization and reduction of delayed postpartum complications were not benefitted.", "Nineteen patients with pre-eclampsia were randomised to receive 40 mg of frusemide or placebo by mouth daily for 7 days in the first post-partum week. Outcome measures included mean and maximum blood pressure, the need for additional antihypertensive treatment during that period and mean length of hospital stay. There were no statistically significant differences in outcome between the treatment and placebo groups although there was a trend to more rapid lowering of blood pressure following delivery in those receiving frusemide.", "Despite the importance of pregnancy-induced hypertension (PIH), there are few published investigations of therapeutic approaches for the postpartum management of such patients. Twenty-six gravida patients with PIH were prospectively studied during the first 24 hours after delivery while receiving intravenous magnesium sulfate. Each study subject was randomly assigned to a group also systemically administered either hydralazine or methyldopa. During the study interval, hourly measurements of blood pressure, pulse, fluid intake, and urine output were recorded. Hydralazine was found to be superior in its ability to effect more rapidly a lower mean arterial blood pressure. No significant differences in urine output or time until onset of diuresis were noted among treatment groups. No serious side effects were encountered with the use of either antihypertensive agent. Based on these preliminary findings, it appears that hydralazine is the less costly and more effective medication to lower mean arterial blood pressure in the immediate postpartum period." ]

[ "4336846", "10506267", "1565532", "4310467", "9200361", "11740322", "7013218", "5406220", "15231980" ]

[ "Trimethoprim-sulphamethoxazole in pertussis: comparison with tetracycline.", "A randomized, placebo-controlled trial of erythromycin estolate chemoprophylaxis for household contacts of children with culture-positive bordetella pertussis infection.", "Comparison of erythromycin estolate and erythromycin ethylsuccinate for treatment of pertussis. The Erythromycin Study Group.", "Antimicrobial treatment of pertussis.", "Seven days of erythromycin estolate is as effective as fourteen days for the treatment of Bordetella pertussis infections.", "Efficacy and safety of clarithromycin versus erythromycin for the treatment of pertussis: a prospective, randomized, single blind trial.", "[Treatment of whooping cough in newborn infants with chloramphenicol and sulfadiazine/trimethoprim].", "Comparison between the effect of chloramphenicol and ampicillin in whooping-cough.", "Azithromycin is as effective as and better tolerated than erythromycin estolate for the treatment of pertussis." ]

[ "nan", "Household contacts of patients with pertussis are at increased risk of acquiring infection. Chemoprophylaxis has been recommended to decrease transmission, particularly to young infants who are at increased risk of severe disease. Although epidemiologic investigations of outbreaks have suggested a benefit, there have been no prospective studies evaluating the efficacy of chemoprophylaxis in preventing secondary cases of pertussis.\n To determine whether erythromycin estolate chemoprophylaxis is effective in household contacts of children with culture-positive pertussis.\n Randomized, double-blind, placebo-controlled study.\n Community based.\n All household contacts of 152 children with culture-positive pertussis who provided consent (n = 362). After withdrawals, there were 135 households with 310 contacts. Exclusions included pregnancy, age <6 months, already receiving an erythromycin-containing antibiotic, and erythromycin allergy. INTERVENTUINS: Erythromycin estolate (40 mg/kg/day in 3 divided doses; maximum dose 1 g) or placebo for 10 days. Nasopharyngeal cultures, pertussis antibodies, and clinical symptoms were assessed before and after treatment.\n Measure efficacy of erythromycin estolate chemoprophylaxis calculated by the proportion of households in each group with a member who developed a nasopharyngeal culture positive for Bordetella pertussis.\n There was no difference in the development of respiratory tract symptoms compatible with a case definition of pertussis in the erythromycin- and placebo-treated groups. There were 20 households with secondary culture-positive cases of pertussis; 4 households in the erythromycin-treated group and 15 in the placebo-treated group (efficacy of erythromycin chemoprophylaxis for bacterial eradication 67.5% [95% confidence interval: 7.6-88.7]). However, medication-associated adverse reactions were reported by 34.0% of erythromycin and 15.7% of placebo recipients.\n Under the conditions of this study, erythromycin estolate prevented culture-positive pertussis in household contacts of patients with pertussis but did not prevent clinical pertussis.", "In an open randomized multicenter study 190 culture-positive pediatric ambulatory pertussis patients were treated for 14 days with either erythromycin estolate (EST) (n = 93; 40 mg/kg/day divided in 2 doses) or erythromycin ethylsuccinate (ETH) (n = 97; 60 mg/kg/day divided in 3 doses). On day 14 Bordetella pertussis was recovered from cultures of 2 patients (2.2%) treated with EST and 1 patient (1.0%) treated with ETH. Despite the fact that 151 patients (79.4%) had reached the early paroxysmal stage at initiation of antimicrobial therapy, clinical improvement was seen in the majority (reduced frequency and severity of coughing: EST, 77.4 and 67.7%; ETH, 74.2 and 63.9%, respectively). Drug-related side effects were noted in 11 patients (11.8%) treated with EST and 16 patients (16.5%) treated with ETH (P greater than 0.05) and consisted mainly of minor gastrointestinal complaints. Erythromycin estolate in a lower dose administered only twice a day was equivalent to erythromycin ethylsuccinate in all aspects and proved to be adequate antimicrobial treatment for pertussis patients.", "nan", "Although 14 days of erythromycin is recommended for the treatment of Bordetella pertussis infection, there have been no prospective controlled studies to support the contention that this long course of therapy is required to eradicate the microorganism from the nasopharynx or to prevent bacteriological relapse. We randomly allocated children and adults with culture-positive community-acquired pertussis to either 7 or 14 days of erythromycin estolate treatment (40 mg/kg/d; maximum dose 1 g/d). Nasopharyngeal aspirate cultures were obtained by study nurses during home visits before and at the end of treatment, and 1 week after the completion of treatment. B pertussis-specific antibodies were measured before treatment and 1 month later. Information about clinical symptoms, adverse reactions, and compliance were collected at each scheduled contact.\n A total of 168 participants were eligible for analysis (74 treated for 7 days and 94 treated for 14 days). Bacteriological persistence (positive end of therapy culture) occurred once in each group, and bacteriological relapse (positive culture 1 week after completion of treatment) occurred in one participant treated for 7 days. The overall failure rate (persistence plus relapse) of 2.70% in the 7-day group was not different than the rate of 1.06% in the 14-day group. The study had a power of 99.99% at the 5% level to detect a difference in failure rates of 10% and a power of 80% to detect a difference of 5%. We conclude that 7 days of erythromycin estolate is as effective as 14 days for the eradication of B pertussis.", "Pertussis is still a prevalent public health problem, and antibiotic therapy may decrease disease severity and limit communicability. Erythromycin is the recommended antibiotic for treatment and prophylaxis of pertussis; however, side effects of erythromycin limit its usefulness in some patients. Clarithromycin, a newer macrolide, has good in vitro activity against Bordetella pertussis and a better side effect profile.\n To compare the microbiologic and clinical efficacy and the clinical safety of a 7-day course of clarithromycin vs. a 14-day course of erythromycin in children with pertussis.\n Prospective, randomized, single blind (investigator), parallel group trial.\n Children from 1 month to 16 years of age presenting with a clinically defined pertussis syndrome were eligible for the study. After obtaining informed written consent, we randomized patients to receive either clarithromycin (7.5 mg/kg/dose twice a day for 7 days) or erythromycin (13.3 mg/kg/dose three times a day for 14 days). Nasopharyngeal cultures for B. pertussis were performed at enrollment and after end of treatment. Clinical assessments were performed at enrollment, at end of treatment and at a 1-month follow-up visit. Adverse event data were collected throughout the study.\n The clarithromycin (n = 76) and erythromycin (n = 77) groups were well-matched for age and previous pertussis immunization. Microbiologic eradication and clinical cure rates were 100% (31 of 31) for clarithromycin and 96% (22 of 23) for erythromycin. The clarithromycin group had significantly fewer adverse events [45% (34 of 76) for clarithromycin vs. 62% (48 of 77) for erythromycin; P = 0.035], and compliance with the medication regimen was significantly higher in these patients.\n A 7-day regimen of clarithromycin and a 14-day course of erythromycin were equally effective for treatment of pertussis. Clarithromycin was better tolerated than conventional erythromycin therapy.", "nan", "nan", "Although universal immunization against Bordetella pertussis (whooping cough) infection has resulted in dramatic reductions in the incidence of pertussis, outbreaks continue to occur in countries with excellent vaccine coverage. Treatment of infection may ameliorate symptom severity during the catarrhal phase of pertussis but has no effect on established paroxysms, emesis, or apnea if given during the paroxysmal or convalescent phases. Erythromycin, recommended for treatment of pertussis to prevent transmission of infection, is poorly tolerated because of gastrointestinal side effects. We compared the safety and efficacy of erythromycin with azithromycin for treatment of pertussis in a large, randomized, controlled trial that enrolled children from primary care practices in 1 American and 11 Canadian urban centers.\n Children who were 6 months to 16 years of age and had cough illness that was suspected to be or was culture confirmed as pertussis were randomized to azithromycin (10 mg/kg on day 1 and 5 mg/kg on days 2-5 as a single dose) or erythromycin estolate (40 mg/kg/day in 3 divided doses for 10 days) with stratification by center. The primary outcome measure was bacteriologic cure of infection as determined by cultures of nasopharyngeal aspirates. Culture-positive participants had a second aspirate collected at the end of therapy (days 5-7 for azithromycin, days 10-12 for erythromycin) and 1 week after therapy. Bacteriologic cure was defined as negative cultures at the end of therapy. Bacteriologic relapse was defined as a positive culture 1 week after completion of therapy and after a negative end-of-therapy culture. Secondary outcomes were pertussis diagnosed by serology and polymerase chain reaction (PCR), treatment-associated adverse events, compliance, and presence of clinical symptoms at the end of the treatment course. Serology was performed using standard enzyme-linked immunosorbent assay methods. A participant was considered to have pertussis when the PCR was positive or a 4-fold increase in pertussis toxin antibody between baseline and follow-up visits was observed. PCR was performed using a 1046-bp ClaI DNA fragment from B pertussis. Adverse events (nausea, vomiting, diarrhea, any gastrointestinal complaint, or other) were determined by a parent-completed diary that was reviewed with study personnel during study visits. Compliance was measured by review of the parent medication diary during study visits and observation of medication containers by the pharmacist at study completion. Symptoms were determined by history collected by study personnel at enrollment and subsequently from the diary. The design of the study was an equivalence trial, aimed at demonstrating that the bacteriologic failure rates with the 2 therapies did not differ by >8%. For the safety analysis, all participants who received at least 1 dose of study drug were included. In the per-protocol efficacy analysis, all culture-positive participants with end-of-treatment cultures were considered.\n A total of 477 children were enrolled and randomly assigned to either azithromycin (n = 239) or erythromycin (n = 238). Of these children, 114 (24%) grew B pertussis from nasopharyngeal specimens (azithromycin group: 58 of 239 [24%]; erythromycin group: 56 of 238 [23%]); these children composed the efficacy cohort for the per-protocol and intention-to-treat analyses. Serology and PCR added 52 children to the number considered to have pertussis for a total of 35% (166 of 477) of all children who presented with cough illness. In the safety analysis (antibiotic side effects, compliance) and comparison of cough symptoms after treatment, all randomized children are reported in their assigned treatment group. At end of therapy, bacterial eradication was demonstrated in all 53 patients in the azithromycin group and all 53 patients in the erythromycin group with follow-up cultures available (eradication 100%; 95% confidence interval [CI]: 93.3-100). No bacterial recurrence was demonstrated in children with 1 week posttreatment nasopharyngeal cultures available (51 and 53 participants in the azithromycin and erythromycin arms, respectively [0%, 95% CI: 0-7.0; and 0%, 95% CI: 0-6.7]). No serious adverse events attributable to study drug were observed. Gastrointestinal adverse events were reported less frequently in azithromycin (18.8%; 45 of 239) than in erythromycin estolate (41.2%; 98 of 238) recipients (90% CI on difference: -29.0% to -15.7%) as a result of less nausea (2.9% vs 8.4%; 95% CI: -8.9% to -2.0%), less vomiting (5.0% vs 13.0%; 95% CI: -4.9% to -1.4%), and less diarrhea (7.1% vs 11.8%; 95% CI: -9.0% to -0.3%). Children who were randomized to azithromycin were much more likely to have complied with antimicrobial therapy over the treatment period. In the azithromycin group, 90% of children took 100% of prescribed doses, whereas only 55% of children in the erythromycin group took 100% of prescribed doses.\n In this large, multicenter, randomized trial, we found that azithromycin is as effective as erythromycin estolate for the treatment of pertussis in children. Gastrointestinal adverse events were much more common with erythromycin treatment than azithromycin. Compliance with therapy was markedly better with azithromycin than with erythromycin in this study." ]

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[ "A randomised controlled trial of senior Lay Health Mentoring in older people with ischaemic heart disease: The Braveheart Project.", "Behavior therapy for families of adolescents with diabetes: maintenance of treatment effects.", "Compliance therapy: a randomised controlled trial in schizophrenia.", "Pharmacist telemonitoring of antidepressant use: effects on pharmacist-patient collaboration.", "Do automated calls with nurse follow-up improve self-care and glycemic control among vulnerable patients with diabetes?", "Use of multisystemic therapy to improve regimen adherence among adolescents with type 1 diabetes in chronic poor metabolic control: a randomized controlled trial.", "Caring for poorly controlled diabetes mellitus: a randomized pharmacist intervention.", "Promoting adherence: effects of theory-based asthma education.", "A randomized trial of relapse prevention of depression in primary care.", "Nurse management for hypertension. A systems approach.", "Influence on asthma morbidity of asthma education programs based on self-management plans following treatment optimization.", "The role of the asthma nurse in treatment compliance and self-management following hospital admission.", "Improving adherence to malaria treatment for children: the use of pre-packed chloroquine tablets vs. chloroquine syrup.", "Compliance therapy in psychotic patients: randomised controlled trial.", "Randomised controlled trial of compliance therapy. 18-month follow-up.", "Self-recording of blood pressure in the management of hypertension.", "Effect of antidepressant drug counselling and information leaflets on adherence to drug treatment in primary care: randomised controlled trial.", "How does patient education and self-management among asthmatics and patients with chronic obstructive pulmonary disease affect medication?", "Improvement of medication compliance in uncontrolled hypertension.", "[Efficacy of an intervention to improve treatment compliance in hyperlipidemias].", "Efficacy of an educational and counseling intervention on adherence to highly active antiretroviral therapy: French prospective controlled study.", "Telephone follow-up of patients receiving antibiotic prescriptions from community pharmacies.", "Adherence to antiretroviral therapy in HIV-infected pediatric patients improves with home-based intensive nursing intervention.", "Effects of patient education on compliance with basic treatment regimens and health in recent onset active rheumatoid arthritis.", "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.", "Randomised clinical trial of strategies for improving medication compliance in primary hypertension.", "Effectiveness of pharmacist care for patients with reactive airways disease: a randomized controlled trial.", "Effectiveness of the direct observation component of DOTS for tuberculosis: a randomised controlled trial in Pakistan.", "An intervention programme using the ASE-model aimed at enhancing adherence in adolescents with asthma.", "A comparison of enalapril 20 mg once daily versus 10 mg twice daily in terms of blood pressure lowering and patient compliance.", "Patient and relative education in community psychiatry: a randomized controlled trial regarding its effectiveness.", "A randomized study of serial telephone call support to increase adherence and thereby improve virologic outcome in persons initiating antiretroviral therapy.", "Prospective randomized two-Arm controlled study to determine the efficacy of a specific intervention to improve long-term adherence to highly active antiretroviral therapy.", "Asthma self-management: do patient education programs always have an impact?", "Efficacy of telephone and mail intervention in patient compliance with antihypertensive drugs in hypertension. ETECUM-HTA study.", "Efficacy of a home blood pressure monitoring programme on therapeutic compliance in hypertension: the EAPACUM-HTA study.", "Effect of counseling to improve compliance in Mexican women receiving depot-medroxyprogesterone acetate.", "Family-based intervention for schizophrenic patients in China. A randomised controlled trial.", "Evaluation of two different educational interventions for adult patients consulting with an acute asthma exacerbation.", "Pharmaceutical care of patients with heart failure.", "A randomized trial to improve self-management practices of adults with asthma.", "A randomized controlled evaluation of specialist nurse education following accident and emergency department attendance for acute asthma.", "Penicillin treatment of streptococcal pharyngitis. A comparison of schedules and the role of specific counseling.", "Group discussions with parents have long-term positive effects on the management of asthma with good cost-benefit.", "Couple-focused support to improve HIV medication adherence: a randomized controlled trial.", "The effect of ED prescription dispensing on patient compliance.", "A telecommunications system for monitoring and counseling patients with hypertension. Impact on medication adherence and blood pressure control.", "The role of patient training in the management of seasonal rhinitis and asthma: clinical implications.", "[Adherence to very active antiretroviral treatment: impact of individualized assessment].", "A programmable prompting device improves adherence to highly active antiretroviral therapy in HIV-infected subjects with memory impairment.", "Effectiveness of psychoeducational intervention for rural Chinese families experiencing schizophrenia--a randomised controlled trial.", "A study of efficacy, tolerance and compliance of once-daily versus twice-daily metoprolol (Betaloc) in hypertension. Betaloc Compliance Canadian Cooperative Study Group.", "A cluster randomized trial comparing two interventions to improve treatment of major depression in primary care.", "Impact of an educational program on efficacy and adherence with a twice-daily lamivudine/zidovudine/abacavir regimen in underrepresented HIV-infected patients.", "Does patient education cause side effects? A controlled trial.", "A randomized trial of special packaging of antihypertensive medications.", "A randomised trial of strategies to improve patient compliance with anticonvulsant therapy.", "Impact of pharmacist-conducted home visits on the outcomes of lipid-lowering drug therapy.", "Effect of a pharmacy care program on medication adherence and persistence, blood pressure, and low-density lipoprotein cholesterol: a randomized controlled trial.", "Management of Helicobacter pylori eradication--the influence of structured counselling and follow-up.", "A pharmacy discharge plan for hospitalized elderly patients--a randomized controlled trial.", "Education and telephone case management for children with type 1 diabetes: a randomized controlled trial.", "Informing patients about tardive dyskinesia. Controlled trial of patient education.", "Better maintained adherence on switching from twice-daily to once-daily therapy for HIV: a 24-week randomized trial of treatment simplification using stavudine prolonged-release capsules.", "Effects of a treatment adherence enhancement program on health literacy, patient-provider relationships, and adherence to HAART among low-income HIV-positive Spanish-speaking Latinos.", "Nurse-led adherence support in hypertension: a randomized controlled trial.", "Enhancing compliance not a prerequisite for effective eradication of Helicobacter pylori: the HelP Study.", "A randomized controlled trial to enhance antiretroviral therapy adherence in patients with a history of alcohol problems.", "Pharmaceutical care research and education project: patient outcomes.", "Helicobacter pylori eradication in dyspeptic primary care patients: a randomized controlled trial of a pharmacy intervention.", "Compliance and stability of INR of two oral anticoagulants with different half-lives: a randomised trial.", "Effect of individual cognitive behaviour intervention on adherence to antiretroviral therapy: prospective randomized trial.", "Effect of patient education on adherence to drug treatment for rheumatoid arthritis: a randomised controlled trial." ]

[ "to examine the effects and feasibility of educating and empowering older people with ischaemic heart disease using trained senior lay health mentors.\n randomised controlled trial with blinded evaluation.\n Falkirk and District Royal Infirmary. Participants: inpatients and outpatients aged 60 or over attending secondary care with a diagnosis of angina or acute myocardial infarction. Three-hundred and nineteen entered and 289 completed exit assessments. The intervention group took part in mentoring groups for 1 year, meeting monthly for 2 hours, each led by two trained lay health mentors in addition to standard care.\n primary outcome measures were changes in coronary risk factors, medication usage and actual use of secondary care health services. Secondary outcomes were total and cardiovascular events; changes in medication compliance, non-medical support requirement, health status and psychological functioning, and social inclusion.\n there were significant improvements in a reported current exercise score (mean +0.33, +0.02 to +0.52), in the average time spent walking per week by 72 minutes (+1 to +137 minutes), and in the SF36 Physical Functioning Score (+6.1, +2.4 to +9.5). There was a 1.0% reduction in total fat (95% CI -3.0% to -0.6%) and a 0.6% reduction in saturated fat (95% CI -1.5% to -0.03%). The intervention group showed reduced outpatient attendance for coronary heart disease (-0.25 appointments, -0.61 to -0.08). Attendance rates were high. Socio-economic grouping did not affect participation.\n Lay Health Mentoring is feasible, practical and inclusive, positively influencing diet, physical activity, and health resource utilisation in older subjects with ischaemic heart disease without causing harm.", "This study reports 6- and 12-month follow-up for the families of adolescents with diabetes who participated in a trial of Behavioral-Family Systems Therapy (BFST).\n A total of 119 families of adolescents with type 1 diabetes were randomized to 3 months of treatment with either BFST, an education and support (ES) group, or current therapy (CT). Family relationships, adjustment to diabetes, treatment adherence, and diabetic control were assessed at baseline, after 3 months of treatment, and 6 and 12 months later. This report focuses on the latter two evaluations.\n Compared with CT and ES, BFST yielded lasting improvements in parent-adolescent relationships and diabetes-specific conflict. Delayed effects on treatment adherence emerged at 6- and 12-month follow-ups. There were no immediate or delayed effects on adolescents' adjustment to diabetes or diabetic control.\n BFST yielded lasting improvement in parent-adolescent relationships and delayed improvement in treatment adherence, but it had no effect on adjustment to diabetes or diabetic control. A variety of adaptations to BFST could enhance its impact on diabetes outcomes.", "To evaluate the efficacy of \"compliance therapy\" for improving adherence to prescribed drug treatment among patients with schizophrenia.\n Randomised controlled trial.\n Urban catchment area psychiatric service.\n 94 consecutive admissions of patients with schizophrenia, 56 agreed to participate.\n Compliance therapy and non-specific counselling, each consisting of 5 sessions lasting 30-60 minutes.\n Compliance with drug treatment at one year; attitudes to treatment, symptomatology, insight, and quality of life at one year; length of \"survival\" in the community, bed days, and rehospitalisation rates at two years.\n Compliance therapy did not confer a major advantage over non-specific therapy in improving compliance at one year (43% (12/28) v 54% (15/28), difference -11% (95% confidence interval -37% to 15%) or in any of the secondary outcome measures-symptomatology, attitudes to treatment, insight, global assessment of functioning, and quality of life.\n Compliance therapy may not be of benefit to patients with schizophrenia. Attitudes to treatment at baseline predicted adherence one year later and may be a clinically useful tool.", "To explore the impact of telephone-based education and monitoring by community pharmacists on multiple outcomes of pharmacist-patient collaboration.\n A randomized, controlled, unblinded, mixed experimental design.\n Eight Wisconsin community pharmacies within a large managed care organization.\n A total of 63 patients presenting new antidepressant prescriptions to their community pharmacies.\n Patients were randomized to receive either three monthly telephone calls from pharmacists providing pharmacist-guided education and monitoring (PGEM) or usual pharmacist's care. Usual care is defined as that education and monitoring which pharmacists may typically provide patients at the study pharmacies.\n Patient's frequency of feedback with the pharmacist, antidepressant knowledge, antidepressant beliefs, antidepressant adherence at 3 and 6 months, improvement in depression symptoms, and orientation toward treatment progress.\n Of the 60 patients who completed the study, 28 received PGEM and 32 received usual pharmacist's care. Results showed that PGEM had a significant and positive effect on patient feedback, knowledge, medication beliefs, and perceptions of progress. There were no significant group differences in patient adherence or symptoms at 3 months; however, PGEM patients who completed the protocol missed fewer doses than did the usual care group at 6 months (P < or = .05).\n Antidepressant telemonitoring by community pharmacists can significantly and positively affect patient feedback and collaboration with pharmacists. Longer-term studies with larger samples are needed to assess the generalizability of findings. Future research also needs to explore additional ways to improve clinical outcomes.", "We sought to evaluate the effect of automated telephone assessment and self-care education calls with nurse follow-up on the management of diabetes.\n We enrolled 280 English- or Spanish-speaking adults with diabetes who were using hypoglycemic medications and who were treated in a county health care system. Patients were randomly assigned to usual care or to receive an intervention that consisted of usual care plus bi-weekly automated assessment and self-care education calls with telephone follow-up by a nurse educator. Outcomes measured at 12 months included survey-reported self-care, perceived glycemic control, and symptoms, as well as glycosylated hemoglobin (Hb A1c) and serum glucose levels.\n We collected follow-up data for 89% of enrollees (248 patients). Compared with usual care patients, intervention patients reported more frequent glucose monitoring, foot inspection, and weight monitoring, and fewer problems with medication adherence (all P -0.03). Follow-up Hb A,, levels were 0.3% lower in the intervention group (P = 0.1), and about twice as many intervention patients had Hb A1c levels within the normal range (P = 0.04). Serum glucose levels were 41 mg/dL lower among intervention patients than usual care patients (P = 0.002). Intervention patients also reported better glycemic control (P = 0.005) and fewer diabetic symptoms (P <0.0001 ), including fewer symptoms of hyperglycemia and hypoglycemia.\n Automated calls with telephone nurse follow-up may be an effective strategy for improving self-care behavior and glycemic control, and for decreasing symptoms among vulnerable patients with diabetes.", "The aim of this study was to determine whether multisystemic therapy (MST), an intensive, home-based psychotherapy, could improve adherence and metabolic control and decrease rates of hospital utilization among adolescents with chronically poorly controlled type 1 diabetes.\n A randomized controlled trial was conducted with 127 adolescents with type 1 diabetes and chronically poor metabolic control (HbA(1c) [A1C] > or =8% for the past year) who received their diabetes care in a children's hospital located in a major Midwestern city. Participants randomly assigned to MST received treatment for approximately 6 months. Data were collected at baseline and at 7 months posttest (i.e., treatment termination). Changes in A1C adherence, as measured by semistructured interviews and blood glucose meters and hospital admissions and emergency department visits, were assessed.\n In intent-to-treat analyses, participation in MST was associated with significant improvements in the frequency of blood glucose testing as assessed by blood glucose meter readings (F[1,125] = 16.75, P = 0.001) and 24-h recall interviews (F[1,125] = 6.70, P = 0.011). Participants in MST also had a decreasing number of inpatient admissions, whereas the number of inpatient admissions increased for control subjects (F[1,125] = 6.25, P = 0.014). Per protocol analyses replicated intent-to-treat analyses but also showed a significant improvement in metabolic control for adolescents receiving MST compared with control subjects (F[1,114] = 4.03, P = 0.047).\n Intensive, home-based psychotherapy improves the frequency of blood glucose testing and metabolic control and decreases inpatient admissions among adolescents with chronically poorly controlled type 1 diabetes.", "There is limited information from randomized controlled studies about the influence of pharmacist interventions on diabetes control.\n To evaluate the effect of a pharmacist intervention on improving diabetes control; secondary endpoints were medication appropriateness and self-reported adherence.\n A randomized, controlled, multi-clinic trial was conducted in the University of Washington Medicine Neighborhood Clinics. Seventy-seven subjects, > or =18 years old with a hemoglobin (Hb) A(1c) > or =9% at baseline and taking at least one oral diabetes medication, were randomized to receive a pharmacist intervention (n = 43) or usual care (n = 34) for 6 months followed by a 6-month usual-care observation period for both groups. Subjects met with a clinical pharmacist to establish and initiate a diabetes care plan followed by weekly visits or telephone calls to facilitate diabetes management and adherence. HbA(1c), medication appropriateness, and self-reported adherence were assessed at baseline, 6 months, and 12 months.\n The mean HbA(1c) did not differ between groups over the 12-month period (p = 0.61). A reduction in HbA(1c) was noted for both groups over time compared with baseline (p = 0.001); however, control subjects relied more heavily on provider visits. Medication appropriateness was not improved for diabetes medications (p = 0.65). Self-reported adherence was not significantly improved by the intervention.\n This pharmacist intervention did not significantly improve diabetes control, but did allow for similar HbA(1c) control with fewer physician visits. Medication appropriateness and self-reported adherence compared with usual care in individuals with poorly controlled diabetes were not changed.", "This study compared the effects of a theoretically focused audiotape and a standard educational booklet on asthma preventive medication adherence and other asthma outcomes. Forty-six adult asthmatics were randomly assigned to receive either an experimental audiotape incorporating components of protection motivation theory, a standard asthma management booklet, both, or no educational materials. Outcomes were assessed at baseline, 3 months, and 6 months. Mean pharmacy-verified adherence improved 15% to 19% in the intervention groups and declined 22% in the control group at 6 months. Using analysis of covariance (ANCOVA) to control for baseline adherence, these changes were significant between the control and booklet group (t = 2.47; p = .02) and between control and combined group (t = 2.07; p = .04). Providing a minimal educational intervention can have a beneficial effect on asthma medication adherence that persists at least 6 months.", "Despite high rates of relapse and recurrence, few primary care patients with recurrent or chronic depression are receiving continuation and maintenance-phase treatment. We hypothesized that a relapse prevention intervention would improve adherence to antidepressant medication and improve depression outcomes in high-risk patients compared with usual primary care.\n Three hundred eighty-six patients with recurrent major depression or dysthymia who had largely recovered after 8 weeks of antidepressant treatment by their primary care physicians were randomized to a relapse prevention program (n = 194) or usual primary care (n = 192). Patients in the intervention group received 2 primary care visits with a depression specialist and 3 telephone visits over a 1-year period aimed at enhancing adherence to antidepressant medication, recognition of prodromal symptoms, monitoring of symptoms, and development of a written relapse prevention plan. Follow-up assessments were completed at 3, 6, 9, and 12 months by a telephone survey team blinded to randomization status.\n Those in the intervention group had significantly greater adherence to adequate dosage of antidepressant medication for 90 days or more within the first and second 6-month periods and were significantly more likely to refill medication prescriptions during the 12-month follow-up compared with usual care controls. Intervention patients had significantly fewer depressive symptoms, but not fewer episodes of relapse/recurrence over the 12-month follow-up period.\n A relapse prevention program targeted to primary care patients with a high risk of relapse/recurrence who had largely recovered after antidepressant treatment significantly improved antidepressant adherence and depressive symptom outcomes.", "Standard office-based approaches to controlling hypertension show limited success. Such suboptimal hypertension control reflects in part the absence of both an infrastructure for patient education and frequent, regular blood pressure (BP) monitoring. We tested the efficacy of a physician-directed, nurse-managed, home-based system for hypertension management with standardized algorithms to modulate drug therapy, based on patients' reports of home BP.\n We randomized outpatients requiring drug therapy for hypertension according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) criteria to receive usual medical care only (UC, n = 76) or usual care plus nurse care management intervention (INT, n = 74) over a 6-month period.\n Patients receiving INT achieved greater reductions in office BP values at 6 months than those receiving UC: 14.2 +/- 18.1 versus 5.7 +/- 18.7 mm Hg systolic (P < .01) and 6.5 +/- 10.0 versus 3.4 +/- 7.9 mm Hg diastolic, respectively (P < .05). At 6 months, we observed one or more changes in drug therapy in 97% of INT patients versus 43% of UC patients, and 70% of INT patients received two or more drugs versus 46% of UC. Average daily adherence to medication, measured by electronic drug event monitors, was superior among INT subjects (mean +/- SD, 80.5% +/- 23.0%) than among UC subjects (69.2 +/- 31.1%; t(113) = 2.199, P = .03). There were no significant adverse drug reactions in either group.\n Telephone-mediated nurse management can successfully address many of the systems-related and patient-related issues that limit pharmacotherapeutic effectiveness for hypertension.", "The objective of this study was to evaluate the effectiveness of an asthma education program on morbidity, knowledge, and compliance with inhaled corticosteroid treatment using a prospective, randomized, controlled, one-year-before/one-year-after protocol. After rigorous optimization of asthma therapy under the care of respirologists, patients were assigned to one of three groups: Group C (control group: no formal education), Group P (education and action plan based on peak-flow monitoring), and Group S (education with action plan based on monitoring of asthma symptoms). A total of 188 subjects with moderate to severe asthma were enrolled and 149 completed the study. Asthma morbidity decreased significantly in all groups (p = 0.001). Mean values one-year-before/one-year-after in Groups C, P, and S were: unscheduled medical visits, 2.4/0.8, 2.3/0.7, and 1.9/ 0.7; hospitalizations, 0.21/0.04, 0.24/0.04, and 0.40/0.09; oral steroid treatments; 1.3/0.5, 1.2/0.7, and 1.3/0.9; absenteeism from work/school, 9.6/5.2, 8.8/2.2, and 6.3/2.9. Between-group differences did not reach statistical significance (p > 0.05). Asthma knowledge increased in both educated groups compared with the control group (p < 0.001) as did short-term compliance with inhaled corticosteroids. These results confirm that treatment optimization coupled with sustained high quality care in motivated patients can lead to a significant decrease in asthma morbidity. In such clinical settings, structured asthma education significantly improved short-term compliance with treatment and knowledge about asthma, although it could not add extra benefit with regard to morbidity. Nevertheless, this study does not refute the potential benefit of educational interventions aimed at improving asthma-related morbidity over a longer time period or in patients with less optimal care or with high-risk factors.", "Effective self-management and treatment compliance is important in achieving good symptom control in asthma. The aim of this study was to determine whether asthma nurse intervention during hospital admission could increase knowledge and improve self-management and whether this would influence the number of emergency call-out visits by Genera Practitioners (GPs) and hospital re-admissions. Patients with acute asthma (n=80) were assessed by the asthma nurse within 24 h of admission using a British Thoracic Society (BTS) guideline-based questionnaire. Main outcome measures were: know edge of inhalers, self-management plans, peak flow monitoring, recognition of worsening symptoms and appropriate emergency action, Following randomization, half received nurse intervention during hospitalization. All received a follow-up questionnaire 6 weeks post-discharge and again at 6 months (response rates 86% and 81% respectively). GPs were contacted by postal questionnaire after 4 months. Questionnaire responses indicated an increase in knowledge in the intervention group, along with an ability to identify appropriate action on worsening symptoms. Emergency GP call-outs were more frequent in the control group in the 4 months post-discharge. Hospital re-admission rates were similar in both groups. Asthma nurse intervention appeared to increase knowledge of asthma management, maintained throughout the study period, but had no significant impact on reducing re-admissions to hospital.", "Malaria is a major cause of morbidity and mortality among children under five in sub-Saharan Africa. Prompt diagnosis and adequate treatment of acute clinical episodes are essential to reduce morbidity and prevent complications and mortality. In many countries, chloroquine syrup is the mainstay of malaria treatment for children under five. Not only is syrup more expensive than tablets, adherence to the prescribed dose at home is a problem because mothers use wrongly sized measuring devices or have difficulty with the instructions. We investigated the impact of introducing pre-packed tablets for children on adherence to treatment and compared the total cost of the tablets with that of syrup. Children aged 0--5 years diagnosed with malaria at the clinic over a 6-week period received either pre-packed tablets or syrup by random assignment. The principal caregivers were interviewed at home on day 4 after attending the clinic. Of the 155 caregivers given pre-packed tablets, 91% (n=141) adhered to the recommended dosage, while only 42% (n=61) of 144 who were provided syrup did. Only 20% of caregivers who received syrup used an accurate 5 ml measure. The cost of treatment with tablets was about one-quarter that of syrup and 62% (n=96) of caregivers preferred tablets. Pre-packed chloroquine tablets are a viable alternative to syrup.", "To determine whether compliance therapy, a cognitive-behavioural intervention, could improve compliance with treatment and hence social adjustment in acutely psychotic inpatients, and if so, whether the effect persisted six months later.\n Randomised controlled trial of compliance therapy and non-specific counselling, each comprising 4-6 sessions lasting 10-60 minutes.\n Acute psychiatric admissions ward serving an inner London catchment area.\n 47 patients with psychosis.\n Informant and observer reported measure of compliance; observer assessed global functioning after intervention and three and six months later; self-rated attitudes to drug treatment after the intervention and one month later; symptom scores after intervention and six months later.\n 25 patients received compliance therapy and showed significantly greater improvements in their attitudes to drug treatment and in their insight into illness and compliance with treatment compared with the control group. These gains persisted for six months. The intervention group was 5.2 times more likely than the control group to reach a criterion level of compliance (95% confidence interval 1.5 to 18.3). Global functioning showed a tendency to improve more in the intervention group after a delay (odds ratio 3.0 (0.8 to 11.5) to reach the criterion level at six months). Four subjects given compliance therapy and six in the control group were readmitted during follow up (odds ratio 2.0 (0.48 to 8.2)).\n Compliance therapy is a pragmatic method for improving compliance with drug treatment in psychotic inpatients and its gains persist for at least six months. Overall functioning may also be enhanced.", "A randomised controlled trial was conducted in an acute treatment setting to examine the effectiveness of compliance therapy, a brief pragmatic intervention targeting treatment adherence in psychotic disorders, based on motivational interviewing and recent cognitive approaches to psychosis.\n Seventy-four patients with psychotic disorders according to DSM-III-R criteria recruited from consecutive admissions to an acute in-patient unit, received 4-6 sessions of either compliance therapy or non-specific counselling, and were followed-up over 18 months. The principal outcome measures were observer-rated compliance, attitudes to treatment, insight and social functioning.\n Significant advantages were found for the compliance therapy group post-treatment on measures of insight, attitudes to treatment and observer-rated compliance which were retained over the follow-up period. Global social functioning improved relatively more over time in the compliance therapy group compared with the control group. Survival in the community prior to readmission was significantly longer in the compliance therapy group.\n The results support the effectiveness of compliance therapy in improving functioning and community tenure after an acute psychotic episode.", "The efficacy of self-recording of blood pressure in the management of hypertension was assessed in a randomized clinical trial involving 140 persons who had been receiving antihypertensive therapy for a year or more, but whose diastolic blood pressure had remained at 95 mm Hg or higher. To control for the increased attention implicit in self-recording, which might affect blood pressure, the patients were assigned at random to one of the four groups: self-recording and monthly home visits, self-recording only, monthly home visits only, and neither self-recording nor monthly home visits. This design also permitted assessment of the effect of home visits. During the 6-month experiment no significant differences were apparent between the groups in either compliance or diastolic blood pressure. However, both self-recording and monthly home visits produced a reduction in blood pressure among patients who admitted to difficulty remembering to take their pills; a reduction was not seen among patients who said they had no such difficulty. This confirmed an earlier observation suggesting that this easily identified group of patients may be the most responsive to intervention programs.", "To evaluate two different methods of improving adherence to antidepressant drugs.\n Factorial randomised controlled single blind trial of treatment leaflet, drug counselling, both, or treatment as usual.\n Primary care in Wessex\n 250 patients starting treatment with tricyclic antidepressants.\n Adherence to drug treatment (by confidential self report and electronic monitor); depressive symptoms and health status.\n 66 (63%) patients continued with drugs to 12 weeks in the counselled group compared with 42 (39%) of those who did not receiving counselling (odds ratio 2.7, 95% confidence interval 1.6 to 4.8; number needed to treat=4). Treatment leaflets had no significant effect on adherence. No differences in depressive symptoms were found between treatment groups overall, although a significant improvement was found in patients with major depressive disorder receiving drug doses of at least 75 mg (depression score 4 (SD 3.7) counselling v 5.9 (SD 5.0) no counselling, P=0.038).\n Counselling about drug treatment significantly improved adherence, but clinical benefit was seen only in patients with major depressive disorder receiving doses >/=75 mg. Further research is required to evaluate the effect of this approach in combination with appropriate targeting of treatment and advice about dosage.", "The effect of patient education on steroid inhaler compliance and rescue medication utilization in patients with asthma or chronic obstructive pulmonary disease (COPD) has not been previously investigated in a single study. We randomized 78 asthmatics and 62 patients with COPD after ordinary outpatient management. Intervention consisted of two 2-h group sessions and 1 to 2 individual sessions by a trained nurse and physiotherapist. A self-management plan was developed. We registered for 12 mo medication dispensed from pharmacies according to the Anatomical Therapeutic Chemical (ATC) classification index. Steroid inhaler compliance (SIC) was defined as (dispensed/prescribed) x 100 and being compliant as SIC > 75%. Among asthmatics 32% and 57% were compliant (p = 0.04) with a median (25th/75th percentiles) SIC of 55% (27/96) and 82% (44/127) (p = 0.08) in the control and intervention groups, respectively. Patient education did not seem to change SIC in the COPD group. Uneducated patients with COPD were dispensed double the amount of short-acting inhaled beta(2)-agonists compared with the educated group (p = 0.03). We conclude that patient education can change medication habits by reducing the amount of short-acting inhaled beta(2)-agonists being dispensed among patients with COPD. Educated asthmatics showed improved steroid inhaler compliance compared with the uneducated patients, whereas this seemed unaffected by education in the COPD group.", "38 hypertensive Canadian steelworkers who were neither compliant with medications nor at goal diastolic blood-pressure six months after starting treatment were allocated either to a control group or to an experimental group who were taught how to measure their own blood-pressures, asked to chart their home blood-pressures and pill taking, and taught how to tailor pill taking to their daily habits and rituals; these men were also seen fortnightly by a highschool graduate with no formal health professional training who reinforced the experimental manoeuvres and rewarded improvements in compliance and blood-pressure. Six months later, average compliance had fallen by 1.5% in the control group but rose 21.3% in the experimental group. Blood-pressures fell in 17 of 20 experimental patients (to goal in 6) and in 10 of 18 control patients (to goal in 2).", "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.", "The objective was to evaluate the impact of an intervention for improving adherence to antiretroviral therapies (HAART) in HIV-infected patients.\n We designed a prospective, controlled, randomized trial to assess the impact of an educational and counseling intervention in addition to standard of care. At M0, the study enrolled 244 HAART-treated patients who attended a medical consultation between September and December 1999 who were not included in another protocol. Patients in the intervention group (IG) were offered three individual sessions by trained nurses. The proportions of adherent patients at 6 months followup (M6) and the change in HIV RNA between M0 and M6 were measured.\n Between M0 and M6, HIV RNA significantly decreased in the 123 patients of the IG (mean difference = -0.22 log [+/-0.86], p =.013), while it increased (+0.12 log [+/-0.90], p =.14) in the 121 patients of the control group. However, the proportion of patients with HIV RNA <40 copies/mL remained similar in both groups. In an intent-to-treat analysis, the only significant predictor of 100% adherence at M6 was the intervention group (p =.05) after adjustment for baseline adherence (p =.001). Among the 202 patients with available data on adherence, the proportion of adherent patients was similar in both groups at M0 (58% vs. 63%, p =.59) but became higher in the IG at M6 (75% vs. 61%, p =.04).\n The educational and counseling intervention was efficient for increasing adherence to HAART and could be implemented in most clinical settings.", "The impact of a community pharmacist telephone follow-up intervention (PTFI) on clinical outcomes, pharmaceutical care, and costs for patients undergoing antibiotic treatment was studied.\n Patients receiving usual pharmacist intervention (UPI) were compared with PTFI patients in a multicenter, randomized, controlled trial.\n Compared with the UPI group (n = 129), the PTFI group (n = 126) had more drug-related problems (DRPs) (PTFI = 53%, UPI = 8%; p < 0.001). Oral recommendations (PTFI = 52%, UPI = 6%; p < 0.001), as well as recognized (PTFI = 10%, UPI = 2%; p = 0.015) and study-specific (PTFI = 5%, UPI = 1%; p = 0.064) pharmaceutical advices, were issued for more patients. The mean difference in the change in the number of infectious symptoms between the two groups (-0.24 symptom, 95% confidence interval [CI] = -1.22 to 0.74) and the change in the infection severity score (mean difference = -0.05 unit, 95% CI = -0.35 to 0.25) were small and not statistically significant. Adherence to treatment and patient satisfaction did not differ across the two intervention groups. The incremental direct costs of the PTFI varied from $2.65 to $5.11 (Canadian dollars) per patient, depending on whether cognitive services were reimbursed.\n A telephone follow-up by community pharmacists during antibiotic therapy was simple and quick and created opportunities to intervene with patients, but it did not create a greater change in the number of infectious symptoms or the infection severity score than did usual care.", "Adherence to combination antiretroviral therapy (ART) has been shown to be a determining factor in controlling viral replication, maintaining immunologic function and long-term survival in HIV-positive individuals. Little information is available on strategies to improve adherence in pediatric HIV-infected patients. We conducted a randomized, nonblinded, pilot study to determine if a home-based nursing intervention would improve medication adherence. The study was offered to all eligible HIV-positive patients receiving care at Connecticut Children's Medical Center's (CCMC) Pediatric and Youth HIV Program. Sixty-seven percent (37/55) of the patients and their caretakers participated. We randomized participants to either standard of care or the intervention trial. The intervention was designed to improve knowledge and understanding of HIV infection and HIV medications and to resolve or modify barriers to adherence. Both groups completed pre- and post-intervention questionnaires, assessing their knowledge and understanding of HIV, ART, and adherence. Adherence was estimated objectively from medication refill history and subjectively from a self-report score. We also inferred adherence from pre- to post-test plasma viral load and CD4+ T-cell percentages. The knowledge score (p = 0.02) and medication refill history (p = 0.002) improved significantly in the intervention group. The adherence self-report score improved, although not significantly (p = 0.07). We did not observe statistical differences in CD4+ T-cell counts or viral load between groups. We conclude that our home-based nursing intervention helped HIV-positive children and their families in better adhering to prescribed medication regimens.", "To determine the effects of patient education on compliance and on health in patients with active, recent onset rheumatoid arthritis (RA).\n A randomised, controlled, assessor blinded, one year trial. The experimental group followed an education programme. All patients started on sulphasalazine therapy. Compliance with sulphasalazine was measured by pill counting. Compliance rates with regimens of physical exercise, endurance activities, and energy conservation were measured by questionnaires. Compliance with prescriptions of joint protection was scored using a test for joint protection performance. Health was measured by a Disease Activity Score (function of erythrocyte sedimentation rate, Ritchie score, and number of swollen joints), C reactive protein, Dutch-AIMS scores, and M-HAQ scores, range of motion of shoulder, elbow, and knee joints. Parameters were scored at baseline and after three, six, and 12 months.\n Sixty of 65 patients gave informed consent, five of them withdrew from follow up. Compliance with sulphasalazine exceeded 80% with no differences between groups. Compliance with physical exercise (at three months), energy conservation (at three and at 12 months), and joint protection (at three months) improved significantly more in the experimental group. The improvements of health were not different in the groups.\n Compliance with sulphasalazine among patients with active, recent onset RA is high, whether formal patient education is followed or not. Compliance with physical exercise, energy conservation, and joint protection was increased by patient education. Formal patient education did not improve health status.", "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.", "230 Canadian steelworkers with hypertension took part in a randomised trial to see if compliance with antihypertensive drug regimens could be improved. For care and follow-up these men were randomly allocated to see either their own family doctors outside working-hours or industrial physicians during work shifts; the same men were randomly allocated to receive or not receive an educational programme aimed at instructing them about hypertension and its treatment. Surprisingly, the convenience of follow-up at work had no effect upon these men's compliance with antihypertensive drug regimens. Similarly, although men receiving health education learned a lot about hypertension, they were not more likely to take their medicine.", "It is not known whether patient outcomes are enhanced by effective pharmacist-patient interactions.\n To assess the effectiveness of a pharmaceutical care program for patients with asthma or chronic obstructive pulmonary disease (COPD).\n Randomized controlled trial conducted at 36 community drugstores in Indianapolis, Ind. We enrolled 1113 participants with active COPD or asthma from July 1998 to December 1999. Outcomes were assessed in 947 (85.1%) participants at 6 months and 898 (80.7%) at 12 months.\n The pharmaceutical care program (n = 447) provided pharmacists with recent patient-specific clinical data (peak expiratory flow rates [PEFRs], emergency department [ED] visits, hospitalizations, and medication compliance), training, customized patient educational materials, and resources to facilitate program implementation. The PEFR monitoring control group (n = 363) received a peak flow meter, instructions about its use, and monthly calls to elicit PEFRs. However, PEFR data were not provided to the pharmacist. Patients in the usual care group (n = 303) received neither peak flow meters nor instructions in their use; during monthly telephone interviews, PEFR rates were not elicited. Pharmacists in both control groups had a training session but received no components of the pharmaceutical care intervention.\n Peak expiratory flow rates, breathing-related ED or hospital visits, health-related quality of life (HRQOL), medication compliance, and patient satisfaction.\n At 12 months, patients receiving pharmaceutical care had significantly higher peak flow rates than the usual care group (P =.02) but not than PEFR monitoring controls (P =.28). There were no significant between-group differences in medication compliance or HRQOL. Asthma patients receiving pharmaceutical care had significantly more breathing-related ED or hospital visits than the usual care group (odds ratio, 2.16; 95% confidence interval, 1.76-2.63; P<.001). Patients receiving pharmaceutical care were more satisfied with their pharmacist than the usual care group (P =.03) and the PEFR monitoring group (P =.001) and were more satisfied with their health care than the usual care group at 6 months only (P =.01). Despite ample opportunities to implement the program, pharmacists accessed patient-specific data only about half of the time and documented actions about half of the time that records were accessed.\n This pharmaceutical care program increased patients' PEFRs compared with usual care but provided little benefit compared with peak flow monitoring alone. Pharmaceutical care increased patient satisfaction but also increased the amount of breathing-related medical care sought.", "DOTS is the control strategy for tuberculosis promoted by WHO. Pakistan is currently developing its National Tuberculosis Programme, and requires guidance on types of direct observation of treatment appropriate for the local conditions. We did a randomised trial to assess the effectiveness of different packages for tuberculosis treatment under operational conditions in Pakistan.\n We enrolled 497 adults with new sputum-positive tuberculosis. 170 were assigned DOTS with direct observation of treatment by health workers; 165 were assigned DOTS with direct observation of treatment by family members; and 162 were assigned self-administered treatment. The trial was done at three sites that provide tuberculosis services strengthened according to WHO guidelines for the purposes of the research, with a standard daily short-course drugs regimen (2 months of isoniazid, rifampicin, pyrazinamide, and ethambutol, followed by 6 months of isoniazid and ethambutol). The main outcome measures were cure, and cure or treatment completion. Analysis was by intention to treat.\n Within the strengthened tuberculosis services, the health-worker DOTS, family-member DOTS, and self-administered treatment strategies gave very similar outcomes, with cure rates of 64%, 55%, and 62%, respectively, and cure or treatment-completed rates of 67%, 62%, and 65%, respectively.\n None of the three strategies tested was shown to be superior to the others, and direct observation of treatment did not give any additional improvement in cure rates. The effectiveness of direct observation of treatment remains unclear, and further operational research is needed.", "A randomised controlled trial, involving 112 adolescents with asthma, and a 2-year follow-up was conducted to assess the impact of an intervention programme aimed at enhancing adherence to asthma medication. This programme had a duration of 1 year and consisted of an experimental group which received usual care from a paediatrician, but additionally attended individual and group sessions with an asthma nurse, and a control group which received usual care only. The programme aimed at enhancing adherence by stimulating a positive attitude, increasing feelings of social support, and enhancing self-efficacy. At baseline, and after 12-month (T1) and 24-month (T2) follow-up, the participants filled in questionnaires which were based on the concepts of the ASE-model. Adherence was assessed by self-report (range: 1-10) at the same points in time. After 12 months, 97 adolescents (87%) were available for follow-up, decreasing to 86 adolescents (77%) after 24 months. No statistically significant differences were found between the control and the experimental group, except for one. At T2, self-reported adherence appeared to be statistically significantly higher in the experimental group. In conclusion, there seems to have been no substantial effect of the intervention programme.", "To compare enalapril 20 mg once daily with 10 mg twice daily in terms of blood pressure reduction and patient compliance.\n Cross-over study of patients randomly assigned to a sequence of enalapril 20 mg once daily or 10 mg twice daily in three 4-week periods following a 4-week placebo run-in.\n General practices in the greater Belfast and Lisburn area in Northern Ireland.\n Twenty-five hypertensive patients who had a mean diastolic blood pressure of between 90 and 110 mm Hg after receiving placebo for 4 weeks.\n Reduction in blood pressure and estimation of patient compliance.\n Patient compliance was superior on the once daily regimen. However, the twice daily regimen was associated with a greater blood pressure reduction which almost reached statistical significance at the 5% level.\n Enalapril 20 mg should be prescribed as 10 mg twice daily and measures taken to improve patient compliance.", "Family psychoeducation has a well-documented effect on the short-term prognosis in schizophrenia. Less is known about the effectiveness of shorter programmes with the main focus on information for patients (patient education) or for patients and relatives (family education).\n A randomized study of the effectiveness of an eight-session psychoeducational programme for patients with schizophrenia and for their relatives was conducted in two community mental health centres, in Arhus and Viborg (Denmark). Patient outcome measures were knowledge, relapse, compliance, insight and satisfaction, and relative outcome measures were knowledge and satisfaction. Post-intervention outcome and follow-up evaluation 1 year after the start of the intervention are presented.\n A statistically significant increase in knowledge of schizophrenia in both relatives and patients was demonstrated at postintervention and a non-significant trend at 1-year follow-up. Statistically significant changes in the Verona Service Satisfaction Scale Scores in the subdimension of satisfaction with Relatives involvement were demonstrated both for patients and relatives postintervention and for patients at 1-year follow-up. There was a tendency that time-to-relapse increased in the intervention group at postintervention and that the schizophrenia subscore of the Brief Psychiatric Rating Scale was reduced in the intervention group at 1-year follow-up. No differences were found between the groups regarding compliance, insight into psychosis, psychosocial function (General Assessment of Function) or in relatives' expressed emotion scores postintervention or at 1-year follow-up.\n A short patient and relative education programme seems to be able to influence knowledge and some aspects of satisfaction, but does not seem to be sufficient to influence important variables such as relapse, compliance, psychopathology, insight or psychosocial functioning.", "Adherence to antiretroviral therapy is difficult, and methods to increase it are needed.\n We tested the impact of supportive telephone calls in an adherence substudy of a treatment trial. Subjects initiating antiretroviral therapy received either each site's usual adherence support measures or usual support measures and scripted serial telephone calls (16 calls during 96 weeks).\n A total of 282 subjects enrolled: 140 in the usual support measures group and 142 in the calls group. A total of 75% of expected calls were completed. Virologic failure occurred in 97 (34%) subjects: 52 (37%) of those in the usual support measures group and 45 (32%) of those in the calls group; time to virologic failure was not different (P=.32). In each group, >72% of subjects reported > or =95% adherence, with no difference between groups. Independent predictors of higher rates of virologic failure were <95% adherence, receiving the 4-drug regimen with nelfinavir, and female sex; older age was associated with decreased likelihood of virologic failure. Receiving the 4-drug regimen with nelfinavir, higher stress scores, older age, and higher call completion rates were independently associated with higher adherence.\n Serial telephone calls did not improve virologic outcome but had an impact on self-reported adherence.", "Nearly perfect compliance seems to be indispensable to obtain the maximum benefit from highly active antiretroviral therapy (HAART). Interventions to ensure a high level of adherence during a relatively long-term period of therapy are necessary.\n This is a prospective, randomized, two-arm controlled study including patients starting their first-or second-line HAART who were randomized to receive psychoeducative intervention to implement adherence (experimental group [EG]) or a usual medical follow-up (control group [CG]). We aimed to study the efficacy of a psychoeducative intervention to ensure long-term adherence to HAART, its relation with the virologic efficacy of treatment, and to determine the variables related to long-term adherence. Visits were made at weeks 0, 4, 24, and 48 for data collection. Self-reported adherence was registered at each visit and its veracity was tested by randomized blood analyses performed without previous warning to 40% of patients. Appropriate adherence was defined as the consumption of >/=95% of medication prescribed. Statistical analyses were performed both by the as treated (AT) and the intention to treat missing = failure (ITT) methods.\n In all, 116 patients were included. At week 48, 94% of patients in the EG versus 69% controls achieved adherence >/=95% (p =.008); 89% of patients in the EG versus 66% controls had HIV-1 RNA levels <400 copies/ml (p =.026). Overall, 85% of patients with adherence >/=95% but only 45% of those with adherence <95% had viral load (VL) <400 copies/ml (p =. 008). In multivariate analysis, variables significantly related to adherence were having received a psychoeducative intervention (odds ratio [OR], 6.58; p =.04), poor effort to take medication (OR, 5.38; p =.03), and high self-perceived capacity to follow the regimen (OR, 13.76; p =.04). Self-reported adherence and drug plasma levels coincided in 93% of cases. However, differences in adherence did not reach statistical significance in the ITT analysis although a clear tendency toward benefit was observed in EG.\n Specific and maintained psychoeducative interventions based on excellence on clinical practice are useful to keep high levels of adherence as well as high levels of viral suppression. There is a clear relation between high adherence levels and virologic success. Assessment of certain specific variables related to adherence may be helpful to monitor patient's compliance in the clinical setting.", "During the past 15 years, programs to improve self-management practices in adults with asthma have reported improvement in functional status and reduction of inappropriate use of health care services. However, these programs usually represent an ideal approach, applying multiple patient education methods. Consequently, when these programs are found to be efficacious, it is important to replicate the programs as well as to evaluate less complex methods that may be more appropriate for nonacademic health care settings.\n We compared the following 3 standardized self-management treatments in a randomized, controlled trial: (1) a replication of the self-management program developed at a university medical center that was previously shown to be efficacious; (2) a modified version of this program including only the core elements; and (3) a usual-care program. Outcome measures included medication and inhaler regimen adherence, asthma symptoms, respiratory illness, functional status, and use of health care resources.\n All 3 groups improved on measures of respiratory illnesses, use of health care services, and functional status. Patients in both education groups did no better than the usual-care group.\n The results are inconsistent with the results of the first asthma self-management study at this institution and with those of efficacy studies of similar programs. Two factors, selection of the patient population and historical changes in asthma treatment, most likely contributed to the lack of impact of the self-management programs. As a result of the improved standards for usual care due to both factors, the opportunity to effect patient outcomes was substantially reduced.", "To study the efficacy of telephone and mail intervention in therapeutic compliance among patients with mild to moderate hypertension.\n A prospective controlled multicenter clinical trial.\n Eighty-five primary care centers in Spain, with a duration of 6 months.\n A total of 636 patients with newly diagnosed or uncontrolled hypertension were included. Interventions. The patients were randomized and distributed between the following groups: (i) control (CG) - under routine clinical management; (ii) mail intervention (MIG) - received a mailed message reinforcing compliance and reminding of the visits (15 days, 2 and 4 months); (iii) telephone intervention (TIG) - received a telephone call at 15 days, then at 7 and 15 weeks.\n Five visits were scheduled, with the measurement of blood pressure and counting of tablets. Compliers were defined as subjects showing 80-110% drug consumption. Calculations were made of mean percentage compliance (MPC) and compliers, mean blood pressure and percentage controlled subjects.\n Five hundred and thirty-eight patients completed the study (261 males); 85.5% were compliers (CI = 82.5-88.5; n = 460). The MPC was 95.1+/-19.6% (CI = 93.28-96.92). The CG consisted of 182 individuals, MIG = 172 and TIG = 184. Compliers represented 69.2% of the CG (CI 62.5-75.9%), 91.3% (CI = 87.1-95.5) of the MIG (p = 0.0001) and 96.2% of the TIG (CI 93.5-98.9%); the final MPC was 89.6%+/-15 in CG, 96.6%+/-12 in MIG and 99.1+/-26.8 in TIG (p = 0.0001). The percentage of controlled subjects was 47.2% in CG (CI = 40-54.4), 61.3% in MIG (CI = 54.1-68.5%) and 63.3% in TIG (CI = 56.4-70.2%) (p<0.05).\n TIG and MIG are effective measures for improving patient compliance in hypertension.", "To evaluate the efficacy of a programme of home blood pressure measurement (HBPM) on therapeutic compliance in mild-to-moderate hypertension.\n A prospective controlled multicentre clinical trial.\n Forty primary care centres in Spain, with a duration of 6 months.\n A total of 250 patients with newly diagnosed or uncontrolled hypertension were included.\n The patients were randomly selected and distributed in two groups: (1) the control group (CG) who received standard health intervention; (2) the intervention group (IG): the patients in this group received an OMRON in their homes for a programme of HBPM.\n Four visits were scheduled, for the measurement of blood pressure (BP). They were provided with an electronic monitor for measuring compliance (monitoring events medication system; MEMS). Therapeutic compliance was defined as a drug consumption of 80-110%. A number of variables were calculated using the MEMS. The mean BP were calculated and the percentage of controlled patients.\n A total of 200 patients completed the study (100 in each group). Compliance was observed in 74 and 92%, respectively, in the CG and IG [95% confidence interval (CI) 63.9-84.1 and 86.7-97.3; P = 0.0001], the mean percentage compliances were 87.6 and 93.5% (95% CI 81.2-94 and 80.7-98.3; P = 0.0001), the percentages of correct days were 83.6 and 89.4%, the percentages of subjects who took the medication at the prescribed time were 79.89 and 88.06%, and the levels of therapeutic cover were 86.7 and 93.1%. The number needed to treat to avoid one case of non-compliance was 5.6 patients. The differences in the mean decreases in BP were significant for diastolic BP, with a greater decrease observed in the IG.\n An HBPM programme using electronic monitors is effective in improving compliance in arterial hypertension, measured using the MEMS.", "This study purported to determine the effect of pretreatment counseling upon discontinuation of 150 mg depot-medroxyprogesterone acetate (Depo-Provera) given for contraception. A total of 350 Mexican women participated: 175 received detailed structured pretreatment counseling about the hormonal effects of the injectable vs. routine counseling upon duration of use and efficacy of the method. Study termination rates were significantly lower in the structured counseling group than in the control group. Cumulative life table discontinuation rates were 17% (30/175) and 43.4% (76/175), respectively (p <0.05). The most common reasons for terminating DMPA were menstrual changes (8.6 and 32% for counseling and control group, respectively). The findings suggest that pretreatment counseling on expected side effects increases the continuation rates of DMPA users.", "We developed and evaluated a comprehensive, ongoing intervention for families of schizophrenic patients appropriate for China's complex family relationships and unique social environment.\n Sixty-three DSM-III-R schizophrenic patients living with family members were enrolled when admitted to hospital and randomly assigned to receive standard care or a family-based intervention that included monthly 45-minute counselling sessions focused on the management of social and occupational problems, medication management, family education, family group meetings, and crisis intervention.\n At 6, 12, and 18-month follow-ups by blind evaluators, the proportion of subjects rehospitalised was lower, the duration of rehospitalisation was shorter, and the duration of employment was longer in the experimental group than in the control group; these differences were statistically significant at the 12 and 18-month follow-ups and were not explained by differences in drug compliance. Family intervention was associated with significantly lower levels of family burden.\n This intervention is less costly than standard treatment, is suitable for urban families of schizophrenic patients in China and feasible given the constraints of the Chinese mental health system.", "Asthma education decreases the number of emergency visits in specific subgroups of patients with asthma. However, it remains unknown whether this improvement is related only to the use of an action plan alone or to other components of the educational intervention. A total of 126 patients consulting urgently for an acute asthma exacerbation were recruited; 98 completed the study. The first 45 patients were assigned to Group C (control; usual treatment). Thereafter, patients were randomized to either Group LE (limited education; teaching of the inhaler technique plus self- action plan given by the on call physician) or Group SE (same as group LE plus a structured educational program emphasizing self-capacity to manage asthma exacerbations). At baseline, there was no difference between groups in asthma morbidity, medication needs, or pulmonary function. After 12 mo, only Group SE showed a significant improvement in knowledge, willingness to adjust medications, quality of life scores, and peak expiratory flows. In the last 6 mo, the number of unscheduled medical visits for asthma was significantly lower in Group SE in comparison with groups C and LE (p = 0.03). The number (%) of patients with unscheduled medical visits also decreased significantly in Group SE compared with Groups C and LE (p = 0.02). We conclude that a structured educational intervention emphasizing self-management improves patient outcomes significantly more than a limited intervention or conventional treatment.", "The aim of this study was to investigate the impact of a pharmacist-led pharmaceutical care programme, involving optimization of drug treatment and intensive education and self-monitoring of patients with heart failure (HF) within the United Arab Emirates (UAE), on a range of clinical and humanistic outcome measures.\n The study was a randomized, controlled, longitudinal, prospective clinical trial at Al-Ain Hospital, Al-Ain, UAE. Patients were recruited from the general medical wards and from cardiology and medical outpatient clinics. HF patients who fulfilled the entrance criteria, and had no exclusion criteria present, were identified for inclusion in the study. After recruitment, patients were randomly assigned to one of two groups: intervention group or control group. Intervention patients received a structured pharmaceutical care service while control patients received traditional services. Patient follow-up took place when patients attended scheduled outpatient clinics (every 3 months). A total of 104 patients in each group completed the trial (12 months). The patients were generally suffering from mild to moderate HF (NYHA Class 1, 29.5%; Class 2, 50.5%; Class 3, 16%; and Class 4, 4%).\n Over the study period, intervention patients showed significant (P < 0.05) improvements in a range of summary outcome measures [AUC (95% confidence limits)] including exercise tolerance [2-min walk test: 1607.2 (1474.9, 1739.5) m.month in intervention patients vs. 1403.3 (1256.5, 1549.8) in control patients], forced vital capacity [31.6 (30.8, 32.4) l.month in the intervention patients vs. 27.8 (26.8, 28.9) in control patients], health-related quality of life, as measured by the Minnesota living with heart failure questionnaire [463.5 (433.2, 493.9) unit.month in intervention patients vs. 637.5 (597.2, 677.7) in control patients; a lower score in this measure indicates better health-related quality of life]. The number of individual patients who reported adherence to prescribed medications was higher (P < 0.05) in the intervention group (85 vs. 35), as was adherence to lifestyle advice (75 vs. 29) at the final assessment (12 months). There was a tendency to have a higher incidence of casualty department visits by intervention patients, but a lower rate of hospitalization.\n The research provides clear evidence that the delivery of pharmaceutical care to patients with HF can lead to significant clinical and humanistic benefits.", "The prevalence and impact of adult asthma are substantial, and poor self-management practices, especially failures to adhere to treatment regimens, appear to be a significant problem. Desirable characteristics of an intervention program to improve self-management were identified through needs assessment and review of existing patient education resources. A comprehensive program was developed that integrated a workbook with one-to-one counseling and adherence-enhancing strategies. A longitudinal 1-year study compared patients receiving this self-management program with \"usual care\" patients receiving standard asthma pamphlets. Patients were randomly assigned to conditions. Baseline score and asthma severity were statistically controlled. Self-management patients had substantially better adherence than usual care patients, as well as improved functional status, at follow-up. Hospital and emergency department visits decreased in both groups but did not differ between groups.", "We investigated whether hospital-based specialist asthma nurses improved recognition and self-treatment of asthma episodes by patients followed up after attending accident and emergency departments (A&E) for asthma exacerbations. We carried out a randomized prospective controlled trial of adult asthma self-management, following a hospital outpatient nurse consultation in two outer-London District General Hospitals (secondary care centres). The study included 211 adults, over 18 years old (mean age 40 years) who attended for asthma in two accident and emergency departments over 13 months. One hundred and eight evaluable patients were randomized into the control group who continued with their usual medical treatment and were not offered any intervention during the study period. One hundred and three evaluable patients were randomized into the intervention group. They were offered three 6-weekly outpatient appointments with one of two specialist asthma nurses for a structured asthma consultation, after attendance at the accident and emergency department. Following assessment of their asthma treatment and control, the nurses advised patients, through the use of self-management-plans, how to recognize and manage uncontrolled asthma and when to seek medical assistance. Medication and inhaler device type were altered if necessary The primary outcome was patient reported self-management of asthma exacerbations for 6 months. Secondary outcomes were assessed at baseline, 3 months and 6 months. These included home peak flow and symptom diaries, structured telephone questionnaires and audit of general practitioner records to determine utilization of services (6 months before and after A&E). Data were analysed on an intention to treat basis by multiple and logistic regression. The intervention group increased their use of inhaled topical steroids in 31/61 (51%) vs. 15/70 (21%) attacks in controls (OR 3.91 CI 1.8-8.4, P<0.001) and their use of rescue medication in 54/61 (89%) severe attacks vs. 53/70 (76%) controls (OR 2.88 CI 1.1-7.9, P<0.05). Intervention patients had significantly higher (mean 20.1 l min(-1); CI 0.4-39.7; P<0.05) and less variable PEF and significantly lower and less variable symptom scores 6 months after entry. Thirty-four percent of intervention patients vs. 42% controls had severe attacks (61 and 70 respectively, OR 0.96 CI 0.7-1.4) during the 6 months. Intervention patients had fewer days off work than controls in the first 3 months (NS) but similar days off during the 6-month period. Intervention patients had fewer episodes away from work in the first (0.34 vs. 0.54, P = 0.08) and the second 3 months (0.25 vs. 0.30, NS) than the controls. Over 80% of the patients records were audited by their general practitioners; the active group had less routine consultations with the doctor (P = 0.03) and practice nurse (P = 0.03), less consultations for uncontrolled episodes (P = 0.06) and less hospital visits (NS) than the controls. Hospital-based specialist nurses reduced asthma morbidity by improving patient self-management behaviour in acute attacks leading to reduced symptoms, improved lung function, less time off work and fewer consultations with health professionals.", "nan", "To investigate if an intervention with extra information and support in a group setting to parents of preschool children could improve adherence and clinical outcome.\n This is a controlled, prospective study where the parents of 60 newly diagnosed preschool asthmatic children aged 3 mo-6 y were randomized to either a control group or to an intervention that consisted of four group sessions in close connection with the diagnosis. The basic education on asthma and the written treatment plan were the same in both groups. The outcome measures were questionnaires to the parents and classification of the children according to symptoms and medication. The adherence rate and the burden of asthma were calculated with the help of diaries and weighing of the MDIs used between 12 and 18 mo after inclusion.\n The follow-up rate was 85% after 18 mo. The parents' presence in the sessions was around 70%, with no gender difference. The parents' view on adherence issues improved significantly in the intervention group. In the control group, 30% had poor adherence compared to 8% in the intervention group (p=0.015). Both the parents and the paediatricians underestimated the number of children with poor adherence. The children in the intervention group had significantly fewer exacerbation days during the last 6 mo-2.1 compared to 3.9 d/child-although they had lower inhaled steroid doses after 18 mo. An economic calculation showed that the intervention was profitable.\n This intervention resulted in an improvement in the parents' view on adherence, in the measured adherence rates and in the clinical outcome.", "To assess the efficacy of a couple-based intervention to improve medication-taking behavior in a clinic population with demonstrated adherence problems.\n A randomized controlled trial (SMART Couples Study) conducted between August 2000 and January 2004.\n Two HIV/AIDS outpatient clinics in New York City.\n Heterosexual and homosexual HIV-serodiscordant couples (n = 215) in which the HIV-seropositive partner had < 80% adherence at baseline. The sample was predominantly lower-income racial/ethnic minorities.\n Participants were randomly assigned to a four-session couple-focused adherence intervention or usual care. The intervention consisted of education about treatment and adherence, identifying adherence barriers, developing communication and problem-solving strategies, optimizing partner support, and building confidence for optimal adherence.\n Medication adherence at week 8 (2 weeks after the intervention) compared with baseline, assessed with a Medication Event Monitoring System cap.\n Intervention participants showed higher mean medication adherence at post-intervention when compared with controls whether adherence was defined as proportion of prescribed doses taken (76% versus 60%) or doses taken within specified time parameters (58% versus 35%). Also, participants in the intervention arm were significantly more likely to achieve high levels of adherence (> 80%, > 90%, or > 95%) when compared with controls. However, in most cases, effects diminished with time, as seen at follow-up at 3 and 6 months.\n The SMART Couples program significantly improved medication adherence over usual care, although the level of improved adherence, for many participants, was still suboptimal and the effect was attenuated over time.", "The objective of this study was to evaluate whether dispensing prescriptions in the ED affects patient compliance and return visits to the hospital. Seventy-four patients who were deemed suitable candidates for outpatient therapy with a macrolide antibiotic were identified and prospectively randomized to receive either an entire course of azithromycin from the ED or a prescription for azithromycin to be filled at a local pharmacy free of charge. Pharmacy records and telephone interview were used to measure compliance with patients. Significantly fewer patients filled their prescription in the pharmacy group (74.2%) compared with the ED group, in which all patients received their medication. However, there was no difference in the self-reported compliance of completing the entire course of antibiotics between patients in the ED group (94.3%) and in the pharmacy group (96.8%). There was no significant difference between groups in return ED visits or hospital admissions. We conclude that delivery of prescriptions in the ED significantly increases the likelihood that the patient will obtain the medication prescribed. Whether the patients actually take the medication as directed is unknown. Patient's self-report did not accurately reflect true compliance and more objective means for measuring compliance is warranted.", "This study was conducted to evaluate the effect of automated telephone patient monitoring and counseling on patient adherence to antihypertensive medications and on blood pressure control. A randomized controlled trial was conducted in 29 greater Boston communities. The study subjects were 267 patients recruited from community sites who were >or= 60 years of age, on antihypertensive medication, with a systolic blood pressure (SBP) of >or= 160 mm Hg and/or a diastolic blood pressure (DBP) of >or= 90 mm Hg. The study compared subjects who received usual medical care with those who used a computer-controlled telephone system in addition to their usual medical care during a period of 6 months. Weekly, subjects in the telephone group reported self-measured blood pressures, knowledge and adherence to antihypertensive medication regimens, and medication side-effects. This information was sent to their physicians regularly. The main study outcome measures were change in antihypertensive medication adherence, SBP and DBP during 6 months, satisfaction of patient users, perceived utility for physicians, and cost-effectiveness. The mean age of the study population was 76.0 years; 77% were women; 11% were black. Mean antihypertensive medication adherence improved 17.7% for telephone system users and 11.7% for controls (P = .03). Mean DBP decreased 5.2 mm Hg in users compared to 0.8 mm Hg in controls (P = .02). Among nonadherent subjects, mean DBP decreased 6.0 mm Hg for telephone users, but increased 2.8 mm Hg for controls (P = .01). For telephone system users, mean DBP decreased more if their medication adherence improved (P = .03). The majority of telephone system users were satisfied with the system. Most physicians integrated it into their practices. The system was cost-effective, especially for nonadherent patient users. Therefore, weekly use of an automated telephone system improved medication adherence and blood pressure control in hypertension patients. This system can be used to monitor patients with hypertension or with other chronic diseases, and is likely to improve health outcomes and reduce health services utilization and costs.", "Allergic rhinitis is an inflammatory disease often associated with bronchial asthma. Intranasal corticosteroids and oral antihistamines are the first-choice drugs. Patient training is relevant to asthma management, but little is known about its impact on rhinitis. We evaluated the role of patient training in the treatment of allergic rhinitis and its effects on nasal and bronchial symptoms.\n One hundred and one patients (M/F = 62/39, age range 12-62 years) with pollen-induced rhinitis (32 with concomitant mild asthma) were enrolled. They were randomized into three groups: A (n = 30) with drug therapy alone, B (n = 35) with drug therapy plus training on the use of nasal spray, and C (n = 36) the same as B plus a lesson on rhinitis and asthma. All patients received mometasone furoate nasal spray for 8 weeks as regular therapy, plus rescue medications on demand. Symptoms and drug consumption were evaluated during the pollen season.\n The rate of noncompliance/dropout was highest in the untrained patients (P = 0.001). No difference in nasal symptoms was seen among the three groups. On the other hand, group C had significantly fewer asthma symptoms (P = 0.02) and less albuterol use (P = 0.005) than group A. Moreover, the trained group globally used less rescue medication than the other groups (P = 0.02).\n Detailed training of patients seems to improve compliance with treatment, reduce concomitant asthma symptoms, and reduce the use of symptomatic drugs.", "To determine if the intervention of individual advice improves adherence and effectiveness to highly active antiretroviral therapy.\n Randomized open trial. Patients treated with zidovudine + lamivudine + indinavir were assigned (2/1) to conventional care or individual advise. Individual advise consists in adaptation to treatment to patient style of live and detailed information of therapy. Adherence were estimated with structured interview and pillo counts and were considered correct when more than 90% of prescribed drugs were taken.\n Patients 170, conventional care: 110 and IA: 60. Follow-up: 24 weeks. Baseline characteristics were similar in both groups. Correct adherence were estimated in 52.7% of conventional care and in 76.7% of individual advise (p = 0.002, relative risk: 1.45; CI 95%: 1.16-1.82). Undetectable viral load (NASBA < 50 copies/ml) in 54.5% of conventional care and in 65% of individual advise (p = 0.18, relative risk: 1.19; CI 95%: 0.93-1.53). Reduction of viral load in the conventional care group 1.02 +/- 0.5 log10/ml, and in the individual advise group 1.98 +/- 0.7 log10/ml.\n The individual advice improve adherence with a tendency to improve effectiveness of highly active antiretroviral therapy.", "Background. Patients cite \"forgetting\" as a reason for nonadherence to highly active antiretroviral therapy (HAART). We measured the effect of a memory-prompting device on adherence to HAART in memory-intact and memory-impaired human immunodeficiency virus (HIV)-infected subjects.Methods. The study was a prospective, randomized, controlled trial involving 64 HIV-infected adults. The intervention was the Disease Management Assistance System (DMAS) device, combined with monthly adherence counseling. Control subjects received only adherence counseling. The DMAS was programmed with HAART regimen data to provide verbal reminders at dosing times. Adherence was measured for 24 weeks using electronic drug exposure monitor (eDEM) caps.Results. A total of 58 subjects completed the 24-week study period; 28 were HAART naive (12 DMAS users and 16 control subjects). Mean adherence scores did not differ significantly between DMAS users (80%) and control subjects (65%). Post hoc analysis of 31 memory-impaired subjects (14 DMAS users and 17 control subjects) revealed significantly higher adherence rates among DMAS users (77%), compared with control subjects (57%) (P=.001). However, analysis of memory-intact subjects showed that adherence was not significantly improved for DMAS users (83%), compared with control subjects (77%) (P=.25). At week twelve, 38% of the DMAS users and 14% of the control subjects had an undetectable plasma HIV RNA load (P=.014), and at week 24, the plasma HIV RNA load was undetectable for 34% of the DMAS users and 38% of the control subjects (P=.49). CD4(+) cell counts did not differ between the study arms. Virological and immunological responses were not related to DMAS use in memory-impaired subjects.Conclusion. The DMAS prompting device improved adherence for memory-impaired subjects but not for memory-intact subjects.", "The aim of this study was to explore the characteristics and efficacy of psychoeducational family intervention for persons with schizophrenia in rural China.\n A cluster randomised controlled trial of psychoeducational family intervention for families experiencing schizophrenia (three groups, 326 cases) was conducted in Xinjin County, Chengdu. Treatment groups consisted of family intervention and medication, medication alone, and a control.\n The results showed a gain in knowledge, a change in the relatives' caring attitudes towards the patients, and an increase in treatment compliance in the psychoeducational family intervention group (p < 0.05, 0.001). Most importantly, the relapse rate over 9 months in this group (16.3 %) was half that of the drug-only group (37.8 %), and just over one-quarter of that of the control group (61.5 %) (p < 0.05). Antipsychotic drug treatment and families' attitudes towards patients after the 9-month follow-up were significantly associated with clinical outcome (p < 0.05).\n In rural China, family intervention should focus on improving the relatives' recognition of illness, the caring attitude towards the patients, treatment compliance, relapse prevention, and the training of the patients' social functioning. This trial, one of the largest in the literature, has shown that psychoeducational family intervention is effective and suitable for psychiatric rehabilitation in Chinese rural communities.", "The effects of metoprolol (Betaloc tablets) in a group of 193 hypertensives were compared with the effects of a slow-release formulation (Betaloc Durules) in a further group of 196 patients. Patients were selected at random for treatment. There were no differences between the groups in terms of age, weight, sex, blood pressure, concurrent illness or concomitant therapy. Blood pressure control and apparent adverse effects were similar for both groups; the overall withdrawal rate from each group was similar. Compliance, assessed by tablet counts, was significantly improved in the group receiving once-daily therapy. Simplification of the dosage regimen to once-daily therapy appears to improve the patient's willingness to comply with the physician's instructions.", "Many patients with major depression are non-adherent to antidepressant medication and do not receive care according to current guidelines. There is increasing evidence that treatment of depression in primary care can be improved. Comparison between effective interventions may help to establish the active ingredients of such interventions.\n In a randomized trial two interventions to improve treatment of major depression in primary care were compared (1) a depression care programme, targeting general practitioners (GPs), patients, and systematic follow-up, and (2) a systematic follow-up programme. Thirty GPs were randomized and 211 primary-care patients with current major depression were included. All patients were prescribed a selective serotonin reuptake inhibitor. Outcome measures included adherence to antidepressant medication, and depression outcome.\n No significant differences in adherence rates and treatment outcome measures were demonstrated between interventions at week 10 or week 26. Adherence rates were high and treatment outcome was favourable.\n The depression care programme was not superior to the systematic follow-up programme. Systematic follow-up in depression treatment in primary care seems to be an intervention per se, having the potential to improve adherence and treatment outcome.", "A 24-week open-label clinical trial was conducted in 195 HIV-infected adults commonly underrepresented in research (35% female, 71% African American, 21% Hispanic, and 20% injection drug users [IDUs]) to evaluate the effect of an HIV educational program on efficacy and adherence with a simple, compact, twice-daily triple nucleoside regimen containing a lamivudine (150 mg)/zidovudine (300 mg) combination (COM) tablet plus abacavir (ABC), 300 mg. At baseline, the patients' median plasma HIV-1 RNA level was 4.18 log10 copies/mL and the median CD4+ cell count was 379 cells/mm3. Patients were randomized 1:1 to 4 modules of the Tools for Health and Empowerment HIV education intervention plus routine counseling (EI + RC; n = 96) or to routine counseling alone (RC; n = 99). No differences between the EI + RC and RC treatment arms were observed with respect to the proportion of patients achieving plasma HIV-1 RNA levels <40 copies/mL (60% [33/55] vs. 55% [38/69]; P = 0.529) or <400 copies/mL (80% [44/55] vs. 80% [55/69]; P = 0.689) at week 24 (intent-to-treat observed analysis), increase in median CD4 cell count above baseline at week 24 (78.3 vs. 104.8 cells/mm3; P = 0.498), or mean overall adherence rates as measured by the Medication Event Monitoring System (MEMS) (70% vs. 74%). COM + ABC was generally well tolerated, and no association was observed between interruptions in treatment and the development of ABC hypersensitivity (5 suspected cases). In conclusion, in underrepresented patients, the EI used in this study did not affect the efficacy and adherence results with ABC + COM to any greater degree than did RC.", "Ninety-eight adults treated with erythromycin for a variety of illnesses were randomized to two groups: the informed group received patient education about drug side effects, and the uninformed group were given no such information. Overall, 10% of the uniformed and 8% of the informed group felt the erythromycin bothered them in some way. There were no significant differences in the occurrence of various individual side effects. Compliance with therapy and the results of treatment were the same for both groups. In this study, informing patients about side effects of therapy did not have any detectable adverse effects.", "This article reports a randomized controlled trial designed to test the effects of special packaging of antihypertensive medication on compliance and blood pressure control. One hundred eighty subjects who had exhibited elevated blood pressure greater than 90 mmHg in the two years prior to the study were recruited from patients receiving care at a community hospital-based family medicine practice. After completing preenrollment interviews and blood pressure measurements, subjects were randomly assigned to receive their antihypertensive medications either in the usual vials or in special unit dose-reminder packaging. Follow-up interviews, pill counts, and blood pressure measurements were performed at three-month intervals. There were no statistically significant differences between the control and experimental groups with regard to age, sex, race, employment, education, marital status, insurance coverage, or blood pressure regimens. Prior to the intervention, the experimental group had slightly lower diastolic blood pressure and reported better compliance than the control group. Analyses performed on 165 subjects completing the first follow-up visit revealed no significant improvements in blood pressure control or compliance for patients receiving special medication packaging. While some patients found it easy to remember to take pills packaged using this format, they also found the packages somewhat more difficult and inconvenient to use. In contrast to previously reported work, this study did not demonstrate any significant improvement in compliance with special packaging of antihypertensive medications.", "Fifty-three hospital outpatients with epilepsy were randomly allocated to either a control or an intervention group. Patients in the intervention group were subjected to a combination of compliance-improving strategies: patient counselling, a special medication container, self-recording of medication intake and seizures, and mailed reminders to collect prescription refills and attend clinic appointments. Compliance with anticonvulsant therapy (as measured by plasma anticonvulsant levels and prescription refill frequencies), and seizure frequency, were evaluated in each patient prior to intervention and 6 months afterwards. Patient compliance and clinical control improved significantly in the intervention group patients. Seizure frequency was, on average, halved following intervention. Compliance and seizure frequency were unaltered in the control group. Intervention failed to improve clinic appointment keeping. Poor compliance with drug therapy commonly confounds the treatment of epilepsy. This study shows that compliance can be improved and seizure frequency lessened by strategies that are easily incorporated into the routine management of epileptic patients.", "To evaluate a pharmacist-conducted educational and monitoring programme, designed to promote dietary and lifestyle modification and compliance with lipid-lowering drug therapy, for patients with dyslipidaemia.\n This was a prospective, randomized, controlled study. The participants were 94 adults, with 81 completing the study (intervention group: 39; control group: 42), with a cardiovascular-related diagnosis and discharged from hospital, between April and October 2001, on lipid-lowering drug therapy. Patients in the intervention group were visited at home monthly by a pharmacist, who educated the patients on the goals of lipid-lowering treatment and the importance of lifestyle issues in dyslipidaemia and compliance with therapy, assessed patients for drug-related problems, and measured total blood cholesterol levels using point-of-care testing. Patients in the control group received standard medical care. The main outcome measure was total blood cholesterol levels after 6 months, and an evaluation of patient and general practitioner satisfaction with the programme.\n There was no significant difference in baseline total blood cholesterol levels between the two groups. The reduction over the course of the study in cholesterol levels within the intervention group was statistically significant (4.9 +/- 0.7 to 4.4 +/- 0.6, P<0.005), whereas there was no change within the control group (P=0.26). At follow-up, 44% of the intervention group patients and 24% of the control group patients had cholesterol levels below 4.0 mmol/L (P=0.06). The reduction in total cholesterol in the intervention group should translate to an expected 21% reduction in cardiovascular mortality risk and a 16% reduction in total mortality risk--more than twice the risk reduction achieved in the control group. In addition, the programme was very well received by the patients and their general practitioners, by satisfaction questionnaire.\n A pharmacist-conducted educational and monitoring intervention improved the outcomes of lipid-lowering drug therapy.", "Poor medication adherence diminishes the health benefits of pharmacotherapies. Elderly patients with coronary risk factors frequently require treatment with multiple medications, placing them at increased risk for nonadherence.\n To test the efficacy of a comprehensive pharmacy care program to improve medication adherence and its associated effects on blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C).\n A multiphase, prospective study with an observational phase and a randomized controlled trial conducted at the Walter Reed Army Medical Center of 200 community-based patients aged 65 years or older taking at least 4 chronic medications. The study was conducted from June 2004 to August 2006.\n After a 2-month run-in phase (measurement of baseline adherence, BP, and LDL-C), patients entered a 6-month intervention phase (standardized medication education, regular follow-up by pharmacists, and medications dispensed in time-specific packs). Following the intervention phase, patients were randomized to continued pharmacy care vs usual care for an additional 6 months.\n Primary end point of the observation phase was change in the proportion of pills taken vs baseline; secondary end points were the associated changes in BP and LDL-C. Primary end point of the randomization phase was the between-group comparison of medication persistence.\n A total of 200 elderly patients (77.1% men; mean [SD] age, 78 [8.3] years), taking a mean (SD) of 9 (3) chronic medications were enrolled. Coronary risk factors included drug-treated hypertension in 184 patients (91.5%) and drug-treated hyperlipidemia in 162 (80.6%). Mean (SD) baseline medication adherence was 61.2% (13.5%). After 6 months of intervention, medication adherence increased to 96.9% (5.2%; P<.001) and was associated with significant improvements in systolic BP (133.2 [14.9] to 129.9 [16.0] mm Hg; P = .02) and LDL-C (91.7 [26.1] to 86.8 [23.4] mg/dL; P = .001). Six months after randomization, the persistence of medication adherence decreased to 69.1% (16.4%) among those patients assigned to usual care, whereas it was sustained at 95.5% (7.7%) in pharmacy care (P<.001). This was associated with significant reductions in systolic BP in the pharmacy care group (-6.9 mm Hg; 95% CI, -10.7 to -3.1 mm Hg) vs the usual care group (-1.0 mm Hg; 95% CI, -5.9 to 3.9 mm Hg; P = .04), but no significant between-group differences in LDL-C levels or reductions.\n A pharmacy care program led to increases in medication adherence, medication persistence, and clinically meaningful reductions in BP, whereas discontinuation of the program was associated with decreased medication adherence and persistence.\n clinicaltrials.gov Identifier: NCT00393419", "Helicobacter pylori (H. pylori) eradication rate varies according to the treatment regimen used and other factors, e.g. antimicrobial resistance and patient compliance. The aim of the present study was to evaluate the influence of patient counselling and follow-up on H. pylori eradication rates and to document the effectiveness of a 1 week eradication regimen consisting of lansoprazole (30 mg once daily), amoxicillin (1 g twice daily) and clarithromycin (500 mg twice daily).\n Seventy-six dyspeptic patients, who at endoscopy were found to have gastritis, duodenitis or ulceration, and a positive H. pylori urease test, were recruited. Patients were randomly assigned to an intervention group (n = 38) or a control group (n = 38). Intervention patients received their medicines via the hospital pharmacy and were counselled (and followed up) by a hospital pharmacist. Control patients were given a standard advice sheet and referred to their GP who prescribed the same therapy.\n Intervention patients exhibited a statistically significant improvement in the H. pylori eradication rate (94.7% vs 73.7%; P = 0.02) and compliance (92.1% vs 23.7; P < 0.001). Of the 64 H. pylori eradicated patients, 62 were able to eliminate their antisecretory medication compared with only 12 of the H. pylori persistent patients (P < 0.001). A pharmacoeconomic evaluation indicated that counselling and follow-up reduced the direct costs of eradication by approximately 30 UK pounds per patient.\n Structured patient counselling and follow-up can have a significant effect on H. pylori eradication rates and should be a routine part of therapy.", "to investigate the effectiveness of a pharmacy discharge plan in elderly hospitalized patients.\n randomized controlled trial.\n we randomized patients aged 75 years and older on four or more medicines who had been discharged from three acute general and one long-stay hospital to a pharmacy intervention or usual care.\n the hospital pharmacist developed discharge plans which gave details of medication and support required by the patient. A copy was given to the patient and to all relevant professionals and carers. This was followed by a domiciliary assessment by a community pharmacist. In the control group, patients were discharged from hospital following standard procedures that included a discharge letter to the general practitioner listing current medications.\n the primary outcome was re-admission to hospital within 6 months. Secondary outcomes included the number of deaths, attendance at hospital outpatient clinics and general practice and proportion of days in hospital over the follow-up period, together with patients' general well-being, satisfaction with the service and knowledge of and adherence to prescribed medication.\n we recruited 362 patients, of whom 181 were randomized to each group. We collected hospital and general practice data on at least 91 and 72% of patients respectively at each follow-up point and interviewed between 43 and 90% of the study subjects. There were no significant differences between the groups in the proportion of patients re-admitted to hospital between baseline and 3 months or 3 and 6 months. There were no significant differences in any of the secondary outcomes.\n we found no evidence to suggest that the co-ordinated hospital and community pharmacy care discharge plans in elderly patients in this study influence outcomes.", "The purpose of the study was to compare three nursing interventions and their impact on glycemic control among children with type I diabetes. The 75 subjects' mean +/- SD age was 12.5 +/- 3.4 years, 55% were boys, and 55% were White. Subjects were randomly assigned to a standard care (SC), an education (ED), or an education and telephone case management (ED + TCM) group. The primary outcome measure was glycemic control (hemoglobin A1c, or HbA1c). Secondary outcome measures were diabetes knowledge (KNOW), parent-child teamwork (TEAM), and adherence (ADH). After 6 months of follow-up, results demonstrated no significant differences among groups in HbA1c. KNOW and TEAM scores improved slightly in the ED and ED + TCM groups, but no statistically significant differences were found among the three groups. Significant improvement in ADH scores among ED + TCM groups was reported when compared with the ED and SC groups. This change may represent a move toward improved adherence to diabetes care and subsequent improvement in diabetes control. The challenges of recruitment and retention of subjects in this study will also be discussed.", "This paper evaluates the effects on knowledge and clinical stability of an educational intervention about tardive dyskinesia.\n Fifty-six patients receiving antipsychotic maintenance completed a questionnaire assessing their knowledge about tardive dyskinesia. After random allocation to either an educational intervention or a control group, their knowledge was reassessed at six months.\n Ninety-five per cent of patients completed the study. The study patients gained significantly more knowledge than the controls, who made modest gains. There were no significant differences in clinical outcome between the groups.\n Patients can learn about serious toxic effects of antipsychotic treatment with a low risk of non-compliance. Discussion about tardive dyskinesia is necessary in the process of obtaining informed consent to treatment.", "Adherence to antiretroviral therapy is critical to treatment outcomes. Adherence studies in other therapeutic areas of medicine suggest that once-daily regimens support improved adherence when compared to twice-daily therapy. An expansion in the range of once-daily antiretrovirals is making once-daily therapy possible for persons with HIV infection.\n A 24-week randomized open-label simplification study of twice-daily regimens based on stavudine immediate release or zidovudine to an all once-daily regimen based on the stavudine prolonged-release capsule (PRC), in persons with complete virological suppression on regimens also including efavirenz and lamivudine, was carried out. Subjects were assessed for adherence [using the Medication Event Monitoring System (MEMS) cap; Aardex Corporation, Union City, CA, USA], quality of life, tolerability and efficacy.\n Forty-three patients were randomly assigned: 21 remained on their original regimen and 22 switched to once-daily therapy with stavudine PRC. Although high levels of adherence and good quality of life were present at study enrollment, adherence declined to a significantly lesser extent at week 24 in the group that switched to once-daily therapy. Efficacy was maintained in both groups and there were no differences in tolerability or toxicity.\n Subjects switching from twice-daily therapy to once-daily therapy demonstrate less of a decline in adherence over 24 weeks. A once-daily regimen including stavudine PRC is as effective and tolerable as a regimen containing the twice-daily formulation.", "The impact of an adherence enhancement program for low income HIV-infected Spanish-speaking Latinos on health literacy, patient-provider relationships, and adherence to HAART was examined. Evaluations were conducted at baseline, 6 weeks, and 6 months for participants (n = 85) randomly assigned to either the intervention group or a comparison group; 69 (81%) remained in the study for the entire 6-month duration. The intervention group scored significantly better than the comparison group on 3 of 5 measures of HIV health literacy at 6 weeks and on 2 of 5 measures, at 6 months. While there was a weak trend for the intervention group to report an increase in self-efficacy of medication adherence management, baseline to 6 weeks, no other changes were significant. Perceptions of the quality of relationship and communications with their HIV-treating physicians improved both at 6 weeks (p = 0.04) and at 6 months (p < 0.001). The comparison group showed little change baseline to 6 weeks and baseline to 6 months. While there was a trend for the pilot group to report better medication adherence, these differences were not statistically significant. Further evaluation of the impact of this adherence enhancement program is needed.", "Lack of medication adherence is a common reason for poor control of blood pressure in the community, increasing the risk of heart attacks and strokes.\n To evaluate the effect of nurse-led adherence support for people with uncontrolled high blood pressure compared with usual care.\n We recruited 245 women and men with uncontrolled hypertension (> or = 150/90 mmHg) from 21 general practices in Bristol, UK. Participants were randomized to receive nurse-led adherence support or usual care alone. Main outcome measures were adherence to medication ('timing compliance') and blood pressure.\n Mean baseline timing compliance (+/- SD) was high in both the intervention (90.8 +/- 15.6%) and the control group (94.5 +/- 7.6%). There was no evidence of an effect of the intervention on timing compliance at follow-up (adjusted difference in means -1.0%; 95% confidence interval (CI) -5.1 to 3.1). There was also no difference at follow-up between the groups with regard to systolic blood pressure (-2.7 mmHg; 95% CI -7.2 to 1.8) or diastolic blood pressure (0.2 mmHg; 95% CI -1.9 to 2.3). Projected costs for the primary care sector per consultation were 6.60 pound sterling for the intervention compared with 5.08 pound sterling for usual care.\n In this study, adherence to blood pressure medication was much higher than previously reported. There was no evidence of an effect of nurse-led adherence support on medication adherence or blood pressure compared with usual care. Nurse-led adherence support was also more expensive from a primary care perspective.", "The aim of this study was to compare cure rates of Helicobacter pylori (H. pylori) infection, compliance, and side effects in patients given 10 days of omeprazole 20 mg b.d., amoxycillin 500 mg t.d.s., and metronidazole 400 mg t.d.s. (OAM) or 10 days OAM plus compliance enhancing measures.\n A total of 119 H. pylori-positive patients were prospectively randomized to receive either 10 days OAM or 10 days OAM plus compliance enhancing measures (medication in a dose dispensing unit, medication chart, an information sheet about H. pylori treatment, and phone call 2 days after starting therapy). H. pylori eradication was assessed by 13C-UBT at least 4 wk after cessation of therapy, compliance by phone interview on the last day of therapy and returned pill count, and side effects by phone interview and returned side effects form.\n In 113 patients attending 13C-UBT H. pylori was eradicated in 51 of 57 patients (89.5%) after 10 days OAM and in 48 of 56 (85.7%) after 10 days OAM plus compliance enhancing measures (p = 0.54). In both groups 97% of medications were taken. Side effects were common (82% of patients). Both side effects (p = 0.001) and ulcer versus nonulcer at endoscopy (p = 0.016) were independent predictors of treatment failure; side effects also predicted noncompliance (p = 0.02).\n Ten days of OAM was effective for H. pylori eradication in our clinical population. Patient compliance was excellent and attempts to increase compliance had no impact on outcome or compliance. Side effects were very common and were significantly associated with treatment failure and decreased compliance.", "To assess the effectiveness of an individualized multicomponent intervention to promote adherence to antiretroviral therapy (ART) in a cohort of HIV-infected individuals with a history of alcohol problems.\n We conducted a randomized controlled trial to compare the usual medical follow-up with an adherence intervention.\n The principal enrolment site was Boston Medical Center, a private, not-for-profit, academic medical institution.\n HIV-infected patients with a history of alcohol problems on ART. A total of 151 were enrolled and 141 (93%) were assessed at follow-up. Intervention: A nurse, trained in motivational interviewing, completed the following over 3 months in four encounters: addressed alcohol problems; provided a watch with a programmable timer to facilitate pill taking; enhanced perception of treatment efficacy; and delivered individually tailored assistance to facilitate medication use.\n Prior 30-day adherence > or =95%, prior 3-day adherence of 100%, CD4 cell count, HIV RNA and alcohol consumption, each at both short- and long-term follow-up.\n At follow-up, no significant differences in medication adherence, CD4 cell count, HIV RNA or alcohol consumption were found (all P values >0.25).\n A multicomponent intervention to enhance adherence among HIV-infected individuals with a history of alcohol problems was not associated with changes in medication adherence, alcohol consumption or markers of HIV disease progression. The failure to change adherence in a group at high risk for poor adherence, despite utilizing an intensive individual-focused patient intervention, supports the idea of addressing medication adherence with supervised medication delivery or markedly simplified dosing regimens.", "To compare patients' adherence to therapy, expectations, satisfaction with pharmacy services, and health-related quality of life (HRQOL) after the provision of pharmaceutical care with those of patients who received traditional pharmacy care.\n Randomized controlled cluster design.\n Sixteen community pharmacies in Alberta, Canada.\n Ambulatory elderly (> or = 65 years of age) patients covered under Alberta Health & Wellness's senior drug benefit plan and who were concurrently using three or more medications according to pharmacy profiles.\n Pharmacies were randomly assigned to either treatment (intervention) or control (traditional pharmacy care) groups. Patients at treatment pharmacies were recruited into the study, and pharmacists provided comprehensive pharmaceutical care services. Pharmacists at control pharmacies continued to provide traditional pharmacy care.\n Study participants' opinions, adherence to therapy, and scores on the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36).\n Compared with those of patients receiving traditional care, treatment patients' expectations that their pharmacist would perform activities congruent with pharmaceutical care changed over the study period. Treatment patients' satisfaction with the constructs \"trust,\" \"evaluation and goal setting,\" and \"communicates with doctor\" were also positively affected. HRQOL and patient adherence were not significantly affected by pharmaceutical care interventions.\n Successful implementation of a pharmaceutical care practice model has the potential to increase patients' satisfaction with their pharmacists' activities and may increase patients' expectations that pharmacists will work on their behalf to assist them with their health care needs. If pharmaceutical care affects patients' HRQOL, instruments more specific than the SF-36 may be needed to detect the differences.", "To determine the effectiveness of structured adherence counseling by pharmacists on the eradication of Helicobacter pylori when using a standard drug treatment regimen.\n Randomized controlled clinical trial.\n Nonprofit group-practice health maintenance organization (HMO).\n HMO primary care providers referred 1,393 adult dyspeptic patients for carbon 14 urea breath testing (UBT).\n Those whose tests were positive for H pylori (23.3%) were provided a standard antibiotic regimen and randomly assigned to receive either usual-care counseling from a pharmacist or a longer adherence counseling session and a follow-up phone call from the pharmacist during drug treatment. All subjects were given the same 7-day course of omeprazole, bismuth subsalicylate, metronidazole, and tetracycline hydrochloride (OBMT). Dyspepsia symptoms were recorded at baseline and following therapy.\n The main outcome was eradication of H pylori as measured by UBT at 3-month follow-up. Secondary outcomes were patient satisfaction and dyspepsia symptoms at 3-month follow-up.\n Of the 333 participants randomly assigned to treatment, 90.7% completed the 3-month follow-up UBT and questionnaires. Overall eradication rate with the OBMT regimen was 80.5% with no significant difference in eradication rates between the 2 groups (P=0.98). Conclusions In this study, additional counseling by pharmacists did not affect self-reported adherence to the treatment regimen, eradication rates, or dyspepsia symptoms but did increase patient satisfaction.", "The aim of the study was to assess the respective roles of the half-life of elimination of oral anticoagulants and patient education as causes of instability of anticoagulation level in patients on oral anticoagulant therapy. Patients were randomised to receive either warfarin (long half-life) or acenocoumarol (short half-life) and either intensive or standard education, according to a factorial design. Instability of oral anticoagulant therapy was evaluated by the percentage of INRs and the time within the target range, and the variability between successive measurements. Compliance was assessed by means of electronic pill bottles. Eighty-six patients were included. Apart from the variability index, instability was similar between groups. Correlations between compliance and instability were observed only in the acenocoumarol group. No difference was found between the education groups. In patients starting oral anticoagulant therapy, dose determination may be the most important factor contributing to instability.", "A high level of adherence to antiretroviral therapy is required for complete suppression of HIV replication, immunological and clinical effectiveness. We investigated whether cognitive behaviour therapy can improve medication adherence.\n Prospective randomized 1-year trial.\n Collaboration of HIV university outpatient clinic and psychotherapists in private practice.\n 60 HIV-infected persons on stable antiretroviral combination therapy and viral load below 50 copies/ml.\n Cognitive behaviour intervention in individual patients, in addition to standard of care.\n Feasibility and acceptance of intervention; adherence to therapy assessed using medication event monitoring system (MEMS) and self-report questionnaire; virological failure; psychosocial measures.\n The median number of sessions for cognitive behaviour intervention per patient during the 1-year trial was 11 (range 2-25). At months 10-12, mean adherence to therapy as assessed using MEMS was 92.8% in the intervention and 88.9% in the control group (P=0.2); the proportion of patients with adherence > or = 95% was 70 and 50.0% (P=0.014), respectively. While there was no significant deterioration of adherence during the study in the intervention arm, adherence decreased by 8.7% per year (P=0.006) in the control arm. No differences between the intervention group and standard of care group were found regarding virological outcome. Compared with the control group, participants in the intervention group perceived a significant improvement of their mental health during the study period.\n Cognitive behavioural support in addition to standard of care of HIV-infected persons is feasible in routine practice, and can improve medication adherence and mental health.", "To determine whether a patient education programme (PE) would improve rates of adherence to a slow acting antirheumatic drug and to assess any subsequent effect on patient outcome.\n A randomly controlled study comprising 100 patients with rheumatoid arthritis (49 control CG; 51 experimental EG) requiring D-penicillamine (DPA). The same practitioner saw patients on seven occasions, for the same length of time. The EG received 7 x 30 minute one to one sessions of PE, while the CG received standard management. The primary measure of adherence was a pharmacological marker (phenobarbitone) encapsulated with the DPA assayed at monthly intervals for six months. Plasma viscosity (PV), C reactive protein, articular index, morning stiffness, and pain score were used to assess outcome.\n 454 blood samples were collected and assayed and the pharmacological marker showed the EG to be significantly more adherent on more occasions than the CG (p<0.05). Patterns of adherence over time showed that at 12 weeks 86% (38/44) of those in the EG compared with 64% (29/45) of the CG remained adherent (p=0.01). These trends continued and by the end of the study 85% (29/34) of the EG compared with 55% (23/42) of the CG were taking their DPA as prescribed. Fifteen patients (12 from the EG) experienced side effects requiring study withdrawal and 14 patients requested study withdrawal (two from the EG). On study entry patients in the CG had significantly higher levels of PV than the EG and this remained so throughout the research. However, on completion, the health status of patients in both groups had improved significantly (p<0.01).\n PE significantly increased adherence to DPA and its effects persisted over a period of six months. No additional clinical benefit was detected in the EG in comparison with the CG." ]

[ "11900159", "10335753" ]

[ "How disclosing HMO physician incentives affects trust.", "Further validation and reliability testing of the Trust in Physician Scale. The Stanford Trust Study Physicians." ]

[ "Opinions are deeply divided over whether rewarding physicians for lowering costs decreases trust in physicians or insurers. To explore the effects of disclosing physician payment methods in HMOs, members of two similar HMO plans were randomized to intervention and control groups, and the experimental arm was told how the HMO paid their primary care physician. Separate disclosures were developed for each plan, one describing primarily capitation payment, and the other (mixed-incentive plan) describing fee-for-service payment with a bonus that rewards cost savings, satisfaction, and preventive services. The disclosures pointed out more of the positive than the negative features of these incentives. We found that the disclosures doubled the number of subjects with substantial knowledge of the physician incentives and halved the number with no knowledge. Nevertheless, the disclosures had no negative effects on trust of either physicians or insurers. The capitated plan disclosure had a small positive effect on trust of physicians. Disclosing the positive and negative features of incentives and increasing knowledge of these incentives does not, in the short term, reduce trust in physicians or insurers and may have a mild positive impact on physician trust, perhaps as a consequence of displaying candor and increasing understanding of positive features.", "To further validate and assess the reliability and validity of the Trust in Physician Scale.\n Consecutive adult patients (n = 414) from 20 community-based, primary care practices were enrolled in a prospective, 6-month study. At enrollment, subjects completed the 11-item Trust in Physician Scale plus measures of demographics, preferences for care, and satisfaction with care received from the physician. Continuity, satisfaction with care, and self-reported adherence to treatment were measured at 6 months. Reliability, construct validity, and predictive validity were assessed using correlation coefficients and analysis of variance techniques.\n The Trust in Physician Scale showed high internal consistency (Cronbach's alpha = .89) and good 1-month test-retest reliability (intraclass correlation coefficient = .77). As expected, trust increased with the length of the relationship and was higher among patients who actively chose their physician, who preferred more physician involvement, and who expected their physician to care for a larger proportion of their problems (P < 0.001 for all associations). Baseline trust predicted continuity with the physician, self-reported adherence to medication, and satisfaction at 6 months after adjustment for gender, age, education, length of the relationship, active choice of the physician, and preferences for care. After additional adjustment for baseline satisfaction with physician care, trust remained a significant predictor of continuity, adherence, and satisfaction.\n The Trust in Physician Scale has desirable psychometric characteristics and demonstrates construct and predictive validity. It appears to be related to, but still distinct from, patient satisfaction with the physician and, thus, provides a valuable additional measure for assessment of the quality of the patient-physician relationship." ]

[ "9322500", "16244538", "8998124", "10896910", "12557135" ]

[ "Effect of growth hormone, glutamine, and diet on adaptation in short-bowel syndrome: a randomized, controlled study.", "Growth hormone, glutamine, and an optimal diet reduces parenteral nutrition in patients with short bowel syndrome: a prospective, randomized, placebo-controlled, double-blind clinical trial.", "Low-dose recombinant human growth hormone increases body weight and lean body mass in patients with short bowel syndrome.", "Effect of high dose growth hormone with glutamine and no change in diet on intestinal absorption in short bowel patients: a randomised, double blind, crossover, placebo controlled study.", "Low-dose growth hormone in adult home parenteral nutrition-dependent short bowel syndrome patients: a positive study." ]

[ "The effects of parenteral growth hormone, glutamine supplementation, and a high carbohydrate-low fat (HCLF) diet on gut adaptation in short-bowel syndrome are unclear. The aim of this study was to compare effects of this treatment regimen and placebo in patients with short-bowel syndrome.\n A randomized, 6-week, double-blind, placebo-controlled, crossover study in 8 patients with short-bowel syndrome (average small bowel length, 71 cm; mean duration, 12.9 years) was performed. Active treatment was growth hormone (0.14 mg.kg-1.day-1), oral glutamine (0.63 g.kg-1.day-1), and the HCLF diet for 21 days. The weight, basal metabolic rate, nutrient and electrolyte balance, serum insulin-like growth factor I levels, D-xylose absorption, morphology and DNA proliferation of small intestinal mucosa, and gastrointestinal transit were evaluated. Treatments were compared by paired t test.\n Active treatment transiently increased body weight, significantly but modestly increased the absorption of sodium and potassium, and decreased gastric emptying. The assimilation of macronutrients, stool volumes, and morphometry of small bowel mucosa were not statistically different in the two treatment arms.\n Although treatment with growth hormone, glutamine, and HCLF diet for 3 weeks resulted in modest improvements in electrolyte absorption and delayed gastric emptying, there were no improvements in small bowel morphology, stool losses, or macronutrient absorption.", "To determine if growth hormone (GH) and glutamine (Gln) might allow for a reduction in parenteral nutrition (PN) in individuals with short bowel syndrome.\n Following massive intestinal resection, patients frequently sustain severe nutrient malabsorption and are dependent on PN for life. GH treatment with or without Gln might allow for a reduction in PN.\n A prospective, double-blind, randomized, placebo-controlled clinical trial performed in 41 adults dependent on PN. Following screening, patients were admitted to an in-house facility for 6 weeks. After 2 weeks of stabilization and dietary optimization, patients were randomized to one of 3 treatment arms (1:2:2 ratio): oral Gln (30 g/day) + GH placebo (control group, n = 9), Gln placebo + GH (0.1 mg/kg per day, n = 16), or Gln + GH (n = 16). Standard criteria based on clinical and laboratory measurements were followed to determine PN volume and content. After 4 weeks of treatment, patients were discharged and monitored; GH and GH placebo were discontinued, but the diet with Gln or Gln placebo was continued for 3 months.\n Patients receiving GH + Gln placebo + diet showed greater reductions in PN volume (5.9 +/- 3.8 L/wk, mean +/- SD), PN calories (4338 +/- 1858 calories/wk), and PN infusions (3 +/- 2 infusions/wk) than corresponding reductions in the Gln + diet group (3.8 +/- 2.4 L/wk; 2633 +/- 1341 calories/wk; 2 +/- 1 infusions/wk, P < 0.05). Patients who received GH + Gln + diet showed the greatest reductions (7.7 +/- 3.2 L/wk; 5751 +/- 2082 calories/wk; 4 +/- 1 infusions/wk, P < 0.001 versus Gln + diet). At the 3-month follow-up, only patients who had received GH + Gln + diet maintained significant reductions in PN (P < 0.005) compared with the Gln + diet.\n Treatment with GH + diet or GH + Gln + diet initially permitted significantly more weaning from PN than Gln + diet. Only subjects receiving GH + Gln + diet maintained this effect for at least 3 months.", "The authors investigate the effects of low dose recombinant human growth hormone (rhGH) on body composition and absorptive capacity in patients with short bowel syndrome from Crohn's disease.\n Patients with short bowel syndrome usually are malnourished because of malabsorption. The anabolic effects of high doses of rhGH have been tested in different clinical catabolic conditions, recently including patients with short bowel syndrome. The authors have investigated the effects of low-dose rhGH in short bowel syndrome in a placebo-controlled crossover clinical trial.\n Ten patients were treated with daily subcutaneous doses of rhGH/placebo (0.5 international units/kg-1 per week-1 = 0.024 mg/kg-1 per day-1) for 8 weeks in a randomized, double-blind, placebo-controlled crossover clinical trial with a minimum of 12 weeks wash-out. Absorptive capacity and biochemical parameters were investigated in a metabolic ward before treatment and during first and last week of treatment. Body composition was determined by DEXA-Scan (Lunar DPX, Scanexport Medical, Helsingborg, Sweden), impedance analysis, and whole body potassium counting.\n Low-dose rhGH doubled serum levels of insulin-like growth factor-1 (IGF-1) and increased body weight, lean body mass, and total body potassium by 5% (p < 0.05). Fat-free mass and total body water increased by 6% (p = 0.008). Increases in IGF-1 levels correlated with increases in fat-free mass (r = 0.77, p < 0.02). No significant changes in absorptive capacity of water, energy, or protein were detected.\n Eight weeks of low-dose rhGH treatment leads to increases in body weight, lean body mass, and fat-free mass in patients with short bowel syndrome, correlated to increases in IGF-1 levels.", "High dose growth hormone, glutamine, and a high carbohydrate diet may improve intestinal function in short bowel patients.\n To investigate if growth hormone with glutamine and no change in diet improved intestinal function.\n Eight short bowel patients were randomised in a double blind crossover study between placebo and growth hormone (mean 0.12 mg/kg/day) with oral (mean 28 g/day) and parenteral glutamine (mean 5.2 g/day) for 28 days. Balance studies were performed at baseline and five days after placebo and treatment were terminated. Dietary energy, carbohydrate, and fat were maintained as usual.\n Growth hormone with glutamine did not improve intestinal absorption of energy (baseline, placebo, treatment, mean: 46%, 48%, 46% of oral intake, respectively), carbohydrate (71%, 70%, 71%), fat (20%, 15%, 18%), nitrogen (27%, 18%, 19%), wet weight (37%, 39%, 31%), sodium (-16%, -16%, -36%), potassium (43%, 47%, 33%), calcium (-16%, -16%, -15%) or magnesium (-3%, 4%, 2%) compared with placebo or baseline (p>0.05) five days after treatment was terminated. All patients experienced adverse effects.\n Combined high dose growth hormone and glutamine administered for four weeks did not improve intestinal absorption five days after treatment was terminated in short bowel patients on their usual diet.", "Controversy surrounds a 3-week treatment with a high-dose (0.14 mg. kg(-1). day(-1)) growth hormone (GH), glutamine, and high carbohydrate diet in home parenteral nutrition (HPN)-dependent patients with short-bowel syndrome (SBS). This study assessed treatment with low-dose GH in these patients.\n Twelve adult HPN-dependent (duration, 7 +/- 1 years; mean +/- SEM) patients with SBS (small-bowel remnant length, 48 +/- 11 cm) who were on an unrestricted hyperphagic diet were randomized in a double-blind, placebo-controlled, crossover study. Patients received daily low-dose GH (0.05 mg. kg(-1). day(-1)) and placebo for two 3-week periods separated by a 1-week washout period. Net intestinal absorption of macronutrients was assessed using a duplicate diet; nutritional assessment and blood tests were performed. Data from each group were compared using Wilcoxon rank sum test.\n Treatment with GH increased intestinal absorption of energy (15% +/- 5%, P < 0.002), nitrogen (14% +/- 6%, P < 0.04), carbohydrates (10% +/- 4%, P < 0.04), and fat (12% +/- 8%, NS). The increased food absorption represented 37% +/- 16% of total parenteral energy delivery. Body weight (P < 0.003), lean body mass (P < 0.006), D-xylose absorption (P < 0.02), insulin-like growth factor 1 (P < 0.002), and insulin-like growth factor binding protein 3 (P < 0.002) increased, whereas uptake of GH binding protein decreased (P < 0.01), without any major adverse effect.\n Three weeks of low-dose GH significantly improved intestinal absorption in HPN-dependent SBS patients who were on a hyperphagic western diet." ]

[ "21442835" ]

[ "[Eighty cases of intractable hiccup treated by acupuncture]." ]

[ "nan" ]

[ "2278074", "11552913", "22114904", "7721374", "8617554", "8465408", "12196811", "17333792", "4661554", "8953680", "15191380", "8900567", "2694502", "15069729", "17589034" ]

[ "Mebendazole and metronidazole in giardial infections.", "Randomized clinical study of nitazoxanide compared to metronidazole in the treatment of symptomatic giardiasis in children from Northern Peru.", "Albendazole versus metronidazole in the treatment of adult giardiasis: a randomized, double-blind, clinical trial.", "A randomised multicentre study to compare the safety and efficacy of albendazole and metronidazole in the treatment of giardiasis in children.", "A comparative clinical trial of albendazole versus metronidazole in children with giardiasis.", "Albendazole as a treatment for infections with Giardia duodenalis in children in Bangladesh.", "[COMPARATIVE STUDY OF ALBENDAZOLE VERSUS NITROFURANS AND NITROIMIDAZOLES IN THE TREATMENT OF GIARDIASIS IN CHILDREN]", "Albendazole versus metronidazole in the treatment of patients with giardiasis in the Islamic Republic of Iran.", "Standard and single dosage regimens of \"Flagyl\" (metronidazole) in giardiasis in children.", "Alternative treatment protocols in giardiasis: a pilot study.", "Albendazole as an alternative therapeutic agent for childhood giardiasis in Turkey.", "[Randomized study comparing the safety and efficacy of albendazole and metronidazole in the treatment of giardiasis in children].", "Failure of mebendazole treatment in Giardia lamblia infection.", "Albendazole versus metronidazole treatment of adult giardiasis: An open randomized clinical study.", "Comparison of mebendazole with metronidazole and furazolidone in the treatment of Giardiasis in children." ]

[ "nan", "Enteric infection by Giardia intestinalis is a common cause of diarrhoea world-wide and a significant cause of morbidity in children.\n To compare the efficacy and safety of nitazoxanide and metronidazole in the treatment of diarrhoea caused by G. intestinalis in children.\n A total of 110 children presenting with diarrhoea caused by G. intestinalis were randomized to treatment with either a 3-day course of nitazoxanide (100 mg b.d., age range 2-3 years; 200 mg b.d., age range 4-11 years) or a 5-day course of metronidazole (125 mg b.d., age range 2-5 years; 250 mg b.d., age range 6-11 years). The patients were followed-up for a determination of clinical response 7 days after the initiation of treatment, and two subsequent stool samples were collected for parasitological examination.\n Diarrhoea had resolved in 47 children out of 55 (85%) in the nitazoxanide treatment group before the day 7 follow-up visit, compared to 44 out of 55 (80%) for metronidazole. Diarrhoea resolved within 4 days in most cases. Only mild, transient adverse events were reported.\n A 3-day course of nitazoxanide suspension is as efficacious as a standard 5-day course of metronidazole suspension in treating giardiasis in children.", "Albendazole (ABZ) is a benzimidazole carbamate compound currently in use for human medical practice against enterobiasis and soil-transmitted helminthiasis (STH); However, its spectrum of activity is broad and goes beyond these infections.\n This study compares the efficacy and safety of ABZ versus metronidazole (MTZ) in human giardiasis.\n A randomized, double-blind, clinical trial was carried out at the Centre of Hygiene, Epidemiology and Microbiology in Matanzas City, Cuba. Adult patients with confirmed symptomatic G. duodenalis mono-infection were randomly assigned to receive either ABZ [400 mg daily (n = 75)] or MTZ [250 mg t.i.d. (n = 75)], both for 5 days. Follow-up fecal samples were obtained at 3, 5, 7 days after treatment end.\n The efficacy was similar for both treatment groups: ABZ (82.6%) and MTZ (85.3%); p > 0.05. Side-effects including bitter taste, headache, vomiting and dizziness were significantly higher in the MTZ group. Abdominal pain was significantly higher in ABZ group.\n ABZ was found as effective as MTZ in the treatment of G. duodenalis infections in adult patients from Cuba and could be a useful drug in areas where co-infection with STH infections is common.", "A randomised control multicentre study to compare the safety and efficacy of albendazole and metronidazole in the treatment of giardiasis in children is reported. One hundred and fifty children of either sex (age range: 2-10 years) were randomised to receive either a single dose of 400 mg of albendazole suspension, or 22.5 mg/kg/day of metronidazole in 3 divided doses for 5 consecutive days. At the end of therapy, majority of children in both treatment groups were symptom free. Two days after completion of therapy, 97% of children in both treatment groups were giardia free in the stools. Side effects were noted in 3 children in the albendazole group, and in 20 children in the metronidazole group. We conclude that albendazole suspension is as effective as metronidazole in the treatment of giardial infection in children. It is safe and has fewer side effects as compared to metronidazole.", "The adverse effects and treatment failures to some of the currently recommended drugs for giardia infection have given rise to the need for alternative antigiardial agents. In an open, randomized parallel group study, the safety and efficacy of albendazole was compared with metronidazole for the treatment of giardiasis in children. Sixty four children of age ranging from 2-12 years was randomized to receive either albendazole suspension 400 mg daily for 5 days or metronidazole suspension 400 mg daily for 5 days or metronidazole suspension 7.5 mg/Kg thrice daily for 5 days. The mean days required for cure, as evident by absence of cysts and/or trophozoites in the stool specimen, were 3.7 +/- 1.4 and 4.5 +/- 1.1 days, respectively for children on albendazole and metronidazole therapy. Six children on metronidazole therapy developed anorexia 2 to 4 days after the treatment. Albendazole proved as effective as metronidazole in the treatment of giardia infection in children with the added advantage of the absence of anorexia.", "Albendazole, a broad spectrum anthelmintic recently shown to be active in vitro against Giardia duodenalis, was given at 4 different dosages and compared with metronidazole in the treatment of children in Bangladesh infected with Giardia. Three stools were collected over 10 d after treatment and examined microscopically. Albendazole was found to be effective: single doses of either 600 mg (n = 103) or 800 mg (n = 114) successfully treated 62% and 75% of infections, respectively; 400 mg given either once a day for 3 d (n = 116) or for 5 d (n = 115) successfully treated 81% and 95% of all infections, respectively. Albendazole given daily at 400 mg for 5 d was as effective as metronidazole, which cured 97% of infections (n = 230). Albendazole may thus be an alternative treatment for infections with Giardia, while the moderate efficacy of single doses may provide a benefit in addition to its effects on several species of intestinal helminths.", "A prospective, longitudinal, comparative, open and aleatory study in Jaen (Cajamarca--Peru), was performed during November 1997 and January of 1998. The objective was to demonstrate the efficacy and tolerance of Albendazol compared with Metronidazol, Furazolidona, Tinidazol and Secnidazol in the treatment of giardiasis in children. 79 children with giardiasis, confirmed by parasitologic studies were evaluated and distributed randorrily for aleatory code in A,B,C,D and E groups. The A group received Albendazol (5 days), the B group Metronidazol (10 days), the C group Furazolidona (10 days), the D group Tinidazol (1 d a) and the E group Secnidazol (1 d a); Clinical controls and coproparasitologic studies were performad during and after the treatment. The cl nical efficacy in the groups was of 100% and the efficacy coproparas tological of 94.1% with Albendazol, 93.3% with Secnidazol and 100% with Metronidazol. Furazolidona and Tinidazol. The global efficacy was excel lent with Al bendazol in 64,7% and in less than 40% with the other drugs, being the biggest pharmacological tolerance with Albendazol (82,3%) and Secnidazol (80%). We conclude that Albendazol is as effective as Metronidazol, Furazolidona, Tinidazol and Secnidazol but faster in eradicating the Giardia lambila in children and with better tolerance that Metronidazol, Furazolidona and Tinidazol. We consider necessary to control Epidemiological factor associated, to eradicate the parasite permanently.", "We examined the therapeutic effects of albendazole compared to metronidazole in 120 patients with giardiasis in Hamdan. Patients were randomized to receive albendazole (400 mg, once daily for 5 days) or metronidazole (250 mg, 3 times a day for 5 days). Demographic data of the patients, results of stool examination for Giardia trophozoites before and after treatment, and drug side-effects were recorded. After treatment 6 (10.0%) of the albendazole group had trophozoites compared with 14 (23.3%) of metronidazole group (P < 0.05). Patients in the albendazole group had fewer side-effects while 43.3% of the metronidazole group experienced a metallic taste and 35.0% experienced loss of appetite. Albendazole is an easy, safe and effective treatment for giardiasis.", "nan", "The aim of the study was to test new treatment protocols for giardiasis, which are less toxic, cheaper, and easier to use than the conventional treatment. 48 children who had been diagnosed as having giardiasis in a health-screening program involving 2 schools, were randomized to receive four different treatment protocols. The children were split into 4 treatment groups: I, mebendazole 100 mg t.i.d. for 1 day; II, mebendazole 100 mg t.i.d. for 7 days; III, metronidazole 15 mg/kg as one dose for 7 days; and IV, ornidazole 40 mg/kg as a single dose. The results were evaluated by microscopic examination of stools. The responses to the treatments revealed that the effectiveness of ornidazole was 100%, metronidazole 92.9%, mebendazole for 7 days 58.3%, and mebendazole for 1 day 41.7%. Minor side-effects were seen in only 3 children receiving ornidazole: 1 had urticaria, while the other 2 suffered from vertigo and nausea. The results of this study show that ornidazole as a single dose can be used as an alternative protocol for treating giardiasis. Further studies should be done to determine the safest effective total single dose.", "The efficacy of albendazole for the treatment of giardiasis has been indicated by previous in-vitro and in-vivo studies. In order to compare the therapeutic efficacy of albendazole and metronidazole, 107 Giardia-positive children (aged 3-15 years), diagnosed by three consecutive positive stool examinations, were enrolled in the study. Of these children, 52 were given a single daily dose of albendazole 10 mg/kg for 5 days, and 55 were given metronidazole 20 mg/kg daily in three doses for 7 days. Parasite eradication was achieved in 47 (90.4%) of 52 children treated with albendazole and 49 (89.1%) of 55 children treated with metronidazole (p > 0.05). These results suggest that albendazole is an effective treatment option for childhood giardiasis.", "An open, randomized study was carried out with 100 children to compare the efficacy and security of albendazole and metronidazole to eradicate Giardia lamblia. We included 100 patients in primary school age with giardiasis confirmed by parasitoscopic test who had not received treatment during the 2 previous months. A complete clinical study was performed. By using an aleatory code, the children were distributed in 2 groups: A and B. The clinical data was corroborated and the following tests were made: cell blood count, blood chemistry, direct and concentrated coproparasitoscopic study. Both groups were given an antiparasite treatment consisting of albendazole for group A or metronidazole for group B. Clinical, parasitological and blood controls were conducted before, during and after the treatment. A therapeutic efficacy of 94% and 98% for group A and B, respectively, was found. We concluded that albendazole and metronidazole are equally effective in a 5 days treatment period, but some undesirable effects may occur with metronidazole.", "nan", "To investigate the efficacy and tolerability of albendazole and metranidazole treatment in giardiasis.\n The open comparative randomized trial was carried out prospectively from December 1999 to July 2001 in Duzce City of Turkey. The diagnosis was based on the presence of signs and symptoms compatible with giardiasis including a positive stool examination of giardia cysts or trophozoite. Metranidazole group consisted of 29 patients and was given metranidazole 500 mg, three times a day for 5 d and albendazole group was consisted of 28 patients and was given albendazole 400 mg/d for 5 d.\n There were no significant differences in demographical and therapeutical effects and patient's compliance between both groups. But side effects were seen more in metranidazole group than in albendazole group.\n Albendazole is as effective as metranidazole in adults' giardiasis. Albendazole has less side effect potentials than metranidazole in the treatment of giardiasis.", "nan" ]

[ "10624430", "9676903", "3873960", "8013716", "7821456", "19158556", "20839670" ]

[ "Recurrent symptoms following traumatic corneal abrasion: prevalence, severity, and the effect of a simple regimen of prophylaxis.", "The influence of excimer laser ablation on recurrent corneal erosions: a prospective randomized study.", "Pathogenesis and treatment of recurrent erosion.", "The natural history and management of recurrent corneal erosion: a prospective randomised trial.", "Oral tetracycline in the treatment of recurrent corneal erosions.", "Diamond burr polishing for recurrent corneal erosions: results from a prospective randomized controlled trial.", "Efficacy of different excimer laser techniques in the management of recurrent corneal erosions." ]

[ "(i) To describe the course of ocular symptoms and recurrent corneal erosion (RCE) following traumatic corneal abrasion (TCA). (ii) To assess the efficacy of a regimen of nightly eye ointment in preventing symptoms and RCE.\n Patients presenting with TCA were treated with g. cyclopentolate 1% stat. and oc. chloramphenicol q.d.s. for 5 days. Eye pads were not used. For injuries caused by a fingernail, patients were randomised to receive either this 'standard regimen' alone, or to follow with a lubricating ointment (Lacrilube) nocte for 2 months. Follow-up was by telephone, using a symptom-based questionnaire. Recurrent symptoms were graded as: (i) none or minimal, (ii) mild, (iii) moderate (difficulty with some activities, or sought further opinion) and (iv) disabling (confirmed macroform RCE). After 2 years, case-notes were reviewed. The study is continuing, with further telephone follow-up taking place.\n Three-month follow-up was completed for 42 'fingernail' injuries and 32 'non-fingernail' TCAs. When treated with our standard regimen, 'mild' symptoms were reported in 10% of 'fingernail' and 10% of 'non-fingernail' injuries. Symptoms were 'moderate' in 0 and 12% respectively. Chisquared test confirmed a significantly higher prevalence of recurrent symptoms in the 'additional nightly ointment' group of 'fingernail' injuries (p = 0.016). Two macroform RCEs were confirmed by 2 years: one from each treatment group of 'fingernail' injury.\n When TCA is managed as above, there is a high prevalence of recurrent symptoms in the following 3 months. Additional nightly ointment appears to worsen prognosis. Macroform RCE is not common in the 2 years following TCA.", "We sought to evaluate the effect of excimer laser ablation on wound healing in patients with a history of recurrent corneal erosions.\n In a prospective, randomized study, 56 patients were treated either with epithelial removal only (n = 28) or epithelial removal followed by excimer laser ablation (n = 28). Patients were followed up at 1, 3, 6, and 12 months postoperatively. Visual acuity, refraction, intraocular eye pressure, and patients' symptoms, as well as their degree. were recorded before and after treatment. A recurrent erosion was regarded as a treatment failure. A Summit ExciMed 200 was used for the ablation. The laser was set to a 5-microm ablation by using a 6.5-mm in diameter treatment.\n With regard to ocular symptoms and recurrence of corneal erosions, treatment with excimer laser after epithelial removal was significantly better (p < 0.005) than epithelial removal alone on the healing of recurrent corneal erosions. No complications and no change in visual acuity, refraction, or intraocular pressure occurred.\n The use of excimer laser ablation after epithelial removal improved wound healing in patients with recurrent corneal erosions.", "A series of recurrent corneal erosions secondary to map-dot-fingerprint dystrophy is presented. Erosions were closely related to the Hudson-Stahli line, and this may be a factor in pathogenesis. Traumatic abrasions did not demonstrate such localisation, evidence that trauma is not a primary cause. A trial of management with therapeutic contact lenses versus topical medication was performed. Therapeutic contact lenses were shown to be inferior and had a high complication rate. Recurrent erosion is often considered an indication for therapeutic contact lenses, but this is questioned and great caution recommended in such use.", "One hundred and seventeen patients with a history of recurrent corneal erosion were recruited at initial hospital presentation. Seventy-five cases had a history of shallow corneal injury, 23 had epithelial basement membrane dystrophy (EBMD), 8 had both and 11 had neither. Mean age at presentation was 38 years and follow-up ranged from 6 to 16 months (mean 10.6 months). Sixty-one patients presented with a first acute corneal erosion, 21 with a subsequent acute corneal erosion and 35 with chronic symptoms. Patients with EBMD or a trauma-related focal epithelial basement membrane abnormality were more likely to present with chronic recurrent symptoms than trauma-related cases with no abnormality on examination. Both EBMD and trauma-related cases typically recurred in the lower half of the cornea, frequently in the midline (z = 7.3, p < 0.0001), suggesting an intrinsic or acquired abnormality of the epithelial basement membrane at this site. Only four of 82 acute episodes did not resolve by 5 days with simple patching, cycloplegia and topical antibiotic ointment. In the vast majority of patients presenting with an acute erosion, simple management measures only are required. Of 117 cases started on prophylactic ointment at night, further therapy due to prophylaxis failure was required in only 5. EBMD was a risk factor for failure (relative risk 10.77). There was no difference in efficacy between once daily prophylactic paraffin and hypertonic saline ointments (p = 0.17), suggesting they both have only a lubricant action.", "We report the results of a prospective, randomised controlled, 24 week trial to assess the efficacy of oral tetracycline and oral tetracycline with topical prednisolone in the treatment of recalcitrant recurrent corneal erosions, i.e. those which fail to respond to standard therapy. A total of 30 patients were randomly allocated to either standard treatment (group A), standard treatment and oral tetracycline (group B) or standard treatment, oral tetracycline and topical prednisolone (group C). Treatment groups B and C were instructed to perform daily lid hygiene. There was a significant reduction in the number of recurrent corneal erosions during the 24 week study period in group B (p = 0.04) and in group C (p = 0.0003) but not in group A (p = 0.66). There was a significant difference in the accelerated healing time of recurrent corneal microerosions between groups A and B (p = 0.001) and between groups A and C (p = 0.001). There was a significant improvement in the symptom scores during the study in treatment groups B and C (p = 0.005) but not in group A (p = 0.15). We conclude that lid hygiene and oral oxytetracycline 250 mg twice daily for 12 weeks with or without topical prednisolone for the first 7 days is beneficial in the management of recalcitrant recurrent corneal erosions.", "To evaluate the use of diamond burr polishing as an in-office treatment for recurrent corneal erosion (RCE).\n A double-masked randomized controlled trial was conducted. Patients with RCE secondary to trauma or anterior basement membrane dystrophy underwent epithelial debridement (ED) or diamond burr superficial keratectomy (DBSK) at the slit lamp. Patients were followed up for 6 months, and the recurrence rates of RCE and visual outcomes were compared.\n Forty-eight eyes of 48 patients were recruited. The mean +/- SD age was 38.3 +/- 12.9 years. Twenty-five patients underwent DBSK, and 23 patients received ED alone. There was no significant difference in the baseline demographics between the 2 groups. Kaplan-Meier survival analysis showed significantly less major and minor recurrences and less need for repeated surgical interventions in the DBSK group compared with the ED group (P < 0.001). Eyes in the DBSK group also had significantly lower mean magnitude of astigmatism after treatment compared to the ED group (P = 0.021).\n Diamond burr polishing is a safe, convenient, and inexpensive treatment option for the management of RCE and resulted in better outcomes compared to simple epithelial debridement.", "To investigate the efficacy of two excimer laser techniques for recurrent corneal erosions (RCEs).\n Of 100 patients with RCEs not responding to common treatments, 50 received transepithelial (group 1) and 50 received subepithelial (group 2) treatment of 20 pulses of a 193-nm excimer laser (170 J/cm(2)). Postoperative follow-up occurred at 4 and 52 weeks. Outcome measures were frequency of RCEs, haze formation, and refractive changes.\n At first follow-up, 7 patients (14%) in each group displayed recurrence. At second follow-up, 12 patients in group 1 (24%) and 10 patients in group 2 (20%) had RCE. Follow-up recurrence risk was 6% to 27% in both groups at 4 weeks and 13% to 38% in group 1 and 10% to 34% in group 2 at 52 weeks. The spherical equivalent remained unaffected in group 1, but a statistically significant change was observed in group 2.\n Excimer laser treatment (transepithelial and subepithelial) of RCEs can be performed successfully on the intact epithelium without adjunct therapy or pain. The transepithelial technique is a simple and relatively painless way to reduce the rate of RCE and is equivalent to the well-established subepithelial treatment.\n Copyright 2010, SLACK Incorporated." ]

[ "2145877", "12019686", "15676878", "18025444", "1533832", "9628709", "6458250", "10730357" ]

[ "The influence of prophylactic orthoses on abdominal strength and low back injury in the workplace.", "A field trial of back belts to reduce the incidence of acute low back injuries in New York City home attendants.", "An evaluation of a weightlifting belt and back injury prevention training class for airline baggage handlers.", "Lumbar supports to prevent recurrent low back pain among home care workers: a randomized trial.", "Controlled trial of a back support ('Lumbotrain') in patients with non-specific low back pain.", "Lumbar supports and education for the prevention of low back pain in industry: a randomized controlled trial.", "Evaluation of low back pain and assessment of lumbar corsets with and without back supports.", "[Effects of elastic lumbar belts on the effect of a muscle training program for patients with chronic back pain]." ]

[ "This study was designed to determine the effect of multimodal intervention and the prevention of back injury, and to evaluate the adverse side effects of using a lumbosacral corset in the workplace. Subjects were 90 male warehouse workers randomly selected from over 800 employees at a grocery distribution center. Subjects were assigned to three groups: true controls, no back school, no brace orthoses; back school only; and back school plus wearing a custom molded lumbosacral orthosis. Comparisons of pre-testing and 6-month follow-up post-testing for abdominal strength, cognitive data, work injury incidence and productivity and use of health care services were evaluated. Controls and training-only group showed no changes in strength productivity or lost time. Orthoses and training-group showed no changes in strength productivity or accident rate; however, they showed substantially less lost time. This study supports the concept of using education and prophylactic bracing to prevent back injury and reduce time loss. It appears that the use of intermittent prophylactic bracing has no adverse affects on abdominal muscle strength and may contribute to decreased lost time from work injuries.", "To determine the effect of black belt use on the incidence of low back injury in home attendants, a cluster-randomized trial involving employees of nine home attendant agencies in New York City was conducted. Nine agencies employing 12,772 home attendants between June 1997 and September 1999 were randomized into three groups-one group received back belts with use instruction, one group received lifting advice only, and one group served as a control. Low back injury rates per 100 full-time equivalents and rate ratios adjusted for potential confounders were estimated with random-effects Poisson regression. The back-belt group had a lower rate of low back injury than did those in both the advice-only and control groups, though the differences were marginally significant. Age, body mass index, history of back injury, years worked as a home attendant, and level of exercise were associated with risk of low back injury. The findings suggest that use of back belts is associated with some reduction in risk of low back injury.", "This study evaluated the efficacy of a commercially available weightlifting belt in relation to reduction of lumbar injury incident rate and severity of injuries over an 8-month period. The study used 642 baggage handlers working for a major airline company as participants. Four treatment groups were randomly selected: a group receiving the belt only, a group receiving a 1 h training class only, a group receiving both a belt and a 1 h training class, and a control group receiving nothing. Two treatment groups were added which contained participants who discontinued use of the belt prior to the end of an 8-month study period. Results indicated that there were no significant differences for total lumbar injury incident rate, restricted workday case injury incident rate, lost workdays and restricted workdays rate, and worker's compensation rates. There was, however, a marginal significant difference for lost workday case injury incident rate. Groups with participants who wore the belt for a while then discontinued its use had a higher lost day case injury incident rate than did either the group receiving training only or the control group. Compliance was an overriding factor as the belt questionnaire response indicated that 58% of participants in the belt groups discontinued use of the belt before the end of 8 months. Comments made on the survey forms indicated that the belt was too hot. Similarly, comments suggested that the belt rubbed, pinched, and bruised ribs. Based on these results, the weightlifting belt used for this study cannot be recommended for use in aid of lifting during daily work activities of baggage handlers. Results indicate that use of the belts may, in fact, increase the risk of injury when not wearing a belt following a period of wearing a belt. As industries are experimenting with the use of belts, it is recommended that great care be taken in any further evaluation and close attention directed towards injuries which occur when not wearing the belt following a period of wearing the belt (ie, off-the-job injuries).", "People use lumbar supports to prevent low back pain. Secondary analyses from primary preventive studies suggest benefit among workers with previous low back pain, but definitive studies on the effectiveness of supports for the secondary prevention of low back pain are lacking.\n To determine the effectiveness of lumbar supports in the secondary prevention of low back pain.\n Randomized, controlled trial.\n Home care organization in the Netherlands.\n 360 home care workers with self-reported history of low back pain.\n Short course on healthy working methods, with or without patient-directed use of 1 of 4 types of lumbar support.\n Primary outcomes were the number of days of low back pain and sick leave over 12 months. Secondary outcomes were the average severity of low back pain and function (Quebec Back Pain Disability scale) in the previous week.\n Over 12 months, participants in the lumbar support group reported an average of -52.7 days (CI, -59.6 to -45.1 days) fewer days with low back pain than participants who received only the short course. However, the total sick days in the lumbar support group did not decrease (-5 days [CI, -21.1 to 6.8 days]). Small but statistically significant differences in pain intensity and function favored lumbar support.\n Study participants were unblinded, and a substantial amount of missing data required imputation. Objective data on sick days due to low back pain were not available.\n Adding patient-directed use of lumbar supports to a short course on healthy working methods may reduce the number of days when low back pain occurs, but not overall work absenteeism, among home care workers with previous low back pain. Further study of lumbar supports is warranted.", "A randomized, controlled, parallel-group clinical trial was carried out in general practice to assess the clinical efficacy of a new back support ('Lumbotrain') compared with 'standard therapy' of advice on rest and lifestyle in the treatment of patients with non-specific low back pain. A total of 216 patients entered this study (111 'Lumbotrain' group, 105 control group). All patients were allowed to take 1 g paracetamol up to 4-times daily if necessary for control of pain. Self-assessments were made daily by patients, over a period of 21 days, of pain levels at rest, on activity, at night, and limitation of activity using visual analogue scales. Details were also recorded of their ability to work or not, and the number of doses of paracetamol taken. At the end of the study period, patients assessed their overall response to treatment and those in the 'Lumbotrain' group were questioned on the comfort and ease of use of the back support. A clinical examination was carried out by the doctor at the start and end of the study period and an assessment made of the total range of active and passive back movement. Analysis of the daily diary records showed there were progressive, significant reductions in mean scores for all the pain and activity criteria in both groups and these were significantly greater in the 'Lumbotrain' group from Day 7 onwards. The times taken for reduction of symptom scores to 10% of initial values were significantly less in the 'Lumbotrain' group, such a degree of recovery occurring 2 to 4 days more rapidly than in the control group. A significantly higher proportion of patients in the 'Lumbotrain' group became able to work normally. After 3 weeks, 85% of patients in the 'Lumbotrain' group could work normally, as compared with 67% in the control group (p less than 0.02). Total analgesic consumption during the trial was significantly lower (p less than 0.0001) in the 'Lumbotrain' group (median 24.5 doses) than in the control group (median 51 doses). Overall clinical assessment scores were significantly superior in the 'Lumbotrain' group (p less than 0.002). Improvement was seen in 106 (95%) of 111 patients in the 'Lumbotrain' group, as compared with 79 (77%) of 103 of those in the control group (p less than 0.0002).(ABSTRACT TRUNCATED AT 400 WORDS)", "Low back pain is a frequent and costly health problem. Prevention of low back pain is important both for the individual patient and from an economic perspective.\n To assess the efficacy of lumbar supports and education in the prevention of low back pain in industry.\n A randomized controlled trial with a factorial design.\n The cargo department of an airline company in the Netherlands.\n A total of 312 workers were randomized, of whom 282 were available for the 6-month follow-up.\n Subjects were randomly assigned to 4 groups: (1) education (lifting instructions) and lumbar support, (2) education, (3) lumbar support, and (4) no intervention. Education consisted of 3 group sessions on lifting techniques with a total duration of 5 hours. Lumbar supports were recommended to be used during working hours for 6 months.\n Low back pain incidence and sick leave because of back pain during the 6-month intervention period.\n Compliance with wearing the lumbar support at least half the time was 43%. In the 282 subjects for whom data were available, no statistically significant differences in back pain incidence (48 [36%] of 134 with lumbar support vs 51 [34%] of 148 without, P=.81) or in sick leave because of low back pain (mean, 0.4 days per month with lumbar support vs 0.4 days without, P=.52) were found among the intervention groups. In a subgroup of subjects with low back pain at baseline, lumbar supports reduced the number of days with low back pain per month (median, 1.2 vs 6.5 days per month; P=.03).\n Overall, lumbar supports or education did not lead to a reduction in low back pain incidence or sick leave. The results of the subgroup analysis need to be confirmed by future research. Based on our results, the use of education or lumbar supports cannot be recommended in the prevention of low back pain in industry.", "A method is described for evaluating the progress of patients with back pain. Various symptoms were scored on analogue scales and spinal motion was measured by various techniques. These data were integrated to make subjective and objective indices respectively. Reasonable reproducibility of the measurements was obtained. This technique was used to elucidate the role of the lumbar support in surgical corsets in relief of back pain. Sufferers from back pain were randomly allocated to corsets with and without lumbar supports. There was significant improvement in those with a support compared with those without. On the other hand objective changes measured with the corset removed did not differ between the 2 groups. This study indicates that the spinal support in a lumbosacral corset makes a significant contribution towards the relief of symptoms.", "Aim of the study was to evaluate the influence of elastic lumbar belts on the effect of muscle training for patients with low back pain.\n 97 male subjects aged from 23 to 42 years with and without low back pain participated in the investigation. The low back pain patients (n = 63) were randomized into a training group without and a training group with elastic lumbar belts and a control group. The subjects with healthy backs (n = 34) were divided age-matched into a training group with elastic lumbar belts and a control group. The three training groups took part in a muscle strenghtening program over 8 weeks. The control groups did not receive any alternative physiotherapeutic treatment. All groups were tested at the beginning, after 8 weeks and further 6 months later.\n The data obtained for the control groups remained virtually unchanged over the period of investigation. However, a significant increase of the muscle flexibility of the lower limbs could be proved for the training groups. Furthermore the coordination between the lumbar spine and pelvis when flexing the trunk deeply forward was more leveled out for the training groups with patients suffered low back pain. The results confirmed a reduction for pain severity and for limitations in activities of daily living as well. The modifications for the criteria investigated were significant stronger for the training group with patients using the elastic lumbar belt.\n The effectiveness of the muscle strengthening program for patients with low back pain could be improved significantly by means of the elastic lumbar belt as an applicable therapy instrument in the functional rehabilitation of spinal injuries." ]

[ "12453954", "12106522", "9952201", "12610037", "12547849", "11692178", "9796881" ]

[ "Effects of tadalafil on erectile dysfunction in men with diabetes.", "[Efficacy and safety of sildenafil in men with type 2 diabetes mellitus and erectile dysfunction].", "Sildenafil for treatment of erectile dysfunction in men with diabetes: a randomized controlled trial. Sildenafil Diabetes Study Group.", "Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double-blind placebo-controlled fixed-dose study.", "Sildenafil citrate for treatment of erectile dysfunction in men with type 1 diabetes: results of a randomized controlled trial.", "Sildenafil citrate for the treatment of erectile dysfunction in men with Type II diabetes mellitus.", "Sildenafil: study of a novel oral treatment for erectile dysfunction in diabetic men." ]

[ "To evaluate the efficacy and safety of tadalafil taken as needed before sexual activity by men with diabetes and erectile dysfunction (ED).\n Men with type 1 or type 2 diabetes and a minimum 3-month history of ED were randomly allocated to one of three groups: placebo (n = 71), tadalafil 10 mg (n = 73), or tadalafil 20 mg (n = 72) taken up to once daily for 12 weeks. Changes from baseline in mean scores on the erectile function domain of the International Index of Erectile Function (IIEF) and changes from baseline in the proportion of \"yes\" responses to question 2, \"Were you able to penetrate?,\" and 3, \"Were you able to complete intercourse?,\" of the Sexual Encounter Profile were coprimary outcome measures.\n A total of 191 (88%) of 216 patients completed the study. Treatment with tadalafil significantly improved all primary efficacy variables, regardless of baseline HbA(1c) level. Therapy with tadalafil also significantly improved a number of secondary outcome measures, including changes in other IIEF domains, individual IIEF questions, and percentage of positive responses to a global assessment question measuring erection improvement. Treatment with tadalafil did not alter mean HbA(1c) levels. Tadalafil was well tolerated, with headache and dyspepsia being the most frequent adverse events with active treatment.\n Tadalafil therapy significantly enhanced erectile function and was well tolerated by men with diabetes and ED.", "Erectile dysfunction is a common complication in patients with diabetes mellitus, which impairs quality of life, decreases self-esteem and can affect partners relationships. Sildenafil improves nitric oxide-dependent relaxation of smooth muscle in corpora cavernosa--induced by an increase in cGMP via inhibition of phosphodiesterase 5.\n Multicenter, randomized, double-blind, placebo-controlled study with flexible doses of sildenafil. The study was performed in 16 centers and recruited a total of 112 subjects with diabetes mellitus who had erectile dysfunction. At the start and end of the study, the following questionnaires were administered: International Index of Erectile Function (IIEF), Global Efficacy Assessment Question and Quality of Life Questionnaire (Fugl-Meyer). Of the 112 initially recruited patients, 92 received treatment, sildenafil in 44 and placebo in 48.\n A clear improvement was observed in the capacity to achieve and maintain an erection; 55.3% diabetic patients receiving sildenafil had at least one successful sexual intercourse (15.6% in the placebo group). In addition, significant improvements were seen in other aspects of the sexual activity of treated subjects. Among those treated with sildenafil, 46.3% reported a clear improvement of erections as compared to their baseline conditions (i.e, prior to treatment) vs only 14.9% in the placebo group. The percentage of a successful intercourse clearly increased, from 6 to 49%. Sildenafil was well-tolerated. Side effects were mild and transient.\n Sildenafil is an effective, safe treatment for erectile dysfunction in diabetic patients.", "Erectile dysfunction is common in men with diabetes.\n To assess the efficacy and safety of oral sildenafil citrate in the treatment of erectile dysfunction in men with diabetes.\n A multicenter, randomized, double-blind, placebo-controlled, flexible dose-escalation study conducted May through November 1996.\n Patients' homes and 19 clinical practice centers in the United States.\n A total of 268 men (mean age, 57 years) with erectile dysfunction (mean duration, 5.6 years) and diabetes (mean duration, 12 years).\n Patients were randomized to receive sildenafil (n = 136) or placebo (n = 132) as needed, but not more than once daily, for 12 weeks. Patients took the study drug or placebo 1 hour before anticipated sexual activity. The starting dose of sildenafil citrate was 50 mg, with the option to adjust the dose to 100 mg or 25 mg based on efficacy and tolerability, to be taken as needed.\n Self-reported ability to achieve and maintain an erection for sexual intercourse according to the International Index of Erectile Function and adverse events.\n Two hundred fifty-two patients (94%) completed the study (131/136 in the sildenafil group, 121/132 in the placebo group). By intention-to-treat analysis, at 12 weeks, 74 (56%) of 131 patients in the sildenafil group reported improved erections compared with 13 (10%) of 127 patients in the placebo group (P<.001). The proportion of men with at least 1 successful attempt at sexual intercourse was 61 % (71/ 117) for the sildenafil group vs 22% (25/114) for the placebo group (P<.001). Adverse events related to treatment were reported for 22 (16%) of 136 patients taking sildenafil and 1 (1%) of 132 patients receiving placebo. The most common adverse events were headache (11% sildenafil, 2% placebo), dyspepsia (9% sildenafil, 0% placebo), and respiratory tract disorder (6% sildenafil, 2% placebo), predominantly sinus congestion or drainage. The incidence of cardiovascular adverse events was comparable for both groups (3% sildenafil, 5% placebo).\n Oral sildenafil is an effective and well-tolerated treatment for erectile dysfunction in men with diabetes.", "This study evaluated the efficacy and safety of vardenafil treatment for erectile dysfunction (ED) in men with diabetes.\n In this prospective multicenter double-blind placebo-controlled fixed-dose parallel-group phase III trial, 452 patients with diabetes (type 1 or type 2) and ED were randomized to take 10 or 20 mg vardenafil or placebo as needed for 12 weeks. Efficacy responses were assessed by International Index of Erectile Function domain scores, rates of vaginal penetration and successful intercourse, and a global assessment question (GAQ) about erection improvement during the previous 4 weeks.\n After 12 weeks of treatment, a dose-dependent (P = 0.02) improvement in erections was noted for the GAQ, with 57 and 72% of men taking 10 mg or 20 mg vardenafil, respectively, reporting improved erections, in contrast to 13% after taking placebo (P < 0.0001). For the erectile function domain, dose-dependent (P = 0.03) final scores for the 10- and 20-mg dose were 17.1 and 19.0 compared with 12.6 for placebo (P < 0.0001). Both vardenafil doses significantly enhanced the rates of successful penetration (P < 0.0001) and successful intercourse (P < 0.0001) compared with placebo. Vardenafil treatment was effective in increasing intercourse success rates at all levels of baseline ED severity, at each level of plasma HbA(1c), and for type 1 and 2 diabetes. Treatment-emergent adverse events were primarily mild to moderate headache (<or=13%), flushing (<or=10%), and rhinitis (<or=10%).\n Vardenafil statistically improved erectile function and was generally well tolerated in these diabetic patients with ED.", "In the 5-10% of diabetic men with type 1 diabetes, erectile dysfunction (ED) may be a particularly common and unwanted complication. This is the first study focusing exclusively on the effects of sildenafil in men with type 1 diabetes and ED.\n A total of 188 patients were entered into a double-blind, placebo-controlled, parallel-group, flexible-dose study and were randomized to receive sildenafil (25-100 mg; n = 95) or placebo (n = 93) for 12 weeks. Efficacy was evaluated using questions three (Q3; achieving an erection) and four (Q4; maintaining an erection) from the International Index of Erectile Function (IIEF), a global efficacy question (GEQ; \"Did treatment improve your erections?\"), and a patient event log of sexual activity.\n Improvements in mean scores from baseline to end-of-treatment for IIEF Q3 (35.7 vs. 19.9%) and Q4 (68.4 vs. 26.5%) were significant in patients receiving sildenafil compared with those receiving placebo (P = 0.0001). Moreover, the percent of improved erections (GEQ, 66.6 vs. 28.6%) and successful intercourse attempts (63 vs. 33%) was significantly increased with sildenafil compared with placebo. Improvements in sexual function were seen irrespective of the degree of ED severity. Adverse events were generally mild to moderate in severity, with headache (20 vs. 8%), flushing (18 vs. 3%), and dyspepsia (8 vs. 1%) reported more often in the sildenafil than in placebo-treated patients.\n Treatment with sildenafil for ED was effective, resulting in an increased percentage of successful attempts at intercourse, and was well tolerated among men with type 1 diabetes.", "Ninety percent of all men with diabetes have Type II (non-insulin-dependent) diabetes mellitus, and erectile dysfunction (ED) is common in this patient group. This study evaluated the effects of sildenafil on men with erectile dysfunction and Type II diabetes and compared the results with glycated haemoglobin concentrations and chronic diabetic complications.\n Patients (mean age, 59 years) in this double-blind, placebo-controlled trial were randomised to sildenafil (25-100 mg; n = 110) or matching placebo (n = 109) for 12 weeks. Primary criteria for efficacy included questions 3 (achieving an erection) and 4 (maintaining an erection) from the International Index of Erectile Function (IIEF, score range, 0-5). Secondary outcome measures included a global efficacy question (GEQ), patient event logs, a life satisfaction checklist, and the remaining IIEF questions.\n After 12 weeks, the mean scores for questions 3 and 4 had improved significantly in patients receiving sildenafil (3.42 +/- 0.23 and 3.35 +/- 0.24) compared with placebo (1.86 +/- 0.22 and 1.84 +/- 0.23; p < 0.0001). Similarly, the GEQ score was higher in the sildenafil (64.6 %) than the placebo group (10.5 %). Even when correlating efficacy with glycated haemoglobin concentrations ( < or = 8.3 % or > 8.3 %, the median concentration found in this study) or the number of diabetic complications (0 or > or = 1), the mean scores for the GEQ and questions 3 and 4 from the IIEF remained higher for all the sildenafil groups compared with the placebo groups (p < 0.0001).\n Sildenafil was well-tolerated and effective in improving erectile dysfunction in men with Type II diabetes, even in patients with poor glycaemic control and chronic complications.", "The efficacy and safety of oral sildenafil, a potent inhibitor of phosphodiesterase type 5, were evaluated in men with diabetes mellitus and erectile dysfunction (ED). Twenty-one men (aged 42-65 years) were enrolled in a double-blind, placebo-controlled, three-way crossover study conducted in two parts. In part I, the effect of a single dose (25 mg or 50 mg) of sildenafil or placebo on penile rigidity was assessed by penile plethysmography during visual sexual stimulation. In part II, daily diary records of erectile activity and a global efficacy question were used to evaluate once-daily dosing with 25 mg or 50 mg of sildenafil or placebo for 10 days. After a single 50 mg dose of sildenafil, the adjusted geometric mean duration (min) of penile rigidity >60% at the base of the penis during visual sexual stimulation was significantly increased (10.1 min) compared with placebo (2.8 min; p = 0.0053). In part II, sildenafil significantly increased the number of erections considered sufficiently hard for vaginal penetration compared with placebo (p = 0.0005). Improved erections were reported by 50% and 52% of patients treated with 25 mg and 50 mg of sildenafil, respectively, compared with 10% of those receiving placebo (p values < 0.05). Adverse events were mostly mild or moderate in nature and included muscular pains, headache, and dyspepsia. Sildenafil is a well-tolerated and potentially efficacious oral treatment for ED in men with diabetes mellitus." ]

[ "1596225", "1596224" ]

[ "Vitrectomy with silicone oil or perfluoropropane gas in eyes with severe proliferative vitreoretinopathy: results of a randomized clinical trial. Silicone Study Report 2.", "Vitrectomy with silicone oil or sulfur hexafluoride gas in eyes with severe proliferative vitreoretinopathy: results of a randomized clinical trial. Silicone Study Report 1." ]

[ "Between September 1987 and October 1990, 265 eyes with rhegmatogenous retinal detachment and severe (with a classification of at least C-3) proliferative vitreoretinopathy were treated with vitrectomy and randomized to treatment with perfluoropropane gas or silicone oil; 131 eyes had undergone no prior vitrectomy (group 1) while 134 eyes had undergone vitrectomy with intraocular gas tamponade (group 2). At the last examination, there were no differences between perfluoropropane gas and silicone oil in achieving visual acuity greater than or equal to 5/200 (43% vs 45% for group 1, 38% vs 33% for group 2) and complete posterior retinal reattachment (73% vs 64% for group 1, 73% vs 61% for group 2). For group 1 eyes followed up for at least 18 months, there was an advantage favoring perfluoropropane gas in achieving complete posterior retinal reattachment (83% vs 60% at 36 months, P = .045). The rates of reoperation and keratopathy were similar, while hypotony was more prevalent in eyes randomized to perfluoropropane gas (group 2). Regardless of tamponade, groups 1 and 2 had similar anatomic and visual success. However, hypotony was twice as prevalent in group 2 (perfluoropropane), and the prevalence of keratopathy increased with follow-up in group 2 (either tamponade). Either tamponade produced better results than those seen with sulfur hexafluoride gas (Silicone Study Report 1).", "Between September 1985 and September 1987, 101 eyes with rhegmatogenous retinal detachment and severe (with a classification of at least C-3) proliferative vitreoretinopathy but without prior vitrectomy were treated with vitrectomy and randomized to either a mixture of 20% sulfur hexafluoride gas and air or to 1000 centistokes of silicone oil. Between 50% and 60% of eyes that received silicone oil had visual acuity better than or equal to 5/200 compared with 30% to 40% of the eyes that received sulfur hexafluoride gas (P less than .05). Macula attachment was more frequent in eyes that received silicone oil than in those that received sulfur hexafluoride gas (80% vs 60%, P less than .05). Hypotony was more prevalent in eyes with a detached macula (40% to 50% for sulfur hexafluoride gas vs 25% to 30% for silicone oil) when compared with those with attached maculas (less than 5% for either modality). Keratopathy was more prevalent in eyes with detached maculas (about 55% to 60% for either modality) compared with eyes with attached maculas (25% to 30% for sulfur hexafluoride gas vs 10% to 15% for silicone oil). In a companion article, we show that these differences between a gas tamponade and silicone oil are not found for perfluoropropane gas." ]

[ "18370559", "15903284", "10974963", "15385274", "19093922", "11298072", "7935897", "16905764" ]

[ "Drug use in Swedish nursing homes.", "Does the addition of a pharmacist transition coordinator improve evidence-based medication management and health outcomes in older adults moving from the hospital to a long-term care facility? Results of a randomized, controlled trial.", "Effects of a pharmacist's medication review in nursing homes. Randomised controlled trial.", "An outreach geriatric medication advisory service in residential aged care: a randomised controlled trial of case conferencing.", "Effect of computerized provider order entry with clinical decision support on adverse drug events in the long-term care setting.", "Outcomes of a randomized controlled trial of a clinical pharmacy intervention in 52 nursing homes.", "[Drug therapy in a nursing home; favorable effect of feedback by the pharmacist on family physician's prescribing behavior].", "Clinical medication review by a pharmacist of elderly people living in care homes--randomised controlled trial." ]

[ "To describe the overall drug use in Swedish nursing homes and to comment on the impact of regular multidisciplinary team interventions on the quantity of inappropriate medications.\n This randomised, controlled trial was carried out in a sample of 33 nursing homes, 15 experimental homes and 18 control homes, representing 5% of all Swedish nursing homes.\n The sample consisted of 1854 nursing home residents with an average age of 83 years. 70% of the residents were female and 42% had a documented diagnosis of dementia. An additional 5% had a psychotic disorder and 7% had a diagnosis of depression.\n Lists of each resident's prescriptions were collected 1 month before and 1 month after the 12-month intervention. Measures included the proportion of residents receiving any particular drug. The number of drugs classified by guidelines as inappropriate was also measured before and after the intervention period.\n The nursing home residents were prescribed on average 7.7 medications, the majority on a regular basis. The most frequently prescribed group of drugs was laxatives, followed by psychotropic agents and cardiovascular drugs. Some groups of drugs decreased in the intervention homes.\n Extensive and somewhat inappropriate drug use in Swedish nursing homes is a significant and serious problem. Careful monitoring is necessary to ensure well tolerated drug therapy in this frail population. Neither written information from the Medical Products Agency, nor the campaign in the pharmacies alone had an impact on drug use in Swedish nursing homes. Multidisciplinary team discussions contributed to improved drug use, but more research is needed to understand the mechanisms behind this finding.", "Poorly executed transfers of older patients from hospitals to long-term care facilities carry the risk of fragmentation of care, poor clinical outcomes, inappropriate use of emergency department services, and hospital readmission.\n This study was conducted to assess the impact of adding a pharmacist transition coordinator on evidence-based medication management and health outcomes in older adults undergoing first-time transfer from a hospital to a long-term care facility.\n This randomized, single-blind, controlled trial enrolled hospitalized older adults awaiting transfer to a long-term residential care facility for the first time. Patients were randomized either to receive the services of the pharmacist transition coordinator (intervention group) or to undergo the usual hospital discharge process (control group). The intervention included medication-management transfer summaries from hospitals, timely coordinated medication reviews by accredited community pharmacists, and case conferences with physicians and pharmacists. The primary outcome was the quality of prescribing, measured using the Medication Appropriateness Index (MAI). Secondary outcomes were emergency department visits, hospital readmissions, adverse drug events, falls, worsening mobility, worsening behaviors, increased confusion, and worsening pain.\n One hundred ten older adults (67 women, 43 men; mean [SD] age, 82.7 [6.4] years) were recruited from 3 metropolitan hospitals and assigned to 85 metropolitan long-term care facilities. Fifty-six patients were randomized to the intervention group and 54 to the control group; 44 patients in each group were evaluable at 8-week follow-up. There were no significant differences in baseline characteristics between treatment groups, with the exception of the number of medications discontinued during hospitalization: a mean of 1.1 more drugs was discontinued in the control group compared with the intervention group (P = 0.011). The majority of patients (35 [62.5%] in the intervention group, 41 [76.0%] in the control group) changed physicians as part of the transition to a long-term care facility. At 8-week follow-up, there was no change in MAI from baseline in the intervention group, whereas it had worsened in the control group (mean [95% CI], 2.5 [1.4-3.7] vs 6.5 [3.9-9.1], respectively; P = 0.007). Patients who received the intervention and were alive at follow-up exhibited a significant protective effect of the intervention against worsening pain (relative risk ratio [95% CI], 0.55 [0.32-0.94]; P = 0.023) and hospital usage (i.e., the combination of emergency department visits and hospital readmissions) (0.38 [0.15-0.99]; P = 0.035), but did not differ from control patients in terms of adverse drug events (1.05 [0.66-1.68]), falls (1.19 [0.71-1.99]), worsening mobility (0.39 [0.13-1.15]), worsening behaviors (0.52 [0.25-1.10]), or increased confusion (0.59 [0.28-1.22]). When data for patients who had died were included, the intervention had no effect on hospital usage in all patients (0.58 [0.28-1.21]).\n Older people transferring from hospital to a long-term care facility are vulnerable to fragmentation of care and adverse events. In this study, use of a pharmacist transition coordinator improved aspects of inappropriate use of medicines across health sectors.", "Older people in nursing and residential homes often have complex disabilities and behavioural disturbances. Recent publicity has highlighted the dangers of medication in this group, and controls over prescribing have been suggested.\n To investigate the effect of a review of medication by a pharmacist.\n An 8-month prospective trial of an active medication review by a pharmacist was carried out on 330 residents in nursing homes in Manchester.\n The intervention group experienced greater deterioration in cognitive function and behavioural disturbance than the control group, but the changes in depression and quality of life were similar for both groups. The number of drugs prescribed fell in the intervention group, but not in the control group, with a corresponding saving in drug costs. The number of deaths was significantly smaller in the intervention homes during the intervention period (4 v. 14) but not overall during the study period as a whole (26 v. 28).\n This clinical intervention reduced the number of medicines prescribed to elderly people in nursing homes, with minimal impact on their morbidity and mortality.", "efficient strategies are needed to provide specialist advice in nursing homes to ensure quality medical care. We describe a case conference intervention involving a multidisciplinary team of health professionals.\n to evaluate the impact of multidisciplinary case conferences on the appropriateness of medications and on patient behaviours in high-level residential aged care facilities.\n cluster-randomised controlled trial.\n ten high-level aged care facilities.\n 154 residents with medication problems and/or challenging behaviours were selected for case conference by residential care staff.\n two multidisciplinary case conferences involving the resident's general practitioner, a geriatrician, a pharmacist and residential care staff were held at the nursing home for each resident.\n outcomes were assessed at baseline and 3 months. The primary outcome was the Medication Appropriateness Index (MAI). The behaviour of each resident was assessed via the Nursing Home Behaviour Problem Scale.\n 45 residents died before follow-up. Medication appropriateness improved in the intervention group [MAI mean change 4.1, 95% confidence interval (CI) 2.1-6.1] compared with the control group (MAI mean change 0.4, 95% CI -0.4-1.2; P < 0.001). There was a significant reduction in the MAI for benzodiazepines (mean change control -0.38, 95% CI -1.02-0.27 versus intervention 0.73, 95% CI 0.16-1.30; P = 0.017). Resident behaviours were unchanged after the intervention and the improved medication appropriateness did not extend to other residents in the facility.\n multidisciplinary case conferences in nursing homes can improve care. Outreach specialist services can be delivered without direct patient contact and achieve improvements in prescribing.", "To evaluate the efficacy of computerized provider order entry with clinical decision support for preventing adverse drug events in long-term care.\n Cluster-randomized controlled trial.\n Two large long-term care facilities.\n One thousand one hundred eighteen long-term care residents of 29 resident care units.\n The 29 resident care units, each with computerized provider order entry, were randomized to having a clinical decision support system (intervention units) or not (control units).\n The number of adverse drug events, severity of events, and whether the events were preventable.\n Within intervention units, 411 adverse drug events occurred over 3,803 resident-months of observation time; 152 (37.0%) were deemed preventable. Within control units, there were 340 adverse drug events over 3,257 resident-months of observation time; 126 (37.1%) were characterized as preventable. There were 10.8 adverse drug events per 100 resident-months and 4.0 preventable events per 100 resident-months on intervention units. There were 10.4 adverse drug events per 100 resident-months and 3.9 preventable events per 100 resident-months on control units. Comparing intervention and control units, the adjusted rate ratios were 1.06 (95% confidence interval (CI)=0.92-1.23) for all adverse drug events and 1.02 (95% CI=0.81-1.30) for preventable adverse drug events.\n Computerized provider order entry with decision support did not reduce the adverse drug event rate or preventable adverse drug event rate in the long-term care setting. Alert burden, limited scope of the alerts, and a need to more fully integrate clinical and laboratory information may have affected efficacy.", "To evaluate whether a year long clinical pharmacy program involving development of professional relationships, nurse education on medication issues, and individualized medication reviews could change drug use, mortality and morbidity in nursing home residents.\n A cluster randomised controlled trial, where an intervention home was matched to three control homes, was used to examine the effect of the clinical pharmacy intervention on resident outcomes. The study involved 905 residents in 13 intervention nursing homes and 2325 residents in 39 control nursing homes in south-east Queensland and north-east New South Wales, Australia. The outcome measures were: continuous drug use data from government prescription subsidy claims, cross-sectional drug use data on prescribed and administered medications, deaths and morbidity indices (hospitalization rates, adverse events and disability indices).\n This intervention resulted in a reduction in drug use with no change in morbidity indices or survival. Differences in nursing home characteristics, as defined by cluster analysis with SUDAAN, negated intervention-related apparent significant improvements in survival. The use of benzodiazepines, nonsteroidal anti-inflammatory drugs, laxatives, histamine H2-receptor antagonists and antacids was significantly reduced in the intervention group, whereas the use of digoxin and diuretics remained similar to controls. Overall, drug use in the intervention group was reduced by 14.8% relative to the controls, equivalent to an annual prescription saving of A64 dollars per resident (approximately 25 pound sterling).\n This intervention improved nursing home resident outcomes related to changes in drug use and drug-related expenditure. The continuing divergence in both drug use and survival at the end of the study suggests that the difference would have been more significant in a larger and longer study, and even more so using additional instruments specific for measuring outcomes related to changes in drug use.", "Investigating whether and how the prescribing behaviour of general practitioners (GPs) can be changed by the pharmacist's feedback.\n Randomised, prospective.\n Residential home 'Bernlef', Groningen, the Netherlands.\n In the period 2 February-18 March 1993 the effect of different ways of sending prescriptions by the pharmacist on medication use was investigated. The 43 GPs of the inhabitants were randomly divided in 3 groups. Group A formed the control group and was requested to send their prescriptions as before, group B moreover received a list with the medication used by their patients, group C also got a list with the actual medication of their patients as well as recommendations by the pharmacist. Effects on medication use were determined after 4 weeks.\n The 196 inhabitants used an average of 6.5 drugs (range 0-19). No difference was found between group A and group B, but there was a difference with group C. In all three groups the number of added drugs increased by 5%, but the number of deleted drugs was 7% in group C, as against only 3% in groups A and B (p < 0.05). The feedback of the pharmacist that for 44% of GPs contained new information resulted 9 times in the ending of medication and 4 times in decreasing of the dose.\n Pharmacist's feedback by means of remarks on prescribed medication positively influences prescription behaviour of the GP.", "to measure the impact of pharmacist-conducted clinical medication review with elderly care home residents.\n randomised controlled trial of clinical medication review by a pharmacist against usual care.\n sixty-five care homes for the elderly in Leeds, UK. Participants: a total of 661 residents aged 65+ years on one or more medicines. Intervention: clinical medication review by a pharmacist with patient and clinical records. Recommendations to general practitioner for approval and implementation. Control patients received usual general practitioner care.\n primary: number of changes in medication per participant. Secondary: number and cost of repeat medicines per participant; medication review rate; mortality, falls, hospital admissions, general practitioner consultations, Barthel index, Standardised Mini-Mental State Examination (SMMSE).\n the pharmacist reviewed 315/331 (95.2%) patients in 6 months. A total of 62/330 (18.8%) control patients were reviewed by their general practitioner. The mean number of drug changes per patient were 3.1 for intervention and 2.4 for control group (P < 0.0001). There were respectively 0.8 and 1.3 falls per patient (P < 0.0001). There was no significant difference for GP consultations per patient (means 2.9 and 2.8 in 6 months, P = 0.5), hospitalisations (means 0.2 and 0.3, P = 0.11), deaths (51/331 and 48/330, P = 0.81), Barthel score (9.8 and 9.3, P = 0.06), SMMSE score (13.9 and 13.8, P = 0.62), number and cost of drugs per patient (6.7 and 6.9, P = 0.5) (pounds sterling 42.24 and pounds sterling 42.94 per 28 days). A total of 75.6% (565/747) of pharmacist recommendations were accepted by the general practitioner; and 76.6% (433/565) of accepted recommendations were implemented.\n general practitioners do not review most care home patients' medication. A clinical pharmacist can review them and make recommendations that are usually accepted. This leads to substantial change in patients' medication regimens without change in drug costs. There is a reduction in the number of falls. There is no significant change in consultations, hospitalisation, mortality, SMMSE or Barthel scores." ]

[ "15802410", "16723306", "7040192", "3781003" ]

[ "Effect of a levonorgestrel intrauterine system on women with type 1 diabetes: a randomized trial.", "Contraception in perimenopausal women with diabetes mellitus.", "Oral contraception in diabetic women. A cross-over study on serum and high density lipoprotein (HDL) lipids and diabetes control during progestogen and combined estrogen/progestogen contraception.", "Oral contraceptives in diabetic women: metabolic effects of four compounds with different estrogen/progestogen profiles." ]

[ "Women with diabetes need safe, effective contraception. Although intrauterine devices provide superior contraception, concerns remain that progestin absorbed systemically from the levonorgestrel-releasing device may impair carbohydrate metabolism. To examine the effect of the levonorgestrel-releasing intrauterine system on glucose metabolism in diabetic women.\n We randomly assigned 62 women with uncomplicated insulin-dependent diabetes mellitus to either a levonorgestrel-releasing or a copper T 380A intrauterine device. The primary outcome to assess glucose metabolism was glycosylated hemoglobin; fasting serum-glucose levels and daily insulin dose requirements over 12 months of observation were examined as well.\n Outcome data were available for 29 women using the levonorgestrel-releasing and 30 using the copper device. At 12 months, mean glycosylated levels were similar for women of the 2 groups (6.3%, standard deviation [SD] +/- 1.5 compared with 6.3%, SD +/- 1.3, respectively). The same was true for mean fasting-serum glucose levels (7.4 mM, SD +/- 4.2 compared with 7.5 mM, SD +/- 4.2) and daily insulin doses (35.1 units, SD +/- 12.8 compared with 36.4 units, SD +/- 9.0). No important differences were noted at either 6 weeks or 6 months.\n The levonorgestrel-releasing device had no adverse effect on glucose metabolism, even at the 6-week observation when systemic levels of levonorgestrel would have been higher than at later observations. Concern about a potential adverse effect of this contraceptive on glucose control is unwarranted, and its use in women with diabetes should be liberalized.\n I.", "To assess the effect of combined oral contraceptives (COCs) and intrauterine devices (IUDs) on carbohydrate and lipid metabolism and hemostasis in perimenopausal diabetic women.\n The open randomized study included a total of 113 diabetic women using COCs with different estrogen/progestogen profiles - ethinylestradiol (EE) 20 microg/desogestrel 150 microg, EE 30 microg/desogestrel 150 microg and EE 30 microg/gestodene 75 microg - and levonorgestrel-releasing or copper IUDs. Average daily insulin requirements, levels of glycosylated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, the state of coagulation hemostatis and fibrinolytic activity were determined at baseline and after 3, 6, 9 and 12 months of contraception. The control group was composed of 40 age-matched diabetic women who did not use any methods of contraception.\n Neither COCs nor IUDs influenced glycosylated hemoglobin and had little or no influence on the elevation in the requirements for insulin preparations. The majority of the preparations did not exert any unfavorable effect on the blood lipid profile. Taking COCs was accompanied by increased intravascular activation of blood platelets and to a lesser degree by alterations in parameters of hemostatic homeostasis. The use of IUDs had a neutral effect on blood coagulation and fibrinolysis systems.\n Comparing lipid levels and hemostatic variables as a function of glycosylated hemoglobin level, we conclude that diabetes control has greater influence on these parameters than the type and dose of steroids involved in the contraceptive devices.", "Twenty-three young women with insulin-dependent diabetes were randomly allocated to contraceptive treatment with either a progestogen only (Lynestrenol 0.5 mg) (LYN) or a combined oral contraceptive (OC) (ethinyl estradiol 50 micrograms + lynestrenol 2.5 micrograms) (EE + LYN). After six months treatment the medication was withdrawn for at least two months, after which the patients were placed on the other preparation. Diabetes control and serum and high density lipoprotein (HDL) lipids were assessed before and after 1, 3 and 6 months of treatment. Low-dose LYN administration did not alter the insulin requirement, blood glucose or body weight while the combined EE + LYN treatment increased the insulin requirement (p less than 0.01) without altering blood glucose or body weight. Low-dose LYN reduced serum triglycerides (p less than 0.001), serum cholesterol (p less than 0.001) and serum phospholipids (p less than 0.01) without affecting HDL lipids, while EE + LYN gave an inconsistent increase in serum triglycerides (p less than 0.01) but no change in HDL lipids. These findings confirm our earlier results and we conclude that EE + LYN influences diabetes control slightly more (although still not seriously) than the low-dose LYN. It is suggested that insulin-dependent diabetics (in contrast to non-diabetics) are more sensitive to the influence of 19-norprogestogens than to alkylated estrogens, with respect to lipid metabolism.", "The metabolic effects of four oral contraceptives with different estrogen/progestogen profiles (monophasic nonalkylated estrogen/norethindrone, low-dose monophasic ethinyl estradiol (EE2)/norethindrone, progestogen only treatment with norethindrone, and triphasic EE2/levonorgestrel) were examined in insulin-dependent diabetic women. During the 6-month study period, no differences were found in fasting plasma glucose, 24-hour insulin requirements, glycated hemoglobin, free fatty acids, low-density lipoprotein cholesterol concentrations, or high-density lipoprotein cholesterol/total cholesterol ratio between the patients in each treatment group. Compared with the nonalkylated estrogen/norethindrone and the triphasic EE2/levonorgestrel formulations, the low-dose EE2/norethindrone combination resulted in small but significant increases in plasma triglyceride and very low-density lipoprotein cholesterol levels (P less than 0.01), which seemed unfavorable from a clinical point of view. Norethindrone-only treatment appeared to be an appropriate alternative to both the nonalkylated estrogen/norethindrone combination and the triphasic EE2/levonorgestrel formulations." ]

[ "8873389", "18799552", "7475716", "20140352", "15545857", "12850358", "11738746" ]

[ "Immunization with a pneumococcal capsular polysaccharide vaccine during pregnancy.", "Effectiveness of maternal influenza immunization in mothers and infants.", "Serum, breast milk, and infant antibody after maternal immunisation with pneumococcal vaccine.", "Ineffectiveness for infants of immunization of mothers with pneumococcal capsular polysaccharide vaccine during pregnancy.", "Serotype-specific pneumococcal antibodies in breast milk of Gambian women immunized with a pneumococcal polysaccharide vaccine during pregnancy.", "Maternal immunization with pneumococcal polysaccharide vaccine in the Philippines.", "Maternal immunization with pneumococcal polysaccharide vaccine in the third trimester of gestation." ]

[ "The feasibility of preventing invasive pneumococcal infections during the first few months of life by immunization during pregnancy has been investigated. One hundred and fifty Gambian women were immunized with either a 23-valent pneumococcal polysaccharide vaccine or a meningococcal polysaccharide vaccine during the last trimester of pregnancy. Pregnant women showed a good antibody response to five of the six pneumococcal polysaccharides tested (types 1, 3, 5, 6, 14 and 19) but not to type 6 polysaccharide. Mean cord blood/maternal blood IgG antibody ratios varied from 24% (type 1) to 49% (type 3) and differed substantially between individual mother/infant pairs. Pneumococcal antibody levels were higher at birth in infants of women immunized with pneumococcal polysaccharide vaccine than in control infants. However, these antibodies disappeared rapidly during the first few months of life and it is uncertain how much clinical protection against pneumococcal infection maternal immunization would have provided.", "Young infants and pregnant women are at increased risk for serious consequences of influenza infection. Inactivated influenza vaccine is recommended for pregnant women but is not licensed for infants younger than 6 months of age. We assessed the clinical effectiveness of inactivated influenza vaccine administered during pregnancy in Bangladesh.\n In this randomized study, we assigned 340 mothers to receive either inactivated influenza vaccine (influenza-vaccine group) or the 23-valent pneumococcal polysaccharide vaccine (control group). Mothers were interviewed weekly to assess illnesses until 24 weeks after birth. Subjects with febrile respiratory illness were assessed clinically, and ill infants were tested for influenza antigens. We estimated the incidence of illness, incidence rate ratios, and vaccine effectiveness.\n Mothers and infants were observed from August 2004 through December 2005. Among infants of mothers who received influenza vaccine, there were fewer cases of laboratory-confirmed influenza than among infants in the control group (6 cases and 16 cases, respectively), with a vaccine effectiveness of 63% (95% confidence interval [CI], 5 to 85). Respiratory illness with fever occurred in 110 infants in the influenza-vaccine group and 153 infants in the control group, with a vaccine effectiveness of 29% (95% CI, 7 to 46). Among the mothers, there was a reduction in the rate of respiratory illness with fever of 36% (95% CI, 4 to 57).\n Inactivated influenza vaccine reduced proven influenza illness by 63% in infants up to 6 months of age and averted approximately a third of all febrile respiratory illnesses in mothers and young infants. Maternal influenza immunization is a strategy with substantial benefits for both mothers and infants. (ClinicalTrials.gov number, NCT00142389.)\n Massachusetts Medical Society", "Pneumococci are a leading cause of severe bacterial disease in infants and children world wide. A possible means of protecting infants in the first few months of life is immunisation of the mother during pregnancy. We prospectively assessed pneumococcal immunisation of pregnant women to determine the amount of pneumococcal antibody transmitted to the infants in serum and milk and the half-life of the passively acquired antibody. Healthy pregnant women in Dhaka, Bangladesh, were randomised to receive pneumococcal or meningococcal vaccine with routine prenatal tetanus immunisation at 30-34 weeks of gestation. Serum and breast milk specimens from the mothers and sera from infants were collected up to 22 weeks of age and assayed for specific serum IgG, IgG1, and IgG2 and for milk IgA antibodies to pneumococcal serotypes 6B and 19F. 55 mothers and 56 infants were followed from birth to five months. Women who received pneumococcal vaccine had geometric mean antibody increases of 2.6 and 3.4 to types 6B and 19F, respectively. The mean infant/maternal antibody ratios were 0.56 and 0.59 (range 0.11-1.46) for these serotypes. Infant cord antibody titres correlated with maternal titres. Infant/maternal IgG ratios correlated with the interval between immunisation and birth and were higher for specific IgG1 than for IgG2. Infants of pneumococcal vaccine recipients had geometric mean antibody concentrations of 6.8 and 7.5 micrograms/mL to serotypes 6B and 19F in cord blood; in cord blood and in all subsequent serum specimens the concentrations were 2-3 fold higher than in control infants. The median half-life of passive antibody was about 35 days; at five months of age 63-71% of infants of pneumococcal vaccine recipients had antibody concentrations greater than 0.15 micrograms/mL. Breast milk IgA antibodies for pneumococcal serotype 19F, but not for type 6B, were significantly higher in vaccine recipients up to five months after delivery. If maternal pneumococcal polysaccharide antibodies do not interfere with active immunisation of the infant with new glycoprotein conjugate pneumococcal vaccines, passive-active immunisation of infants can be a feasible strategy for developing regions.", "Pneumococcal (Pnc) carriage is associated with pneumococcal diseases. Breast feeding and maternal vaccination may be a useful approach to prevent pneumococcal infection in young infants. We examined the risk of Pnc carriage by infants at six months of age after pneumococcal polysaccharide vaccination of pregnant women. We selected 139 pregnant woman. The woman were randomly allocated to receive 23-valent polysaccharide vaccines during pregnancy (Group 1) after pregnancy (Group 2) or not receive any vaccine (Group 3). Nasopharyngeal swabs were collected from the infants at three and six months of age. The infants were evaluated monthly during the first six months. We included 47 mothers in Group 1, 45 mothers in Group 2 and 47 mothers in Group 3. Forty-seven percent of the babies were exclusively breast fed until six months, 26% received both breast feeding and artificial feeding and 13% received only artificial feeding. Among those patients, 26% were colonized by Pnc at six months (12 from Group 1, 13 from Group 2, and 12 from Group 3). There was no significant difference in colonization between the three groups. Thirty percent of the children were colonized by a non-susceptible strain. We concluded that young infants (three months old) are already susceptible to pneumococcal carriage. Vaccination during pregnancy with a polysaccharide vaccine did not decrease Pnc colonization.", "In breast-feeding populations, immunization during pregnancy with pneumococcal polysaccharide offers a potentially useful approach to preventing pneumococcal disease in young infants.\n Breast milk samples were collected at 0, 2, 4 and 6 months after delivery from Gambian women vaccinated during pregnancy (24-32 weeks gestation) with Pneumovax II (n = 56) or Mengivax A&C (n = 57). Specimens were examined for secretory immunoglobulin A (s-IgA) concentration, subclass distribution and avidity specific to pneumococcal serotypes 4, 6B, 14, 19F and 23F and the antigen mixture in Pneumovax II by enzyme-linked immunosorbent assay. Colostral s-IgA and IgG concentrations in paired maternal sera were compared.\n Colostral s-IgA concentrations specific to all pneumococcal polysaccharide antigens investigated were significantly higher (P < 0.05) among Pneumovax II vaccinees. Titers specific to serotypes 4, 6B and 14 and the vaccine formula remained significantly higher during 6 months, and those for 19F were higher during 4 months. Significantly higher concentrations of vaccine antigen-specific s-IgA antibody were sustained for 6 months after delivery (P = 0.011). Comparison of colostral s-IgA and IgG in serum revealed a significant correlation only among Mengivax A&C vaccinees for pneumococcal polysaccharide 23F (rs= 0.68; P < or = 0.0001). Vaccination elicited trends toward increased s-IgA2, reaching significance for serotype 14 and the vaccine formula. Immunization elicited significantly higher s-IgA avidities specific to all pneumococcal polysaccharide antigens studied during 6 months.\n The public health value of immunization during pregnancy with pneumococcal polysaccharide vaccine in breast-feeding populations warrants further evaluation, particularly in populations with a high incidence of pneumococcal disease in early infancy.", "A randomized, controlled study was conducted to evaluate the immunogenicity and reactogenicity of the 23-valent pneumococcal (Pnc) polysaccharide (PS) vaccine among pregnant women and to ascertain the transfer of anti-Pnc antibody (Ab) from mother to infant. One hundred and sixty women received either one dose of Pnc PS vaccine, Haemophilus influenzae type b conjugate vaccine and tetanus toxoid (TT) (Pnc vaccine group, N=106) or TT only (control group, N=54). Sera were obtained from all mothers prior to vaccination and 4 weeks after from the vaccinated group. Cord blood was obtained in 75% of deliveries. Anti-Pnc Ab for serotypes 1, 5, 6B, 14, 18C and 19F was determined using enzyme immunoassay. The Pnc vaccine and control groups were comparable in terms of age, parity, gravidity, prior doses of TT, and pre-vaccination geometric mean concentration (GMC in microg/ml) of anti-Pnc Ab. Between 66 and 87% of the mothers had type-specific Ab prior to vaccination. There was a significant rise in anti-Pnc Ab (varying from 3.3- to 9.1-fold for the individual serotypes) between the pre and post-vaccination samples. Adverse reactions were mild and required no treatment. The level of anti-Pnc Ab in cord blood was significantly lower in the control group compared to the Pnc vaccine group. Vaccination of pregnant women with Pnc Ps vaccine induces good immune response and Ab can be transferred to their infants via cord blood thus providing enhanced protection.", "In a randomized, double blinded study, 23-valent pneumococcal polysaccharide vaccine (PSV) or conjugate Haemophilus influenzae type b (HbOC) vaccine was administered to 60 healthy women in the third trimester of gestation. Total IgG, IgG1, and IgG2 antibodies to pneumococcal serotypes 6B, 14, 19F and 23F were measured by ELISA in mothers prior to immunization, at delivery and 7 months after delivery, and in infants at birth (cord blood), 2 and 7 months after delivery. IgA was evaluated in breast milk at 2 and 7 months, and opsonophagocytic activity in cord blood. PSV was safe and immunogenic in pregnant women. Transplacental transmission of vaccine-specific antibodies was efficient. Maternal immunization with PSV resulted in significantly higher concentrations of pneumococcal antibodies in infants at birth and at 2 months of age, and greater functional opsonophagocytic activity of passively acquired IgG antibody." ]

[ "5334978" ]

[ "A double-blind trial of oral isoxuprine in the prevention of premature labour." ]

[ "nan" ]

[ "1819425", "2997259", "8453254", "1099484", "4310499", "10222389", "8027227", "14315706", "7601080", "3381638", "9625105", "9084692", "10447245", "9109607", "6084463", "6278919" ]

[ "[Evolution of endemic goiter in Malian women and children after a year of enrichment of drinking water with iodine using diffusers made of silicone].", "The effectiveness of oral iodized oil in the treatment and prophylaxis of endemic goiter.", "Development of thyroid gland volume during the first 3 months of life in breast-fed versus iodine-supplemented and iodine-free formula-fed infants.", "The Journal of Laboratory and Clinical Medicine. October, 1917. Volume III, No. 1, Pages 40-49. The prevention of simple goiter in man. A survey of the incidence and types of thyroid enlargements in the schoolgirls of Akron (Ohio), from the 5th to the 12th grades, inclusive-the plan of prevention proposed.", "Prophylaxis and treatment of endemic goiter in Peru with iodized oil.", "Biochemical hypothyroidism secondary to iodine deficiency is associated with poor school achievement and cognition in Bangladeshi children.", "Oral iodized oil for correcting iodine deficiency: optimal dosing and outcome indicator selection.", "PRELIMINARY REPORT OF AN EXPERIMENT IN THE KANGRA VALLEY FOR THE PREVENTION OF HIMALAYAN ENDEMIC GOITRE WITH IODIZED SALT.", "The effect of varying doses of oral iodized oil in the prophylaxis of endemic goitre in elementary schools children.", "Effect of voluntary intake of iodinated salt on prevalence of goitre in children.", "Intermittent oral administration of potassium iodide solution for the correction of iodine deficiency.", "Salt: an ineffective vehicle for iodine delivery to young children in rural Sarawak.", "Randomized clinical trial comparing different iodine interventions in school children.", "Infant survival is improved by oral iodine supplementation.", "Prophylaxis and treatment of endemic goitre in Western Sudan with intramuscular iodized oil.", "The effects of oral iodized oil on intelligence, thyroid status, and somatic growth in school-age children from an area of endemic goiter." ]

[ "A new method for iodine deficiency disorders prevention is tested during one year in a rural area of Mali. Silicone and sodium iodide made diffusers are set up inside 2 villages' drillings. Their efficiency is compared with a placebo. Supervision criteria are evolution of goiter, rates of iodine in water and ioduria of the population, specially women and children. In the treated villages a decrease of goiters' size of the younger people is observed. Iodine rates in treated drillings water stay during 12 months between 150 and 300 micrograms/l with a minimum intake of 150 micrograms/day/person. The means of ioduria rates from less than 25 micrograms/l before treatment (severe deficiency) increase to more than 100 micrograms/l after six months of treatment (no deficiency).", "In a longitudinal study carried out for 2 yr in the Darfur region, western Sudan, 2316 school children received a single dose of 2 capsules of iodized oil (400 mg iodine) orally, and 1161 school children received 1 ml of the same preparation im (475 mg iodine); 2393 school children served as controls. One year after treatment, goiter prevalence was reduced from 67.0% to 36.0% among the children who had received oral iodized oil and from 71.0% to 42.0% in those who received it im. The prevalence in the control group did not change. The prevalences in each group were approximately the same 2 yr after treatment. Urinary iodine excretion increased after treatment and remained significantly higher than the initial value during the trial. In subjects from rural Darfur, serum T4 levels were increased 1 yr after treatment with oral iodized oil (P less than 0.001) and im iodized oil (P less than 0.01), and remained high in the former (P less than 0.05) but not in the latter. This increase was accompanied by reduction of serum T3 and TSH levels. Sialadenitis occurred in 3.7% of the children who received oral iodized oil. Thyroid antibodies were not detected before treatment, but microsomal antibodies were detected in 2 of the 128 subjects studied who received iodized oil orally. Comparable results occurred when oral and im iodized oil were given to 841 individuals covering a wider age range. It is concluded that a single oral dose of iodized oil is effective in the correction of iodine deficiency, reducing the goiter size and preventing the recurrence of goiter for at least 2 yr.", "The spontaneous development of thyroid gland volume (TGV) during the first 3 months of life was studied in entirely breast-fed infants (n = 21) and compared to those fed an iodine-supplemented formula (n = 19), an iodine-free formula (n = 5), or partially breast-fed in addition to an iodine-free (n = 4) or an iodine-supplemented formula (n = 16). The TGV of the infants and their mothers was determined sonographically in addition to their urinary iodine concentrations 5-7 days postpartum and 3 months later. In ten additional lactating mothers the breast milk concentrations of thyroid hormones and iodine were determined. It was shown that at 3 months of age an infant consuming about 1000 ml breast milk per day receives about 2 micrograms thyroid hormones and 55 micrograms iodine per day. At the end of their first week of life the infants showed a TGV between 0.28 and 1.5 ml (median 0.61 ml) and a urinary iodine concentration between 0.03 and 16.3 micrograms/dl (median 3.0 micrograms/dl). At 3 months of age the TGV of the breast-fed infants had decreased by a median of 0.24 ml (= -34%; median of percentage changes) whereas those fed a formula without iodine had increased by a median of 0.26 ml (= +50%; median of percentage changes). Those receiving an iodine-supplemented formula showed a TGV reduction of 0.14 ml (= +2%; median of percentage changes). The TGV development of the partially breast-fed infants lay between those being exclusively breast or formula fed.(ABSTRACT TRUNCATED AT 250 WORDS)", "nan", "nan", "Iodine deficiency in pregnancy leads to poor cognitive function in the offspring; however, the effect of concurrent iodine deficiency on school-aged children is not clear. Several studies have shown that school children in iodine-deficient villages have poorer cognitive function than children in iodine-sufficient villages. However, villages differ in many factors that may also detrimentally affect children's development. In addition, the children's nutritional and health status has not usually been taken into account. In this study, we compared the cognitive function and school achievement levels of 170 children who had recently had low thyroxine (T4) levels [T4 </= 45 nmol/L (hypothyroid)] with children who had not had low T4 levels [T4 >/=70 nmol/L (euthyroid)]. The children were matched for school and grade level and came from the same iodine-deficient regions in rural Bangladesh. They were given a battery of cognitive, motor and school achievement tests. We also measured their nutritional status, examined their stools for geohelminths and assessed their home environments. A factor analysis of cognitive and motor function tests yielded two factors, a general cognitive factor and a fine motor factor. The children's height and arm circumference, experience of hunger, parental characteristics and stimulation in the home made independent contributions to their test scores. Controlling for these variables, the hypothyroid children performed worse than the euthyroid children on reading and spelling and the general cognitive factor. These findings indicate that a large number of disadvantages including hypothyroidism are related to the poor development of these children.", "Oral iodized oil is the major alternative to iodized salt for correcting endemic iodine deficiency. This study responds to a need for better guidelines in its use. Schoolchildren, aged 6-11 yr, from a severely iodine-deficient area of Algeria received iodized poppy seed oil (Lipiodol) in a single oral dose containing 120, 240, 480, or 960 mg iodine (groups A-D) or in an im injection of 480 mg iodine (group E). Thyroid volume by ultrasonography had not changed 395 days after treatment in groups A, B, and C, had decreased in groups D and E. Urinary iodine concentration rose rapidly from an initial median of 0.21 mumol/L, but fell below 0.79 mumol/L (the currently accepted level for indicating iodine deficiency) by 150 days for groups A and B, and by 395 days for groups C and D. Median serum TSH and T4 levels were normal before and after treatment, whereas high initial serum thyroglobulin values decreased in all groups after iodized oil treatment. For correcting iodine deficiency in children, we recommend single oral doses of Lipiodol containing 240 mg iodine for 6-month coverage or 480 mg for 12 months. These doses may not completely sustain iodine sufficiency, but will prevent the worst of the iodine deficiency disorders. Additionally, we conclude that the urinary iodine concentration is the most useful epidemiological indicator for assessing current iodine status, and thyroid volume and serum thyroglobulin levels are the best markers for assessing chronic effects.", "This report incorporates the results of an investigation designed to test the effectiveness of potassium iodide and potassium iodate in the control of Himalayan endemic goitre when these compounds are added in small physiological doses to the domestic salt habitually consumed by the people in the endemic belt. In a prospective study lasting five years, a striking reduction in the prevalence of goitre was observed in areas receiving salt fortified with either potassium iodide or potassium iodate. During the same period, goitre prevalence remained unchanged in the control zone, which received plain, unfortified salt. The study has an important bearing on the problem of goitre control in developing countries that use moist, coarsely crystalline salt.", "The effect of oral iodine supplementation on total goitre rate (%TGR) and urinary iodine excretion among school children 4 to 16 years of age was studied. In the first group (n = 57) 200mg oral iodized oil reduced %TGR from 31.6% to 17.5% and 33.3% to 24.6% in males and females respectively, while in the second group (n = 53), 400mg iodine reduced the %TGR from 34.0% to 20.8% in males and 35.9% to 24.5% in females after 13 months of intervention. This gave a relative indication that the 200mg is as effective as the 400mg in goitre reduction. In subsequent tests, the maximum urinary iodine excretion was obtained from the groups which received two doses of iodized oil 24 hours after the intervention. A significant (p = 0.003) greater increase in urinary iodine excretion was noted at 24 hours among both male and female children administered 400mg than among those who received 200mg. Measurements after 24 hours showed no significant difference between urinary iodine excretion of the two dose groups. These results suggest that: (i) 200mg is likely equally effective as 400mg for iodine deficiency disorders control and prevention among children and (ii) iodine could be administered annually rather than biannually.", "The availability of iodinated salt containing 20 mg of iodine as iodate/kg salt consumed on a voluntary basis enabled us to investigate its effect on goitre prevalence and iodine excretion in urine in a longitudinal, prospective, randomized study over 4 years. With this salt, under the assumption of a consumption of 5 g salt per day and person, an additional intake of 100 micrograms of iodine can be achieved. The study was performed on initially 334 children (168 boys, 166 girls) at the age of 10 years living in an area of iodine deficiency. After 4 years, 286 children still participated in the study. Initially, goitre prevalence as assessed by palpation was found to be 30.5% (37.4% in girls and 23.8% in boys). Neck circumference was found to be significantly higher in children with goitre compared with those without (30.2 +/- 1.4 vs 29.4 +/- 1.4 cm; P less than 0.001). Iodine excretion in the urine was significantly lower in children with goitre compared with those without (40.4 +/- 16.7 micrograms/g creatinine vs 46.1 +/- 24.9 micrograms/g creatinine; x +/- SD; P less than 0.05). The children were randomly assigned to two different groups: group A (N = 146) was asked to use iodinated salt, group B (N = 188) non-iodinated salt. Over the 4 years, a continuous increase in iodine excretion in urine could be demonstrated in group A.(ABSTRACT TRUNCATED AT 250 WORDS)", "Iodized salt and iodized oil are the main methods used to prevent iodine deficiency, but sometimes alternative approaches are needed. We tested the efficacy of various regimens for the intermittent administration of potassium iodide in Hwedza, Zimbabwe, an area of known severe iodine deficiency. We divided 304 schoolchildren aged 7-13 y into five equal groups that received iodine as a 10% solution of potassium iodide as follows: 8.7 mg every 2 wk (group A), 29.7 mg every month (group B), 148.2 mg every 3 mo (group C), 382 mg every 6 mo (group D), or 993 mg once (group E). The follow-up period was 13 mo. No adverse effects were encountered with any of these doses. After 6 mo, the median blood spot thyroglobulin concentration had decreased in all groups and had normalized in groups A and B to values found in iodine-sufficient populations. The number of children with elevated thyroid-stimulating hormone concentrations decreased in groups A-C, but the changes were not significant. Urine iodine concentration generally remained low in all groups but increased in group A. After 13 mo, mean thyroid volume measured by ultrasound had decreased in groups A and B to values comparable with those in iodine-sufficient areas, and was unchanged in the other groups. We conclude that oral potassium iodide is effective for the prophylaxis of iodine deficiency if given as a dose of 30 mg I monthly or 8 mg biweekly.", "The urinary iodine excretions of women (15-40 y) and young children (< or = 6 y) from two longhouse villages in the iodine-deficient district of Lubok Antu, Sarawak, were compared. One longhouse (Mengkak) was provided with freshly produced iodized salt every two months (one kg per family) while the other (Menjiling) was provided with iodized water via fortification of the village piped-water supply. Spot urines were collected for iodine determination at baseline and at 6 and 12 months after the start of the study. Salt and water samples were collected at monthly intervals. Goiter assessment was performed on the women at the start and end of the one-year study. The mean iodine concentrations in the salt samples from Mengkak and Menjiling were, respectively, 47.1 +/- 9.7 mg/kg (n = 60) and 0.8 +/- 3.4 mg/kg (n = 60) while the mean iodine concentration in the water samples from Menjiling was 138.6 +/- 43.2 micrograms/L (n = 24); iodine could not be detected in the water samples from Mengkak. There were significant and sustained increases in median urinary iodine excretions of both women and young children in Menjiling; in Mengkak, however, significant and sustained increases in median urinary iodine excretions were observed only in women while the median urinary iodine excretions of children remained essentially unchanged throughout the study period. Goiter prevalences in the women were reduced in both longhouses. The above observations reveal the inadequacy of iodized salt as a vehicle for iodine delivery to young rural Sarawakian children and indicate the need for other means of delivering supplemental iodine to this age group in areas where salt iodization is the only strategy for IDD control. In contrast, iodization of village water supply by itself is adequate in delivering iodine uniformly to the whole community.", "The purpose of this trial was to compare three different iodine interventions.\n School children aged 8-10 years were randomized into one of three groups: group A was provided with iodized salt by researchers with an iodine concentration of 25 ppm; group B purchased iodized salt from the market; and group C was similar to group B with the exception that they were given iodized oil capsules containing 400 mg iodine at the beginning of the study. Salt iodine content was measured bimonthly for 18 months and indicators of iodine deficiency were measured at baseline and 6, 9, 12 and 18 months after randomization.\n The prevalence of abnormal thyroid volumes, based on the World Health Organization (WHO) body surface area reference >97th percentile, was 18% at baseline and declined to less than 5% by 12 months in groups A and C, and to 9% after 18 months in group B. Results for goitre by palpation were similar. The median urinary iodine was 94 microg l(-1) at baseline and increased in all groups to > 200 microg l(-1) at the 6-month follow-up.\n In this population of school children with initially a low to moderate level of iodine deficiency, the group receiving salt with 25 ppm (group A) was not iodine deficient on all indicators after 18 months of study. When the iodine content of the salt varied, such as in group B, by 18 months thyroid sizes had not yet achieved normal status.", "Although reports suggest that infant mortality is increased during iodine deficiency, the effect of iodine supplementation on infant mortality is unknown. A double-masked, randomized, placebo-controlled, clinical trial of oral iodized oil was conducted in Subang, West Java, Indonesia to evaluate the effect of iodine supplementation on infant mortality. Infants were allocated to receive placebo or oral iodized oil (100 mg) at about 6 wk of age and were followed to 6 mo of age. Six hundred seventeen infants were enrolled in the study. Infant survival was apparently improved, as indicated by a 72% reduction in the risk of death during the first 2 mo of follow-up (P < 0.05) and a delay in the mean time to death among infants who died in the iodized oil group compared with infants who died in the placebo group (48 days vs. 17.5 d, P = 0.06). Other infant characteristics associated with reduced risk of death included weight-for-age at base line, consumption of solid foods, female gender and recent history of maternal iodine supplementation. Oral iodized oil supplementation had a stronger effect on the mortality of males compared with females. This study suggests that oral iodized oil supplementation of infants may reduce infant mortality in populations at risk for iodine deficiency.", "A single injection of iodized oil was administered intramuscularly in a dose of 0.2-2 ml (475 mg iodine per ml) to 383 children from the villages of Kas and Dibbis of the Darfur region in Western Sudan, where goitre is prevalent. After one year the prevalence of goitre had declined from 76% to 49.6%. Of the goitrous children, 81.1% showed either complete resolution of goitre or definite regression of its size. None of the nongoitrous children developed goitre and none of the existing goitres became larger. No cases of hyper- or hypothyroidism were observed. The full 270 children were followed up for four-and-a-half years after treatment and compared with untreated controls from the same area. The prevalence of goitre was significantly lower in the treated than in the untreated group. In treated children the mean urinary iodine excretion three-and-a-half years after treatment was 188.7 micrograms/g creatinine. This was significantly higher than in the untreated group (P less than 0.001). One year later the mean urinary excretion of iodine in the treated children had decreased to 87.1 micrograms/g creatinine. There was no difference in the mean serum values of T3 and T4 in the treated and untreated groups. The level of thyroid stimulating hormone was significantly lower in the treated [mean (S.D.) = 3.5 (0.9)] than in the untreated children [6.0 (3.5)]. It is concluded that a single injection of iodized oil is safe and effective in prevention of goitre development, reduces goitre size and maintains a sufficient iodine supply to prevent goitre for at least four-and-a-half years in children from goitre-endemic areas in Western Sudan.", "One hundred goitrous school children received 475 mg iodized oil by mouth, while 100 controls received mineral oil, on a double-blind basis. On follow-up 22 months later the urinary iodine had increased and goiter size had decreased in both groups, more strikingly in the iodine-treated children. There were no consistent differences between the two treatment groups in rate of somatic growth or performance on the Stanford-Binet and Bender tests. Because of the complexities introduced by increases in urinary iodine in the controls, we compared goiter reduction with improvement in IQ score in all children, regardless of group, and found a significant relationship (p = 0.014), particularly in girls (p = 0.029). We conclude that oral iodized oil is an attractive alternative to its injection but we recommend an approximate doubling of the dose used here for more effective control. Also, while our data are not conclusive, they support the possibility that correction of iodine deficiency may improve mental performance in school age children, particularly girls." ]

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[ "The effects of a swimming intervention for children with asthma.", "Individualized aerobic and high intensity training for asthmatic children in an exercise readaptation program. Is training always helpful for better adaptation to exercise?", "Comparison of morning and afternoon exercise training for asthmatic children.", "Training of aerobic and anaerobic fitness in children with asthma.", "Effect of aerobic exercise training on pulmonary function and tolerance of activity in asthmatic patients.", "Individualized training reduces excessive exercise hyperventilation in asthmatics.", "Benefits and problems of a physical training programme for asthmatic patients.", "Children with asthma and physical exercise: effects of an exercise programme.", "Cardiorespiratory fitness evaluation by the shuttle test in asthmatic subjects during aerobic training.", "Effects of aerobic training on airway inflammation in asthmatic patients.", "Effects of aerobic training on psychosocial morbidity and symptoms in patients with asthma: a randomized clinical trial.", "Physical training does not increase allergic inflammation in asthmatic children.", "Deep diaphragmatic breathing: rehabilitation exercises for the asthmatic patient.", "Effects of swimming training on aerobic capacity and exercise induced bronchoconstriction in children with bronchial asthma.", "Benefits of swimming in asthma: effect of a session of swimming lessons on symptoms and PFTs with review of the literature.", "Exercise training on disease control and quality of life in asthmatic children." ]

[ "Asthma is a common paediatric airway disease with increasing prevalence. Studies comparing swimming with other sports have found that swimming is unlikely to provoke unstable asthma but possible benefits are not defined. This study investigated the benefits of a 6 week swimming intervention on pulmonary function tests (PFT), PEF and severity of asthma in children.\n Young asthmatics were randomly assigned to the experimental or the control group, with 15 subjects in each group. In addition to regular treatment for asthma, the experimental group received swimming training for 6 weeks. PFT, PEF and severity of asthma were measured.\n There was a significant improvement (P < 0.01) in PEF in the experimental group compared with the control group (330 L/min, 95% CI: 309-351 vs. 252 L/min, 95% CI: 235-269) after the swimming intervention. There was also a significant improvement (P < 0.05) in the severity of asthma in the experimental group compared with the control group.\n These data suggest that a swimming programme for asthmatic children can improve some disease parameters (PEF and the severity of asthma). Swimming may be an effective non-pharmacological intervention for the child or adolescent with asthma.", "In order to define the role of individualized training intensity in a conditioning program for asthmatic children, we have trained seven asthmatics (age = 11.4 +/- 1.8 years) at their ventilatory threshold (VTh) intensity level for a three-month period (aerobic training) and at maximal intensity also for three months (high intensity training). VTh is the point at which a nonlinear increase of VE occurs. Another group of seven asthmatics (age = 11.4 +/- 1.5) served as control subjects. Cardiopulmonary fitness was determined on a cycle ergometer before and after each training session. This study demonstrated that aerobic training, correctly adapted to the child's physical ability, induces the following: (1) a rapid and marked cardiovascular fitness increase; and (2) a decrease in VE over a given work range so that VTh is increased. This is of great importance because hyperventilation is a major determinant of exercise-induced bronchospasm. In contrast, even if high intensity training is well tolerated in an indoor swimming pool, the long-term effects are unsuitable for asthmatic children because the decrease of VTh will involve an increase of hyperventilation, even when exercise is performed at submaximal intensity.", "Fitness improvement was used to compare morning with afternoon exercise periods for asthmatic children. Children with persistent moderate asthma (according to GINA criteria), 8 to 11 years old, were divided into 3 groups: morning training group (N = 23), afternoon training group (N = 23), and non-training group (N = 23). The program was based on twice a week 90-min sessions for 4 months. We measured the 9-min running distance, resting heart rate and abdominal muscle strength (sit-up number) before and after the training. All children took budesonide, 400 microg/day, and an on demand inhaled ss-agonist. The distance covered in 9 min increased (mean +/- SEM) from 1344 +/- 30 m by 248 +/- 30 m for the morning group, from 1327 +/- 30 m by 162 +/- 20 m for the afternoon group, and from 1310 +/- 20 m by 2 +/- 20 m for the control group (P < 0.05 for the comparison of morning and afternoon groups with the control group by ANOVA and P > 0.05 for morning with afternoon comparison). The reduction of resting heart rate from 83 +/- 1, 85 +/- 2 and 86 +/- 1 bpm was 5.1 +/- 0.8 bpm in the morning group, 4.4 +/- 0.8 bpm in the afternoon group, and -0.2 +/- 0.7 bpm in the control group (P > 0.05 for morning with afternoon comparison and P < 0.05 versus control). The number of sit-ups in the morning, afternoon and control groups increased from 22.0 +/- 1.7, 24.3 +/- 1.4 and 23 +/- 1.1 sit-ups by 9.8 +/- 0.9, 7.7 +/- 1.4, and 1.9 +/- 0.7 sit-ups, respectively (P > 0.05 for morning with afternoon comparison and P < 0.05 versus control). No statistically significant differences were detected between the morning and afternoon groups in terms of physical training of asthmatic children.", "To assess the effect of a training protocol on aerobic and anaerobic fitness in children with asthma.\n Sixteen boys (mean age: 13 years; range: 10-16 years) with mild-to-moderate asthma participated in a rehabilitation program that included 6 weeks of individualized training on a cycle ergometer. Two groups were randomly formed: the control group (CG, n = 7) and the training group (TG, n = 9), which exercised at an intensity set at the heart rate corresponding to the ventilatory threshold, with 1-minute sprints against the maximal aerobic power (MAP) every 4 minutes. Session duration was 45 minutes, 3 sessions per week. Changes in maximal oxygen uptake (VO(2)max), MAP, short-term peak power (PP), and pulmonary function were assessed.\n Two patients of the training group did not complete the study. Pulmonary function remained unchanged in both groups. Improvement in both aerobic and anaerobic fitness was significant only in the training group (TG vs CG): VO(2)max +18% +/- 2.1% versus +9% +/- 4.5% (P <.05), MAP +32% +/- 5% versus 12% +/- 7% (P <.05), PP +21% +/- 5.7% versus +8.8% +/- 10% (P <.01).\n Exercise training with high-intensity bouts is well tolerated in children with mild-to-moderate asthma. When included in a global rehabilitation program, this type of training improves both aerobic and anaerobic fitness. Anaerobic activities should be considered in sports rehabilitation programs for children with asthma.", "The aim of the present study was to examine the effects of a course of aerobic exercise on pulmonary function and tolerance of activity in asthmatic patients. Among the asthmatic patients, 36 patients (M= 16, F= 20) were chosen after clinical examinations, pulmonary function test, skin prick test (SPT) for aeroallergen and a six minute walk test (6MWT) on their own free will. A patient was said to have Exercise Induced Asthma (EIA) when he/she fulfilled the following criteria; (1) FEV1 less than 80%, (2) 12% increase or more in FEV1 or PEF after short-acting ss2 agonist prescription and (3) 15% decrease in FEV1 or PEF after 6MWT with 70% or 80% of maximum heart rate. The patients were randomly put into two groups of case (M=8, F=10, Mean age=27) and control (M=8, F=10, Mean age=29). Case group participated in eight-week aerobic exercise plan, while control group had no plan of exercise. Pulmonary function tests were done before and after the course of exercise. There were significant changes in FEV1, FVC, PEF, FEF25-75%, MVV, RF and 6MWT between asthmatic patients of the two groups (P less than or equal to 0.05), but FEV1/FVC showed no significant change. Mean of changes in FEV1, FVC, PEF, FEF25-75%, MVV, RF and 6MWT were -25.56, -17.19, 32.09, -27.93, -22.18, 5.63 and -307.5 in case group respectively while they were 6.2, 4.67, 1.96, 6.65, 15.56,-2.87 and 18.78 in the control group. This study shows that aerobic exercises in asthmatic patients lead to an improvement in pulmonary functions. Aerobic exercise rehabilitation can be a complement to medical treatment of asthma.", "nan", "The clinical and physiological effects of a medically supervised, indoor physical training programme were investigated in 36 asthmatic subjects aged 16-40 years. After clinical evaluation, lung function assessment, and progressive incremental exercise testing subjects were randomly allocated to control and training groups. The measurements were repeated after a six week run in period and after a further three months in which those in the training group underwent an indoor training programme. The measurements made at three months were compared with those at the end of the run in period. There was no significant change in anthropometric characteristics, blood lipid profiles, or the provocative concentration of histamine causing a 20% fall in FEV1 (histamine PC20) in the group who underwent training. After training there were significant increases in mean maximal oxygen uptake (ml kg-1 min-1) from 23 (5) to 28 (6), oxygen pulse (ml/beat) from 8.8 (2.3) to 10.8 (2.4), and anaerobic threshold (1/min) from 1.11 (0.27) to 1.38 (0.33). These changes were significantly greater in the group undergoing training than in the control group. There was also a significant fall in breathlessness scores (Borg ratings), blood lactate, carbon dioxide output, and minute ventilation during submaximal exercise in the training group, with no change in the control group. The subject's motivation, the initial level of fitness, and the symptom score at the time of training were the most important factors influencing improvements in cardiorespiratory fitness. Thus submaximal physical exercise of controlled intensity, sustained for three months, produced significant improvements in fitness and cardiorespiratory performance that should be advantageous to the exercising asthmatic patient. The availability of medical supervision throughout the exercise programme appears to have contributed to the successful outcome.", "To evaluate the effects of a physical exercise programme for children with asthma on an outpatient basis.\n Intervention study: a randomized pretest-post-test control group design.\n Forty-seven children with clinically diagnosed asthma participated in the intervention study, including 34 boys and 13 girls, from 8 to 13 years of age (mean age 10.6).\n The physical exercise programme consisted of regular group exercises and home exercises for a period of three months. It was based on a theoretical model describing the relationships between physical competence (condition), perceived physical competence, self-esteem and coping behaviour.\n Maximum incremental exercise test, endurance test, the Self-Perception Profile for Children (CBSK), the Asthma Coping Test (ACBT), lung function and exercise-induced bronchoconstriction.\n The results showed significant effects of the intervention programme on physical condition. There was a significant improvement of 15 W on the maximal workload (Wmax) (p < 0.001), of 7% on VO2max (oxygen uptake) (p = 0.002) and a significant decrease on heart rate submaximal of 6% (p = 0.001). There was also a significant improvement of 50% in running time measured with the endurance test (p = 0.021). Furthermore, a significant effect of the intervention was seen on coping with asthma (p = 0.003).\n It was concluded that participation in the physical exercise programme not only enhanced physical fitness, but also improved coping behaviour with asthma.", "The purpose of this study was to assess the validity of the 20-m shuttle test with 1-min stages (20-MST) to estimate maximal oxygen uptake (VO2 max) and its ability to register cardiorespiratory modifications over the course of an individualized aerobic training program for mild to moderately asthmatic children acclimatized to moderate altitude.\n Forty-eight asthmatic subjects aged 12 to 17 years performed both a maximal incremental exercise test on a cycle ergometer and the 20-MST. Ten of the subjects were then randomly chosen and trained three times per week at their ventilatory threshold (Vth) intensity level for three months. Another group of ten asthmatic subjects served as control subjects. Training intensity was adjusted monthly; heart rate values at Vth were increased by the same proportion as the increase in Vo2 max as measured by the 20-MST. At the end of training, both groups were again evaluated with the two tests. The Vo2 max values by direct measurement and by the 20-MST were not significantly different for the entire population (46.5 +/- 1.6 vs 47.2 +/- 2.1 ml.min-1.kg-1). In addition, the two test results were in close agreement (r = 0.84; p < 0.01). After training, a sharp improvement in the direct Vo2 max (44.1 +/- 2.4 to 51.2 +/- 1.9 ml.min-1.kg-1) was noted in the training group as well as an increase in the Vth (25.6 +/- 1.9 to 32.1 +/- 3.4 ml.min-1.kg-1), the maximal power (152 +/- 7.1 to 185 +/- 3.8 W), and the maximal oxygen pulse (0.24 +/- 0.007 to 0.27 +/- 0.008 ml.beat-1.kg-1).\n The indirect measure confirmed these results: a simultaneous increase in VO2 max (43.7 +/- 2.5 to 53.8 +/- 2.1 ml.min-1.kg-1), maximal oxygen pulse (0.22 +/- 0.004 to 0.27 +/- 0.006 ml.beat-1.kg-1), and the number of stages completed (7 +/- 1.4 to 10.1 +/- 1.3) was observed. It was concluded that the 20-MST has sufficient validity to assess VO2 max and to register cardiorespiratory modifications over the course of individualized aerobic training programs in mild and moderately asthmatic children. It thus may be used to adjust training intensities during these programs.", "there is evidence suggesting that physical activity has anti-inflammatory effects in many chronic diseases; however, the role of exercise in airway inflammation in asthma is poorly understood. We aimed to evaluate the effects of an aerobic training program on eosinophil inflammation (primary aim) and nitric oxide (secondary aim) in patients with moderate or severe persistent asthma.\n sixty-eight patients randomly assigned to either control (CG) or aerobic training (TG) groups were studied during the period between medical consultations. Patients in the CG (educational program + breathing exercises; N = 34) and TG (educational program + breathing exercises + aerobic training; N = 34) were examined twice a week during a 3-month period. Before and after the intervention, patients underwent induced sputum, fractional exhaled nitric oxide (FeNO), pulmonary function, and cardiopulmonary exercise testing. Asthma symptom-free days were quantified monthly, and asthma exacerbation was monitored during 3 months of intervention.\n at 3 months, decreases in the total and eosinophil cell counts in induced sputum (P = 0.004) and in the levels of FeNO (P = 0.009) were observed after intervention only in the TG. The number of asthma symptom-free days and VO(2max) also significantly improved (P < 0.001), and lower asthma exacerbation occurred in the TG (P < 0.01). In addition, the TG presented a strong positive relationship between baseline FeNO and eosinophil counts as well as their improvement after training (r = 0.77 and r = 0.9, respectively).\n aerobic training reduces sputum eosinophil and FeNO in patients with moderate or severe asthma, and these benefits were more significant in subjects with higher levels of inflammation. These results suggest that aerobic training might be useful as an adjuvant therapy in asthmatic patients under optimized medical treatment.", "Asthma symptoms reduce patients' daily activities, impair their health-related quality of life (HRQoL), and increase their reports of anxiety and depression, all of which seem to be related to a decrease in asthma control. Aerobic exercise training is known to improve aerobic fitness and reduce dyspnea in asthmatics; however, its effect in reducing psychologic distress and symptoms remains poorly understood. We evaluated the role of an aerobic training program in improving HRQoL (primary aim) and reducing psychologic distress and asthma symptoms (secondary aims) for patients with moderate or severe persistent asthma.\n A total of 101 patients were randomly assigned to either a control group or an aerobic training group and studied during the period between medical consultations. Control group patients (educational program plus breathing exercises) (n = 51) and training group patients (educational program plus breathing exercises plus aerobic training) (n = 50) were followed twice a week during a 3-month period. HRQoL and levels of anxiety and depression were quantified before and after treatment. Asthma symptoms were evaluated monthly.\n At 3 months, the domains (physical limitations, frequency of symptoms, and psychosocial) and total scores of HRQoL significantly improved only in the training group patients (P < .001); the number of asthma-symptom-free days and anxiety and depression levels also significantly improved in this group (P < .001). In addition, a linear relationship between improvement in aerobic capacity and the days without asthma symptoms was observed (r = 0.47; P < .01).\n Our results suggest that aerobic training can play an important role in the clinical management of patients with persistent asthma. Further, they may be especially useful for patients with higher degrees of psychosocial distress. Trial registration: clinicaltrials.gov; Identifier: NCT-00989365.", "The effects of a 3-month physical training programme on airway inflammation and clinical outcomes were studied in school-aged children with asthma. Subjects with persistent allergic asthma (aged 12.7+/-3.4 yrs; n = 34) were randomly allocated into training and control groups. Exercise consisted of twice-weekly 50-min sessions for 12 weeks. Inflammation was assessed by levels of exhaled nitric oxide, blood eosinophils, eosinophil cationic protein, C-reactive protein, and total and mite-specific immunoglobulin (Ig)E. Lung volumes and bronchial responsiveness to methacholine were determined. The Paediatric Asthma Quality of Life Questionnaire and Paediatric Asthma Caregiver's Quality of Life Questionnaire were used to evaluate activity restrictions, symptoms and emotional stress. The efficacy of the training was assessed by accelerometry. Following the programme, the exercise group spent twice as much time as the controls undertaking moderate-to-vigorous activities. No differences in changes were seen between groups for asthma outcomes. However, total IgE decreased more in the exercise group, as did mite-specific IgE. Training did not increase inflammation in children with persistent asthma, and may have decreased both total and allergen-specific immunoglobulin E levels. It is concluded that there is no reason to discourage asthmatic children with controlled disease to exercise.", "A new diaphragmatic breathing technique practiced without the aid of a physical corset is outlined, and the findings from a study of its application in the respiratory rehabilitation of asthmatic patients are presented. Sixty-seven asthmatic adults randomly assigned to either deep diaphragmatic breathing training, physical exercise training, or a waiting list control group participated in a 16-week program. Deep diaphragmatic training resulted in significant reductions in medication use and in the intensity of asthmatic symptoms. Importantly, a nearly 300% increase in time spent in physical activities also resulted from deep diaphragmatic training. A follow-up at two months found many patients had returned to earlier medication levels and sedentary habits. A strengthened musculature can replace the need for a physical aid in this respiratory habilitation; adherence to its use may require individually-tailored encouragement.", "A study was undertaken to determine whether swimming training improved aerobic capacity, exercise induced bronchoconstriction (EIB), and bronchial responsiveness to inhaled histamine in children with asthma.\n Eight children with mild or moderate asthma participated in swimming training every day for six weeks. The intensity of training was individually determined and set at 125% of the child's lactate threshold (LT), measured using a swimming ergometer. Another group of eight asthmatic children served as control subjects. Aerobic capacity and the degree of EIB were assessed by both cycle ergometer and swimming ergometer before and after swimming training.\n The mean (SD) aerobic capacity at LT increased by 0.26 (0.11) kp after training when assessed with the swimming ergometer and by 10.6 (4.5) W when assessed with the cycle ergometer, and these changes were significantly different from the control group. The mean (SD) maximum % fall in forced expiratory volume in one second (FEV1) to an exercise challenge (cycle ergometer) set at 175% of LT decreased from 38.7 (15.4)% before training to 17.9 (17.6)% after training, but with no significant difference from the control group. There was, however, no difference in histamine responsiveness when compared before and after the training period.\n A six week swimming training programme has a beneficial effect on aerobic capacity but not on histamine responsiveness in children with asthma.", "A study involving eight children with moderate persistent asthma was undertaken to determine whether standard swimming lessons improved symptoms and pulmonary function tests (PFTs) in asthmatic children. Five children ages 7-12 years old with moderate persistent asthma were randomized to a swimming lesson group (5- to 6-week session) and three to a control group. Both groups completed pre- and poststudy period PFTs and symptom questionnaires. Swimming lessons did not produce a significant change in asthma symptoms or PFTs. Review of previous literature found that swimming has been shown to have definite benefits in improving cardiorespiratory fitness in asthmatic children. Swimming has been shown to be less asthmogenic than other forms of exercise. Some studies have also shown improvement in asthma symptoms in children participating in exercise programs.", "Aerobic training has been shown to be effective in improving cardiopulmonary fitness in asthmatic children. However, the actual impact of physical training on clinical indicators of disease control remains controversial.\n Thirty-eight children with moderate to severe persistent asthma were randomly assigned to control (N=17) and training (N=21) groups. Spirometry, exercise challenge, and maximum incremental cardiopulmonary exercise tests were performed 16 wk apart. Daily doses of inhaled steroids and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) scores were also recorded.\n Physical training was associated with significant improvements in physiological variables at peak and submaximal exercise (P<0.05); in contrast, no significant changes were found in controls. Severity of exercise-induced bronchoconstriction (EIB) and postexercise breathlessness were significantly lessened in trained patients; improvement in fitness and EIB, however, were not linearly related (P>0.05). In addition, PAQLQ scores improved only in trained children (P<0.01). Daily doses of inhaled steroids were reduced in trained patients (52%), but they remained unchanged or increased in controls (70.6%) (P=0.07).\n Supervised exercise training might be associated with beneficial effects on disease control and quality of life in asthmatic children. These data suggest an adjunct role of physical conditioning on clinical management of patients with more advanced disease." ]

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[ "A clinical comparison of molindone hydrochloride with trifluoperazine in psychotic outpatients.", "High dose trifluoperazine therapy in chronic schizophrenia.", "Controlled trial of sulpiride in chronic schizophrenic patients.", "A twelve month comparison of penfluridol and trifluoperazine in chronic schizophrenic outpatients.", "Differential drug effects of two phenothiazines. (A controlled comparison of thioridazine and trifluoperazine in chronic schizophrenics).", "A double-blind comparative trial of loxapine and trifluoperazine in acute and chronic schizophrenic patients.", "A standard- (trifluoperazine) controlled clinical study with pimozide in the maintenance treatment of schizophrenic patients, II.", "A comparative study of fluphenazine enanthate and trifluoperazine in chronic schizophrenic patients.", "Pimozide: a comparative study in the treatment of chronic schizophrenic patients.", "A comparative study of molindone and trifluoperazine.", "A comparison of two butyrophenones with trifluoperazine.", "Acute paranoid schizophrenia. (Treatment with chlorpromazine, trifluoperazine and placebo).", "Thiothixene: a controlled evaluation of the intramuscular antipsychotic preparation.", "A double-blind comparison of pimozide vs. trifluoperazine in schizophrenic outpatients.", "A double-blind study of SKF 14336 vs. trifluoperazine in schizophrenic patients.", "A double-blind comparison of loxapine succinate and trifluoperazine in newly admitted schizophrenic patients.", "A double-blind comparison of once-a-day pimozide, trifluoperazine, and placebo in the maintenance care of chronic schizophrenic outpatients.", "A double-blind comparison of the acridane derivative, clomacran phosphate and trifluoperazine in schizophrenia.", "WITHDRAWAL OF LONG-TERM PHENOTHIAZINES FROM CHRONICALLY HOSPITALIZED PSYCHIATRIC PATIENTS.", "Double blind comparison of thiothixene and trifluoperazine in acute schizophrenia.", "Loxapine: a controlled evaluation in chronic schizophrenic patients.", "GP-45795: a controlled evaluation in chronic schizophrenic patients.", "A double-blind comparison of molindone and trifluoperazine in the treatment of acute schizophrenia.", "Chlorpromazine, trifluoperazine and placebo with long-term mental hospital patients.", "[Comparative study of clothiapine and trifluoperazine in acute episodes of paranoid schizophrenia].", "A comparison of thioridazine, trifluoperazine, chlorpromazine, and placebo: a double-blind controlled study on the treatment of chronic, hospitalized, schizophrenic patients.", "Efficacy of trifluoperazine on withdrawal in chronic schizophrenia.", "Centbutindole vs trifluoperazine: a double-blind controlled clinical study in acute schizophrenia.", "A controlled clinical trial of trifluperidol on a group of chronic schizophrenic patients.", "Haloperidol--new addition to the drug treatment of schizophrenia.", "Comparison of the clinical and electroencephalographical effects of molindone and trifluoperazine in acute schizophrenic patients.", "Management of hostile, suspicious patients. Trifluoperazine versus haloperidol.", "A comparison of fluspirilene and trifluoperazine in the treatment of acute schizophrenic psychosis.", "Trifluperidol and trifluoperazine in acute schizophrenic patients.", "A double-blind comparison of trifluperidol and trifluoperazine in acute schizophrenic patients.", "Haloperidol in controlling the symptoms of acute psychoses. II. A double-blind evaluation of haloperidol and trifluoperazine.", "Loxapine in newly admitted chronic schizophrenic patients.", "A standard- (trifluoperazine) controlled clinical study with pimozide in the maintenance treatment of schizophrenic patients, I.", "Comparative effects of intramuscular thiothixene and trifluoperazine in psychotic patients.", "A controlled study of SK&F 14336 in acute schizophrenia.", "Thiothixene versus trifluoperazine in newly-admitted schizophrenic patients.", "A CONTROLLED EVALUATION OF BUTAPERAZINE IN CHRONIC SCHIZOPHRENIC PATIENTS.", "A COMPARISON OF SKF-7261 AND TRIFLUOPERAZINE (STELAZINE) IN THE TREATMENT OF CHRONIC SCHIZOPHRENIC PATIENTS." ]

[ "nan", "nan", "In a double-blind comparative trial of sulpiride (600-1,800 mg/day) and trifluoperazine (15-45 mg/day) in 38 chronic schizophrenic patients, ratings of therapeutic results and unwanted effects were made at two-weekly interviews during the six weeks treatment period. The results show that sulpiride has neuroleptic properties and a spectrum of therapeutic activity similar to that of trifluoperazine. There was an association between plasma sulpiride levels and therapeutic response after four weeks' treatment.", "This investigation is a 52-week double-blind study comparing the efficacy and safety of penfluridol and trifluoperazine in 25 chronic schizophrenic outpatients. Penfluridol was administered once weekly and trifluoperazine daily. Measurements were made at baseline, various fixed intervals during the study period and termination. The data reveals that both agents were similarly effective in maintaining control of the symptoms of chronic schizophrenic patients at a level commensurate with or better than that provided by their previous medication. Besides being effective, medications were also well tolerated. The side effects were characteristic of marketed neuroleptics. Akathisia was more common with penfluridol but readily controlled with anti-parkinsonian medication. Other side effects were similar in severity and occurrence between study-drug groups. Both agents had low autonomic liability, and neither agent was depressogenic.", "nan", "A double-blind comparative trial of loxapine and trifluoperazine was carried out in 57 acute and chronic schizophrenic patients. In both groups of patients loxapine proved to be equivalent in its effects to trifluoperazine and there were suggestions it might be rather more effective in chronic patients. Side-effects were similar with the two drugs but anticholinergic effects, excitement, dizziness and faintness occurred rather more commonly with loxapine. Laboratory tests, urine analysis, cardiovascular and ophthalmological investigations showed no significant abnormalities.", "nan", "nan", "nan", "nan", "nan", "nan", "nan", "nan", "nan", "A study was conducted evaluating the efficacy of loxapine succinate in newly admitted schizophrenic patients through a four-week double-blind comparison with trifluoperazine. Twenty-four patients received between 40 and 80 mg loxapine succinate daily and 19 patients received between 20 and 50 mg trifluoperazine daily. The two groups showed comparable significant improvement on the BPRS and CGI. The discharge and termination rates of the two groups were not significantly different and the incidence and severity of side effects, most frequently extrapyramidal signs, were similar in both groups. Loxapine succinate was judged to be an effective treatment for newly admitted schizophrenic patients.", "nan", "nan", "nan", "nan", "nan", "nan", "nan", "nan", "nan", "nan", "nan", "Twenty-nine acute schizophrenic patients were treated under double-blind conditions for six weeks with either centbutindole in a dose range of 3 mg/day to 4.5 mg/day or trifluoperazine in the dose range of 15 mg/day to 22.5 mg/day. Both drugs produced a significant improvement in initial psychopathology. No significant differences were demonstrated between the two treatment conditions.", "nan", "nan", "nan", "In a population of hostile suspicious patients mostly fitting into the paranoid schizophrenic category, haloperidol and trifluoperazine when compared in double-blind fashion were equal in global clinical ratings. Haloperidol showed significantly more improvement on the Brief Psychiatric Rating Scale and on the Global Paranoia rating. On the Global Hostility rating and in speed of onset of activity, the effects of the two drugs were not significantly different. In a small sub-sample of extremely uncooperative patients haloperidol showed marked effects, but trifluoperazine showed only minimal or moderate effects.", "nan", "nan", "nan", "nan", "The standard drug Stelazine (STEL), at a dose of 50 mg/day, exhibited therapeutic activity significantly different from placebo (PL) activity on several variables, most notably BPRS, attesting to the sensitivity of the experiment. On the other hand, the investigational drug, loxapine (LOX), in doses of 100 mg/day for four weeks, could be differentiated from PL as treatment in the described population on only one variable (NGI-Imp.) and one item of the BPRS. On several variables, positive trends were noted, but the differences from PL did not attain the critical values necessary for statistical significance at P smaller than 0.05. One might speculate that the relatively short duration of treatment in this study might account for the difference between these disappointing results and the more gratifying results of a previous loxapine study in chronic long-term institutionalized schizophrenics with the same oral dose.", "nan", "nan", "nan", "nan", "nan", "nan" ]

[ "16545747", "347221", "10437184", "18209514", "2520420", "12390610", "17868354", "16674760", "8182401", "15606569", "15870415", "3982837", "3898645", "17115982", "18624803", "15023828" ]

[ "Efficacy of acupuncture for the prophylaxis of migraine: a multicentre randomised controlled clinical trial.", "[Management of migraine using acupuncture in a double-blind study].", "Does psychological testing help to predict the response to acupuncture or massage/relaxation therapy in patients presenting to a general neurology clinic with headache?", "Acupuncture in migraine prevention: a randomized sham controlled study with 6-months posttreatment follow-up.", "A controlled trial of the treatment of migraine by acupuncture.", "Acupuncture in the prophylactic treatment of migraine without aura: a comparison with flunarizine.", "Traditional acupuncture in migraine: a controlled, randomized study.", "Acupuncture in migraine prophylaxis: a randomized sham-controlled trial.", "Acupuncture versus metoprolol in migraine prophylaxis: a randomized trial of trigger point inactivation.", "Role of the needling per se in acupuncture as prophylaxis for menstrually related migraine: a randomized placebo-controlled study.", "Acupuncture for patients with migraine: a randomized controlled trial.", "The effects of acupuncture versus placebo in the treatment of headache.", "[A muscle and vascular oriented relaxation program for the treatment of chronic migraine patients. A randomized clinical comparative study].", "Effectiveness and tolerability of acupuncture compared with metoprolol in migraine prophylaxis.", "Acupuncture in patients with headache.", "Acupuncture for chronic headache in primary care: large, pragmatic, randomised trial." ]

[ "Our aim was to assess the efficacy of a part-standardised verum acupuncture procedure, in accordance with the rules of traditional Chinese medicine, compared with that of part-standardised sham acupuncture and standard migraine prophylaxis with beta blockers, calcium-channel blockers, or antiepileptic drugs in the reduction of migraine days 26 weeks after the start of treatment.\n This study was a prospective, randomised, multicentre, double-blind, parallel-group, controlled, clinical trial, undertaken between April 2002 and July 2005. Patients who had two to six migraine attacks per month were randomly assigned verum acupuncture (n=313), sham acupuncture (n=339), or standard therapy (n=308). Patients received ten sessions of acupuncture treatment in 6 weeks or continuous prophylaxis with drugs. Primary outcome was the difference in migraine days between 4 weeks before randomisation and weeks 23-26 after randomisation. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN52683557.\n Of 1295 patients screened, 960 were randomly assigned to a treatment group. Immediately after randomisation, 125 patients (106 from the standard group) withdrew their consent to study participation. 794 patients were analysed in the intention-to-treat popoulation and 443 in the per-protocol population. The primary outcome showed a mean reduction of 2 .3 days (95% CI 1.9-2.7) in the verum acupuncture group, 1.5 days (1.1-2.0) in the sham acupuncture group, and 2.1 days (1.5-2.7) in the standard therapy group. These differences were statistically significant compared with baseline (p<0.0001), but not across the treatment groups (p=0.09). The proportion of responders, defined as patients with a reduction of migraine days by at least 50%, 26 weeks after randomisation, was 47% in the verum group, 39% in the sham acupuncture group, and 40% in the standard group (p=0.133).\n Treatment outcomes for migraine do not differ between patients treated with sham acupuncture, verum acupuncture, or standard therapy.", "nan", "Patients with chronic headache were offered treatment by acupuncture or massage with relaxation instead of a change in their prescribed medication. They were randomly allocated to either treatment. There was a significant improvement in pain ratings with both treatment types. Specifically a greater effect was seen in migraine patients treated by massage with relaxation when compared to acupuncture. No psychological factors were found to predict response to either treatment. At the end of the study, 13% of patients were significantly more worried that there may be a more serious cause underlying their headache despite reassurance and an improvement in their headache scores.", "To assess the efficacy of acupuncture in migraine prophylaxis.\n Thirty-seven patients with migraine were enrolled in a randomized control trial at the Headache clinic located in a University Hospital. Real and sham acupuncture groups received 16 acupuncture sessions over 3 months. Treatment was individualized in the real acupuncture group and minimal acupuncture was used in the sham group. The primary end point was the percentage of patients with a >or=50% reduction in their migraine attack frequency in the second, third, fourth, fifth, and sixth (months) compared with the first one (baseline period). Primary and secondary end points were measured comparing headache diaries.\n Real acupuncture group showed improvement with significant differences compared with the sham acupuncture group in the primary efficacy end point (P=0.021) at the second month of the treatment. Differences also appeared in 2 secondary end points: number of days with migraine per month (P=0.007) in the second month and the percentage of patients with >or=40% reduction in migraine attack frequency in the first (P=0.044) and second months (P=0.004) of the treatment. These differences disappeared in the third (last) month of the treatment as a consequence of the high improvement of the sham acupuncture group. Comparisons within each group showed that several migraine parameters evaluated improved significantly in both groups.\n Individualized treatment based on traditional Chinese medicine plays a role in preventing migraine attacks. Nevertheless, sham acupuncture had similar effects. Major conclusions were limited by the small sample sizes however the observed trends may contribute to design future trials.", "A randomised controlled trial comparing true and sham acupuncture was conducted on 30 patients suffering from chronic migraine. Diary measures of headache and medication intake were recorded throughout the study, and measures of headache quality, anxiety, and pain behaviour were taken. The credibility of the true and sham treatment procedures was also assessed. True acupuncture was significantly more effective than the control procedure in reducing the pain of migraine headache. Posttreatment reductions in pain scores and medication of 43 and 38%, respectively, were recorded in the true acupuncture group and were maintained at 4-month and 1-year follow-up.", "In a randomized controlled trial extending over 6 months, we evaluated the effectiveness of acupuncture versus flunarizine in the prophylactic treatment of migraine without aura.\n One hundred sixty women with migraines were randomly assigned to acupuncture treatment (group A, n = 80) or to an oral therapy with flunarizine (group F, n = 80). In group A, acupuncture was carried out in weekly sessions for the first 2 months and then once a month for the next 4 months. The same acupoints were used at each treatment: LR3 Taichong, SP6 Sanyinjiao, ST36 Zusanli, CV12 Zhongwan, LI4 Hegu, PC6 Neiguan, GB20 Fengchi, GB14 Yangbai, EX-HN5 Taiyang, GV20 Baihui. In group F, 10 mg flunarizine were given daily for the first 2 months and then for 20 days per month for the next 4 months.\n The frequency of attacks and use of symptomatic drugs significantly decreased during treatment in both groups. The number of attacks after 2 and 4 months of therapy was significantly lower in group A than in group F, and analgesic consumption was significantly lower in group A at 2 months of treatment. At 6 months no such differences existed between the two treatment groups. Pain intensity was significantly reduced only by acupuncture treatment. Side effects were significantly less frequent in group A.\n Acupuncture proved to be adequate for migraine prophylaxis. Relative to flunarizine, acupuncture treatment exhibited greater effectiveness in the first months of therapy and superior tolerability.", "To check the effectiveness of a true acupuncture treatment according to traditional Chinese medicine (TCM) in migraine without aura, comparing it to a standard mock acupuncture protocol, an accurate mock acupuncture healing ritual, and untreated controls.\n Migraine prevalence is high and affects a relevant rate of adults in the productive phase of their life. Acupuncture has been increasingly advocated and used in Western countries for migraine treatment, but the evidence of its effectiveness still remains weak. A large variability of treatments is present in published studies and no acupoint selection according to TCM has been investigated so far; therefore, the low level of evidence of acupuncture effectiveness might partly depend on inappropriate treatment.\n A prospective, randomized, controlled study was performed in 160 patients suffering from migraine without aura, assessed according to the ICD-10 classification. The patients were divided into the following 4 groups: (1) group TA, treated with true acupuncture (according to TCM) plus Rizatriptan; (2) group RMA, treated with ritualized mock acupuncture plus Rizatriptan; (3) group SMA, treated with standard mock acupuncture plus Rizatriptan; (4) group R, without prophylactic treatment with relief therapy only (Rizatriptan). The MIDAS Questionnaire was administered before treatment (T0), at 3 (T1) and 6 months (T2) from the beginning of treatment, and the MIDAS Index (MI) was calculated. Rizatriptan intake was also checked in all groups of patients at T0, T1, and T2. Group TA and RMA were evaluated according to TCM as well; then, the former was submitted to true acupuncture and the latter to mock acupuncture treatment resembling the same as TA. The statistical analysis was conducted with factorial ANOVA and multiple tests with a Bonferroni adjustment.\n A total of 127 patients completed the study (33 dropouts): 32 belonged to group TA, 30 to group RMA, 31 to group SMA, and 34 to group R. Before treatment the MI (T(0)) was moderate to severe with no significant intergroup differences. All groups underwent a decrease of MI at T(1) and T(2), with a significant group difference at both T(1) and T(2) compared to T(0) (P < .0001). Only TA provided a significant improvement at both T(1) and T(2) compared to R (P < .0001). RMA underwent a transient improvement of MI at T(1). The Rizatriptan intake paralleled the MI in all groups.\n TA was the only treatment able to provide a steady outcome improvement in comparison to the use of only Rizatriptan, while RMA showed a transient placebo effect at T1.", "The purpose of the present trial was to evaluate semi-standardized acupuncture efficacy in migraine prophylaxis. Twenty-eight subjects with migraine were randomized to the real or sham acupuncture groups. Semi-standardized and standardized minimal acupuncture were used, respectively, in the two groups of patients. They were all treated with 16 acupuncture sessions in 12 weeks. Both groups exhibited similar reductions in: percentage of patients with reduction of migraine>or=40% and >or=50% regarding frequency of migraine attacks, days with migraine, frequency of migraine attacks, average duration of a migraine attack, rate of rescue medication used, average headache severity rate and other parameters compared with the baseline period. Associated symptoms, such as nausea and vomiting, also showed equal estimates in both groups. These findings showed that semi-standardized acupuncture shows no difference from sham acupuncture in preventing migraine attacks.", "To compare the effects of dry needling of myofascial trigger points in the neck region to metoprolol in migraine prophylaxis.\n Randomized, group comparative study. patients, investigator and statistician were blinded as to treatment, the therapist was blinded as to results.\n Outpatient pain clinic in the northern Copenhagen area. Patients were referred by general practitioners or respondents to newspaper advertisements.\n Included were patients with a history of migraine with or without aura for at least 2 years. Excluded were persons with contraindications against treatment with beta blockers, chronic pain syndromes, pregnancy or previous experience with acupuncture or beta-blocking agents. A total of 85 patients were included; 77 completed the study.\n After a 4-week run-in period, patients were allocated to a 17-week regimen either with acupuncture and placebo tablets or to placebo stimulation and metoprolol 100 mg daily.\n Both groups exhibited significant reduction in attack frequency (P < 0.01). No difference was found between the groups regarding frequency (P > 0.20) or duration (P > 0.10) of attacks, whereas we found a significant difference in global rating of attacks in favour of metoprolol (P < 0.05).\n Trigger point inactivation by dry needling is a valuable supplement to the list of migraine prophylactic tools, being equipotent to metoprolol in the influence on frequency and duration (but not severity) of attacks, and superior in terms of negative side-effects.", "The objectives were to introduce a new method for controlled trials of acupuncture in the field of headache research and to examine the role of needling per se. Women with menstrually related migraine were randomized to three months of treatment with verum or placebo needles. Three standard size casts were moulded to secure the placebo needles in the head. No significant differences were found between the verum group (n=15) and the placebo group (n=13) during treatment or follow up three and six months later, either in the attack frequency or in the number of days per month with migraine, headache intensity or drug-use. The casts held the needles exactly in place despite movements of the head, and are validated as practical, hygienic and extremely durable. This method is satisfactory for controlled studies of acupuncture in headache. It is possible that the positive results in earlier clinical trials on acupuncture in migraine are attributable to other mechanisms than needling of subcutaneous tissue.", "Acupuncture is widely used to prevent migraine attacks, but the available evidence of its benefit is scarce.\n To investigate the effectiveness of acupuncture compared with sham acupuncture and with no acupuncture in patients with migraine.\n Three-group, randomized, controlled trial (April 2002-January 2003) involving 302 patients (88% women), mean (SD) age of 43 (11) years, with migraine headaches, based on International Headache Society criteria. Patients were treated at 18 outpatient centers in Germany.\n Acupuncture, sham acupuncture, or waiting list control. Acupuncture and sham acupuncture were administered by specialized physicians and consisted of 12 sessions per patient over 8 weeks. Patients completed headache diaries from 4 weeks before to 12 weeks after randomization and from week 21 to 24 after randomization.\n Difference in headache days of moderate or severe intensity between the 4 weeks before and weeks 9 to 12 after randomization.\n Between baseline and weeks 9 to 12, the mean (SD) number of days with headache of moderate or severe intensity decreased by 2.2 (2.7) days from a baseline of 5.2 (2.5) days in the acupuncture group compared with a decrease to 2.2 (2.7) days from a baseline of 5.0 (2.4) days in the sham acupuncture group, and by 0.8 (2.0) days from a baseline if 5.4 (3.0) days in the waiting list group. No difference was detected between the acupuncture and the sham acupuncture groups (0.0 days, 95% confidence interval, -0.7 to 0.7 days; P = .96) while there was a difference between the acupuncture group compared with the waiting list group (1.4 days; 95% confidence interval; 0.8-2.1 days; P<.001). The proportion of responders (reduction in headache days by at least 50%) was 51% in the acupuncture group, 53% in the sham acupuncture group, and 15% in the waiting list group.\n Acupuncture was no more effective than sham acupuncture in reducing migraine headaches although both interventions were more effective than a waiting list control.", "Forty-eight patients were entered into a placebo (mock TNS) versus acupuncture study to assess the effect of these therapies on headache. Treatment was evaluated by the use of patient diaries; each patient completed a daily diary for 4 weeks prior to treatment during 6 weeks of therapy and for 24 weeks of follow-up. Thirty-nine patients completed treatment and follow-up. At most acupuncture appears to be approximately 20% more effective than a placebo in alleviating headache but no statistically significant difference between these two treatments could be demonstrated. The implications of this result particularly with respect to determining treatment success and study method employed are discussed.", "The study compares in a randomized clinical control-group design with a waiting list-and acupuncture therapy control-group the short term (three months) effectiveness of a newly developed psychological biobehavioral treatment program in 30 chronic migraine patients. The results show a significant reduction of vascular and tension related headache-frequency and intensity (primary outcome criteria) in both the acupuncture and psychological treatment condition. The waiting list control-group remained almost unchanged over the whole observation period. The improvement in both treatment conditions remained stable throughout the post therapy period to the three months follow-up, but only the psychological treatment condition revealed a highly significant reduction in the use of all kinds of medication in comparison to the pre-treatment period. Single case analyses showed a slight superiority of the psychological treatment condition over the acupuncture therapy due to a more generalized improvement in all secondary outcome variables (psychological restrictions in every day life, medication, duration of headache). The effect of specific components of the psychological treatment program are examined and possible general implication for a treatment of severely disturbed chronic migraine patients are discussed.", "In a randomized controlled multicenter trial extending over 24 weeks, we investigated whether acupuncture is as effective and safe as metoprolol in the prophylactic treatment of migraine under conditions similar to routine care.\n One hundred fourteen migraine patients could be randomized to treatment over 12 weeks either with acupuncture (8 to 15 sessions) or metoprolol (100 to 200 mg daily). Main outcome measure was the difference in the number of migraine days between baseline and the weeks 9 to 12 after randomization (derived from a headache diary).\n Two of 59 patients randomized to acupuncture withdrew prematurely from the study compared to 18 of 55 randomized to metoprolol. The number of migraine days decreased by 2.5 +/- 2.9 days (baseline 5.8 +/- 2.5 days) in the acupuncture group compared to 2.2 +/- 2.7 days (baseline 5.8 +/- 2.9 days) in the metoprolol group (P= .721). The proportion of responders (reduction of migraine attacks by > or =50%) was 61% for acupuncture and 49% for metoprolol. Both physicians and patients reported fewer adverse effects in the acupuncture group.\n Due to missing the recruitment target (480 patients) and the high drop-out in the metoprolol group the results must be interpreted with caution. Still, they suggest that acupuncture might be an effective and safe treatment option for patients unwilling or unable to use drug prophylaxis.", "We aimed to investigate the effectiveness of acupuncture in addition to routine care in patients with primary headache (> 12 months, two or more headaches/month) compared with treatment with routine care alone and whether the effects of acupuncture differ in randomized and non-randomized patients. In a randomized controlled trial plus non-randomized cohort, patients with headache were allocated to receive up to 15 acupuncture sessions over 3 months or to a control group receiving no acupuncture during the first 3 months. Patients who did not consent to randomization received acupuncture treatment immediately. All subjects were allowed usual medical care in addition to study treatment. Number of days with headache, intensity of pain and health-related quality of life (SF-36) were assessed at baseline, and after 3 and 6 months using standardized questionnaires. Of 15,056 headache patients (mean age 44.1 +/- 12.8 years, 77% female), 1613 were randomized to acupuncture and 1569 to control, and 11,874 included in the non-randomized acupuncture group. At 3 months, the number of days with headache decreased from 8.4 +/- 7.2 (estimated mean +/-s.e.) to 4.7 +/- 5.6 in the acupuncture group and from 8.1 +/- 6.8 to 7.5 +/- 6.3 in the control group (P < 0.001). Similarly, intensity of pain and quality of life improvements were more pronounced in the acupuncture vs. control group (P < 0.001). Treatment success was maintained through 6 months. The outcome changes in non-randomized patients were similar to those in randomized patients. Acupuncture plus routine care in patients with headache was associated with marked clinical improvements compared with routine care alone.", "To determine the effects of a policy of \"use acupuncture\" on headache, health status, days off sick, and use of resources in patients with chronic headache compared with a policy of \"avoid acupuncture.\"\n Randomised, controlled trial.\n General practices in England and Wales.\n 401 patients with chronic headache, predominantly migraine. Interventions Patients were randomly allocated to receive up to 12 acupuncture treatments over three months or to a control intervention offering usual care.\n Headache score, SF-36 health status, and use of medication were assessed at baseline, three, and 12 months. Use of resources was assessed every three months.\n Headache score at 12 months, the primary end point, was lower in the acupuncture group (16.2, SD 13.7, n = 161, 34% reduction from baseline) than in controls (22.3, SD 17.0, n = 140, 16% reduction from baseline). The adjusted difference between means is 4.6 (95% confidence interval 2.2 to 7.0; P = 0.0002). This result is robust to sensitivity analysis incorporating imputation for missing data. Patients in the acupuncture group experienced the equivalent of 22 fewer days of headache per year (8 to 38). SF-36 data favoured acupuncture, although differences reached significance only for physical role functioning, energy, and change in health. Compared with controls, patients randomised to acupuncture used 15% less medication (P = 0.02), made 25% fewer visits to general practitioners (P = 0.10), and took 15% fewer days off sick (P = 0.2).\n Acupuncture leads to persisting, clinically relevant benefits for primary care patients with chronic headache, particularly migraine. Expansion of NHS acupuncture services should be considered." ]

[ "21967845", "18678826", "20410089" ]

[ "Effects of n-3 fatty acids on cognitive decline: a randomized, double-blind, placebo-controlled trial in stable myocardial infarction patients.", "Effect of fish oil on cognitive performance in older subjects: a randomized, controlled trial.", "Effect of 2-y n-3 long-chain polyunsaturated fatty acid supplementation on cognitive function in older people: a randomized, double-blind, controlled trial." ]

[ "Epidemiological studies suggest a protective effect of n-3 fatty acids derived from fish (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) against cognitive decline. For α-linolenic acid (ALA) obtained from vegetable sources, the effect on cognitive decline is unknown. We examined the effect of n-3 fatty acid supplementation on cognitive decline in coronary heart disease patients.\n The analysis included 2911 coronary patients (78% men) aged 60 to 80 years who participated in a double-blind placebo-controlled trial of n-3 fatty acids and cardiovascular diseases (Alpha Omega Trial). By using a 2 × 2 factorial design, patients were randomly assigned to margarines that provided 400 mg/d of EPA-DHA, 2 g/d of ALA, both EPA-DHA and ALA, or placebo for 40 months. Cognitive function was assessed by the Mini-Mental State Examination (MMSE) at baseline and after 40 months. The effect of n-3 fatty acids on change in MMSE score was assessed using analysis of variance. Logistic regression analysis was used to examine the effects on risk of cognitive decline, defined as a decrease of 3 or more points in MMSE score or incidence of dementia.\n Patients in the active treatment groups had an additional intake of 384 mg of EPA-DHA, 1.9 g of ALA, or both. The overall MMSE score in this cohort was 28.3 ± 1.6 points, which decreased by 0.67 ± 2.25 points during follow-up. Changes in MMSE score during intervention did not differ significantly between EPA-DHA and placebo (-0.65 vs -0.69 points, P = .44) or between ALA and placebo (-0.60 vs -0.74 points, P = .12). The risk of cognitive decline was 1.03 (95% confidence interval: 0.84-1.26, P = .80) for EPA-DHA (vs placebo) and 0.90 (0.74-1.10, P = .31) for ALA (vs placebo).\n This large intervention study showed no effect of dietary doses of n-3 fatty acids on global cognitive decline in coronary heart disease patients.\n Copyright © 2012 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.", "High intake of n-3 polyunsaturated fatty acids may protect against age-related cognitive decline. However, results from epidemiologic studies are inconclusive, and results from randomized trials in elderly subjects without dementia are lacking.\n To investigate the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on cognitive performance.\n Double-blind, placebo-controlled trial involving 302 cognitively healthy (Mini-Mental State Examination score > 21) individuals aged 65 years or older. Participants were randomly assigned to 1,800 mg/d EPA-DHA, 400 mg/d EPA-DHA, or placebo capsules for 26 weeks. Cognitive performance was assessed using an extensive neuropsychological test battery that included the cognitive domains of attention, sensorimotor speed, memory, and executive function.\n The mean age of the participants was 70 years, and 55% were male. Plasma concentrations of EPA-DHA increased by 238% in the high-dose and 51% in the low-dose fish oil group compared with placebo, reflecting excellent compliance. Baseline scores on the cognitive tests were comparable in the three groups. Overall, there were no significant differential changes in any of the cognitive domains for either low-dose or high-dose fish oil supplementation compared with placebo.\n In this randomized, double-blind, placebo-controlled trial, we observed no overall effect of 26 weeks of eicosapentaenoic acid and docosahexaenoic acid supplementation on cognitive performance.", "Increased consumption of n-3 (omega-3) long-chain polyunsaturated fatty acids (LC PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may maintain cognitive function in later life.\n We tested the hypothesis that n-3 LC PUFA supplementation would benefit cognitive function in cognitively healthy older people.\n At total of 867 cognitively healthy adults, aged 70-79 y, from 20 general practices in England and Wales were randomly assigned into a double-blind controlled trial of daily capsules providing 200 mg EPA plus 500 mg DHA or olive oil for 24 mo. Treatment-allocation codes were obtained from a central computerized randomization service. Trained research nurses administered a battery of cognitive tests, including the primary outcome, the California Verbal Learning Test (CVLT), at baseline and 24 mo. Intention-to-treat analysis of covariance, with adjustment for baseline cognitive scores, age, sex, and age at leaving full-time education, included 748 (86%) individuals who completed the study.\n The mean age of participants was 75 y; 55% of the participants were men. Withdrawals and deaths were similar in active (n = 49 and n = 9, respectively) and placebo (n = 53 and n = 8, respectively) arms. Mean (+/-SD) serum EPA and DHA concentrations were significantly higher in the active arm than in the placebo arm at 24 mo (49.9 +/- 2.7 mg EPA/L in the active arm compared with 39.1 +/- 3.1 mg EPA/L in the placebo arm; 95.6 +/- 3.1 mg DHA/L in the active arm compared with 70.7 +/- 2.9 mg DHA/L in the placebo arm). There was no change in cognitive function scores over 24 mo, and intention-to-treat analysis showed no significant differences between trial arms at 24 mo in the CVLT or any secondary cognitive outcome.\n Cognitive function did not decline in either study arm over 24 mo. The lack of decline in the control arm and the relatively short intervention period may have limited our ability to detect any potential beneficial effect of fish oil on cognitive function in this study. The Older People And n-3 Long-chain polyunsaturated fatty acids (OPAL) Study was registered at www.controlled-trials.com as ISRCTN 72331636." ]

[ "7519567", "12740260", "6404203" ]

[ "Effects of chlormadinone acetate, acetazolamide and oxygen on awake and asleep gas exchange in patients with chronic obstructive pulmonary disease (COPD).", "Comparison of acetazolamide and medroxyprogesterone as respiratory stimulants in hypercapnic patients with COPD.", "Relative effectiveness of acetazolamide versus medroxyprogesterone acetate in correction of chronic carbon dioxide retention." ]

[ "The purpose of this study was to assess the short-term effects of chlormadinone acetate (CMA), a synthetic progestogen, acetazolamide (ACET) and oxygen on awake and asleep blood gas values. The study was conducted according to a randomized, double-blind and placebo-controlled design in 53 hypoxaemic patients with chronic obstructive pulmonary disease. On the first two consecutive nights, all patients received either room air or oxygen, via a nasal cannula, in random order. They then received either CMA (25 mg), ACET (250 mg) or placebo twice a day, all in identical capsules. On the third study night, after one week of drug treatment, the patients were tested breathing room air. CMA and ACET therapy decreased mean daytime arterial carbon dioxide tension (PaCO2) by 0.7 and 0.5 kPa, respectively, and night-time end-tidal carbon dioxide tension (PETCO2) by 0.5 and 0.3 kPa, respectively. Supplemental oxygen caused increased CO2 retention during the day and night (0.6 and 0.3 kPa, respectively. Daytime arterial oxygen tension (PaO2) increased to the same extent during ACET (1.9 kPa) and oxygen (2.5 kPa). Asleep oxygen saturation improved most with oxygen supplementation (7%), although ACET also caused significant improvement (4%). CMA administration had virtually no effect on mean awake and asleep hypoxaemia. ACET therapy significantly improved subjective sleep quality. On CMA, minute ventilation increased in association with an augmentation of the hypercapnic ventilatory response. ACET treatment increased both hypercapnic and hypoxic ventilatory responses. We conclude from the group of patients with COPD studied, that the short-term effects of ACET treatment on gas exchange compare favourably with those of CMA. Oxygen therapy improves oxygenation slightly more than ACET, but aggravates CO2 retention.", "Acetazolamide and medroxyprogesterone acetate (MPA) are two respiratory stimulants that can be used in patients with stable hypercapnic COPD.\n The effects of acetazolamide, 250 mg bid, and MPA, 30 mg bid, on daytime and nighttime blood gas values and the influences on the hypercapnic and hypoxic ventilatory and mouth occlusion pressure (P(0.1)) at 100 ms response were studied in a crossover design in 12 hypercapnic patients with stable COPD (FEV(1), 33 +/- 4% predicted [mean +/- SEM]).\n Daytime PaCO(2) decreased from 47.3 +/- 0.8 mm Hg (placebo) to 42.0 +/- 1.5 mm Hg during acetazolamide treatment (p < 0.05) and to 42.8 +/- 1.5 mm Hg during MPA treatment (p < 0.05). Daytime PaO(2) improved with acetazolamide from 65.2 +/- 2.3 to 75.0 +/- 3.0 mm Hg (p < 0.05), whereas no significant changes were seen with MPA. Mean nocturnal end-tidal carbon dioxide tension decreased with both treatments, from 42.0 +/- 2.3 to 35.3 +/- 2.3 mm Hg with acetazolamide (p < 0.05) and to 34.5 +/- 0.8 mm Hg with MPA (p < 0.05). The percentage of time that the nocturnal arterial oxygen saturation was < 90% was reduced significantly with acetazolamide, from 34.9 +/- 10.7% to 16.3 +/- 7.5% (p < 0.05). Mean nocturnal saturation did not change with MPA. Resting minute ventilation increased significantly only with MPA from 9.6 +/- 0.7 to 10.8 +/- 0.8 L/min (p < 0.05). The slope of the hypercapnic ventilatory response did not change during acetazolamide and MPA therapy. The hypoxic ventilatory response increased from - 0.2 +/- 0.05 to - 0.4 +/- 0.1 L/min/% during acetazolamide (p < 0.05) and to - 0.3 +/- 0.1 L/min/% during MPA (p < 0.05). The hypoxic P(0.1) response improved with acetazolamide treatment from - 0.05 +/- 0.008 to - 0.15 +/- 0.02 mm Hg/% (p < 0.05).\n This study shows that acetazolamide and MPA both have favorable effects on daytime and nighttime blood gas parameters in ventilatory-limited patients with stable COPD. However, the use of acetazolamide is preferred because of its extra effect on nocturnal saturation.", "nan" ]

[ "17092691", "18165460", "17690599", "17601495", "19411369", "17466492", "17224706" ]

[ "Treatment of schizophrenia with paliperidone extended-release tablets: a 6-week placebo-controlled trial.", "Safety and tolerability of oral paliperidone extended-release tablets in elderly patients with schizophrenia: a double-blind, placebo-controlled study with six-month open-label extension.", "A double-blind, placebo-controlled, randomized study evaluating the effect of paliperidone extended-release tablets on sleep architecture in patients with schizophrenia.", "Efficacy and safety of paliperidone extended-release tablets: results of a 6-week, randomized, placebo-controlled study.", "Randomized, double-blind, placebo-controlled study of paliperidone extended-release and quetiapine in inpatients with recently exacerbated schizophrenia.", "Efficacy, safety and early response of paliperidone extended-release tablets (paliperidone ER): results of a 6-week, randomized, placebo-controlled study.", "Paliperidone extended-release tablets for prevention of symptom recurrence in patients with schizophrenia: a randomized, double-blind, placebo-controlled study." ]

[ "Paliperidone extended-release tablet (paliperidone ER) is an investigational oral psychotropic developed for schizophrenia treatment. It utilizes OROS technology to provide a unique pharmacokinetic profile, eliminating the need for titration and potentially leading to improved tolerability. Furthermore, paliperidone undergoes limited hepatic metabolism.\n The efficacy and safety of once-daily paliperidone ER (6 mg, 9 mg and 12 mg) were assessed versus placebo in 628 patients with acute schizophrenia in a 6-week, multicenter, double-blind, randomized, parallel-group study.\n All doses of paliperidone ER demonstrated significant improvement in PANSS score, all PANSS Marder factor scores (p<0.001) and personal and social functioning versus placebo (p<0.001). The PANSS total score also improved significantly in the olanzapine treatment arm. Significantly higher percentages of paliperidone ER patients demonstrated a > or =30% reduction in PANSS total score versus placebo (p<0.001). The incidence of movement disorder-related AEs and rating scales measurements were similar to placebo for the paliperidone ER 6 mg group and higher in the 9 mg and 12 mg groups. In the paliperidone ER groups there were no reports of glucose-related AEs or clinically relevant changes in plasma lipid levels and changes in mean bodyweight<1 kg.\n In this study, all doses of paliperidone ER were effective in significantly improving the symptoms of schizophrenia and personal and social functioning and were generally well tolerated. Paliperidone ER offers a distinctive treatment profile and may provide a valuable new treatment option for patients with schizophrenia.", "The objective of this multicenter, international study was to evaluate safety and tolerability of paliperidone extended-release (ER) tablets in elderly (age > or =65 years) patients with schizophrenia. The authors conducted a 6-week, double-blind, randomized, placebo-controlled, optional 24-week open-label extension study. Interventions consisted of flexible, once-daily doses of paliperidone ER (3-12 mg/day; 6-mg starting dose, adjusted in 3-mg dose increments) or placebo (2:1) during double-blind treatment and paliperidone ER only during open-label treatment. Measurements included adverse events, laboratory tests, physical examinations, 12-lead electrocardiograms, movement disorder rating scales, Positive and Negative Syndrome Scale, and Clinical Global Impression scale. The study was not powered to show statistical differences.\n Patients (N = 114) were predominantly female (73%); mean age was 70 years (double-blind phase). Concomitant disease presence was consistent with that of an older population. During the double-blind phase, discontinuation rates resulting from adverse events were similar between groups (paliperidone ER: 7%, placebo: 8%) as were incidences of treatment-emergent adverse events (paliperidone ER: 67%, placebo: 71%). Serious adverse events occurred in 3% of the paliperidone ER- and 8% of the placebo-treated patients. Elevated prolactin levels occurred in approximately one half of patients. No prolactin- or glucose treatment-related adverse events or noteworthy mean changes in body weight (0 kg [standard deviation: 2.1] and 0 kg [standard deviation: 2.3] for paliperidone ER and placebo, respectively) were observed. Safety and tolerability results in the extension were consistent with the shorter-term results. Efficacy measures did not show consistent statistical improvement between treatment groups.\n Paliperidone ER (3-12 mg/day) treatment over a 30-week period was generally well-tolerated and may improve symptom severity in elderly patients with schizophrenia.", "The effects of paliperidone extended-release on sleep architecture in patients with schizophrenia-related insomnia were evaluated in this multicenter, double-blind, randomized, placebo-controlled study. Patients received paliperidone extended-release 9 mg/day or matching placebo during the 14-day double-blind phase. Sleep architecture and sleep continuity were evaluated using polysomnograms. Subjective sleep measures were evaluated daily using the Leeds Sleep Evaluation Questionnaire. Efficacy and safety were also assessed. Thirty-six patients (17 on paliperidone extended-release, 19 on placebo; mean age 32.2 years) completed the study. Paliperidone extended-release treatment vs. placebo resulted in clinically and statistically significant differences in sleep measurements from baseline to endpoint including a reduction in: persistent sleep latency (41 min), sleep onset latency (35 min), number of awakenings after sleep onset (7), time awake in bed (50 min), and stage 1 sleep duration (12 min); prolongation in: total sleep time (53 min), sleep period time (42 min), stage 2 sleep duration (51 min), and rapid eye movement sleep duration (18 min); and an increase in sleep efficiency index (11%). Paliperidone extended-release, compared with placebo, did not exacerbate daytime somnolence and improved symptoms of schizophrenia. Paliperidone extended-release was well tolerated and improved sleep architecture and sleep continuity in patients diagnosed with schizophrenia and concomitant insomnia.", "Paliperidone extended-release tablet (paliperidone ER; Invega, Janssen L.P., Titusville, New Jersey) is an oral psychotropic for schizophrenia treatment.\n Efficacy and safety of once-daily paliperidone ER (6 and 12 mg) were assessed versus placebo in 444 patients with acute schizophrenia in a 6-week, multicenter, double-blind, randomized, parallel-group study. An olanzapine (10 mg) treatment arm was included to confirm trial validity.\n Both doses of paliperidone ER demonstrated significant improvement in Positive and Negative Syndrome Scale (PANSS) total score (p < or = .006) and certain PANSS Marder factor scores compared with placebo (p < or = .025); PANSS total score also improved in the olanzapine treatment arm. Paliperidone ER 6 mg (p < or = .008), but not 12 mg, was associated with significant improvements in personal and social performance. The incidence of treatment-emergent adverse events (AEs) for paliperidone ER 6 mg was comparable with placebo and slightly greater with paliperidone ER 12 mg. Changes in blood glucose and lipid levels with paliperidone ER were comparable with placebo. Two patients treated with paliperidone ER experienced glucose-related AEs. Body-weight increases of 1-2 kg were observed with paliperidone ER. Although there were increases in plasma prolactin levels with paliperidone ER treatment, the incidence of prolactin-related AEs was < or =1%.\n In this study, paliperidone ER, particularly the 6-mg dose, was effective and well tolerated, and provides a valuable new treatment option for schizophrenia.", "The authors compared paliperidone extended-release and quetiapine in patients with recently exacerbated schizophrenia requiring hospitalization.\n In a 6-week double-blind study, inpatients with a recent exacerbation of schizophrenia were randomly assigned to treatment with paliperidone extended-release, quetiapine, or placebo. A 2-week monotherapy phase was followed by a 4-week additive-therapy phase. Target doses were at the upper end of recommended ranges: paliperidone extended-release, 9 or 12 mg/day, and quetiapine, 600 or 800 mg/day. The primary endpoint was the difference in mean total change score on the Positive and Negative Syndrome Scale (PANSS) between paliperidone extended-release and quetiapine at the 2-week monotherapy phase endpoint.\n Six-week completion rates were 77.5% (124/160) with paliperidone extended-release, 66.7% (106/159) quetiapine, and 63.8% (51/80) placebo. Improvement in mean PANSS total change score was greater with paliperidone extended-release than with quetiapine from day 5 (-11.4 versus -8.2) through the monotherapy phase endpoint (-23.4 versus -17.1). Only paliperidone extended-release showed significantly greater PANSS improvement compared with placebo at 2 weeks. At the 6-week study endpoint, there was a significantly greater improvement with paliperidone extended-release compared with quetiapine despite similar use of additive therapy (predominantly other antipsychotics). Common adverse events with paliperidone extended-release, quetiapine, and placebo, respectively, were tremor (13.9%, 5.0%, 7.5%), somnolence (8.9%, 11.9%, 1.3%), insomnia (10.1%, 9.4%, 11.3%), and headache (12.0%, 7.5%, 13.8%). Six-week adverse event-related discontinuation rates were 6.3%, 10.1%, and 6.3%, respectively, in the paliperidone extended-release, quetiapine, and placebo groups.\n Compared with quetiapine, paliperidone extended-release improved symptoms earlier and to a greater degree in patients with recently exacerbated schizophrenia requiring hospitalization, with no unexpected tolerability findings.", "Paliperidone extended-release tablet (paliperidone ER) is an oral psychotropic agent developed for schizophrenia treatment. Paliperidone (9-OH-risperidone, metabolite of risperidone), when used with OROS technology has a unique pharmacokinetic profile undergoing limited hepatic metabolism.\n The efficacy and safety of once-daily paliperidone ER (3 mg, 9 mg and 15 mg) were compared with placebo in 618 patients with acute schizophrenia in a 6-week, multicenter, double-blind, randomized, parallel-group study. An assay sensitivity group with known efficacy was included to confirm trial validity (olanzapine 10 mg).\n All doses of paliperidone ER demonstrated significant improvements in PANSS total and PANSS factors scores (p<0.05) and in personal and social functioning (p<0.001) compared with placebo. Symptom improvement has been observed at the first observation assessment (Day 4) (p<0.001) compared with placebo, suggesting a rapid onset of action for paliperidone ER. Paliperidone ER was associated with a low incidence of treatment-emergent adverse events. The incidence of movement disorder-related adverse events and rating scale scores were similar in the paliperidone ER 3 mg and placebo groups and increased with dose. Increases in prolactin plasma levels and dose-related increases in body weight (<2 kg) were observed; there were no significant changes in serum lipid or glucose levels.\n In this study, all doses of paliperidone ER were effective in significantly improving the symptoms of schizophrenia and personal and social functioning and were generally well tolerated. As such, paliperidone ER may provide a valuable new treatment option for patients with schizophrenia.", "We evaluated the efficacy of paliperidone extended-release (ER), an investigational psychotropic agent, in delaying symptom recurrence in adult patients with schizophrenia and its safety and tolerability. In this randomized, double-blind, placebo-controlled, multicenter study, patients' symptoms were stabilized during an 8-week run-in and a 6-week stabilization phases using open-label, flexibly dosed paliperidone ER (3-15 mg once daily, starting dose = 9 mg). The primary efficacy variable was the time of first recurrence of schizophrenia symptoms, which included predefined changes in symptom scores, psychiatric hospitalization, self-injury, and suicidal or aggressive behavior during the double-blind phase (paliperidone ER or placebo treatment). Based on positive efficacy, the study was terminated at the preplanned interim analysis (43 recurrence events). The interim analysis (primary analysis) included 113 patients (mean age = 41 years; 51% men, 85% white). In the intent-to-treat group, 14 paliperidone ER-treated patients (25%) experienced a recurrence event versus 29 (53%) for placebo. Time-to-recurrence was significantly different, favoring the paliperidone ER group (P = 0.005, log-rank test): 25% quantile of time-to-recurrence was 83 days (paliperidone ER) versus 23 days (placebo). Final analyses (n = 205) were confirmatory. During initial open-label treatment with paliperidone ER, symptoms improved significantly. This improvement was maintained with continued treatment, as were functioning and quality-of-life measures. Treatment-emergent adverse events rates were similar: 35% for paliperidone ER and 40% for placebo. Paliperidone ER treatment versus placebo significantly delayed time-to-recurrence in patients with schizophrenia, maintained symptom stability and measures of functioning, and was generally well tolerated in this patient population." ]

[ "681061", "4852229", "10788023", "10764367", "10764366", "11387182", "10764365", "10632281", "9774295", "9476082", "4829073", "9386883" ]

[ "The St John's randomized trial of the family practice nurse: health outcomes of patients.", "Health maintenance service: ambulatory patient care in the general medical clinic.", "A comparison of resource utilization in nurse practitioners and physicians.", "Randomised controlled trial comparing cost effectiveness of general practitioners and nurse practitioners in primary care.", "Randomised controlled trial of nurse practitioner versus general practitioner care for patients requesting \"same day\" consultations in primary care.", "Cluster randomised controlled trial to compare three methods of promoting secondary prevention of coronary heart disease in primary care.", "Nurse management of patients with minor illnesses in general practice: multicentre, randomised controlled trial.", "Primary care outcomes in patients treated by nurse practitioners or physicians: a randomized trial.", "Safety and effectiveness of nurse telephone consultation in out of hours primary care: randomised controlled trial. The South Wiltshire Out of Hours Project (SWOOP) Group.", "A nurse practitioner as the first point of contact for urgent medical problems in a general practice setting.", "The effectiveness of nurse clinicians' service delivery.", "Reducing alcohol consumption. Comparing three brief methods in family practice." ]

[ "From June 1975, to May 1976, in a large family practice in St. John's, Newfoundland, a randomized controlled trial was conducted to assess the effectiveness of a family practice nurse. Effectiveness was assessed using standardized health outcome measures of physical, emotional, and social function which could be applied easily and objectively by non-clinicians to the two groups of patients under study: patients receiving conventional care and patients receiving care from the family practice nurse. After establishing the comparability of these two groups of patients at the beginning of the study, these measurements showed similar levels of physical, emotional, and social function in the two groups after 1 year of receiving either family practice nurse or conventional care. These results agree with previous controlled trials of family practice nurses which have indicated that family practice nurses are effective and safe.", "nan", "Nurse practitioners increasingly provide primary care in a variety of settings. Little is known about how resource utilization for patients assigned to nurse practitioners compares with that for patients assigned to physicians.\n To compare health care resource utilization for adult patients assigned to a nurse practitioner with that for patients assigned to a resident or attending physician.\n Prospective, quasi-randomized study.\n Primary care clinic at a Veterans Affairs medical center.\n 450 new primary care patients: 150 were assigned to a nurse practitioner, 150 to a resident physician, and 150 to an attending physician.\n We collected data on laboratory and radiologic testing, specialty care, primary care, emergency or walk-in visits, and hospitalizations over a 1-year period. We also collected information on baseline chronic illnesses, blood pressure, and weight.\n Resource utilization for patients assigned to a nurse practitioner was higher than that for patients assigned to a resident in 14 of 17 utilization measures (3 were statistically significant) and higher in 10 of 17 measures when compared with patients assigned to an attending physician (3 were statistically significant). None of the utilization measures for patients in the nurse practitioner group was significantly lower than those for either physician group.\n In a primary care setting, nurse practitioners may utilize more health care resources than physicians.", "To compare the cost effectiveness of general practitioners and nurse practitioners as first point of contact in primary care.\n Multicentre randomised controlled trial of patients requesting an appointment the same day.\n 20 general practices in England and Wales.\n 1716 patients were eligible for randomisation, of whom 1316 agreed to randomisation and 1303 subsequently attended the clinic. Data were available for analysis on 1292 patients (651 general practitioner consultations and 641 nurse practitioner consultations).\n Consultation process (length of consultation, examinations, prescriptions, referrals), patient satisfaction, health status, return clinic visits over two weeks, and costs.\n Nurse practitioner consultations were significantly longer than those of the general practitioners (11.57 v 7.28 min; adjusted difference 4. 20, 95% confidence interval 2.98 to 5.41), and nurses carried out more tests (8.7% v 5.6% of patients; odds ratio 1.66, 95% confidence interval 1.04 to 2.66) and asked patients to return more often (37. 2% v 24.8%; 1.93, 1.36 to 2.73). There was no significant difference in patterns of prescribing or health status outcome for the two groups. Patients were more satisfied with nurse practitioner consultations (mean score 4.40 v 4.24 for general practitioners; adjusted difference 0.18, 0.092 to 0.257). This difference remained after consultation length was controlled for. There was no significant difference in health service costs (nurse practitioner 18.ll pound sterling v general practitioner 20.70 pound sterling adjusted difference 2.33 pound sterling - 1.62 pound sterling to 6.28 pound sterling).\n The clinical care an health service costs of nurse practitioners and general practitioners were similar. If nurse practitioners were able to maintain the benefits while reducing their return consultation rate or shortening consultation times, they could be more cost effective than general practitioners.", "To ascertain any differences between care from nurse practitioners and that from general practitioners for patients seeking \"same day\" consultations in primary care.\n Randomised controlled trial with patients allocated by one of two randomisation schemes (by day or within day).\n 10 general practices in south Wales and south west England.\n 1368 patients requesting same day consultations.\n Patient satisfaction, resolution of symptoms and concerns, care provided (prescriptions, investigations, referrals, recall, and length of consultation), information provided to patients, and patients' intentions for seeking care in the future.\n Generally patients consulting nurse practitioners were significantly more satisfied with their care, although for adults this difference was not observed in all practices. For children, the mean difference between general and nurse practitioner in percentage satisfaction score was -4.8 (95% confidence interval -6.8 to -2.8), and for adults the differences ranged from -8.8 (-13.6 to -3.9) to 3.8 (-3.3 to 10.8) across the practices. Resolution of symptoms and concerns did not differ between the two groups (odds ratio 1.2 (95% confidence interval 0.8 to 1.8) for symptoms and 1.03 (0.8 to 1.4) for concerns). The number of prescriptions issued, investigations ordered, referrals to secondary care, and reattendances were similar between the two groups. However, patients managed by nurse practitioners reported receiving significantly more information about their illnesses and, in all but one practice, their consultations were significantly longer.\n This study supports the wider acceptance of the role of nurse practitioners in providing care to patients requesting same day consultations.", "To assess the effectiveness of three different methods of promoting secondary prevention of coronary heart disease in primary care.\n Pragmatic, unblinded, cluster randomised controlled trial.\n Warwickshire.\n 21 general practices received intervention; outcome measured in 1906 patients aged 55-75 years with established coronary heart disease.\n Audit of notes with summary feedback to primary health care team (audit group); assistance with setting up a disease register and systematic recall of patients to general practitioner (GP recall group); assistance with setting up a disease register and systematic recall of patients to a nurse led clinic (nurse recall group).\n At 18 months' follow up: adequate assessment (defined) of 3 risk factors (blood pressure, cholesterol, and smoking status); prescribing of hypotensive agents, lipid lowering drugs, and antiplatelet drugs; blood pressure, serum cholesterol level, and plasma cotinine levels.\n Adequate assessment of all 3 risk factors was much more common in the nurse and GP recall groups (85%, 76%) than the audit group (52%). The advantage in the nurse recall compared with the audit group was 33% (95% confidence interval 19% to 46%); in the GP recall group compared with the audit group 23% (10% to 36%), and in the nurse recall group compared with the GP recall group 9% (-3% to 22%). However, these differences in assessment were not reflected in clinical outcomes. Mean blood pressure (148/80, 147/81, 148/81 mm Hg), total cholesterol (5.4, 5.5, 5.5 mmol/l), and cotinine levels (% probable smokers 17%, 16%, 19%) varied little between the nurse recall, GP recall, and audit groups respectively, as did prescribing of hypotensive and lipid lowering agents. Prescribing of antiplatelet drugs was higher in the nurse recall group (85%) than the GP recall or audit groups (80%, 74%). After adjustment for baseline levels, the advantage in the nurse recall group compared with the audit group was 10% (3% to 17%), in the nurse recall group compared with the GP recall group 8% (1% to 15%) and in the GP recall group compared with the audit group 2% (-6% to 10%).\n Setting up a register and recall system improved patient assessment at 18 months' follow up but was not consistently better than audit alone in improving treatment or risk factor levels. Understanding the reasons for this is the key next step in improving the quality of care of patients with coronary heart disease.", "To assess the acceptability and safety of a minor illness service led by practice nurses in general practice.\n Multicentre, randomised controlled trial.\n 5 general practices in south east London and Kent representing semi-rural, suburban, and urban settings.\n 1815 patients requesting and offered same day appointments by receptionists.\n Patients were assigned to treatment by either a specially trained nurse or a general practitioner. Patients seen by a nurse were referred to a general practitioner when appropriate.\n The general satisfaction of the patients as measured by the consultation satisfaction questionnaire. Other outcome measures included the length of the consultation, number of prescriptions written, rates of referral to general practitioners, patient's reported health status, patient's anticipated behaviour in seeking health care in future, and number of patients who returned to the surgery, visits to accident and emergency, and out of hours calls to doctors.\n Patients were very satisfied with both nurses and doctors, but they were significantly more satisfied with their consultations with nurses (mean (SD) score of satisfaction 78.6 (16. 0) of 100 points for nurses v 76.4 (17.8) for doctors; 95% confidence interval for difference between means -4.07 to -0.38). Consultations with nurses took about 10 minutes compared with about 8 minutes for consultations with doctors. Nurses and doctors wrote prescriptions for a similar proportion of patients (nurses 481/736 (65.4%) v doctors 518/816 (63.5%)). 577/790 (73%) patients seen by nurses were managed without any input from doctors.\n Practice nurses seem to offer an effective service for patients with minor illnesses who request same day appointments.", "Studies have suggested that the quality of primary care delivered by nurse practitioners is equal to that of physicians. However, these studies did not measure nurse practitioner practices that had the same degree of independence as the comparison physician practices, nor did previous studies provide direct comparison of outcomes for patients with nurse practitioner or physician providers.\n To compare outcomes for patients randomly assigned to nurse practitioners or physicians for primary care follow-up and ongoing care after an emergency department or urgent care visit.\n Randomized trial conducted between August 1995 and October 1997, with patient interviews at 6 months after initial appointment and health services utilization data recorded at 6 months and 1 year after initial appointment.\n Four community-based primary care clinics (17 physicians) and 1 primary care clinic (7 nurse practitioners) at an urban academic medical center.\n Of 3397 adults originally screened, 1316 patients (mean age, 45.9 years; 76.8% female; 90.3% Hispanic) who had no regular source of care and kept their initial primary care appointment were enrolled and randomized with either a nurse practitioner (n = 806) or physician (n = 510).\n Patient satisfaction after initial appointment (based on 15-item questionnaire); health status (Medical Outcomes Study Short-Form 36), satisfaction, and physiologic test results 6 months later; and service utilization (obtained from computer records) for 1 year after initial appointment, compared by type of provider.\n No significant differences were found in patients' health status (nurse practitioners vs physicians) at 6 months (P = .92). Physiologic test results for patients with diabetes (P = .82) or asthma (P = .77) were not different. For patients with hypertension, the diastolic value was statistically significantly lower for nurse practitioner patients (82 vs 85 mm Hg; P = .04). No significant differences were found in health services utilization after either 6 months or 1 year. There were no differences in satisfaction ratings following the initial appointment (P = .88 for overall satisfaction). Satisfaction ratings at 6 months differed for 1 of 4 dimensions measured (provider attributes), with physicians rated higher (4.2 vs 4.1 on a scale where 5 = excellent; P = .05).\n In an ambulatory care situation in which patients were randomly assigned to either nurse practitioners or physicians, and where nurse practitioners had the same authority, responsibilities, productivity and administrative requirements, and patient population as primary care physicians, patients' outcomes were comparable.", "To determine the safety and effectiveness of nurse telephone consultation in out of hours primary care by investigating adverse events and the management of calls.\n Block randomised controlled trial over a year of 156 matched pairs of days and weekends in 26 blocks. One of each matched pair was randomised to receive the intervention.\n One 55 member general practice cooperative serving 97 000 registered patients in Wiltshire.\n All patients contacting the out of hours service or about whom contact was made during specified times over the trial year.\n A nurse telephone consultation service integrated within a general practice cooperative. The out of hours period was 615 pm to 1115 pm from Monday to Friday, 1100 am to 1115 pm on Saturday, and 800 am to 1115 pm on Sunday. Experienced and specially trained nurses received, assessed, and managed calls from patients or their carers. Management options included telephone advice; referral to the general practitioner on duty (for telephone advice, an appointment at a primary care centre, or a home visit); referral to the emergency service or advice to attend accident and emergency. Calls were managed with the help of decision support software.\n Deaths within seven days of a contact with the out of hours service; emergency hospital admissions within 24 hours and within three days of contact; attendance at accident and emergency within three days of a contact; number and management of calls in each arm of the trial.\n 14 492 calls were received during the specified times in the trial year (7308 in the control arm and 7184 in the intervention arm) concerning 10 134 patients (10.4% of the registered population). There were no substantial differences in the age and sex of patients in the intervention and control groups, though male patients were underrepresented overall. Reasons for calling the service were consistent with previous studies. Nurses managed 49.8% of calls during intervention periods without referral to a general practitioner. A 69% reduction in telephone advice from a general practitioner, together with a 38% reduction in patient attendance at primary care centres and a 23% reduction in home visits was observed during intervention periods. Statistical equivalence was observed in the number of deaths within seven days, in the number of emergency hospital admissions, and in the number of attendances at accident and emergency departments. Conclusions Nurse telephone consultation produced substantial changes in call management, reducing overall workload of general practitioners by 50% while allowing callers faster access to health information and advice. It was not associated with an increase in the number of adverse events. This model of out of hours primary care is safe and effective.", "The aim of this study was to examine the suitability of nurse practitioners for assessing and managing urgent clinical problems presenting in primary care.\n Patients registered at a suburban group practice presenting with acute medical problems were offered the choice of seeing a GP or a nurse practitioner. The outcomes of 1000 consultations were analysed by recording the repeat consultation rate, the prescription-issue rate and the rate of referral to secondary care, as well as investigating patient satisfaction and the number of dysfunctional consultations and misdiagnoses.\n Patients reported a high level of satisfaction with nurse practitioner consultations, and there were no recorded instances of medical sequelae due to poor diagnosis or mismanagement. Nurse and doctors saw patients with similar age and sex distributions, but the results suggested that there was a significant difference between the morbidity of problems seen. There was also a difference in the outcomes of repeat consultation rate and the prescription issue rate, although there was little difference in the rate of referral for secondary care.\n As patients expressed a high level of satisfaction with the nurse practitioner, this suggests that given the choice, patients in primary care can safely and effectively 'self triage' themselves between GPs and nurse practitioners.", "nan", "To compare the effects of three brief methods of reducing alcohol consumption among family practice patients.\n Patients randomly assigned to one of three interventions were assessed initially and at 3-, 6-, and 12-month follow-up appointments.\n Family practice clinic composed of 12 primary care physicians seeing approximately 6000 adults monthly in a small urban community, population 40,000.\n Through a screening questionnaire, 134 men and 131 women were identified as hazardous drinkers (five or more drinks at least once monthly) during an 11-month screening of 1420 patients. Of 265 patients approached, 180 agreed to participate and 159 (83 men and 76 women) actually participated in the study.\n Three interventions were studied: brief physician advice (5 minutes), two 30-minute sessions with a physician using cognitive behavioural strategies or two 30-minute sessions with a nurse practitioner using identical strategies.\n Quantity and frequency (QF) of drinking were used to assess reduction in hazardous drinking and problems related to drinking over 12 months of follow up.\n No statistical difference between groups was found. The QF of monthly drinking was reduced overall by 66% (among men) and 74% (among women) for those reporting at least one hazardous drinking day weekly at assessment (N = 96). Men reported drinking significantly more than women.\n These results indicated that offering brief, specific advice can motivate patients to reduce their alcohol intake. There was no difference in effect between brief advice from their own physician or brief intervention by a physician or a nurse." ]

[ "11817581", "3581699", "12110735", "10088770", "1613709", "8638750", "11069725" ]

[ "Tidal irrigation as treatment for knee osteoarthritis: a sham-controlled, randomized, double-blinded evaluation.", "Saline washout for knee osteoarthritis: results of a controlled study.", "A controlled trial of arthroscopic surgery for osteoarthritis of the knee.", "Effects of joint lavage and steroid injection in patients with osteoarthritis of the knee: results of a multicenter, randomized, controlled trial.", "Tidal irrigation versus conservative medical management in patients with osteoarthritis of the knee: a prospective randomized study. Tidal Irrigation Cooperating Group.", "Arthroscopic treatment of osteoarthritis of the knee: a prospective, randomized, placebo-controlled trial. Results of a pilot study.", "Visually-guided irrigation in patients with early knee osteoarthritis: a multicenter randomized, controlled trial." ]

[ "To evaluate the effectiveness of tidal irrigation (TI) in comparison with a well-matched sham irrigation (SI) procedure as a treatment for knee osteoarthritis (OA).\n One hundred eighty subjects with knee OA were randomized to receive TI or SI, with clinical followup over the ensuing 12 months. The primary outcomes of interest were change in pain and function, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Subjects and the nurse assessor were blinded, and success of blinding was assessed.\n Although the study groups were otherwise comparable, the baseline WOMAC pain and physical functioning scores were higher (worse) in the SI group. After adjustment for baseline, there were no differences between the effects of", "Twenty patients with persistent symptoms due to osteoarthritis of the knee were randomly allocated to a saline washout or control group. Both groups showed improvement. Knee washout conferred no more benefit than intra-articular saline injection.", "Many patients report symptomatic relief after undergoing arthroscopy of the knee for osteoarthritis, but it is unclear how the procedure achieves this result. We conducted a randomized, placebo-controlled trial to evaluate the efficacy of arthroscopy for osteoarthritis of the knee.\n A total of 180 patients with osteoarthritis of the knee were randomly assigned to receive arthroscopic débridement, arthroscopic lavage, or placebo surgery. Patients in the placebo group received skin incisions and underwent a simulated débridement without insertion of the arthroscope. Patients and assessors of outcome were blinded to the treatment-group assignment. Outcomes were assessed at multiple points over a 24-month period with the use of five self-reported scores--three on scales for pain and two on scales for function--and one objective test of walking and stair climbing. A total of 165 patients completed the trial.\n At no point did either of the intervention groups report less pain or better function than the placebo group. For example, mean (+/-SD) scores on the Knee-Specific Pain Scale (range, 0 to 100, with higher scores indicating more severe pain) were similar in the placebo, lavage, and débridement groups: 48.9+/-21.9, 54.8+/-19.8, and 51.7+/-22.4, respectively, at one year (P=0.14 for the comparison between placebo and lavage; P=0.51 for the comparison between placebo and débridement) and 51.6+/-23.7, 53.7+/-23.7, and 51.4+/-23.2, respectively, at two years (P=0.64 and P=0.96, respectively). Furthermore, the 95 percent confidence intervals for the differences between the placebo group and the intervention groups exclude any clinically meaningful difference.\n In this controlled trial involving patients with osteoarthritis of the knee, the outcomes after arthroscopic lavage or arthroscopic débridement were no better than those after a placebo procedure.", "To evaluate the efficacy of joint lavage and intraarticular steroid injection, alone and in combination, in the treatment of patients with symptomatic knee osteoarthritis (OA).\n Ninety-eight patients with painful tibiofemoral OA were enrolled in a prospective, randomized, controlled, 2 x 2 factorial-design trial of 6 months' duration. The 4 treatment groups consisted of 1) intraarticular placebo (1.5 ml of 0.9% normal saline), 2) intraarticular corticosteroids (3.75 mg of cortivazol in 1.5 ml), 3) joint lavage and intraarticular placebo, and 4) joint lavage and intraarticular corticosteroid. Outcome measures evaluated at baseline, week 1, week 4, week 12, and week 24 included severity of pain (100-mm visual analog scale [VAS]), global status (100-mm VAS), and Lequesne's functional index.\n No interaction between steroid injection and joint lavage was demonstrated. Patients who had undergone joint lavage had significantly improved pain VAS scores at week 24 (P = 0.020). In contrast, corticosteroid injection had no long-term effect (P = 0.313); corticosteroid injection was associated with a decrease in pain only at week 1 (P = 0.003) and week 4 (P = 0.020). After week 4, Lequesne's functional index was not significantly improved regardless of the assigned treatment.\n Compared with placebo, both treatments significantly relieved pain but did not improve functional impairment. The effects of the 2 treatments were additive. Cortivazol provided short-term relief of pain (up to week 4). The effects of joint lavage persisted up to week 24.", "To determine the efficacy of tidal knee irrigation for knee pain due to osteoarthritis (OA), we conducted a randomized, single blind, 14-week prospective trial comparing medical management with tidal knee irrigation in 77 patients with non-end stage OA of the knee and unilateral pain refractory to standard medical treatment. Fifty-seven patients completed the study. Statistically significant differences (p less than 0.05) favoring tidal knee irrigation over medical management were pain after 50' walk, pain after 4-stair climb, most intense pain in previous day, frequency of knee stiffness with inactivity, days of morning knee stiffness in previous week, physician assessment of knee tenderness and overall assessments of therapy effectiveness by both patient and physician. Tidal knee irrigation results in more favorable improvement of pain due to OA than can be accomplished with traditional medical management.", "The reasons why many patients seemingly benefit from arthroscopic treatment of osteoarthritis of the knee remain obscure. The purpose of this pilot study was to determine if a placebo effect might play a role in arthroscopic treatment of this condition. After giving full informed consent, including full knowledge of the possibility and nature of a placebo surgery, five subjects were randomized to a placebo arthroscopy group, three subjects were randomized to an arthroscopic lavage group, and two subjects were randomized to a standard arthroscopic debridement group. The physicians performing the postoperative assessment and the patients remained blinded as to treatment. Patients who received the placebo surgery reported decreased frequency, intensity, and duration of knee pain. They also thought that the procedure was worthwhile and would recommend it to family and friends. Thus, there may be a significant placebo effect for arthroscopic treatment of osteoarthritis of the knee. The small numbers in this preliminary study preclude a valid statistical analysis, and no conclusions can be drawn regarding the superiority of one treatment over another. A larger study is needed to evaluate fully the efficacy of an arthroscopic procedure for this condition and to decide if it is reasonable to expend health care resources for this treatment; the larger study should include a placebo control group.", "To determine if visually-guided arthroscopic irrigation is an effective therapeutic intervention in patients with early knee osteoarthritis.\n Ninety patients with knee osteoarthritis were randomized in a double-blind fashion to receive either arthroscopic irrigation with 3000 ml of saline (treatment group) or the minimal amount of irrigation (250 ml) required to perform arthroscopy (placebo group). The primary outcome variable was aggregate WOMAC score.\n The study did not demonstrate an effect of irrigation on arthritis severity as measured by aggregate WOMAC scores, the primary outcome variable; the mean change in aggregate WOMAC score at 12 months was 15.5 (95% CI 7.7, 23.4) for the full irrigation group compared to 8.9 (95% CI 4.9, 13.0) for the minimal irrigation group (P=0.10). Full irrigation did have a statistically significant effect on patients' self-reported pain as measured by the WOMAC pain subscale and by a visual analog scale (VAS) (the secondary outcome variables). Mean change in WOMAC pain scores decreased by 4.2 (95% CI -0.9, 9.4) for the full irrigation group compared with a mean decrease of 2.3 (95% CI -0.1, 4.7) in the minimal irrigation group (P=0.04). Mean VAS pain scores decreased by 1.47 (95% CI -1.2, 4.1) in the full irrigation group compared to a mean decrease of 0.12 (95% CI 0.0, 0.3) in the minimal irrigation group (P=0.02). A hypothesis-generating post-hoc analysis of the effect of positively birefrigent intraarticular crystals showed that patients with and without intraarticular crystals had statistically significant improvements in pain assessments and aggregate WOMAC scores at 12 months; patients with crystals had statistically greater improvements in pain.\n Visually-guided arthroscopic irrigation may be a useful therapeutic option for relief of pain in a subset of patients with knee OA, particularly in those who have occult intraarticular crystals.\n Copyright 2000 OsteoArthritis Research Society International." ]

[ "22429944", "11769996", "7002129" ]

[ "Corticosteroid treatment of idiopathic sudden sensorineural hearing loss: randomized triple-blind placebo-controlled trial.", "Steroids, carbogen or placebo for sudden hearing loss: a prospective double-blind study.", "The efficacy of steroids in the treatment of idiopathic sudden hearing loss. A double-blind clinical study." ]

[ "To compare the effect of Prednisolone and placebo on the recovery of unilateral idiopathic sudden sensorineural hearing loss.\n Prospective, randomized, triple-blind, placebo-controlled multicenter trial.\n Four tertiary and 10 secondary referral centers.\n Of 103 patients randomly assigned, 93 were included in the modified intention-to-treat analysis. The patients, aged 18 to 80 years, were seeking care within 1 week after onset of acute unilateral sensorineural hearing loss with a mean decrease of 30 dB or greater in the 3 most affected contiguous frequencies.\n Patients were randomly assigned in permuted blocks of 10 to receive Prednisolone or placebo in tapering doses from 60 mg for 3 days and, thereafter, 10 mg less each day until Day 8. If complete recovery, no more medication given, otherwise medication continued at 10 mg per day until Day 30. Final follow-up was after 3 months with audiogram; 47 patients received Prednisolone and 46 placebo.\n The primary endpoint was efficacy of treatment on recovery at Day 90. Secondary endpoints were prognostic factors for hearing recovery. Analyses were by modified intention-to-treat and per protocol.\n Hearing improvement for 47 Prednisolone-treated patients was 25.5 ± 27.1 dB compared to 26.4 ± 26.2 dB for 46 placebo-treated patients at Day 8 and 39 ± 20.1 dB versus 35.1 ± 38.3 dB after 3 months. Vertigo had significant negative effect on hearing improvement and inflammatory signs in the laboratory workup-a positive prognostic effect, irrespective of treatment.\n Prednisolone in customary dosage does not seem to influence recovery of idiopathic sudden sensorineural hearing loss.", "There is no consensus regarding treatment modalities for idiopathic sudden sensorineural hearing loss (SNHL). In order to evaluate the effectiveness of steroid or carbogen inhalation therapies, a prospective double-blind placebo controlled study was designed. All 41 patients enrolled in the study had unilateral SNHL with no prior history of SNHL, otological pathological history or otoscopic findings. Patients were assigned to four treatment groups: prednisone tablets, placebo tablets, carbogen inhalation or room air inhalation. All were treated for 5 days. The audiometric data at admission was compared to that at day 6 and to data collected at follow-up (average 33 days). Results revealed no significant difference between the groups for early or late audiometric outcome. Age, time from onset of symptoms to initiation of treatment, tinnitus, audiogram configuration, and the presence of vertigo at onset did not significantly affect the outcome. The discrimination scores that were poor in all patient groups on admission improved within days in all groups. These findings suggest that steroids or carbogen inhalation have no therapeutic advantage over placebo. Also, regardless of treatment modality, hearing continued to improve for at least a month after treatment was stopped.", "Double-blind studies were conducted for the treatment of idiopathic sudden hearing loss (ISHL) with oral steroids. The condition was defined as not less than a 30-dB loss over three contiguous frequencies in three days or less. Follow-up audiograms were obtained four weeks and three months later. Specific audiologic guidelines for the assessment of hearing recovery were used to ensure objectivity. Steroids had a statistically significant effect on the recovery of hearing in patients with moderate hearing losses. The nature of the hearing loss and its susceptibility to improvement with steroid therapy lend support to the hypothesis that viral cochlitis is the primary cause of ISHL." ]

[ "8612863", "10357958" ]

[ "Comparison of intravenous albumin and transfer of fresh embryos with cryopreservation of all embryos for subsequent transfer in prevention of ovarian hyperstimulation syndrome.", "Elective cryopreservation of all pronucleate embryos in women at risk of ovarian hyperstimulation syndrome: efficiency and safety." ]

[ "To compare the efficacy of administration i.v. albumin to prevent severe ovarian hyperstimulation syndrome (OHSS) in patients undergoing ovarian stimulation for IVF with a standard policy of cryopreserving all embryos and to assess the impact of the two methods of treatment on pregnancy rates (PRs).\n Prospective randomized study.\n A tertiary referral center for assisted conception.\n Twenty-six patients undergoing IVF treatment cycles who were considered to be at high risk of developing severe OHSS on the basis of their serum E2 concentrations on the day of hCG administration and the number of oocytes collected.\n In group 1 (n = 13) all the generated embryos were cryopreserved to be transferred subsequently in hormonally manipulated cycles. In group 2 (n = 13) patients received IV infusions of albumin on the day of oocyte retrieval and 5 days later. Patients in group 2 had transfers of fresh embryos.\n The total dosage of hMG used, total number of follicles developed, number of follicles > 14 mm in diameter, serum E2 concentrations and endometrial thickness on day of hCG administration, number of oocytes retrieved, number and quality of embryos generated, PRs per cycle commenced, and onset and degree of any OHSS developed.\n There were no significant differences in the above parameters between the two groups, except for PRs that were significantly higher in patients who had all embryos cryopreserved (38.6% versus 0%).\n The policy of cryopreserving all generated embryos appears as effective as the administration of i.v. albumin in preventing OHSS in high-risk patients and produces significantly higher PRs.", "In a prospective randomized study, we analysed 125 patients at risk of ovarian hyperstimulation syndrome (OHSS), selected in the period between January 1996 and July 1997. All the patients had blood oestradiol concentration >/=1500 pg/ml on the day of human chorionic gonadotrophin (HCG) administration and >/=15 oocytes were collected. The patients were matched in two groups: group A, control group (n = 67), had fresh embryo transfers; group B (n = 58) had cryopreservation of all obtained pronucleate embryos. Pregnancy, live birth rates and the incidence of OHSS were compared between the two groups. There were no significant differences in terms of pregnancies per patient (46.3 versus 48.3%) and live birth rates (38. 8 versus 39.6%). No cases of OHSS occurred in group B, while four patients developed the syndrome in group A. The implantation rate was slightly but not significantly lower in group B (chi2 = 1.03). These results suggest that elective cryopreservation of all zygotes might prevent the risk of OHSS in patients undergoing IVF treatment. In contrast to what has been reported by other authors, our results show that the elective cryopreservation of zygotes does not affect pregnancy and live birth rates." ]

[ "10790551", "12297935", "11928028", "11928032", "12963662", "14598412", "10653232", "12618946", "11136308", "16365239", "10790552", "12657387", "11478009" ]

[ "Pain after microlaparoscopic cholecystectomy. A randomized double-blind controlled study.", "Is minisite cholecystectomy less traumatic? Prospective randomized study comparing minisite and conventional laparoscopic cholecystectomies.", "Microlaparoscopic vs conventional laparoscopic cholecystectomy: a prospective randomized double-blind trial.", "Sympathetic nervous system activity during laparoscopic and needlescopic cholecystectomy.", "Minilaparoscopic and laparoscopic cholecystectomy: a comparative study.", "Randomized clinical trial of laparoscopic cholecystectomy performed with mini-instruments.", "Minimizing ports to improve laparoscopic cholecystectomy.", "Micropuncture cholecystectomy vs conventional laparoscopic cholecystectomy: a randomized controlled trial.", "Randomized trial of needlescopic versus laparoscopic cholecystectomy.", "Advantages of mini-laparoscopic vs conventional laparoscopic cholecystectomy: results of a prospective randomized trial.", "Prospective randomized blinded trial of pulmonary function, pain, and cosmetic results after laparoscopic vs. microlaparoscopic cholecystectomy.", "Early minilaparoscopic cholecystectomy in patients with acute cholecystitis.", "Post-operative pain in needlescopic versus conventional laparoscopic cholecystectomy: a prospective randomised trial." ]

[ "Laparoscopic cholecystectomy (LC) is traditionally performed with two 10-mm and two 5-mm trocars. The effect of smaller port incisions on pain has not been established in controlled studies.\n In a double-blind controlled study, patients were randomized to LC or cholecystectomy with three 2-mm trocars and one 10-mm trocar (micro-LC). All patients received a multimodal analgesic regimen, including incisional local anesthetics at the beginning of surgery, NSAID, and paracetamol. Pain was registered preoperatively, for the first 3 h postoperatively, and daily for the 1st week.\n The study was discontinued after inclusion of 26 patients because five of the 13 patients (38%) randomized to micro-LC were converted to LC. In the remaining 21 patients, overall pain and incisional pain intensity during the first 3 h postoperatively increased in the LC group (n = 13) compared with preoperative pain levels (p<0.01), whereas pain did not increase in the micro-LC group (n = 8).\n Micro-LC in combination with a prophylactic multimodal analgesic regimen reduced postoperative pain for the first 3 h postoperatively. However, the micro-LC led to an unacceptable rate of conversion to LC (38%). The micro-LC instruments therefore need further technical development before this surgical technique can be used on a routine basis for laparoscopic cholecystectomy.", "The main objectives of minisite cholecystectomy (MC) are to have smaller incisions, better cosmetic results, less trauma, and a lower morbidity rate. This prospective randomized study compares MC with conventional laparoscopic cholecystectomy (CLC) in terms of surgical trauma and cosmetic results in 44 patients. Conversion from MC to CLC was required in five patients. No conversion to open surgery was needed in the CLC group. The average operating time was slightly longer in the MC group, but the difference was not statistically significant (81 minutes versus 72 minutes, p = 0.22). The population characteristics, postoperative respiratory function measurements, pain scores, and analgesic requirements were similar in the two groups. The average score for scar tissue was significantly lower in the MC group (0.73 versus 1.93, p = 0.0045). Only the cosmetic results of MC were superior to CLC. This technique could be a feasible alternative procedure in patients seeking better cosmetic results. However, further studies with larger sample sizes are needed to evaluate the postoperative morbidity of MC.", "Downsizing the port incisions may reduce pain after laparoscopic cholecystectomy.\n In a double-blind controlled study, 60 patients were randomized to undergo either microlaparoscopic cholecystectomy using one 10-mm and three 3.5-mm trocars (3.5-mm LC) or traditional laparoscopic cholecystectomy using two 10-mm and two 5-mm trocars (LC). Incisional pain at each port incision and overall pain were recorded for 1 week after the operation. Fatigue, nausea and vomiting, pulmonary function, and cosmetic results were also measured.\n Data from 52 patients were analyzed; eight patients were excluded from the study for various reasons. One patient was converted from 3.5-mm LC to LC due to technical problems with the 3.5-mm optic. In the 3.5-mm LC group (n = 25), incisional pain was significantly decreased in the 1st postoperative week as compared with the LC group (n = 27) (p <0.01). In both groups, pain scores at the supraumbilical 10-mm port were significantly higher compared with other port sites (p <0.05). The cosmetic results were significantly better in the 3.5-mm LC group (p <0.01). There were no significant differences in any of the other variables.\n The use of 3.5-mm trocars is feasible in LC, and it both reduces incisional pain and improves the cosmetic result.", "It is difficult to quantify the impact of surgical trauma on patients with conventional measurement techniques. We report our preliminary experience with the determination of sympathetic nervous system activity during laparoscopic and needlescopic cholecystectomy.\n The electroconductivity of representative dermatomes (24 measuring points) was recorded prior, during, and after performing laparoscopic and needlescopic cholecystectomy on 40 consecutive patients according to the method of Nakatani (Ryodoraku). Fifty-five healthy adults served as a control group.\n Median age in the two groups was 52.4 and 54.1 years, respectively. Prior to the operation and on the 1st postoperative day, sympathetic nervous activity was equal in both groups. In the needlescopic patients, sympathetic activity was lesser at 30 min after the start of the laparoscopic procedure (p <0.05).\n The measurement of electroconductivity is a useful noninvasive technique for the evaluation of sympathetic nervous activity. As far as activation of sympathetic nervous system is concerned, the needlescopic technique was found to be superior.", "To evaluate the feasibility and safety of the minilaparoscopic cholecystectomy (MLC) and to compare the clinical benefits experienced by patients who undergo MLC with those who undergo laparoscopic cholecystectomy (LC) or 5-mm laparoscopic cholecystectomy (5-mm LC).\n Prospective consecutive study.\n A tertiary referral center.\n From September 1, 2000, through June 30, 2001, 90 patients with symptomatic gallstones were randomized to undergo 1 of these 3 procedures.\n Minilaparoscopic cholecystectomy, LC, and 5-mm LC.\n Duration of surgery, loss of blood, length of hospital stay, resumption of solid food intake, quantity of analgesic dosage administered, development of complications, degree of pain at ports 24 and 48 hours after surgery, and overall cosmetic result.\n Subsequent to excluding 6 patients who were converted to LC, there were 30 patients in the LC group, 29 patients in the 5-mm LC group, and 25 patients in the MLC group. The MLC necessitated a longer time to complete the procedure than was the case for the other 2 procedures. There was no notable difference in the mean dosage of the meperidine hydrochloride (Pethidine) administered between the LC and MLC groups, but an apparent increase in the analgesia requirements for the 5-mm LC group was noted when compared with those of the other 2 groups. There was no remarkable difference in terms of blood loss, resumption of solid food intake, hospital stay subsequent to surgery, or surgical-related complication between these 3 groups. The MLC group did have a lower pain score in the subxyphoid port only at 24 hours after surgery compared with the other 2 groups. The cosmetic results were evaluated and no notable difference was noted at 1 week, 1 month, and 6 months after surgery.\n Although this study has demonstrated the feasibility and safety of the MLC, it does require a longer surgical time and reflects a reasonably high possibility for the conversion to LC. Furthermore, the MLC did not provide any notable clinical benefit for the tested patients compared with those patients in the LC group. We concluded that there is no reason for the MLC to become the universally accepted mode of treatment for symptomatic gallstones before further improvements are made in the technique and instrumentation.", "The outcomes after traditional laparoscopic cholecystectomy (LC; one 10-mm port, one 12-mm port and two 5-mm ports) and minilaparoscopic cholecystectomy (MLC; three 3-mm ports and one 12-mm port) for gallstone disease were compared.\n The study was a randomized, single-blind trial comparing LC with MLC. Only elective patients were eligible for inclusion. LC was a routine procedure at the institution in which the study was performed, whereas MLC was introduced after a short training period. The randomization period was from January to December 2001.\n Of 175 patients who had elective minimal access cholecystectomy during the randomization period, 135 entered the trial: 68 underwent LC and 67 underwent MLC. The groups were matched for age, sex and preoperative characteristics. Median (range) operating times for LC and MLC were similar (45 (20-120) and 50 (20-170) min respectively). Intraoperative and postoperative complication rates, the time for the patient to resume walking, eating and passing stools, and median hospital stay were the same in the two groups. The level of postoperative pain was lower in the MLC group at 1 h (P = 0.011), 3 h (P = 0.012), 6 h (P = 0.003), 12 h (P = 0.052) and 24 h (P = 0.034). Patients who had MLC received fewer injections of analgesic (P = 0.036) and more patients in this group expressed satisfaction with the cosmetic result (P = 0.001).\n MLC took a similar time to perform and caused less postoperative pain than the standard laparoscopic procedure. Reducing the port size further enhanced the advantages of laparoscopic over open cholecystectomy.\n Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.", "Minimizing the number and scope of ports used to perform laparoscopic cholecystectomy attempts to build on the improvements in postoperative pain control, rapid return to activity and work, patient satisfaction, and cosmetic result achieved by the laparoscopic method.\n We studied 141 patients in two sequential studies: the first a prospective randomized trial with 41 patients, and the second an examination of the more minimal procedure in 100 patients. In the randomized trial, patients underwent laparoscopic cholecystectomy with three ports: three 5-mm ports or two 10-mm ports and one 5-mm port. The 100 patients underwent the three 5-mm port procedure.\n In the randomized trial, differences were not statistically significant. However, on the average, the group with three 5-mm ports required less medication over less time, had less postoperative pain, and took less time to return to activity than the second group with larger ports. A statistically significant difference was found in incisional pain between the smaller group (21 patients) with two 10-mm ports and one 5-mm port and the larger group (100 patients) with three 5-mm ports, whether the measure was overall incisional pain (p = 0.014) or a comparison based on specific ports (p = 0.001). The percentage of cases requiring port enlargement to remove the gallbladder was not significantly different between the groups. There were no conversions to an open procedure, no fourth trocars added, and no complications. No patient required overnight hospitalization.\n Reducing the number and size of ports in laparoscopic cholecystectomy sustains or enhances the improvements initiated by performing laparoscopic rather than open cholecystectomy. In a comparison of microlaparoscopic procedures, patients undergoing the procedure with the shorter incisions experienced significantly less pain.", "The aim of this study was to compare micropuncture laparoscopic cholecystectomy (MPLC), with three 3.3-mm cannulas and one 10-mm cannula with conventional laparoscopic cholecystectomy (CLC).\n Patients were randomized to undergo either CLC or MPLC. The duration of each operative stage and the procedure were recorded. Interleukin-6 (IL-6), adrenocorticotropic hormone (ACTH), and vasopressin were sampled for 24 h. Visual analogue pain scores (VAPS) and analgesic consumption were recorded for 1 week. Pulmonary function and quality of life (EQ-5D) were monitored for 4 weeks. Statistical analysis was performed using the Mann-Whitney test or Fisher's exact test. Results are expressed as median (interquartile range).\n Forty-four patients entered the study, but four were excluded due to unsuspected choledocholithiasis (n = 3) or the need to reschedule surgery (n = 1). The groups were comparable in terms of age, duration of symptoms, and indications for surgery. Total operative time was similar (CLC, 63 [52-81] min vs MPLC 74 [58-95] min; p = 0.126). However, time to place the cannulas after skin incision (CLC, 5:42 [3:45-6:37] min vs MPLC, 7:38 [5:57-10:15] min; p = 0.015) and to clip the cystic duct after cholangiography (CLC, 1:05 [0:40-1:35] min vs MPLC, 3:45 [2:26-7:49] min; p <0.001) were significantly longer for MPLC. Six CLC patients and one MPLC patient required postoperative parenteral opiates (p = 0.04). Oral analgesic consumption was similar in both groups (p = 0.217). Median VAPS were lower at all time points for MPLC, but this finding was not significant (p = 0.431). There were no significant differences in postoperative stay, IL-6, ACTH or vasopressin responses, pulmonary function, or EQ-5D scores.\n The thinner instruments did not significantly increase the total duration of the procedure. MPLC reduced the use of parenteral analgesia postoperatively, which may prove beneficial for day case patients, but it did not have a significant impact on laboratory variables, lung function or quality of life.", "Several studies have reported the feasibility of using 'needlescopic' instruments with a diameter less than 3 mm in minimally invasive surgery. This study reports a comparison of needlescopic cholecystectomy and laparoscopic cholecystectomy.\n Seventy-five patients with symptomatic chronic cholelithiasis were randomized to needlescopic (n = 37) or laparoscopic (n = 38) cholecystectomy.\n The duration of surgery in the two groups was similar. Patients in the needlescopic group had less pain (mean visual analogue score 2.2 versus 3.6; P < 0.003) and had smaller scars (median length 17.0 versus 25.0 mm; P < 0.001). In addition, patients in the needlescopic group tended to require fewer intramuscular pethidine injections (P = 0.05). However, oral analgesic requirements in the two groups were similar. There were no complications in either group.\n Needlescopic cholecystectomy resulted in less postoperative pain and a smaller surgical scar than laparoscopic cholecystectomy in patients with chronic cholecystitis.", "The use of smaller instruments during laparoscopic cholecystectomy (LC) has been proposed to reduce postoperative pain and improve cosmesis. However, despite several recent trials, the effects of the use of miniaturized instruments for LC are not well established. We hypothesized that LC using miniports (M-LC) is safe and produces less incisional pain and better cosmetic results than LC performed conventionally (C-LC).\n A patient- and observer-blinded, randomized, prospective clinical trial.\n A tertiary care, university-based hospital.\n Seventy-nine patients scheduled for an elective LC who agreed to participate in this trial were randomized to undergo surgery using 1 of the 2 instrument sets. The criteria for exclusion were American Society of Anesthesiologists class III or IV, age older than 70 years, liver or coagulation disorders, previous major abdominal surgical procedures, and acute cholecystitis or acute choledocholithiasis.\n Laparoscopic cholecystectomy performed with either conventional or miniaturized instruments.\n Patients' age, sex, operative time, operative blood loss, intraoperative complications, early and late postoperative incisional pain, and cosmetic results.\n Thirty-three C-LCs and 34 M-LCs were performed and analyzed. There were 8 conversions (24%) to the standard technique in the M-LC group. No intraoperative or major postoperative complications occurred in either group. The average incisional pain score on the first postoperative day was significantly less in the M-LC group (3.9 vs 4.9; P = .04). No significant differences occurred in the mean scores for pain on postoperative days 3, 7, and 28. However, 90% of patients in the M-LC group and only 74% of patients in the C-LC group had no pain (visual analog scale score of 0) at 28 days postoperatively (P = .05). Cosmetic results were superior in the M-LC group according to both the study nurse's and the patients' assessments (38.9 vs 28.9; P<.001, and 38.8 vs 33.4; P = .001, respectively).\n Laparoscopic cholecystectomy can be safely performed using 10-mm umbilical, 5-mm epigastric, 2-mm subcostal, and 2-mm lateral ports. The use of mini-laparoscopic techniques resulted in decreased early postoperative incisional pain, avoided late incisional discomfort, and produced superior cosmetic results. Although improved instrument durability and better optics are needed for widespread use of miniport techniques, this approach can be routinely offered to many properly selected patients undergoing elective LC.", "The size of laparoscopic instruments has been reduced for use in abdominal video endoscopic surgery. However, it has yet to be proven that microlaparoscopic surgery will actually result in clinically relevant benefits for patients.\n Fifty patients were randomized in a blinded fashion to receive either elective laparoscopic (MINI), (n = 25) or microlaparoscopic (MICRO) (n = 25) cholecystectomy. Pulmonary function (FVC, FEV (1)), analgesic consumption during patient-controlled analgesia (PCA), pain perception by visual analogue score (VAS), and the cosmetic result (by the patient's self-assessment) were evaluated postoperatively as clinically relevant end points.\n Age, sex, body mass index (BMI), preoperative pulmonary function, pain perception, and operative time were similar for the two groups. At 8:00 PM on the day of surgery, FVC (MINI: 1.96 L [range, 1.48-2.48]; MICRO: 2.13 L) [(range, 1.61.-2.50)] and FEV (1) (MINI: 1.17 L/sec) [range, 0.87-1. 48]; MICRO: 1.34 L/sec [range, 1.05.-2.14] were also similar (each p = 0.5). From surgery to the 3rd postoperative day, cumulative PCA morphine doses were comparable (MINI: 0.15 mg/kg bw [range, 0.09-0. 23]; MICRO: 0.21 mg/kg bw [range, 0.10-0.42]; p = 0.4), but overall VAS scores for pain while coughing were higher in the laparoscopic group (406 [range, 358-514]) than in the microlaparoscopic group (365 [range, 215-427]; p = 0.02). The cosmetic result was judged to be slightly superior by the microlaparoscopic patients (10 [range, 9-10]), as compared to those in the laparoscopic (9 [range, 8-10]) group (p = 0.04).\n Because microlaparoscopic cholecystectomy has some minor advantages over laparoscopic surgery, it should be considered for use in selected patients.", "Recently, techniques using fine-caliber instruments (2 or 3 mm in diameter) for laparoscopic cholecystectomy, called minilaparoscopic cholecystectomy (MLC), were reported to be superior to conventional LC (CLC, using 5 mm instruments) in postoperative course and cosmetic outcome. However, the use of MLC to date has been largely restricted to uncomplicated situations. Since CLC has been proved to be a safe and efficient technique for acute cholecystitis especially if conducted early, this study tests the feasibility and safety of MLC for acute cholecystitis.\n Sixty-nine consecutive patients with acute cholecystitis were prospectively randomized to minilaparoscopic (n = 38) or conventional laparoscopic (n = 31) cholecystectomy, and the operations were conducted within 2 days of admission whenever possible. Despite different operative techniques, both groups of patients received identical preoperative preparation, evaluation and postoperative care. The two groups were compared for patient characteristics, results of laboratory tests, predictive score for LC difficulties, operative time, operative complications, hospitalization days and need for meperidine injection for wound pain.\n The conversion rate was 7.9% (3 of 38) for the MLC group and 6.5% (2 of 31) for the CLC group. Nine patients in the MLC group and 7 in the CLC group had concomitant choledocholithiasis and underwent endoscopic stone retrieval before operation. The age, sex, predictive score for LC difficulties, preoperative leukocyte count, length of hospital stay and requirement of intramuscular meperidine injections were similar for both groups of patients, while, the operative times were marginally longer in the MLC group (113.8 +/- 30.8 versus 98.2 +/- 33.2 minutes, P = 0.056). No major complications occurred in either group.\n The results of cholecystectomy for acute cholecystitis by MLC are as good as those of CLC if the operation is performed early, with obvious smaller incisions and minimal complications. MLC is a safe and effective procedure for patients with acute cholecystitis, and has an acceptable low conversion rate.", "Needlescopic cholecystectomy (NC) utilises instruments and ports smaller than 3 mm in diameter compared with the 5 mm ones used in conventional laparoscopic cholecystectomy (LC). Post-operative pain control and recovery has been thought to be superior in NC, when compared with historical controls with LC, but has not been proven in a prospective fashion.\n A prospective randomised trial of NC versus LC for patients with symptomatic gallstone disease, with standardisation of post-operative analgesia and daily assessment of post-operative pain, using a 5-point visual analogue scale.\n There were 64 eligible patients randomised into NC (28) and LC (36). Four patients who had NC were converted to LC due to technical problems. Another three and six patients from the NC and LC groups, respectively, had conversion to open surgery. Post-operative pain scores were low in both groups. Mean pain scores for those with successful NC and LC were: 1.24 versus 1.43 for the day of operation (P = 0.49), 0.86 versus 0.83 for the first day post-operatively (P = 0.92) and 0.75 versus 0.81 for the second post-operative day (P = 0.87). The mean number of intra-muscular analgesic injections required were 0.76 versus 0.83 after NC and LC, respectively (P = 0.93). There were no significant differences between the two groups in the time taken to return to feeding, eating a normal diet and discharge from hospital.\n There is no advantage of NC over LC in terms of post-operative pain or recovery. Nevertheless, NC can be performed safely and expediently and has an excellent cosmetic outcome and high patient acceptability." ]

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[ "Making better use of scarce resources: the Palestinian experience, 1995-1999.", "Problems with implementing guidelines: a randomised controlled trial of consensus management of dyspepsia.", "Modifying dyspepsia management in primary care: a cluster randomised controlled trial of educational outreach compared with passive guideline dissemination.", "Gatekeeping in primary care: a comparison of internal medicine and family practice.", "Effect of NHS reforms on general practitioners' referral patterns.", "Does the North Staffordshire slot system control demand of orthopaedic referrals from primary care?: A population-based survey in general practice.", "Do clinical guidelines improve general practice management and referral of infertile couples?", "Pragmatic randomised controlled trial to evaluate guidelines for the management of infertility across the primary care-secondary care interface.", "Improving referrals for glue ear from primary care: are multiple interventions better than one alone?", "In-house referral: a primary care alternative to immediate secondary care referral?", "Specialists as consultants to GPs. Private sector services as an alternative way of organising consultant services in health care.", "Prepayment with office-based physicians in publicly funded programs: results from the Children's Medicaid Program.", "General practice based physiotherapy: its use and effect on referrals to hospital orthopaedics and rheumatology outpatient departments.", "The extent of the two tier service for fundholders.", "Effectiveness of joint consultation sessions of general practitioners and orthopaedic surgeons for locomotor-system disorders.", "Cluster randomized trial of a guideline-based open access urological investigation service." ]

[ "Until August 2, 1997, The Eye Hospital-Gaza (EH) provided both primary and secondary eye services to almost 1 million inhabitants in Gaza. This exerted a tremendous load on the hospital's facilities and prevented the hospital from performing its main role as a secondary eye care provider. The training and guidance of primary health care (PHC) providers are essential in order that they can do their share in eye care. A prevention of blindness awareness campaign, training, workshops, and practical instruction took place in Gaza over a three-year span. A new purpose designed referral system was started on August 2, 1997, that resulted in a great change and improvement of the services in the hospital. Primary eye care is an integral part of ophthalmic services. Proper continuous training of PHC providers is essential, not only for providing service to patients near their residence in the shortest time possible, but also to facilitate the smooth, effective, and efficient functioning of the hospital as a secondary and tertiary eye care provider. We believe the system and methodology used is efficient and reproducible in many developing countries.", "To determine the feasibility and benefit of developing guidelines for managing dyspepsia by consensus between general practitioners (GPs) and specialists and to evaluate their introduction on GPs' prescribing, use of investigations, and referrals.\n Randomised controlled trial of effect of consensus guidelines agreed between GPs and specialists on GPs' behaviour.\n Southampton and South West Hampshire Health District, United Kingdom.\n 179 GPs working in 45 practices in Southampton district out of 254 eligible GPs, 107 in the control group and 78 in the study group.\n Rates of referral and investigation and costs of prescribing for dyspepsia in the six months before and after introduction of the guidelines.\n Consensus guidelines were produced relatively easily. After their introduction referral rates for upper gastrointestinal symptoms fell significantly in both study and control groups, but no significant change occurred in either group in the use of endoscopy or radiology, either in terms of referral rates, patient selection, or findings on investigation. No difference was observed between the control and study group in the number of items prescribed, but prescribing costs rose by 25% (from 2634 pounds to 3215 pounds per GP) in the study group, almost entirely due to an increased rate of prescription of ulcer-healing agents.\n Developing district guidelines for managing dyspepsia by consensus between GPs and specialists was feasible. However, their acceptance and adoption was variable and their measured effects on some aspects of clinical behaviour were relatively weak and not necessarily associated with either decreased costs or improved quality of care.", "Quality improvement initiatives in health services rely upon the effective introduction of clinical practice guidelines. However, even well constructed guidelines have little effect unless supported by dissemination and implementation strategies.\n To test the effectiveness of 'educational outreach' as a strategy for facilitating the uptake of dyspepsia management guidelines in primary care.\n A pragmatic, cluster-randomised controlled trial of guideline introduction, comparing educational outreach with postal guideline dissemination alone.\n One-hundred and fourteen general practices (233 general practitioners) in the Salford and Trafford Health authority catchment area in the northwest of England.\n All practices received guidelines by post in July 1997. The intervention group practices began to receive educational outreach three months later. This consisted of practice-based seminars with hospital specialists at which guideline recommendations were appraised, and implementation plans formulated. Seminars were followed up with 'reinforcement' visits after a further 12 weeks. Outcome measures were: (a) the appropriateness of referral for; and (b) findings at, open access upper gastrointestinal endoscopy; (c) costs of GP prescriptions for acid-suppressing drugs, and (d) the use of laboratory-based serological tests for Helicobacter pylori. Data were collected for seven months before and/or after the intervention and analysed by intention-to-treat.\n (a) The proportion of appropriate referrals was higher in the intervention group in the six-month post-intervention period (practice medians: control = 50.0%, intervention = 63.9%, P < 0.05); (b) the proportion of major findings at endoscopy did not alter significantly; (c) there was a greater rise in overall expenditure on acid-suppressing drugs in the intervention as compared with the control group (+8% versus +2%, P = 0.005); and (d) the median testing rate per practice for H pylori in the post-intervention period was significantly greater in the intervention group (four versus O, P < 0.001).\n This study suggests that educational outreach may be more effective than passive guideline dissemination in changing clinical behaviour. It also demonstrates that unpredictable and unanticipated outcomes may emerge.", "Five hundred twenty new patients were randomly and prospectively assigned to receive their care in the Internal Medicine Clinic or Family Practice Clinic of a large university hospital. The patients were followed by residents in training under the supervision of board-certified internists or family physicians. After a mean length of care of slightly over two years, the charts were reviewed for frequency of visits to primary care providers (internal medicine or family practice), Emergency Room, Acute Care Clinic, and all clinics other than the two primary care clinics. The records were also reviewed for laboratory tests ordered. Frequency of visits to the clinic of primary care, Emergency Room, Acute Care Clinic, and broken appointments were all significantly higher for patients randomized to the Internal Medicine Clinic. In addition, the median total annual cost of laboratory tests for patients followed by internal medicine physicians was significantly higher, largely because of higher laboratory charges generated by the specialist consultants. Over the study period, internal medicine patients had a significantly higher number of visits to all nonprimary care clinics and specifically to the dermatology, obstetrics and gynecology, and general surgery consultant clinics. It can be concluded that in this clinical environment, the practice styles of internal medicine and family practice are different.", "To compare outpatient referral patterns in fundholding and non-fundholding practices before and after the implementation of the NHS reforms in April 1991.\n Prospective collection of data on general practitioners' referrals to specialist outpatient clinics between June 1990 and March 1992 and detailed comparison of two time periods: October 1990 to March 1991 (phase 1) and October 1991 to March 1992 (phase 2).\n 10 fundholding practices and six non-fundholding practices in the Oxford region.\n Patients referred to consultant outpatient clinics.\n After implementation of the NHS reforms there was no change in the proportion of referrals from the two groups of practices which crossed district boundaries. Both groups of practices increased their referral rates in phase 2 of the study, the fundholders from 107.3 per 1000 patients per annum (95% confidence interval 106 to 109) to 111.4 (110 to 113) and the non-fundholders from 95.0 (93 to 97) to 112.0 (110 to 114). In phase 2 there was no difference in overall standardised referral rates between fundholders and non-fundholders. Just over 20% of referrals went to private clinics in phase 1. By phase 2 this proportion had reduced by 2.2% (1.0% to 3.4%) among the fundholders and by 2.7% (1.2% to 4.2%) among the non-fundholders.\n Referral patterns among fundholders and non-fundholders were strikingly similar after the implementation of the NHS reforms. There was no evidence that fundholding was encouraging a shift from specialist to general practice care or that budgetary pressures were affecting general practitioners' referral behaviour.", "Attempts to manage general practice demand for orthopaedic outpatient consultations have been made in several areas of the NHS, with little robust evidence on whether or not they work.\n To evaluate the effect of the North Staffordshire 'orthopaedic slot system' on the demand for general practice referrals to orthopaedic outpatients.\n A prospective study of 12 general practices in the slot system, 24 controls, and the 63 other general practices in North Staffordshire. Comparison periods were the baseline year (0); the first calendar year (1); and the first half of the second calendar year (2). A multifactor linear regression model was used.\n Mean referral rate decreased 22% in the slot group in period 1, and was maintained in period 2 (9.40, 7.29, 7.31 referrals per 10,000 population per month for periods 0, 1 and 2, respectively). The control and other groups showed a small decrease in period 1, but in period 2 higher referral rates were observed. The reduction in referrals of 20-40% in participating practices compared to other practices equates to 2-4 referrals per 10,000 patients per month.\n Our study suggests that practices willing and able to take up an offer of a slot system for managing their orthopaedic referrals will be able to significantly reduce referral rates for their patients when compared to similar practices who do not. Further research on the generalisability, effectiveness and cost-effectiveness of such systems is warranted.", "To evaluate guidelines for general practice management and referral of infertile couples. Guidelines were implemented with a disease specific reminder at the time of consultation (the guidelines were embedded within a structured infertility management sheet for each couple).\n Pragmatic randomised controlled trial. Participating practices were randomised to a group that received the guidelines and a control group.\n 82 general practices in Grampian region.\n 100 couples referred by general practitioners receiving the guideline and 100 couples referred by control general practitioners.\n Whether the general practitioner had taken a full sexual history and examined and investigated both partners appropriately.\n Characteristics of patients referred by study and control general practitioners did not differ significantly at baseline. Compliance with the guidelines increased for all targeted activities. General practitioners in the study group were more likely to take a sexual history (for example, couples' use of fertile period, 85% v 69%, p < 0.01); examine both partners (female partner, 68% v 52%, p < 0.05; male partner 39% v 13%, p < 0.01); and investigate both partners (day 21 progesterone, 72% v 41%, p < 0.001; semen analysis, 51% v 41%, p > 0.05). Improvements were greater when general practitioners used the disease specific reminder.\n Receiving guidelines led to improvements in the process of care of infertile couples within general practice. This effect was enhanced when the guidelines were embedded in a structured infertility management sheet for each couple.", "To investigate the effect of clinical guidelines on the management of infertility across the primary care-secondary care interface.\n Cluster randomised controlled trial.\n General practices and NHS hospitals accepting referrals for infertility in the Greater Glasgow Health Board area. Participants: All 221 general practices in Glasgow; 214 completed the trial.\n General practices in the intervention arm received clinical guidelines developed locally. Control practices received them one year later. Dissemination of the guidelines included educational meetings.\n The time from presentation to referral, investigations completed in general practice, the number and content of visits as a hospital outpatient, the time to reach a management plan, and costs for referrals from the two groups.\n Data on 689 referrals were collected. No significant difference was found in referral rates for infertility. Fewer than 1% of couples were referred inappropriately early. Referrals from intervention practices were significantly more likely to have all relevant investigations carried out (odds ratio 1.32, 95% confidence interval 1.00 to 1.75, P=0.025). 70% of measurements of serum progesterone concentrations during the midluteal phase and 34% of semen analyses were repeated at least once in hospital, despite having been recorded as normal when checked in general practice. No difference was found in the proportion of referrals in which a management plan was reached within one year or in the mean duration between first appointment and date of management plan. NHS costs were not significantly affected.\n Dissemination of infertility guidelines by commonly used methods results in a modest increase in referrals having recommended investigations completed in general practice, but there are no detectable differences in outcome for patients or reduction in costs. Clinicians in secondary care tended to fail to respond to changes in referral practice by doctors. Guidelines that aim to improve the referral process need to be disseminated and implemented so as to lead to changes in both primary care and secondary care.", "To evaluate the effect of a risk factor checklist and training video for general practitioners in reducing inter-practice variation and improving the appropriateness of referrals (assessed by their positive predictive value or PPV) of patients with suspected otitis media with effusion (OME or 'glue ear') to secondary care.\n Fifty general practices (177 practitioners) from the NHS Trent region and the West of Scotland were cluster-randomised either to a control group (n = 12) or to one of three intervention groups (training video (n = 16), checklist (n = 11), or both (n = 11)). Data on all paediatric ear, nose and throat (ENT) referrals and diagnostic results at ENT clinics were collected for a one-year period pre- and post-intervention. Referral rates for OME and for closely related conditions were calculated for children aged 0-15 years, based on each practice's list size. PPV was defined as the proportion of referrals resulting in bilateral hearing loss > or = 20 dB at the ENT outpatient department.\n There was a significant improvement in the PPV, adjusted for patients' waiting time between general practitioner (GP) referral and being seen at the ENT department. The improvement in PPV pre- and post-intervention was 15% (95% confidence interval, CI: -12.1% to 41.7%) for the practices receiving both interventions, compared with a degradation of 20% pre- and post-intervention (95% CI: -32.9% to -6.4%) for practices receiving only one intervention and a degradation of 34% for those receiving no intervention.\n Disseminating a risk factor checklist and training video on glue ear to GPs using a multi-channel approach can improve the quality of referrals to ENT.", "Methods are needed to ensure that those patients referred from primary to secondary care are those most likely to benefit. In-house referral is the referral of a patient by a general practitioner to another general practitioner within the same practice for a second opinion on the need for secondary care referral.\n To describe whether in-house referral is practical and acceptable to patients, and the health outcomes for patients.\n Practices were randomized into an intervention or a control group. In intervention practices, patients with certain conditions who were about to be referred to secondary care were referred in-house. If the second clinician agreed referral was appropriate the patient was referred on to secondary care. In control practices patients were referred in the usual fashion. Patient satisfaction and health status was measured at the time of referral, 6 months and one year.\n Eight intervention and seven control practices took part. For the 177 patients referred in-house, 109 (61%) were judged to need referral on to secondary care. For patient satisfaction, the only difference between the groups studied was that at 12 months patients who had been referred in-house reported themselves as being more satisfied than those referred directly to hospital. For health status, the only difference found was that at the time of referral, patients who had been referred in-house and judged to need hospital referral reported themselves as being less able on the 'Physical function' subscale of the SF-36 than patients who were referred in-house and judged to not need hospital referral.\n In-house referral is acceptable to patients and provides a straightforward method of addressing uncertainty over the need for referral from primary to secondary care.", "To assess the effect on referral rate when GPs are given a better opportunity to send their patients to specialists for consultation.\n Intervention study with a control group.\n A 34-month experiment in the City of Turku. The experimental group consisted of 10 GPs working in municipal health centres with a list system and serving 23000 residents. As a control group, there were four GPs without a list system serving 10800 residents.\n GP visits and their referrals to specialists.\n The number of patient visits was higher among GPs in the experimental group than among those in the control group. During the experiment, the referral rate of GPs in the experimental group increased from 5.7% to 6.8%, but there was no change among the control GPs. Of all referrals to specialists, the share to the private sector increased from 5% to 35%, while at the same time the share to the hospital outpatient clinic decreased.\n An enhanced possibility to consult private specialists increases the number of referrals, but there are no consequent changes in the relative shares of the consulted specialties.", "This paper is a report of the results of a demonstration designed to provide empirical evidence regarding the effects of alternative approaches to paying physicians for serving children in the Medicaid program: (1) visit fees set at twice regular Medicaid fees in return for physician agreement to manage utilization and (2) capitation and financial risk-sharing along with the same physician agreement to manage utilization. Participating physicians were assigned randomly to either of the two payment groups. Comparisons of utilization and expenditures were made between these two plans and the regular Medicaid program (fee-for-service, low fees). Results showed no adverse effect of capitation payments on primary care visits to office-based physicians. Capitation physician referrals to specialists decreased relative to all other groups studied, consistent with the theory that the financial incentives in capitation will lead primary care physicians to reduce referrals to specialists.", "In November 1992, a pilot scheme was established in Doncaster to provide an on-site physiotherapy service in six non-fundholding general practices covering a population of approximately 44,000 people.\n The aim of the pilot scheme was to transfer a hospital-based physiotherapy service, to which general practitioners had direct access, to a primary care setting and to reduce referrals to an orthopaedics outpatient department.\n Use of physiotherapy services and referrals to orthopaedics and rheumatology before and during the first year of the scheme were monitored. Comparisons were made with data over the same time periods for general practices that were not in the scheme. The location of management of patients referred to physiotherapy was monitored for an eight-month period during the scheme.\n In the first year the scheme had a utilization rate of 31 per 1000 patients in the participating practices, representing a 164% increase over the hospital-based physiotherapy utilization rate for the year prior to the scheme. Eight per cent of physiotherapy patients received hospital-based treatment during the scheme. Changes in hospital outpatient referral rates attributable to the scheme were reductions of 8% to the orthopaedics department and 17% to the rheumatology department.\n The increase in the use of the physiotherapy service was possibly caused, in part, by general practitioners sending patients to on-site physiotherapy who previously would have been referred to orthopaedics and, largely, by an increase in the treatment of patients who previously would not have been referred to hospital. Physiotherapy based in general practice can be a substitute for hospital-based physiotherapy and can contribute to a reduction in referrals to orthopaedics and rheumatology outpatient departments. However, it can result in an increase in use of physiotherapy services.", "To examine possible differential changes in outpatient referrals to orthopaedic clinics, attendances, and waiting times between fundholding and non-fundholding general practitioners.\n Observational controlled study of referrals by general practitioners to orthopaedic outpatients between April 1991 and March 1995.\n District health authority in south-west England.\n 10 fundholding practices with 108,300 registered patients; 22 control practices with 159,900 registered patients.\n Changes in age standardised referral and outpatient attendance ratios for the year before and the two years after achieving fundholder status; changes in outpatient waiting times.\n In the year before achieving fundholding status both groups were referring more patients than were being seen. Two years later, referral and attendance ratios had increased by 13% and 36% respectively for fundholders and 32% and 59% for controls, and both groups were referring fewer patients than were being seen. Attendances represented 112% of referrals for fundholders and 104% for controls. In 1991-2, a similar proportion of patients in the two groups was seen within three months of referral. The two hospitals that set up specific clinics exclusively for fundholders showed faster access for patients of fundholders by 1993-4, as did a third hospital without such clinics by 1994-5.\n Fundholders increased their orthopaedic referrals less than did controls and achieved a better balance between outpatient appointments and referrals. Their patients were likely to be seen more quickly, particularly if the hospital provided special clinics exclusively for fundholders. Lack of case mix information makes it impossible to judge whether these differences benefit or disadvantage patients.", "Joint consultation sessions between general practitioners (GPs) and specialists to examine patients for whom decisions about referral are difficult are thought to be helpful, but their effects have not been evaluated. In a randomised, controlled trial we studied the effects of joint sessions of GPs and orthopaedic surgeons on referral and intervention rates. During 1.5 years, 12 GPs (in groups of three) held monthly joint consultation sessions with four participating orthopaedic surgeons: patients were seen by one orthopaedic surgeon in the presence of three GPs. Patients were included in the trial if the GP was uncertain about the diagnostic or therapeutic management and if referral was considered; and excluded if referral was urgently necessary or if there was some other clear indication for referral. By a randomised consent design, patients were assigned to joint consultation sessions (n = 144) or a usual-care control group (n = 128). A year later the patients were examined by an independent orthopaedic surgeon. There were significantly fewer referrals (51/144 [35%] vs 87/128 [68%], p < 0.01) and diagnostic actions in the intervention group than in the control group, without negative effects on health or functional status. More patients in the intervention group were symptom-free at 1 year (35% vs 24%, p < 0.05). Joint consultation sessions of GPs and orthopaedic surgeons within the framework of general practice resulted in more efficient care, with better targeted examination, treatment, and referrals.", "Out-patient services are trying to achieve effective and efficient health care in overcrowded, busy clinic settings. \"One stop\" and \"open access\" clinics have been advocated as a way of improving out-patient services.\n Our aim was to evaluate the effectiveness and efficiency of a guideline-based open access urological investigation service.\n General practices were randomized to receive either referral guidelines and access to the investigation service for lower urinary tract symptoms (LUTS) or referral guidelines and access to the investigation service for microscopic haematuria (MH). The study population comprised 66 general practices in the Grampian region of Scotland referring 959 patients. The outcome measures were compliance with guidelines (number of recommended investigations completed), number of general practice consultations, the number and case mix of referrals, waiting time to initial hospital appointment, and the number of patients with a management decision reached at initial appointment and discharged by 12 months after referral.\n GPs' compliance with referral guidelines increased (difference in means 0.5; 95% confidence interval 0.2-0.8, P < 0.001). Approximately 50% of eligible patients were referred through the new system. The number and case mix of referrals were similar. The intervention reduced the waiting time from referral to initial out-patient appointment (ratio of means 0.7; 0.5-0.9, patients with LUTS only) and increased the number of patients who had a management decision reached at initial appointment (odds ratio 5.8; 2.9-11.5, P < 0.00001, both conditions). Patients were more likely to be discharged within 12 months (odds ratio 1.7; 0.9-3.3, P = 0.11). There were no significant changes detected in patient outcomes. Overall the new service was probably cost saving to the NHS.\n The guideline-based open access investigation service streamlined the process of out-patient referral, resulting in a more efficient service with reduced out-patient waiting times, fewer out-patient and investigation appointments and release of specialist and clinic time." ]

[ "2985353", "4061343", "8906006", "2510845", "6475822", "12637400", "19658043", "10357748", "15724045", "10617955", "1958415", "15118650", "2816802", "19902797" ]

[ "Differing effects of low and high bulk maternal dietary supplements during pregnancy.", "Zinc supplementation during pregnancy in low-income teenagers of Mexican descent: effects on selected blood constituents and on progress and outcome of pregnancy.", "Zinc supplementation during pregnancy: a double blind randomised controlled trial.", "Zinc supplementation during pregnancy: a double blind randomised controlled trial.", "Zinc supplementation during pregnancy: effects on selected blood constituents and on progress and outcome of pregnancy in low-income women of Mexican descent.", "Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomised community trial.", "Effects of zinc supplementation during pregnancy on pregnancy outcome in women with history of preterm delivery: a double-blind randomized, placebo-controlled trial.", "Adding zinc to prenatal iron and folate supplements improves maternal and neonatal zinc status in a Peruvian population.", "Oral zinc supplementation in pregnant women and its effect on birth weight: a randomised controlled trial.", "A randomized, placebo-controlled trial of the effect of zinc supplementation during pregnancy on pregnancy outcome in Bangladeshi urban poor.", "Zinc supplementation during pregnancy.", "Randomized controlled trial of prenatal zinc supplementation and the development of fetal heart rate.", "Adolescent pregnancy: associations among body weight, zinc nutriture, and pregnancy outcome.", "Effect of prenatal zinc supplementation on birthweight." ]

[ "The study attempted to determine if the bulk of dietary supplements given to pregnant women after midgestation affects fetal growth. 127 Zulu women were randomly assigned to four groups, two of which received daily food supplements designed to raise their energy, protein and vitamin intakes to levels recommended by the U.S. Food and Nutrition Board. One of these supplements had a high bulk, the other a low bulk. The third supplement contained only zinc and the fourth a placebo. Women in all four groups had a similar weight gain and length of gestation. Birth weights were from 6.5 to 9.5% greater with the low bulk than with the other supplements.", "As a follow-up of our study of pregnant women, we report effects of zinc supplementation during pregnancy in another population of 138 Hispanic teenagers in Los Angeles. Teenagers were randomized (double-blind) to a control or zinc-supplemented group and received similar daily vitamin and mineral supplements except for 20 mg zinc added to the zinc-supplemented group's capsules. Initially, mean dietary zinc intakes of both groups were about 50% of the Recommended Dietary Allowance and their mean serum zinc levels did not differ significantly (69.8 +/- 11.2 micrograms/dl in control and 69.0 +/- 11.4 micrograms/dl in zinc-supplemented group). Zinc supplementation did not maintain mean serum zinc levels during pregnancy but, as in our earlier study, it reduced (p = 0.018) the number of low serum zinc values (less than or equal to 53 micrograms/dl) in late pregnancy. Zinc supplementation did not affect outcome of pregnancy but serum zinc levels were lower (p = 0.038) in teenagers with pregnancy-induced hypertension than in normotensives.", "To investigate whether zinc supplementation during pregnancy improves maternal and fetal outcome.\n Controlled clinical trial started at registration until discharge of mother and child from hospital. Two thousand volunteer mothers were randomly assigned to receive zinc supplementation or placebo in a double blind trial.\n Women less than 20 weeks pregnant at the first visit who agreed to take part in the study. One thousand two hundred and six mothers were available for study.\n Volunteers were randomly selected to receive two tablets of zinc (44 mg zinc in total) or two placebo tablets containing inert substances, indistinguishable in appearance and taste from the zinc tablets.\n Large for gestational age (LGA), small for gestational age (SGA), premature rupture of the membrane (PROM), preterm labor (PL), preeclampsia and bleeding in the second or third trimester.\n There were no differences between mothers given zinc supplementation concerning the outcome parameters and those given placebo.\n Zinc supplementation in pregnancy in a normal healthy middle class population in Denmark does not seem to offer any benefits to the mother or her fetus.", "To see whether zinc supplementation during pregnancy improves maternal and fetal outcome.\n Prospective study started at booking and continued till discharge of mother and baby from the maternity hospital. Mothers were randomly assigned to receive zinc supplementation or placebo in a double blind trial.\n Mothers booking at one hospital.\n Women booking before 20 weeks of gestation who agreed to take part in the study. 494 Mothers were followed up till the end of pregnancy. There was no difference between the groups given zinc and placebo in their social or medical backgrounds.\n Mothers in the active treatment group received one capsule of 20 mg elemental zinc daily and those in the placebo treated group a capsule identical in appearance and taste with the active capsule but which contained inert substances.\n Various adverse outcomes were tested, including maternal bleeding, hypertension, complications of labour and delivery, gestational age, Apgar scores, and neonatal abnormalities. The main outcome measure was birth weight.\n There were no differences whatsoever between mothers given a zinc supplement and those given a placebo.\n Zinc supplementation in pregnancy in the United Kingdom does not seem to offer any benefits to the mother or her fetus.", "The effects of zinc supplementation on levels of various blood constituents and the outcome of pregnancy in 213 Hispanic women attending a prenatal clinic in Los Angeles was assessed in this double-blind study. The women were randomized into either a control (C) or a zinc-supplemented (Z) group and received similar vitamin and mineral supplements except that 20 mg zinc was added to the Z group's capsules. At the final interview, women (C + Z) with low serum Zn levels (less than or equal to 53 micrograms/dl) had higher (p less than 0.01) mean ribonuclease activity and lower (p less than 0.01) mean delta-aminolevulinic acid dehydratase activity than women with acceptable serum zinc levels. The incidence of pregnancy-induced hypertension was higher (p less than 0.003) in the C than in the Z group, but pregnancy-induced hypertension was not associated with low serum zinc levels at either the initial or final interview. The expected increase in serum copper levels was greater (less than 0.001) in women with pregnancy-induced hypertension (C + Z) than in normotensives. Except for pregnancy-induced hypertension, there was a higher incidence of abnormal outcomes of pregnancy in the noncompliers than in the compliers (C + Z).", "To assess the impact on birth size and risk of low birth weight of alternative combinations of micronutrients given to pregnant women.\n Double blind cluster randomised controlled trial.\n Rural community in south eastern Nepal.\n 4926 pregnant women and 4130 live born infants.\n 426 communities were randomised to five regimens in which pregnant women received daily supplements of folic acid, folic acid-iron, folic acid-iron-zinc, or multiple micronutrients all given with vitamin A, or vitamin A alone (control).\n Birth weight, length, and head and chest circumference assessed within 72 hours of birth. Low birth weight was defined <2500 g.\n Supplementation with maternal folic acid alone had no effect on birth size. Folic acid-iron increased mean birth weight by 37 g (95% confidence interval -16 g to 90 g) and reduced the percentage of low birthweight babies (<2500 g) from 43% to 34% (16%; relative risk=0.84, 0.72 to 0.99). Folic acid-iron-zinc had no effect on birth size compared with controls. Multiple micronutrient supplementation increased birth weight by 64 g (12 g to 115 g) and reduced the percentage of low birthweight babies by 14% (0.86, 0.74 to 0.99). None of the supplement combinations reduced the incidence of preterm births. Folic acid-iron and multiple micronutrients increased head and chest circumference of babies, but not length.\n Antenatal folic acid-iron supplements modestly reduce the risk of low birth weight. Multiple micronutrients confer no additional benefit over folic acid-iron in reducing this risk.", "The aim of this study was to assess the effect of high dose zinc (Zn) supplement during pregnancy in pregnancy outcome in healthy pregnant women with a previous preterm delivery in Isfahan, Iran.\n A double-blind placebo-controlled randomized clinical trial was conducted between January 2007 and June 2008. Eighty-four pregnant women with a previous preterm delivery age 19 to 35 years were randomly allocated to receive either 50 mg/day Zn as Zn sulfate or placebo from 12 to 16 weeks of gestation till delivery. Pregnancy outcome was assessed in term of incidence of intrauterine growth retardation (IUGR), birth weight, crown-heel length, head circumference, Apgar score, and gestational age at delivery.\n The mean birth head circumference was higher in Zn supplemented group than in the placebo group (35.0 cm vs. 33.7 cm, P < 0.05). Although gestational age at delivery (37.1 week vs. 36.7 week) and birth weight (2960.6 g vs. 2819.0 g) of babies born in Zn supplemented group was slightly higher than placebo group, it was not statistically significant. No significant differences were seen for infant length, Apgar score, and IUGR.\n Adding Zn supplementation during pregnancy to routine care of women with a previous preterm delivery had no significant effect on the gestational age at delivery and birth weight but increased the birth head circumference.", "Maternal zinc deficiency during pregnancy may be widespread among women in developing countries, but few data are available on whether prenatal zinc supplementation improves maternal and neonatal zinc status.\n We studied whether maternal zinc supplementation improved the zinc status of mothers and neonates participating in a supplementation trial in a shantytown in Lima, Peru.\n Beginning at gestation week 10-24, 1295 mothers were randomly assigned to receive prenatal supplements containing 60 mg Fe and 250 microg folate, with or without 15 mg Zn. Venous blood and urine samples were collected at enrollment, at gestation week 28-30, and at gestation week 37-38. At birth, a sample of cord vein blood was collected. We measured serum zinc concentrations in 538 women, urinary zinc concentrations in 521 women, and cord zinc concentrations in 252 neonates.\n At 28-30 and 37-38 wk, mothers receiving zinc supplements had higher serum zinc concentrations than mothers who did not receive zinc (8.8 +/- 1.9 compared with 8.4 +/- 1.5 micromol/L and 8.6 +/- 1.5 compared with 8.3 +/- 1.4 micromol/L, respectively). Urinary zinc concentrations were also higher in mothers who received supplemental zinc (P < 0.05). After adjustment for covariates and confounding factors, neonates of mothers receiving zinc supplements had higher cord zinc concentrations than neonates of mothers who did not receive zinc (12.7 +/- 2.3 compared with 12.1 +/- 2.1 micromol/L). Despite supplementation, maternal and neonatal zinc concentrations remained lower than values reported for well-nourished populations.\n Adding zinc to prenatal iron and folate tablets improved maternal and neonatal zinc status, but higher doses of zinc are likely needed to further improve maternal and neonatal zinc status in this population.", "Pakistan lies in a zinc deficient area where oral zinc supplementation has been advocated for various reasons. A double blind, randomised case-control study was carried out on pregnant women to evaluate the effects of oral zinc supplementation on the weights of newborns. No significant difference was found in the birth weights between the cases supplemented with 20 mg elemental zinc and controls receiving oral placebos (p=0.57).", "Maternal zinc supplementation has been suggested as a potential intervention to reduce the incidence of low birth weight in developing countries. To date, placebo-controlled trials have all been performed in industrialized countries and the results are inconsistent.\n The objective of this study was to evaluate whether zinc supplementation in Bangladeshi urban poor during the last 2 trimesters of pregnancy was associated with pregnancy outcome.\n We conducted a double-blind, placebo-controlled trial in which 559 women from Dhaka slums, stratified by parity between 12 and 16 wk of gestation, were randomly assigned to receive 30 mg elemental Zn/d (n = 269) or placebo (n = 290). Supplementation continued until delivery. Serum zinc was estimated at baseline and at 7 mo of gestation. Dietary intake was assessed at baseline and anthropometric measurements were made monthly. Weight, length, and gestational ages of 410 singleton newborns were measured within 72 h of birth.\n At 7 mo of gestation, serum zinc concentrations tended to be higher in the zinc-supplemented group than in the placebo group (15.9 +/- 4.4 compared with 15.2 +/- 4.3 micromol/L). No significant effect of treatment was observed on infant birth weight (2513 +/- 390 compared with 2554 +/- 393 g; NS) or on gestational age, infant length, or head, chest, or midupper arm circumference. The incidence and distribution of low birth weight, prematurity, and smallness for gestational age also did not differ significantly after zinc supplementation.\n Supplementation with 30 mg elemental Zn during the last 2 trimesters of pregnancy did not improve birth outcome in Bangladeshi urban poor. These results indicate that interventions with zinc supplementation alone are unlikely to reduce the incidence of low birth weight in Bangladesh.", "nan", "This study was undertaken to evaluate whether prenatal zinc supplementation affects maturation of fetal cardiac patterns.\n A randomized double-blind controlled trial among 242 low-income Peruvian women was performed. Beginning at 10 to 16 weeks' gestation, women received supplements containing 60 mg iron, 250 microg folic acid with or without 25 mg zinc. Fetal heart rate (mean FHR, variability [HRV], number of accelerations) and movements (number and amplitude of movement bouts, time spent moving) were electronically monitored monthly from 20 weeks' gestation. Developmental trends were evaluated by supplement type among 195 women who completed the trial and had no serious complications of pregnancy.\n Zinc supplementation was associated with lower FHR, greater number of accelerations, and greater HRV. Supplementation effects on HRV and accelerations were more pronounced after 28 weeks' gestation. No differences in motor activity were observed.\n Prenatal supplementation of zinc-deficient mothers may be beneficial to fetal neurobehavioral development.", "In a double-blind zinc trial in low-income, pregnant adolescents thought to be at risk for poor zinc nutriture, subjects were randomly assigned to receive 30 mg zinc (gluconate) or placebo. Response to zinc was related to maternal weight. Infants of normal-weight mothers given zinc had reduced rates of prematurity (p = 0.05) and assisted respiration (p = 0.006). Underweight multiparas given zinc had longer gestational lengths (p = 0.008) than did subjects given the placebo. Multiple stepwise regression analysis, used to identify predictors of infant size, revealed that 14-26% more variance was accounted for in the zinc than in the placebo group. Except for gestational age, the predictors selected were entirely different in the two groups. The zinc group had a positive toxemia screen more often, which did not appear to affect outcome. Zinc supplementation improved pregnancy outcome in normal-weight women and in underweight multiparas. The nonresponse in underweight primiparas was perhaps due to multiple limiting factors.", "Although iron and zinc deficiencies are known to occur together and also appear to be high in Ghana, a few supplementation studies addressed this concurrently in pregnancy. In a double-blind, randomized controlled trial, 600 pregnant women in Ghana were randomly assigned to receive either a combined supplement of 40 mg of zinc as zinc gluconate and 40 mg of iron as ferrous sulphate or 40 mg of elemental iron as ferrous sulphate. Overall, there was no detectable difference in the mean birthweight between the study groups, although the effect of iron-zinc supplementation on the mean birthweight was masked by a strong interaction between the type of supplement and the iron status of participants [F (1,179) = 5.614, p = 0.019]. Prenatal iron-zinc supplementation was effective in increasing the mean birthweight among anaemic and iron-deficient women but not among women with elevated iron stores in early pregnancy." ]

[ "10579259", "11008978" ]

[ "Beneficial effects of helium:oxygen versus air:oxygen noninvasive pressure support in patients with decompensated chronic obstructive pulmonary disease.", "Randomized trial of the use of heliox as a driving gas for updraft nebulization of bronchodilators in the emergent treatment of acute exacerbations of chronic obstructive pulmonary disease." ]

[ "To test the hypothesis that, in decompensated chronic obstructive pulmonary disease (COPD), noninvasive pressure support ventilation using 70:30 helium:oxygen instead of 70:30 air:oxygen could reduce dyspnea and improve ventilatory variables, gas exchange, and hemodynamic tolerance.\n Prospective, randomized, crossover study.\n Medical intensive care unit, university tertiary care center.\n Nineteen patients with severe COPD (forced 1-sec expiratory volume of 0.83+/-0.3 l) hospitalized in the intensive care unit for noninvasive pressure support ventilation after initial stabilization with noninvasive pressure support for no more than 24 hrs after intensive care unit admission.\n Noninvasive pressure support ventilation was administered in the following randomized crossover design: a) 45 min with air:oxygen or helium:oxygen; b) no ventilation for 45 min; and c) 45 min with air:oxygen or helium:oxygen.\n Air:oxygen and helium:oxygen decreased respiratory rate and increased tidal volume and minute ventilation. Helium:oxygen decreased inspiratory time. Both gases increased total respiratory cycle time and decreased the inspiratory/total time ratio, the reduction in the latter being significantly greater with helium:oxygen. Peak inspiratory flow rate increased more with helium:oxygen. PaO2 increased with both gases, whereas PaCO2 decreased more with helium:oxygen (values shown are mean+/-SD) (52+/-6 torr [6.9+/-0.8 kPa] vs. 55+/-8 torr [7.3+/-1.1 kPa] and 48+/-6 torr [6.4+/-0.8 kPa] vs. 54+/-7 torr [7.2+/-0.9 kPa] for air:oxygen and helium:oxygen, respectively; p<.05). When hypercapnia was severe (PaCO2 >56 torr [7.5 kPa]), PaCO2 decreased by > or =7.5 torr (1 kPa) in six of seven patients with helium:oxygen and in four of seven patients with air:oxygen (p<.01). Dyspnea score (Borg scale) decreased more with helium:oxygen than with air:oxygen (3.7+/-1.6 vs. 4.5+/-1.4 and 2.8+/-1.6 vs. 4.6+/-1.5 for air:oxygen and helium:oxygen, respectively; p<.05). Mean arterial blood pressure decreased with air:oxygen (76+/-12 vs. 82+/-14 mm Hg; p<.05) but remained unchanged with helium:oxygen.\n In decompensated COPD patients, noninvasive pressure support ventilation with helium:oxygen reduced dyspnea and PaCO2 more than air:oxygen, modified respiratory cycle times, and did not modify systemic blood pressure. These effects could prove beneficial in COPD patients with severe acute respiratory failure and might reduce the need for endotracheal intubation.", "To determine whether the bronchodilator effects of albuterol and ipratropium bromide are greater if updraft nebulization is driven by 80% helium and 20% oxygen (HELIOX) than if driven by compressed room air (AIR) during the treatment of an acute exacerbations of chronic obstructive pulmonary disease (COPD).\n The emergency department of a 750-bed inner-city community hospital.\n Over a 12-month period, a convenience sample of 50 normoxic patients presenting with signs and symptoms of an acute exacerbation of COPD were prospectively randomized to receive either HELIOX or AIR as the driving gas for updraft nebulization of a mixture of albuterol 2.5 mg and ipratropium bromide 0.5 mg. Additional aerosol treatments with albuterol 2.5 mg were given at 20, 40, and 120 mins after randomization using the assigned gas. Spirometry was obtained while breathing room air before the first treatment (baseline) and at 1 hr and 2 hrs after the initiation of treatment. The primary measure of efficacy was the change in percent of predicted forced expiratory volume in 1 sec (FEV1) over the treatment period. A secondary measure of efficacy was the change in percentage of predicted forced expiratory flow after 25% to 75% of vital capacity had been expelled (FEF25-75).\n Twenty-five patients were randomized to each treatment group. Three patients (1 HELIOX, 2 AIR) were unable to complete the study. The baseline FEV1was 44% (95% confidence interval, 35% to 52%) of predicted in the HELIOX group and 39 (31% to 46%) of predicted in the AIR group. There were no adverse outcomes observed in either the HELIOX group or the AIR group. There were no significant differences in the change of FEV1 between the two groups by either the 1 hr or 2 hr time point (1 hr, HELIOX + 10% [7% to 13%], AIR + 9% [5% to 13%]; 2 hr HELIOX + 10% [6% to 15%], AIR + 10% [6% to 14%]). The improvement in FEF25-75 was significantly greater in the HELIOX group than in the AIR group at both the 1 hr time point (HELIOX + 14% [7% to 22%] vs. AIR + 7% [3% to 10%], p = .05) and at the 2 hr time point (HELIOX + 15% [8% to 21%] vs. AIR + 7% [4% to 11%], p = .05).\n Use of HELIOX as a driving gas for the updraft nebulization of bronchodilators during the first 2 hrs of treatment of an acute COPD exacerbation failed to improve FEV1 faster than the use of AIR. The faster improvement in FEF25-75 during the first 2 hrs of treatment was small and of uncertain clinical significance." ]

[ "9219147" ]

[ "A controlled trial of imipramine for the treatment of methamphetamine dependence." ]

[ "At the Drug Detoxification Program of the Haight Ashbury Free Clinics, we conducted a randomized clinical trial of imipramine in the treatment of methamphetamine dependence. The purposes of the trial were to test the efficacy of imipramine as a treatment for methamphetamine dependence and to establish the feasibility of conducting a controlled clinical trial at the Clinic. Thirty-two subjects were randomly assigned to receive either 10 or 150 mg/day of imiprine for 180 days. Imipramine 10 mg/day was the control. Subjects received intensive counseling. Retention in treatment was significantly longer for subjects who were treated with 150 mg of imipramine compared to control (median days: 33.0 vs. 10.5). There were no consistent differences in percent of urine samples positive for methamphetamine, Beck Depression Inventory scores, or craving. Determination of the full extent of imipramine's utility in the treatment of methamphetamine dependence awaits a larger trial." ]

[ "3275486", "2665546", "1101081", "6164480", "2064956", "2213103", "11745871", "19846851" ]

[ "The Intergroup Rhabdomyosarcoma Study-I. A final report.", "Effectiveness of rubidomycin in induction therapy with vincristine, prednisone, and L-asparaginase for standard risk childhood acute lymphocytic leukemia: results of a Dutch phase III study (ALL V). A report on behalf of the Dutch Childhood Leukemia Study Group (DCLSG).", "[Acute lymphatic leukemia in children in the Netherlands; study ALL I, 1972-1973; Dutch Childhood Leukemia Study Group].", "The treatment of Wilms' tumor: results of the Second National Wilms' Tumor Study.", "Results of Medical Research Council Childhood Leukaemia Trial UKALL VIII (report to the Medical Research Council on behalf of the Working Party on Leukaemia in Childhood).", "Multimodal therapy for the management of primary, nonmetastatic Ewing's sarcoma of bone: a long-term follow-up of the First Intergroup study.", "Comparison of long-term outcome of children and adolescents with disseminated non-lymphoblastic non-Hodgkin lymphoma treated with COMP or daunomycin-COMP: A report from the Children's Cancer Group.", "Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma." ]

[ "The results of treatment of 686, previously untreated patients younger than 21 years with rhabdomyosarcoma or undifferentiated sarcoma, who were entered on Intergroup Rhabdomyosarcoma Study-I (IRS-I) were analyzed after a minimum potential follow-up time of 7 years. Patients in Clinical Group I (localized disease, completely resected) were randomized to receive either vincristine, dactinomycin, and cyclophosphamide (VAC) or VAC + radiation. At 5 years, approximately 80% of patients given either treatment were still disease-free and there was no significant difference between treatments in the overall percentages of patients surviving of 93% and 81%, respectively (P = 0.67). Patients in Clinical Group II (regional disease, grossly resected) were randomized to receive either vincristine and dactinomycin (VA) + radiation or VAC + radiation. At 5 years, 72% and 65% of the patients, respectively, were disease-free and there was no evidence of a difference between treatments (P = 0.46). The overall survival percentage at 5 years was approximately 72% for both treatments. Patients in Clinical Groups III (gross residual disease after surgery) and IV (metastatic disease) were randomized to receive either \"pulse\" VAC + radiation or \"pulse\" VAC + Adriamycin (doxorubicin) + radiation. The complete remission (CR) rate was 69% in Clinical Group III and 50% in IV, with no statistically significant difference in CR rates between treatments in either group. Those who achieved a CR had a nearly 60% chance of staying in remission for 5 years in Clinical Group III compared with approximately 30% in Clinical Group IV. The overall survival percentage at 5 years was 52% in Clinical Group III compared to 20% in Clinical Group IV (P less than 0.0001). The 5-year survival percentage for the entire cohort of 686 patients was 55%. Survival after relapse was poor, being 32% at 1 year and 17% at 2 years. The risk of distant metastasis was much greater than the risk of local recurrence within each clinical group, and there was no evidence of differing types of relapses between treatments. Primary tumors of the orbit and genitourinary tract carried the best prognosis, whereas tumors of the retroperitoneum had the worst prognosis. The authors conclude that for the therapeutic regimens evaluated there was no therapeutic advantage to including radiation in the treatment of Clinical Group I disease, or cyclophosphamide given as a daily low-dose oral regimen in the treatment of Clinical Group II disease or Adriamycin in the treatment of Clinical Groups III and IV diseases.", "The Dutch Childhood Leukemia Study Group (DCLSG) performed a phase III study-Study (ALL) V-to evaluate the effectiveness of rubidomycin in induction therapy with vincristine, prednisone, and L-asparaginase for children (0-15 years) with standard risk acute lymphoblastic leukemia (ALL) (white blood cell [WBC] counts less than 50.10(9)/L, absence of mediastinal mass, and/or cerebromeningeal leukemia). Furthermore, the influence of initial patient and disease characteristics on the outcome was analyzed. Between May 1979 and December 1982, 240 patients entered the study and were randomized into two groups: group A (n = 122) received induction treatment with vincristine (VCR), prednisone (Pred), and L-asparaginase (L-Asp); for group B (n = 118), induction therapy consisted of VCR, Pred, L-Asp, and rubidomycin (Rub). All patients subsequently underwent cranial irradiation (doses adjusted to age) in combination with intrathecal methotrexate; maintenance therapy of 6-mercaptopurine and methotrexate for 5 weeks followed by vincristine and prednisone for 2 weeks was given for 24 months. The complete remission (CR) rate was similar in both groups (94.5%). Event-free survival (EFS) 5 years after diagnosis was higher in group B (62.5 +/- 4.5%) than in group A (54.7 +/- 4.5%), although the difference is not significant (p = 0.20). A high initial WBC (greater than or equal to 10.10(9)/L), age (greater than or equal to 10 years), a low platelet count (less than 100.10(9)/L), and a positive acid phosphatase reaction of the leukemic cells were unfavorable prognostic factors (p less than 0.05). Sex, French-American-British (FAB) classification group, immunophenotype, and treatment in specialized centers did not have a significant impact on event-free survival.", "nan", "One-hundred-eighty-eight children up to 16 years of age were randomized in the second National Wilms' Tumor Study (NWTS) with tumors that were confined to the kidney and that had been totally excised (Group I). Most fared well whether treated for six or for 15 months with both actinomycin D (AMD) and vincristine (VCR). No postoperative radiation therapy (RT) was given. The two-year relapse-free survival (RFS) and two-year survival rates were 88 and 95%, respectively. Two-hundred-sixty-eight randomized patients with more advanced local lesions (Groups II and III) and 57 with distant metastases (Group IV) had postoperative RT and were scheduled for 15 months treatment with either AMD and VCR (Reg. C) or AMD plus VCR plus Adriamycin (Reg. D). The 77% two-year RFS rate for Reg. D was significantly different from the 63% with Reg. C. As in the first NWTS, patients with tumors of unfavorable histology (UH) had a significantly worse prognosis than those with favorable histology (FH), as did those with positive nodes. Survival rates at two years were 54% for UH vs. 90% for FH, and 54% vs. 82% for those with and without lymph node involvement.", "During the 1970s, despite apparently similar treatment, the prognosis for children with lymphoblastic leukaemia (ALL) improved more in some countries, notably the United States and West Germany, than in others. To find out why, the first phase of the United Kingdom (UK) Medical Research Council (MRC) childhood ALL trial, UKALL VIII, was designed to see whether similar results to the United States Children's Cancer Study Group (CCSG) could be obtained in the U.K. using an identical protocol (CCG 162). Protocol 162 was one of a series of regimens devised by the American Children's Cancer Study Group in the 1970s and was used specifically for their average risk patients (all children with ALL with an initial white cell count up to 50 x 10(9)/l except those aged 3-6 years with white cell counts under 10 x 10(9)/l). One arm (1A) of their study was adopted by the MRC for all children in the U.K. aged 0-14 years with confirmed ALL. Eight hundred and twenty-nine consecutive patients were entered between 1980 and 1984. The first 199 patients formed a single arm study as per the original protocol 162 (arm 1A), but the subsequent 630 children were randomized to receive or not two doses of daunorubicin on the first 2 d of induction. This randomization was an attempt to answer the important question as to whether event-free survival was influenced by the use of four rather than three induction agents. A second randomization between 2 and 3 years continuing therapy was also introduced at this stage as it had been by the CCSG in their protocol. With a minimum follow up period of more than 5 years, disease-free survival for the whole group is 55%, a considerable improvement on all previous UKALL trials. Results for patients directly comparable with those in CCSG 162 ('average risk' patients) and their American counterparts were similar. Daunorubicin was associated with more early deaths but improved disease-free survival for those achieving remission. More children relapsed who stopped treatment after 2 years than those who continued for 3, but this was balanced by increased treatment mortality in the third year. The fact that for UKALL VIII the results were similar to those of the CCSG suggests that previous MRC protocols were not sufficiently sustained and intensive, particularly during the maintenance phase of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)", "A total of 342 previously untreated eligible children were entered into the first Intergroup Ewing's Sarcoma Study (IESS) between May 1973 and November 1978. In group I institutions, patients were randomized between treatment 1 (radiotherapy to primary lesion plus cyclophosphamide, vincristine, dactinomycin, and Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH] [VAC plus ADR]) or treatment 2 (same as treatment 1 without ADR), and group II institutions randomized patients between treatment 2 or treatment 3 (same as treatment 2 plus bilateral pulmonary radiotherapy [VAC plus BPR]). The percentages of patients relapse-free and surviving (RFS) at 5 years for treatments 1, 2, and 3 were 60%, 24%, and 44%, respectively. There was strong statistical evidence of a significant advantage in RFS for treatment 1 (VAC plus ADR) versus 2 (VAC alone) (P less than .001) and 3 (P less than .05) and also of treatment 3 versus 2 (P less than .001). Similar significant results were observed with respect to overall survival. Patients with disease at pelvic sites have significantly poorer survival at 5 years than those with disease at nonpelvic sites (34% v 57%; P less than .001). Among pelvic cases, there was no evidence of differing survival by treatment (P = .81), but among nonpelvic cases, there was strong evidence of differing survival by treatment (P less than .001). The overall percentage of patients developing metastatic disease was 44%; the percentages by treatments 1, 2, and 3 were 30%, 72%, and 42%, respectively. The overall incidence of local recurrence was 15%, and there was no evidence that local recurrence rate differed by treatment. Patient characteristics related to prognosis, both with respect to RFS and overall survival experience, were primary site (nonpelvic patients were most favorable) and patient age (younger patients were more favorable).", "Early Children's Cancer Group (CCG) trials indicated that the cyclophosphamide, vincristine, methotrexate, and prednisone (COMP) regimen was superior to the LSA2L2 regimen for non-lymphoblastic (NLB) non-Hodgkin lymphoma (NHL). Studies by other groups suggested that addition of anthracyclines to standard therapies could improve outcome. Therefore, in 1983 CCG initiated study CCG-503, a randomized trial of COMP vs. daunomycin-COMP (D-COMP) in children and adolescents with disseminated NLB NHL.\n Between December 1983 and April 1990, 404 eligible patients were entered. Patients without central nervous system (CNS) or marrow involvement were randomized to receive COMP (N = 139) or D-COMP (N = 145). Randomization was stratified by histology and site of disease. Patients with CNS or marrow involvement (stage IV) were non-randomly treated with D-COMP (N = 120).\n Ten-year event-free survival in COMP and D-COMP patients was similar: 55 +/- 4.3% (Estimate +/- SE) vs. 57 +/- 4.2% (not significant). Stage I-III patients with large-cell (LC) NHL had worse 10-year event-free survival (EFS) (48 +/- 4.9%) than those with small non-cleaved cell (SNCC) NHL disease (61 +/- 3.5%, P < 0.05 in multivariate analysis), but equivalent survival (65 +/- 4.7% vs. 63 +/- 3.5%) due to significantly higher salvage rates in LC patients, especially those failing more than 12 months from diagnosis. Ten-year EFS in stage IV patients was 39 +/- 5.2%. Addition of daunomycin resulted in higher rates of grade 3/4 hematologic toxicity and stomatitis, as well as late cardiac-related deaths. The incidence of second malignant neoplasms was 1.0% at 10 years.\n Addition of daunomycin to standard COMP therapy did not improve outcome in pediatric disseminated NLB NHL. Patients with LC disease had a significantly reduced long-term EFS, but were retrieved at a higher rate than patients with SNCC disease, resulting in equivalent long-term survival.\n Copyright 2001 Wiley-Liss, Inc.", "Preoperative cisplatin alone may be as effective as cisplatin plus doxorubicin in standard-risk hepatoblastoma (a tumor involving three or fewer sectors of the liver that is associated with an alpha-fetoprotein level of >100 ng per milliliter).\n Children with standard-risk hepatoblastoma who were younger than 16 years of age were eligible for inclusion in the study. After they received one cycle of cisplatin (80 mg per square meter of body-surface area per 24 hours), we randomly assigned patients to receive cisplatin (every 14 days) or cisplatin plus doxorubicin administered in three preoperative cycles and two postoperative cycles. The primary outcome was the rate of complete resection, and the trial was powered to test the noninferiority of cisplatin alone (<10% difference in the rate of complete resection).\n Between June 1998 and December 2006, 126 patients were randomly assigned to receive cisplatin and 129 were randomly assigned to receive cisplatin plus doxorubicin. The rate of complete resection was 95% in the cisplatin-alone group and 93% in the cisplatin-doxorubicin group in the intention-to-treat analysis (difference, 1.4%; 95% confidence interval [CI], -4.1 to 7.0); these rates were 99% and 95%, respectively, in the per-protocol analysis. Three-year event-free survival and overall survival were, respectively, 83% (95% CI, 77 to 90) and 95% (95% CI, 91 to 99) in the cisplatin group, and 85% (95% CI, 79 to 92) and 93% (95% CI, 88 to 98) in the cisplatin-doxorubicin group (median follow-up, 46 months). Acute grade 3 or 4 adverse events were more frequent with combination therapy (74.4% vs. 20.6%).\n As compared with cisplatin plus doxorubicin, cisplatin monotherapy achieved similar rates of complete resection and survival among children with standard-risk hepatoblastoma. Doxorubicin can be safely omitted from the treatment of standard-risk hepatoblastoma. (ClinicalTrials.gov number, NCT00003912.)\n 2009 Massachusetts Medical Society" ]

[ "8215565", "8229533", "8708885", "1919895", "3142984" ]

[ "Early or late parenteral nutrition for the sick preterm infant?", "Effect of early initiation of intravenous lipid administration on the incidence and severity of chronic lung disease in premature infants.", "Randomised trial of effect of delayed intravenous lipid administration on chronic lung disease in preterm neonates.", "Introduction of intravenous lipid administration on the first day of life in the very low birth weight neonate.", "Decreased lipid intake reduces morbidity in sick premature neonates." ]

[ "No one doubts that good nutrition is an important component of neonatal intensive care, nor that this can only be accomplished by the use of intravenous fat. With regard to the effects of nutrition on bronchopulmonary dysplasia, however, we are facing a dilemma. On the one hand there is the suggestion that inadequate nutrition increases the severity of bronchopulmonary dysplasia and on the other that the use of intravenous fat predisposes to it. In an attempt to narrow the area of uncertainty we randomly allocated 129 infants of less than 1750 g birth weight to receive either early or late lipid containing parenteral nutrition. The median duration of ventilation support in the 'early' group was 8.5 days and in the 'late' group eight days; this was not significantly different.", "To investigate whether intravenous administration of lipid nutrition (Intralipid) within 12 hours of birth to ventilator-dependent premature infants would decrease the incidence or severity, or both, of chronic lung disease.\n We randomly assigned 133 infants to Intralipid or control groups, using two weight strata: 42 Intralipid versus 37 control subjects in the 600 to 800 gm stratum, and 28 Intralipid versus 26 control subjects in the 801 to 1000 gm stratum. The Intralipid group received 20% Intralipid at < 12 hours after birth, starting at a dose of 0.5 gm/kg and increasing to a maximum of 1.5 gm/kg, maintained through day 7. Control infants received no lipid until after day 7. Neither group received enteral feedings until after day 7.\n No significant differences in mortality rates were present in the total population (23/70 = 32.9% vs 16/63 = 25.4%; p = 0.35, Intralipid vs control); however, the mortality rate increased significantly in 600 to 800 gm infants receiving Intralipid versus the control infants (20/41 = 47.5% vs 9/37 = 24.3%; p = 0.032). No significant differences were found in the number of infants in whom chronic lung disease developed (requiring oxygen for > or = 28 days), proportion requiring oxygen for > or = 60 days, number of survivors without chronic lung disease, or total oxygen and ventilation requirements. However, 600 to 800 gm infants receiving Intralipid had significantly more pulmonary hemorrhage, and greater numbers of infants receiving Intralipid in both weight categories required supplemental oxygen at day 7. The incidence of other complications of prematurity, time required to regain birth weight, and duration of hospital stay did not differ between groups.\n Intralipid administration initiated at < 12 hours after birth failed to protect very low birth weight premature infants from chronic lung disease. Some of the results raise questions about possible deleterious effects of Intralipid when administered early in the first week of life.", "A recent sevenfold increase in the annual incidence of chronic neonatal lung disease (CNLD) on an intensive care unit was attributed to the early administration of intravenous lipid (IVL) in ventilated preterm neonates. When logistic regression was used to eliminate other confounding variables, early delivery of IVL was independently associated with an eight-fold increase in the likelihood of CNLD. Consequently, we designed a prospective study to detect a halving of the incidence of CNLD by delaying IVL administration from 5 days (as is routine practice) to 14 days. Sixty-four parenterally fed preterm neonates weighing < 1,500 g at birth were randomised to receive IVL either on day 5 or day 14. Analysis was by intention to treat, since several infants in the latter group required no parenteral nutrition by day 14. Our results showed that the relative risk (95% confidence interval) of CNLD at 28 postnatal days was 1.15 (0.81-1.62); at 36 weeks postconception, it was 1.08 (0.59-1.99). A study population of > 2,000 would be required to determine whether these relative risks were significantly different from 1.", "To investigate lipid tolerance in sick, ventilator-dependent, very low birth weight infants from the first day of life and the effects of early introduction of intravenously administered lipid (IVL) on glucose homeostasis.\n Twenty-nine infants in the neonatal intensive care unit with birth weight less than 1500 gm received isocaloric, isonitrogenous parenteral feedings from day 1 with either IVL, 1 gm/kg from day 1 to 3 gm/kg from day 4 (group I; n = 16), or IVL added only from day 8 (group II; n = 13). Possible adverse clinical effects were monitored. Blood metabolites, nonesterified fatty acids, serum triglycerides, and insulin levels were determined daily. Arterial blood gases were measured and changes in partial pressures of oxygen and of carbon dioxide in arterial blood were compared between the two groups.\n Early lipid infusion did not appear to have deleterious effects on blood gas tensions or to increase respiratory morbidity. The incidence of other adverse clinical effects that may be associated with IVL was not increased by earlier introduction of lipid. Serum lipid values were comparable to those of preterm infants receiving IVL at a later postnatal age. Blood glucose concentrations were higher in group II (mean, 7.50 (SEM 0.43) mmol/L) than in group I (mean, 6.01 (SEM 0.28) mmol/L; p less than 0.05). There was no evidence of increased gluconeogenesis in infants in group I and no correlation between blood glucose concentrations and serum nonesterified fatty acid concentrations.\n When given infusion rates not exceeding 0.15 gm/kg/hr, sick, very low birth weight infants can tolerate IVL with stepwise dose increases from the first day of life without an increased incidence of possible adverse effects.", "For an investigation of the clinical sequelae of parenteral lipid infusions during the first week of life, 42 neonates (less than 1750 gm birth weight) were randomly assigned to receive parenteral alimentation with (IL) (Vitrum) or without a parenteral lipid infusion (NL) for 5 days. Follow-up clinical status was monitored and compared, and plasma prostaglandin levels were analyzed. Chronic lung disease was increased in duration and tended to be more severe after lipid administration. The number of days of mechanical ventilation (37 +/- 35 vs 21 +/- 18) and supplemental oxygen therapy (51 +/- 39 vs 28 +/- 23) was significantly increased in the IL group. Five IL infants developed stage 3 bronchopulmonary dysplasia, in comparison with none of the NL infants. Seven IL infants were discharged on a regimen of supplemental oxygen therapy versus none of the NL infants. Thromboxane B2 levels were significantly increased in the babies receiving Vitrum. We conclude that early administration of Vitrum in the premature neonate is associated with increased respiratory difficulty in the ensuing weeks of life." ]

[ "16452558" ]

[ "Human botulism immune globulin for the treatment of infant botulism." ]

[ "We created the orphan drug Human Botulism Immune Globulin Intravenous (Human) (BIG-IV), which neutralizes botulinum toxin, and evaluated its safety and efficacy in treating infant botulism, the intestinal-toxemia form of human botulism.\n We performed a five-year, randomized, double-blind, placebo-controlled trial statewide, in California, of BIG-IV in 122 infants with suspected (and subsequently laboratory-confirmed) infant botulism (75 caused by type A Clostridium botulinum toxin, and 47 by type B toxin); treatment was given within three days after hospital admission. We subsequently performed a 6-year nationwide, open-label study of 382 laboratory-confirmed cases of infant botulism treated within 18 days after hospital admission.\n As compared with the control group in the randomized trial, infants treated with BIG-IV had a reduction in the mean length of the hospital stay, the primary efficacy outcome measure, from 5.7 weeks to 2.6 weeks (P<0.001). BIG-IV treatment also reduced the mean duration of intensive care by 3.2 weeks (P<0.001), the mean duration of mechanical ventilation by 2.6 weeks (P=0.01), the mean duration of tube or intravenous feeding by 6.4 weeks (P<0.001), and the mean hospital charges per patient by 88,600 dollars (in 2004 U.S. dollars; P<0.001). There were no serious adverse events attributable to BIG-IV. In the open-label study, infants treated with BIG-IV within seven days of admission had a mean length of hospital stay of 2.2 weeks, and early treatment with BIG-IV shortened the mean length of stay significantly more than did later treatment.\n Prompt treatment of infant botulism type A or type B with BIG-IV was safe and effective in shortening the length and cost of the hospital stay and the severity of illness.\n Copyright 2006 Massachusetts Medical Society." ]

[ "12666111", "15534251", "18608103" ]

[ "A randomized sequential trial of creatine in amyotrophic lateral sclerosis.", "A clinical trial of creatine in ALS.", "Creatine monohydrate in ALS: effects on strength, fatigue, respiratory status and ALSFRS." ]

[ "Amyotrophic lateral sclerosis (ALS) is a fatal disease with no cure. In a transgenic mouse model of ALS, creatine monohydrate showed a promising increase in survival. We performed a double-blind, placebo-controlled, sequential clinical trial to assess the effect of creatine monohydrate on survival and disease progression in patients with ALS. Between June 2000 and December 2001, 175 patients with probable, probable-laboratory supported, or definite ALS were randomly assigned to receive either creatine monohydrate or placebo 10 gm daily. A sequential trial design was used with death, persistent assisted ventilation, or tracheostomy as primary end points. Secondary outcome measurements were rate of decline of isometric arm muscle strength, forced vital capacity, functional status, and quality of life. The trial was stopped when the null hypothesis of indifference was accepted. Creatine did not affect survival (cumulative survival probability of 0.70 in the creatine group vs 0.68 in the placebo group at 12 months, and 0.52 in the creatine group vs 0.47 in the placebo group at 16 months), or the rate of decline of functional measurements. Creatine intake did not cause important adverse reactions. This placebo-controlled trial did not find evidence of a beneficial effect of creatine monohydrate on survival or disease progression in patients with ALS.", "Mitochondrial dysfunction occurs early in the course of ALS, and the mitochondria may be an important site for therapeutic intervention. Creatine stabilizes the mitochondrial transition pore, and is important in mitochondrial ATP production. In a transgenic mouse model of ALS, administration of creatine prolongs survival and preserves motor function and motor neurons.\n The authors conducted a randomized double-blind, placebo controlled trial on 104 patients with ALS from 14 sites to evaluate the efficacy of creatine supplementation in ALS. The primary outcome measure was maximum voluntary isometric contraction of eight upper extremity muscles, with secondary outcomes including grip strength, ALS Functional Rating Scale-Revised, and motor unit number estimates. Patients were treated for 6 months, and evaluated monthly.\n Creatine was tolerated well, but no benefit of creatine could be demonstrated in any outcome measure. CI analysis showed that the study, although powered to detect a 50% or greater change in rate of decline of muscle strength, actually made an effect size of greater than 23% unlikely. It was also demonstrated that motor unit number estimation was performed with acceptable reproducibility and tolerability, and may be a useful outcome measure in future clinical trials.\n Any beneficial effect of creatine at 5 g per day in ALS must be small. Other agents should be considered in future studies of therapeutic agents to address mitochondrial dysfunction in ALS. In addition, motor unit number estimation may be a useful outcome measure for future clinical trials in ALS.", "Our objective was to determine the effect of creatine monohydrate on disease progression in patients with amyotrophic lateral sclerosis (ALS). One hundred and seven patients with the diagnosis of probable or definite ALS, of less than five years duration from symptom onset, were randomized to either treatment with daily creatine monohydrate (5 g/d) or placebo. In this multicenter, double-blinded study we followed changes in disease progression: using quantitative measures of strength via maximal isometric voluntary contraction, forced vital capacity, ALSFRS, quality of life, fatigue and survival. Patients were followed for nine months. The results showed that creatine monohydrate did not significantly improve motor, respiratory or functional capacity in this patient population. The drug was well tolerated and the study groups well balanced, especially considering the absence of forced vital capacity criteria for entrance into the study. There was a trend toward improved survival in patients taking daily creatine monohydrate and this was identical to the trend seen in another recently published report of creatine in ALS patients 1. In conclusion, creatine monohydrate (5 g/d) did not have an obvious benefit on the multiple markers of disease progression measured over nine months. We measured fatigue during isometric contraction and found no significant improvement despite anecdotal patient reports prior to and during the study. The trend toward improved survival was also found in another recently completed blinded trial using creatine monohydrate. Further investigation on the possible survival benefit of creatine in this patient population is ongoing." ]

[ "16911345", "16674606", "16139183" ]

[ "A randomized, placebo-controlled study of oxcarbazepine in painful diabetic neuropathy.", "Oxcarbazepine in painful diabetic neuropathy: results of a dose-ranging study.", "Oxcarbazepine in painful diabetic neuropathy: a randomized, placebo-controlled study." ]

[ "To evaluate the efficacy and safety of oxcarbazepine (1200 mg/day) in patients with painful diabetic neuropathy in a multicentre, double-blind, placebo-controlled, 16-week study.\n A total of 141 patients were randomized to oxcarbazepine (1200 mg/day) (n = 71) or placebo (n = 70). The primary efficacy variable was the change in mean visual analogue scale (VAS) score from baseline to the last week the patient participated in the study.\n The reduction in mean VAS score from baseline to the last study week was similar between the oxcarbazepine and placebo groups. The majority of adverse events (most of which first occurred during titration) were mild to moderate in severity and resolved over the course of the study.\n In this study, no statistically significant difference in therapeutic effect was observed between oxcarbazepine (1200 mg/day) and placebo. However, further studies are necessary to assess the effective dose range of oxcarbazepine in the treatment of painful diabetic neuropathy.", "To evaluate the efficacy and safety of oxcarbazepine in patients with diabetic neuropathy in a multicenter, double-blind, placebo-controlled, dose-ranging 16-week study.\n A total of 347 patients were randomized to oxcarbazepine 600 mg/day (n = 83), 1,200 mg/day (n = 87), 1,800 mg/day (n = 88), or placebo (n = 89). The primary efficacy variable was change in mean visual analog scale (VAS) score from baseline to the last week of the study.\n No difference between any oxcarbazepine group and the placebo group was noted for the primary efficacy variable. Both the 1,200- and 1,800-mg/day groups showed a trend toward statistical significance (P = 0.101, P = 0.096, respectively). Statistically significant differences were found between the oxcarbazepine 1,200-mg/day (P = 0.038) and 1,800-mg/day (P = 0.005) groups and placebo in the overall mean weekly VAS scores for the entire double-blind treatment phase.\n Although the primary efficacy variable did not reach statistical significance, patients taking oxcarbazepine 1,200 and 1,800 mg/day showed improvements in VAS scores compared with placebo. Oxcarbazepine may provide clinically meaningful pain relief in patients with painful diabetic neuropathy.", "In this multicentre, placebo-controlled, 16-week trial, the efficacy and safety of oxcarbazepine monotherapy in patients with neuropathic pain of diabetic origin was evaluated. Eligible patients had a 6-month to 5-year history of neuropathic pain symptoms of diabetic origin and a pain rating of > or =50 units on the visual analogue scale (VAS). Oxcarbazepine was initiated at a dose of 300 mg/day and titrated to a maximum dose of 1800 mg/day. In total, 146 patients (oxcarbazepine, n=69; placebo, n=77) were randomized. After 16 weeks, oxcarbazepine-treated patients experienced a significantly larger decrease in the average change in VAS score from baseline compared with placebo (-24.3 vs. -14.7 units, respectively; p=0.01). The reduction from baseline in mean VAS score for oxcarbazepine-treated patients was of a greater magnitude than placebo as early as week 2 (-8.0 vs. -4.7; p<0.05). A significantly greater proportion of oxcarbazepine-treated patients experienced a >50% reduction from baseline in VAS score at the end of treatment compared with placebo (35.2% vs. 18.4%, respectively; p=0.0156; number needed to treat=6.0). Global assessment of therapeutic effect rating was improved in more oxcarbazepine patients than placebo patients (48% vs. 22%, respectively; p=0.0025). Patients on oxcarbazepine were awakened less frequently due to pain than patients on placebo. Most adverse events were mild to moderate in severity, transient, and in line with the known tolerability profile of oxcarbazepine. These observations suggest that oxcarbazepine monotherapy, pending additional trials, may be efficacious and may provide clinically meaningful pain relief in patients with neuropathic pain of diabetic origin." ]

[ "15201136", "8625679", "16408240", "15785917", "12143088", "10591454", "17121868", "12143089", "9155816", "12204875", "12171833", "12231497" ]

[ "Efficacy of positive airway pressure and oral appliance in mild to moderate obstructive sleep apnea.", "A randomized crossover study of an oral appliance vs nasal-continuous positive airway pressure in the treatment of mild-moderate obstructive sleep apnea.", "Efficacy and comorbidity of oral appliances in the treatment of obstructive sleep apnea-hypopnea: a systematic review and preliminary results of a randomized trial.", "Prospective evaluation of an oral appliance in the treatment of obstructive sleep apnea syndrome.", "Mandibular advancement splints and continuous positive airway pressure in patients with obstructive sleep apnoea: a randomized cross-over trial.", "Effects and adverse events of a dental appliance for treatment of obstructive sleep apnoea.", "Randomised study of three non-surgical treatments in mild to moderate obstructive sleep apnoea.", "Mandibular advancement appliances and obstructive sleep apnoea: a randomized clinical trial.", "Comparison of two dental devices for treatment of obstructive sleep apnea syndrome (OSAS).", "Oral appliance therapy improves symptoms in obstructive sleep apnea: a randomized, controlled trial.", "An individually adjustable oral appliance vs continuous positive airway pressure in mild-to-moderate obstructive sleep apnea syndrome.", "Randomized crossover trial of two treatments for sleep apnea/hypopnea syndrome: continuous positive airway pressure and mandibular repositioning splint." ]

[ "The efficacy of currently recommended treatments is uncertain in patients with mild to moderate obstructive sleep apnea (apnea-hypopnea index [AHI], 5-30). A group of 114 sleep clinic patients with an AHI of 5-30 have participated in a randomized controlled crossover trial of 3 months of treatment with each of nasal continuous positive airway pressure (CPAP), a mandibular advancement splint, and a placebo tablet. Outcomes were sleep fragmentation and hypoxemia, daytime sleepiness, quality of life, neurobehavioral function, and blood pressure. Both active treatments improved sleep outcomes, but positive airway pressure had a greater effect. The quality of life, symptoms, and subjective but not objective sleepiness improved to a similar degree with both treatments; however, many of the improvements seen in neuropsychologic function and mood were not better than the placebo effect. Some aspects of nocturnal blood pressure were improved with the splint but not with CPAP. This study has shown that although both CPAP and mandibular advancement splint effectively treated sleep-disordered breathing and sleepiness, the expected response in neurobehavioral function was incomplete. This may be due to the splint having a lesser therapeutic effect and CPAP being poorly tolerated and therefore used less in this patient group.", "To compare efficacy, side effects, patient compliance, and preference between oral appliance (OA) therapy and nasal-continuous positive airway pressure (N-CPAP) therapy.\n Randomized, prospective, crossover study.\n University hospital and tertiary sleep referral center.\n Twenty-seven unselected patients with mild-moderate obstructive sleep apnea (OSA).\n There was a 2-week wash-in and a 2-week wash-out period, and 2 x 4-month treatment periods (OA and N-CPAP). Efficacy, side effects, compliance, and preference were evaluated by a questionnaire and home sleep monitoring.\n Two patients dropped out early in the study and treatment results are presented on the remaining 25 patients. The apnea/hypopnea index was lower with N-CPAP (3.5 +/- 1.6) (mean +/- SD) than with the OA (9.7 +/- 7.3) (p < 0.05). Twelve of the 25 patients who used the OA (48%) were treatment successes (reduction of apnea/hypopnea to <10/h and relief of symptoms), 6 (24%) were compliance failures (unable or unwilling to use the treatment), and 7 (28%) were treatment failures (failure to reduce apnea/hypopnea index to <10/h and/or failure to relieve symptoms). Four people refused to use N-CPAP after using the OA. Thirteen of the 21 patients who used N-CPAP were overall treatment successes (62%), 8 were compliance failures (38%), and there were no treatment failures. Side effects were more common and the patients were less satisfied with N-CPAP (p < 0.005). Seven patients were treatment successes with both treatments, six of these patients preferred OA, and one preferred N-CPAP as a long-term treatment.\n We conclude that OA is an effective treatment in some patients with mild-moderate OSA and is associated with fewer side effects and greater patient satisfaction than N-CPAP.", "The obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common sleep-related breathing disorder characterized by repetitive obstructions of the upper airway during sleep. The modification of pharyngeal patency by oral appliance therapy has been suggested as an alternative to various treatment modalities for OSAHS. To determine the evidence base with respect to the efficacy and comorbidity of the oral appliance therapy in OSAHS, a systematic review of the available literature was conducted. In addition, the preliminary results of a randomized parallel trial are reported on the effectiveness and specific indication of, respectively, the oral appliance and continuous positive airways pressure therapy in OSAHS.", "The purpose of this study was to investigate the effects of an oral appliance (OA), with and without mandible advance, in the treatment of obstructive sleep apnea syndrome (OSA). Twenty-four patients diagnosed with OSA agreed to participate in this study. The patients were treated for 3 months (with a removable soft elastic silicone positioner customized with thermoplastic silicone and with a 5-mm opening). Patients were selected, using a randomized design, to receive an OA model either with (12 patients) or without advance (12 patients). Before treatment, a snoring questionnaire, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), the Functional Outcomes of Sleep Questionnaire (FOSQ), the Epworth Sleepiness Scale (ESS), and polysomnography were completed. Fifteen subjects completed the protocol (13 men, two women). With respect to basal values, the mandible-advanced OA group presented a decrease in the mean apnea-hypopnea index (AHI) (33.8+/-4.7 versus 9.6+/-2.1; p<0.01), number of arousals per hour (33.8+/-13.9 versus 16.0+/-1.5; p<0.05), ESS score (14.7+/-5.1 versus 5.1+/-1.9; p<0.05), snoring score (15.4+/-1.9 versus 10.1+/-3.2; p<0.05), and total FOSQ score (78.1+/-22.6 versus 99.3+/-14.4; p<0.05). After treatment, the non-advanced group presented a decrease in the mean AHI (24.0+/-12.2 versus. 11.7+/-7.9; p<0.05). However, no significant differences were found in the number of arousals per hour, ESS score, snoring, and total FOSQ score in the non-advanced group. Neither study group showed significant difference in mean SF36 scores. Oral appliances, especially those that advance the mandible, offer an effective treatment for OSA.", "This prospective, randomized, cross-over trial was designed to compare the efficacy of a mandibular advancement splint (MAS) with that of nasal continuous positive airway pressure (nCPAP) in patients with obstructive sleep apnoea (OSA). Twenty-four patients (20 males and four females) with mild to moderate OSA (AHI between 10 and 49 events per hour) were enrolled in the study. Each patient used both MAS and nCPAP, with the initial therapy being allocated at random. Treatment periods lasted for two months with a two-week wash-out interval between. Polysomnography was performed prior to the study and after each clinical intervention. Patient and partner questionnaires were used to assess changes in general health and daytime somnolence. The AHI decreased from 22.2 to 3.1 using nCPAP, and to 8.0 using the MAS (P < 0.001 for both devices) and there was no statistically significant difference between the two treatments. The Epworth Sleepiness Score (ESS) fell from 13.4 to 8.1 with nCPAP, and to 9.2 with MAS (P < 0.001), again with no differences between the use of MAS or nCPAP. The questionnaire data showed an improvement in general health scores (P < 0.001) after both treatments, but daytime sleepiness only improved significantly using nCPAP (P < 0.001). Despite this, 17 out of the 21 subjects who completed both arms of the study preferred the MAS. The splints were well tolerated and their efficacy suggests that the MAS may be a suitable alternative to nCPAP in the management of patients with mild or moderate OSA.", "In a prospective study, 95 patients with mild to moderate obstructive sleep apnoea (OSA) were randomised to receive either surgical treatment, uvulopalatopharyngoplasty, (4-6 patients) or treatment with a nocturnal dental appliance for mandibular advancement (49 patients). Of the 49 dental appliance patients, 37 completed the 12-month follow-up. The aim of this study was to evaluate the effects and adverse events of dental appliance treatment from a one-year perspective. Somnography was employed to measure treatment effects before and 12 months post-treatment. At the 12-month control, somnography was performed twice: the first time with the dental appliance and the second time without it. Adverse events were recorded 2 weeks and 3, 6, and 12 months after treatment was initiated. The patients used the dental appliance on average 6 nights/week. After 12 months of treatment, the apnoea, apnoea/hypopnoea, oxygen desaturation, and snoring indices decreased significantly. Ninety-five per cent of the patients reduced their apnoea index by > or = 50% and 78% of the patients were normalised following treatment. At the somnographic registration without the dental appliance, the values were found comparable to what they were before treatment. Mandibular mobility and occlusion were constant throughout the study. The adverse events resulting from using the dental appliance were relatively minor and infrequent, and no serious complications were observed except for two patients who reported pain from the temporomandibular joint. In conclusion, the dental appliance has been shown to be a valuable treatment method for mild to moderate OSA with few adverse events in the stomatognathic system or other complications.", "Patients with mild to moderate obstructive sleep apnoea (OSA) may be managed with different treatment options. This study compared the effectiveness of three commonly used non-surgical treatment modalities.\n Subjects with mild to moderate OSA were randomised to one of three treatment groups for 10 weeks: conservative measures (sleep hygiene) only, continuous positive airways pressure (CPAP) in addition to conservative measures or an oral appliance in addition to conservative measures. All overweight subjects were referred to a weight-reduction class. OSA was assessed by polysomnography. Blood pressure was recorded in the morning and evening in the sleep laboratory. Daytime sleepiness was assessed with the Epworth Sleepiness Scale. Health-related quality of life (HRQOL) was assessed with the 36-Item Short-Form Health Survey (SF-36) and Sleep Apnoea Quality of Life Index (SAQLI).\n 101 subjects with a mean (SEM) apnoea-hypopnoea index (AHI) of 21.4 (1.1) were randomised to one of the three groups. The severity of sleep-disordered breathing was decreased in the CPAP and oral appliance groups compared with the conservative measures group, and the CPAP group was significantly better than the oral appliance group. Relief from sleepiness was significantly better in the CPAP group. CPAP was also better than the oral appliance or conservative measures in improving the \"bodily pain\" domain, and better than conservative measures in improving the \"physical function\" domain of SF-36. Both CPAP and the oral appliance were more effective than conservative measures in improving the SAQLI, although no difference was detected between the CPAP and oral appliance groups. CPAP and the oral appliance significantly lowered the morning diastolic blood pressure compared with baseline values, but there was no difference in the changes in blood pressure between the groups. There was also a linear relationship between the changes in AHI and body weight.\n CPAP produced the best improvement in terms of physiological, symptomatic and HRQOL measures, while the oral appliance was slightly less effective. Weight loss, if achieved, resulted in an improvement in sleep parameters, but weight control alone was not uniformly effective.", "This randomized placebo-controlled cross-over trial assessed the effectiveness of a mandibular advancement appliance (MAA) in managing obstructive sleep apnoea (OSA). Twenty-one adults, with confirmed OSA, were provided with a maxillary placebo appliance and a MAA for 4-6 weeks each, in a randomized order. Questionnaires at baseline and after each appliance assessed bed-partners' reports of snoring severity (loudness and number of nights per week), and patients' daytime sleepiness (Epworth Sleepiness Score, ESS). The Apnoea Hypopnoea Index (AHI) and Oxygen Desaturation Index (ODI) were measured at baseline and with each appliance during single night sleep studies. Seventy-nine per cent of subjects wore their MAA for at least 4 hours at night. Sixty-eight per cent of subjects wore their MAA for 6-7 nights per week. Excessive salivation was the most commonly reported complication. One subject was unable to tolerate the MAA and withdrew from the study. Among the remaining 20 subjects, the MAA produced significantly lower AHI and ODI values than the placebo. However, although the reported frequency and loudness of snoring and the ESS values were lower with the MAA than the placebo, these differences were not statistically significant. When wearing the MAA, 35 per cent of the OSA subjects had a reduction in the pre-treatment ODI to 10 or less, while 33 per cent had an AHI of 10 or less. The MAA was less effective in the subjects with the most severe OSA (pre-treatment ODI > 50 and/or pre-treatment AHI > 50).", "Previous case reports have indicated dental devices can be an effective nonsurgical treatment for snoring and obstructive sleep apnea. This pilot study evaluated the effectiveness of two intraoral devices in reducing the Respiratory Disturbance Index (RDI) and Epworth Sleepiness Scale (ESS) scores in a group of 24 adult volunteers with a history of loud snoring. Subjects were randomly assigned to two groups. Twelve subjects were fitted with a dental device designed to increase vertical dimension and protrude the mandible (device A). The other 12 subjects received a different device designed to minimally increase vertical opening without protruding the mandible (device B). Unattended home sleep monitoring (Edentrace II Digital Recorder, Edentech Corp.) was used to compute RDI at two time periods: (T0) before using any dental device and (T1) while using a dental device 2 weeks after the initial delivery date. The mean RDI and ESS scores at T0 for subjects in the device A group were 35.6 +/- 28.4 and 12.0 +/- 3.9, respectively. Means for the same measures at T1 were 21.1 +/- 21.4 and 8.2 +/- 4.0. For subjects in the device B group, means for RDI and ESS scores at T0 were 36.5 +/- 43.7 and 13.0 +/- 4.5, the means at T1 were 46.8 +/- 47.0 and 12.5 +/- 5.7. The effectiveness of the two devices was estimated by comparing the difference in RDI scores from T0 to T1 for the 10 subjects who were using device A and completed the study and the 8 subjects who were using device B and completed the study. Six subjects withdrew for various reasons. From T0 to T1, device A reduced RDI scores in 9 of 10 subjects, with a mean reduction in RDI of 14.5 (p < or = 0.05) and in ESS score of 3.8 (p < or = 0.005). Device B showed no change or an increased RDI score in 8 of 8 subjects. Seven of the eight subjects who showed no improvement in RDI with device B were then fitted with device A. Four of these seven subjects showed a reduction in RDI and five showed a reduction in ESS after using device A for 2 weeks. The mean reduction in RDI and ESS was 2.4 +/- 19.8 and 2.4 +/- 3.0, respectively. Hence, we conclude that a dental device that advances the mandible and increases the vertical dimension to open the upper airway is more effective in reducing the number of apneic and snoring events during sleep than one which does not.", "The aim of this study was to evaluate the effect of a mandibular advancement splint (MAS) on daytime sleepiness and a range of other symptoms in obstructive sleep apnea (OSA). Using a randomized crossover design, patients received 4 weeks of treatment with MAS and a control device (inactive oral appliance), with an intervening 1-week washout. At the end of each treatment period, patients were reassessed by questionnaire, polysomnography, and multiple sleep latency test. Fifty-nine men and 14 women with a mean (+/- SD) age of 48 +/- 11 years and proven OSA experienced a significantly improved mean (+/- SEM) sleep latency on the multiple sleep latency test (10.3 +/- 0.5 versus 9.1 +/- 0.5 minutes, p = 0.01) and Epworth sleepiness scale score (7 +/- 1 versus 9 +/- 1, p < 0.0001) with the MAS compared with the control device after 4 weeks. The proportion of patients with normal subjective sleepiness was significantly higher with the MAS than with the control device (82 versus 62%, p < 0.01), but this was not so for objective sleepiness (48 versus 34%, p = 0.08). Other OSA symptoms were controlled in significantly more patients with the MAS than with the control device. MAS therapy improves a range of symptoms associated with OSA.", "For the treatment of nonsevere obstructive sleep apnea syndrome (OSAS), mandibular advancement devices (MADs) are employed as an alternative to nasal continuous positive airway pressure (CPAP) therapy. However, very few specific data on the effectiveness of MADs in this group of patients are available. We therefore compared an individually adjustable intraoral sleep apnea device (ISAD) that permits movements of the lower jaw in three dimensions, with CPAP in the treatment of patients with an apnea/hypopnea index (AHI) < or = 30/h.\n In a randomized crossover study, 16 men and 4 women (mean +/- SD age, 56.5 +/- 10.2 years; body mass index, 31.2 +/- 6.4; AHI, 17.5 +/- 7.7/h) were treated for 6 weeks with each modality.\n In the initial phase, a significant improvement in AHI (baseline, 17.5 +/- 7.7/h; ISAD, 10.5 +/- 7.5/h [p < 0.05]; CPAP, 3.5 +/- 2.9/h [p < 0.01]) and in breathing-related arousals (baseline, 8.9 +/- 6.1/h; ISAD, 3.7 +/- 3.3/h [p < 0.01]; CPAP, 1.4 +/- 1.6/h [p < 0.01]) was achieved with both modalities. Considering all 20 subjects, after 6 weeks of treatment, normalization of the respiratory parameters was seen only with CPAP. However, 30% of the patients had a lasting reduction in AHI to < 10/h with the ISAD also. The patients considered the ISAD to be easier to use (scale of 1 to 6: ISAD, 1.8 +/- 1.1; CPAP, 3.1 +/- 1.5 [p < 0.05]), and indicated greater utilization of the device in comparison with CPAP.\n Even in patients with mild-to-moderate OSAS, CPAP is the more effective long-term treatment modality. In the individual case, the better compliance seen with the ISAD may be advantageous.", "Mandibular repositioning splints (MRSs) and continuous positive airway pressure (CPAP) are used to treat the sleep apnea/hypopnea syndrome (SAHS). There are some data suggesting that patients with milder symptoms prefer MRS, but there are few comparative data on outcomes. Therefore, we performed a randomized crossover trial of 8 weeks of CPAP and 8 weeks of MRS treatment in consecutive new outpatients diagnosed with SAHS (apnea/hypopnea index [AHI] >or= 5/hour, and >or= 2 symptoms including sleepiness). Assessments at the end of both limbs comprised home sleep study, subjective ratings of treatment value, sleepiness, symptoms, and well-being, and objective tests of sleepiness and cognition. Forty-eight of 51 recruited patients completed the trial (12 women; age [mean +/- SD], 46 +/- 9 years; Epworth 14 +/- 4; median AHI, 22/hour; interquartile ratio [IQR], 11-43/hour). Significant (p <or= 0.01) differences between MRS and CPAP were observed for 7 of 21 variables (effect sizes, 0.3-0.6 SDs), all favoring CPAP, including AHI (15 +/- 16 and 8 +/- 6/hour, respectively), effectiveness rating, symptoms, Epworth (12 +/- 5 and 8 +/- 5, respectively), functional outcomes of sleepiness questionnaire, short-form 36 health survey mental component, and health transition scores. Objective sleepiness, cognitive performance, and preference for treatments were not different. In patients experiencing a mild form of the syndrome (AHI < 15, n = 18), symptoms, treatment efficacy and satisfaction, and subjective sleepiness were also better with CPAP than with MRS (effect sizes, 0.7-1.1 SDs). These results do not support these MRS devices as first-line treatment for sleepy patients with SAHS." ]

[ "2569550" ]

[ "Routine formal fetal movement counting and risk of antepartum late death in normally formed singletons." ]

[ "The routine recommendation to women to count fetal movements daily during late pregnancy for the prevention of antepartum late fetal death in normally formed singletons has been evaluated. 68,000 women were randomly allocated within thirty-three pairs of clusters either to a policy of routine counting or to standard care, which might involve selective use of formal counting or informal noting of movements. Antepartum death rates for normally formed singletons were similar in the two groups, regardless of cause of prior risk status. Despite the counting policy, most of these fetuses were dead by the time the mothers received medical attention. The study does not rule out a beneficial effect, but at best, the policy would have to be used by about 1250 women to prevent 1 unexplained antepartum late fetal death, and an adverse effect is just as likely. In addition, formal routine counting would use considerable extra resources." ]

[ "9164427", "7862884", "1393304", "1638170", "11838629", "14604447", "10627793", "11754136", "12470127", "12131599", "9862558", "8784653", "9241002", "10327910", "9728642", "10440462", "8619339", "11156811", "12006895", "9790154", "2018160", "9177952", "9534836", "7653696", "8120156", "12934979", "1558463", "10493085", "11106135", "8201073", "11435264", "6834370", "12503837", "9241003" ]

[ "Clinical effects of buspirone in social phobia: a double-blind placebo-controlled study.", "Psychopharmacological treatment of social phobia; a double blind placebo controlled study with fluvoxamine.", "Pharmacotherapy of social phobia. A controlled study with moclobemide and phenelzine.", "Psychopharmacological treatment of social phobia: clinical and biochemical effects of brofaromine, a selective MAO-A inhibitor.", "A randomized, double-blind, fixed-dose comparison of paroxetine and placebo in the treatment of generalized social anxiety disorder.", "Fluvoxamine CR in the long-term treatment of social anxiety disorder: the 12- to 24-week extension phase of a multicentre, randomized, placebo-controlled trial.", "Paroxetine in social phobia/social anxiety disorder. Randomised, double-blind, placebo-controlled study. Paroxetine Study Group.", "Paroxetine for social anxiety and alcohol use in dual-diagnosed patients.", "Efficacy of paroxetine for relapse prevention in social anxiety disorder: a 24-week study.", "Moclobemide is effective and well tolerated in the long-term pharmacotherapy of social anxiety disorder with or without comorbid anxiety disorder.", "Cognitive behavioral group therapy vs phenelzine therapy for social phobia: 12-week outcome.", "Paroxetine in the treatment of generalized social phobia: open-label treatment and double-blind placebo-controlled discontinuation.", "Moclobemide in social phobia: a controlled dose-response trial.", "Fluvoxamine treatment of social phobia (social anxiety disorder): a double-blind, placebo-controlled study.", "Paroxetine treatment of generalized social phobia (social anxiety disorder): a randomized controlled trial.", "Treatment of social phobia with gabapentin: a placebo-controlled study.", "Social phobia: the clinical efficacy and tolerability of the monoamine oxidase -A and serotonin uptake inhibitor brofaromine. A double-blind placebo-controlled study.", "Sertraline treatment of generalized social phobia: a 20-week, double-blind, placebo-controlled study.", "Fluoxetine in social phobia: a double-blind, placebo-controlled pilot study.", "Discontinuation of clonazepam in the treatment of social phobia.", "The assessment and treatment of performance anxiety in musicians.", "The International Multicenter Clinical Trial Group on Moclobemide in Social Phobia. Moclobemide in social phobia. A double-blind, placebo-controlled clinical study.", "Placebo-controlled trial of moclobemide in social phobia.", "Sertraline for social phobia: a double-blind, placebo-controlled crossover study.", "Treatment of social phobia with clonazepam and placebo.", "Efficacy of sertraline in severe generalized social anxiety disorder: results of a double-blind, placebo-controlled study.", "Phenelzine vs atenolol in social phobia. A placebo-controlled comparison.", "Paroxetine in social anxiety disorder: a randomized placebo-controlled study.", "Prevention of relapse in generalized social phobia: results of a 24-week study in responders to 20 weeks of sertraline treatment.", "Social phobia: a comparison of behavior therapy and atenolol.", "Randomised controlled general practice trial of sertraline, exposure therapy and combined treatment in generalised social phobia.", "Effect of pindolol on stress-related disturbances of musical performance: preliminary communication.", "Efficacy of olanzapine in social anxiety disorder: a pilot study.", "Brofaromine for social phobia: a multicenter, placebo-controlled, double-blind study." ]

[ "The results of open pilot studies suggest that the serotonin-1A (5-HT1A) receptor agonist buspirone might be effective in social phobia.\n In the present study, the efficacy of buspirone was investigated in patients with social phobia using a 12-week double-blind placebo-controlled design. Thirty social phobic patients (DSM-IV) were treated with either buspirone 30 mg daily or placebo. Efficacy of treatment was measured using the Social Phobia Scale (subscores anxiety and avoidance) and the Hamilton Rating Scale for Anxiety.\n Taking a reduction of 50% or more on the Social Phobia Scale as a criterion for clinically relevant improvement, only 1 patient on buspirone and 1 on placebo were classified as responder to treatment. A subjective and clinically relevant improvement was reported by 4 patients (27%) on buspirone and 2 patients (13%) on placebo. There were no statistically significant differences between buspirone and placebo on any of the outcome measures. Generally speaking, buspirone was well tolerated.\n The results of the study do not support the results of open studies, in which a reduction of social anxiety and social avoidance was reported in patients with social phobia treated with buspirone.", "Previous studies have shown selective and nonselective monoamine oxidase inhibitors (MAOIs) to be effective in the treatment of social phobia. In this study we investigated the efficacy of selective serotonin reuptake inhibitors (SSRIs) in social phobia. Thirty patients with social phobia (DSM-IIIR) were treated with the SS-RI fluvoxamine (150 mg daily) using a 12-week double-blind placebo controlled design. A substantial improvement was observed in seven (46%) patients on fluvoxamine and in one (7%) on placebo. Statistically significant effects were seen on measures of social anxiety and general (or anticipatory) anxiety in patients treated with fluvoxamine compared with placebo. The level of phobic avoidance decreased also but the difference at endpoint between fluvoxamine and placebo failed to reach statistical significance. It is concluded that treatment with the SSRI fluvoxamine has beneficial effects in patients suffering from social phobia, suggesting that serotonergic mechanisms might be implicated in social anxiety.", "In a double-blind, parallel group trial, 78 subjects with social phobia received moclobemide (a new reversible inhibitor of monoamine oxidase A) phenelzine, or placebo. After eight weeks, both active drugs-phenelzine somewhat more than moclobemide--were clinically and statistically significantly more effective than placebo, as assessed by rating scales. There was some further improvement between weeks 8 and 16, particularly in the moclobemide group; at week 16, 82% of the moclobemide and 91% of the phenelzine-treated patients were almost asymptomatic. Moclobemide was, however, much better tolerated than phenelzine. Patients withdrawn from active drugs had relapsed by week 24, providing additional support for the efficacy of the active drugs.", "There is circumstantial evidence that antidepressants, particularly monoamine oxidase inhibitors (MAOIs) and beta-blockers, may have some beneficial effects in social phobia. In this study 30 patients with social phobia (DSM-IIIR) were treated with the selective and reversible MAO-A inhibitor brofaromine, using a 12-week double-blind placebo controlled design. A clinical relevant improvement was seen in 80% of the patients treated with brofaromine (150 mg daily). A significant improvement was found on measures of social anxiety, phobic avoidance, general (or anticipatory) anxiety and interpersonal sensitivity in patients on brofaromine, but not on placebo. Biochemical measurements revealed a decrease in turnover of noradrenaline, serotonin and dopamine as assessed by the plasma metabolite levels, and an increase in nocturnal release of melatonin. Most prominent side-effect was middle sleep disturbance. No changes in blood pressure were observed. During a follow-up period of 12 weeks a further improvement was found in patients treated with brofaromine.", "This multicenter, double-blind, placebo-controlled study was carried out to determine the effectiveness and safety of various daily dosages of paroxetine for the treatment of generalized social anxiety disorder.\n A 1-week, single-blind, placebo run-in was followed by 12 weeks of double-blind treatment. 384 eligible patients meeting DSM-IV criteria for social anxiety disorder were randomly assigned to receive paroxetine, 20 (N = 97), 40 (N = 95), or 60 mg (N = 97), or placebo (N = 95) once daily in a 1:1:1:1 ratio. Primary efficacy variables included mean change from baseline in the Liebowitz Social Anxiety Scale (LSAS) total score and proportion of patients exhibiting a therapeutic response (defined as a Clinical Global Impressions-Global Improvement scale [CGI-1] score of 1 or 2).\n In the last-observation-carried-forward analyses, patients treated with paroxetine, 20 mg/day, had significantly greater improvement on mean LSAS total scores compared with those receiving placebo (p < .001), while the incidence of responders, based on the CGI-I rating, was significantly greater with paroxetine, 40 mg/day, than with placebo (p = .012). Patients treated with paroxetine, 20 and 60 mg, also had significantly better responses on the social item of the Sheehan Disability Scale than did patients treated with placebo (p < .019). The completer analyses showed a significant difference between the placebo group and the 20-mg and 40-mg paroxetine groups on LSAS total score and rate of response (p < or = .006). There were no serious adverse experiences attributed to paroxetine treatment.\n Paroxetine, 20 mg/day, is an effective and safe treatment for patients with generalized social anxiety disorder and significantly improves social anxiety, avoidance of social interactions, social disability, and overall clinical condition. Further data analyses are needed to determine whether more specific guidelines for paroxetine dosage escalation in social anxiety disorder can be drawn.", "Fluvoxamine CR has been reported effective in the short-term (12-wk) treatment of generalized social anxiety disorder (social phobia). Social anxiety disorder (SAD) is, however, a chronic disorder thought to require maintenance treatment. We report on data from the extension phase of a short-term study, in order to explore the efficacy and safety profile of fluvoxamine CR (100-300 mg/d) in the longer-term treatment of this disorder. Adult outpatients with generalized social anxiety disorder (GSAD) at 35 centres in Europe, South Africa, and USA were included in an acute phase study (12 wk). Subjects who demonstrated at least minimal improvement by endpoint (n=112), were offered participation in an extension phase, in which medication was continued for a further 12 wk under double-blind conditions. Efficacy was assessed using the Liebowitz Social Anxiety Disorder Scale (LSAS), the Clinical Global Impression Global Improvement score (CGI-I), the Clinical Global Impressions Severity of Illness score (CGI-S), and the Sheehan Disability Scale (SDS). Safety and tolerability assessments were also performed at regular intervals. Subjects treated with fluvoxamine CR had a numerically greater decrease in LSAS total scores than subjects treated with placebo at endpoint. Analysis of data from baseline (day 1) to endpoint (last observation carried forward) demonstrated that this difference tended towards significance, while severity of illness on the CGI-S and disability on the SDS were significantly lower in the fluvoxamine CR group than in the placebo group. The same trends were observed when only data from weeks 12-24 were included in the analysis; although the magnitude of changes was smaller in the extension phase than in the acute phase, fluvoxamine CR-treated subjects continued to show improvement compared to placebo-treated subjects. Most treatment-emergent signs and symptoms (TESS) were mild to moderate in severity. No unexpected abnormalities were reported on vital signs, electrocardiagrams, or laboratory investigations. These data support the long-term efficacy, safety, and tolerability of fluvoxamine CR in the treatment of GSAD. Given the prevalence, persistence, and disability associated with GSAD, and the relative paucity of long-term treatment studies of SAD, the current dataset provides empirical support for the current clinical consensus that pharmacotherapy of this disorder should be continued beyond the acute phase.", "Preliminary studies have suggested that paroxetine may be effective in social phobia/social anxiety disorder.\n To assess the efficacy and tolerability of paroxetine in the acute (12-week) treatment of social phobia.\n Two-hundred and ninety patients with social phobia were assigned randomly to paroxetine (20-50 mg/day flexible dose) or placebo for 12 weeks of double-blind treatment. Primary efficacy outcomes were the Liebowitz Social Anxiety Scale (LSAS) total score (patient-rated) and the Clinical Global Impression (CGI) scale global improvement item. The secondary efficacy variables included CGI scale severity of illness score and the patient-rated Social Avoidance and Distress Scale.\n Paroxetine produced a significantly greater reduction in LSAS total score (mean change from baseline: -29.4 v. -15.6; P < or = 0.001) and a greater proportion of responders (score < or = 2 on CGI global improvement) (65.7% v. 32.4%; P < 0.001) compared with placebo at the end of the 12-week study period. Both primary efficacy variables were statistically significant compared with placebo from week 4 onwards. Paroxetine was generally well tolerated.\n Paroxetine is an effective, well-tolerated treatment for patients with social phobia.", "The objective of this study was to compare the efficacy and tolerability of paroxetine to matched placebo in adults with co-occurring social anxiety disorder and alcohol use disorder. Outcome measures included standardized indices of social anxiety and alcohol use. Fifteen individuals meeting DSM-IV criteria for both social anxiety disorder and alcohol use disorder were randomized to treatment. Paroxetine (n = 6) or placebo (n = 9) was given in a double-blind format for 8 weeks using a flexible dosing schedule. Dosing began at 20 mg/d and increased to a target dose of 60 mg/d. There was a significant effect of treatment group on social anxiety symptoms, where patients treated with paroxetine improved more than those treated with placebo on both the Clinical Global Index (CGI) and the Liebowitz Social Anxiety Scale (Ps < or = 0.05). On alcohol use, there was not a significant effect of treatment on quantity/frequency measures of drinking, but there was for the CGI ratings (50% paroxetine patients versus 11% placebo patients were improvers on drinking, P < or = 0.05). This pilot study suggests that paroxetine is an effective treatment for social anxiety disorder in individuals with comorbid alcohol problems, and positive treatment effects can be seen in as little as 8 weeks. Further study is warranted to investigate its utility in helping affected individuals reduce alcohol use.\n Copyright 2001 Wiley-Liss, Inc.", "The efficacy of selective serotonin reuptake inhibitors in the acute treatment of social anxiety disorder (social phobia) is well established.\n To evaluate whether the efficacy of paroxetine hydrochloride in this disorder is maintained in the long term.\n This was a placebo-controlled multicenter study comprising a single-blind acute treatment phase (12 weeks) and a randomized, double-blind maintenance treatment phase (24 weeks) for patients who had responded to paroxetine during the acute phase. Four hundred thirty-seven adult patients with social anxiety disorder (according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria, code 300.23) entered the acute phase, and 323 continued into the maintenance phase (162 paroxetine and 161 placebo). The principal outcome measure was the proportion of patients relapsing during the maintenance phase.\n Two hundred fifty-seven patients completed the study (136 paroxetine-treated and 121 placebo-treated patients). Significantly fewer patients relapsed in the paroxetine group than in the placebo group (14% vs 39%; odds ratio, 0.24; 95% confidence interval, 0.14-0.43; P<.001). At the end of the study, a significantly greater proportion of patients in the paroxetine group showed improvement as shown on the Clinical Global Impression global improvement rating compared with the placebo group (78% vs 51%; odds ratio, 3.66; 95% confidence interval, 2.22-6.04; P<.001). Compared with placebo, paroxetine treatment significantly (P<.001) improved the symptoms of social anxiety as shown on the Liebowitz Social Anxiety Scale, Social Phobia Inventory, Sheehan Disability Scale, Symptom Checklist-90 score, and EuroQol visual analogue scale, indicating decreased disability and increased well-being. Paroxetine was well tolerated.\n Paroxetine is an effective long-term treatment for social anxiety disorder.", "Social phobia (social anxiety disorder) is a highly prevalent and chronic disorder that is associated with significant comorbidity and disability. Despite recent advances in the pharmacotherapy of the disorder, there is a paucity of randomized controlled trials on patients with comorbid disorders and on maintenance treatment. A randomized placebo-controlled, double-blind multi-site trial of moclobemide, a reversible inhibitor of monoamine oxidase A, was undertaken with 390 subjects. After an initial 12 weeks, there was the option of continuing for an additional 6 months of treatment. The primary efficacy parameter chosen was responder status as defined by the Clinical Global Impression scale change item. From week 4 onwards, there was a significantly higher response rate on moclobemide than on placebo. Superiority of medication over placebo was similar in patients with comorbid anxiety disorders (33% of subjects) and without, as well as in patients with different subtypes of social anxiety disorder; indeed, treatment with moclobemide rather than placebo was the strongest predictor of response. Adverse events were similar across treatment groups, and were typically mild and transient. In the extension phase, response rates remained higher in the moclobemide group, and ratings of tolerability were equally high in both groups. Thus, in a large sample of social anxiety disorder patients with and without comorbid anxiety disorders, moclobemide was both effective and well-tolerated in the short as well as long-term. These data confirm and extend previous findings on the value of moclobemide in the treatment of social anxiety disorder, and strengthen the range of therapeutic options for managing this important disorder.", "This article presents results of the acute treatment phase of a 2-site study comparing cognitive behavioral group therapy (CBGT) and treatment with the monoamine oxidase inhibitor phenelzine sulfate for social phobia.\n One hundred thirty-three patients from 2 sites received 12 weeks of CBGT, phenelzine therapy, pill placebo administration, or educational-supportive group therapy (an attention-placebo treatment of equal credibility to CBGT). The \"allegiance effect,\" ie, the tendency for treatments to seem most efficacious in settings of similar theoretical orientation and less efficacious in theoretically divergent settings, was also examined by comparing responses to the treatment conditions at both sites: 1 known for pharmacological treatment of anxiety disorders and the other for cognitive behavioral treatment. RESULTs: After 12 weeks, phenelzine therapy and CBGT led to superior response rates and greater change on dimensional measures than did either control condition. However, response to phenelzine therapy was more evident after 6 weeks, and phenelzine therapy was also superior to CBGT after 12 weeks on some measures. There were few differences between sites, suggesting that these treatments can be efficacious at facilities with differing theoretical allegiances.\n After 12 weeks, both phenelzine therapy and CBGT were associated with marked positive response. Although phenelzine therapy was superior to CBGT on some measures, both were more efficacious than the control conditions. More extended cognitive behavioral treatment and the combination of modalities may enhance treatment effect.", "We conducted an 11-week forced-escalation open-label study of paroxetine in the treatment of 36 patients with generalized social phobia. At the mean dosage of 47.9 +/- 6.2 mg/day, 23 of 30 completers (77%) were deemed responders on the basis of a clinician rating of either \"very much improved\" or \"much improved\" on the Clinical Global Impressions scale. Duke Social Phobia Scale ratings declined from 35.5 +/- 13.1 at baseline to 19.7 +/- 17.4 at week 11 (p < 0.0005), and Liebowitz Social Anxiety Scale ratings declined from 75.1 +/- 25.4 at baseline to 37.2 +/- 32.5 at week 11 (p < 0.0005). Sixteen responders were randomized to an additional 12 weeks of either paroxetine (with no dosage change) or placebo (after a taper period) on a double-blind basis. To the best of our knowledge, this is the first controlled medication-discontinuation study in social phobia. One of eight patients randomized to continue paroxetine relapsed versus five of eight patients randomized to placebo. These findings call for a double-blind, placebo-controlled treatment study of paroxetine in generalized social phobia. They also suggest that relapse rates are high if medication is discontinued early and that further study is needed to determine (1) the optimal duration of maintenance pharmacotherapy for social phobia and (2) if specific psychotherapeutic interventions before medication discontinuation may prevent relapse.", "Although the monoamine oxidase inhibitor phenelzine has proven efficacious in social phobia, the risk of hypertensive crises has reduced its acceptability. The reversible monoamine oxidase inhibitor moclobemide has less potential for such reactions, but its efficacy in this disorder remains unproven. A double-blind, placebo-controlled study was undertaken to assess the efficacy and safety of fixed doses of moclobemide. After a 1-week placebo run-in, subjects with social phobia were randomly assigned to placebo or one of five doses (75 mg, 150 mg, 300 mg, 600 mg, or 900 mg daily) of moclobemide for 12 weeks. Although a trend toward greater efficacy of higher doses of moclobemide was observed at 8 weeks, no differences in response to various doses of the drug and placebo were observed at 12 weeks. At 12 weeks, 35% of subjects on 900 mg of moclobemide and 33% of those on placebo were at least much improved. Moclobemide was well tolerated, insomnia being the only dose-related adverse event observed with the drug. In this dose-response trial, moclobemide did not demonstrate efficacy at 12 weeks. Some other controlled studies have found moclobemide and brofaromine, another reversible monoamine oxidase inhibitor, efficacious in social phobia. Possible reasons for inconsistent findings are discussed.", "The purpose of this study was to determine the efficacy of fluvoxamine for the treatment of social phobia (social anxiety disorder).\n In a 12-week multicenter, double-blind, randomized, placebo-controlled trial, 92 patients with social phobia were treated with the selective serotonin reuptake inhibitor fluvoxamine; 91.3% of the patients had the generalized subtype of the disorder. The primary criterion for response was a rating of \"much improved\" or \"very much improved\" on the Clinical Global Impression of Improvement scale. Secondary response criteria were changes on three specialized rating scales for social phobia symptoms: the Brief Social Phobia Scale, the Social Phobia Inventory, and the Liebowitz Social Anxiety Scale. Psychosocial impairment was assessed in three domains (disruption of work, social life, and home/family life) by using the Sheehan Disability Scale.\n The mean daily dose of fluvoxamine was 202 mg (SD = 86). At study end or with the last observation carried forward, within the evaluable subjects (N = 86) there was a significantly higher proportion of responders in the fluvoxamine group (42.9%, N = 18) than in the placebo group (22.7%, N = 10). Similarly, fluvoxamine was superior to placebo on all social phobia rating scales at week 8 and beyond. Fluvoxamine also resulted in significantly greater decreases in measures of psychosocial disability than did placebo. Overall, fluvoxamine was well tolerated and safe.\n These findings indicate that fluvoxamine is efficacious in the pharmacologic management of serious forms of social phobia.", "The generalized type of social phobia (social anxiety disorder) is a severe and often disabling form of social anxiety that affects approximately 5% of the general population. Earlier research has shown monoamine oxidase inhibitors or benzodiazepines to be effective in treating this condition, but neither has achieved widespread use.\n To compare the efficacy of paroxetine, a selective serotonin reuptake inhibitor, with placebo in adults with generalized social phobia.\n Twelve-week, multicenter, randomized, double-blind trial.\n Thirteen centers across the United States and 1 in Canada.\n Between April 13, 1995, and February 28, 1996, 187 persons meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for generalized social phobia were randomized (and 183 returned for at least 1 efficacy assessment) to treatment.\n After a 1-week, single-blind, placebo, run-in period, patients received a double-blind, 11-week course of either paroxetine or matching-image placebo. The initial daily dosage of paroxetine (or placebo) was 20 mg with increases of 10 mg/d weekly (flexible dosing to a maximum of 50 mg/d) permitted after the second week of treatment.\n Number of responders based on the Clinical Global Impression Global Improvement Item (\"much improved\" or \"very much improved\"); mean change from baseline on the Liebowitz Social Anxiety Scale total score.\n Fifty (55.0%) of 91 persons taking paroxetine and 22 (23.9%) of 92 persons taking placebo were much improved or very much improved at the end of treatment (odds ratio [OR], 3.88; 95% confidence interval [CI], 2.81-5.36). Mean Liebowitz Social Anxiety Scale total scores were reduced by 39.1% (the mean baseline score of 78.0 declined by a mean of 30.5 points at follow-up) in the paroxetine group compared with 17.4% (the mean baseline score of 83.5 declined 14.5 points at follow-up) in the placebo group, a difference of 21.7% (95% CI, 8.7%-34.7%) favoring paroxetine.\n Paroxetine is an effective treatment for patients with generalized social phobia. Short-term (ie, 11-week) treatment results in substantial and clinically meaningful reductions in symptoms and disability. Future research should test whether these may be further reduced by extended treatment or supplementation with specific educational-cognitive-behavioral techniques.", "A randomized, double-blind, placebo-controlled, parallel-group study was conducted to evaluate the efficacy and safety of gabapentin in relieving the symptoms of social phobia. Sixty-nine patients were randomly assigned to receive double-blind treatment with either gabapentin (dosed flexibly between 900 and 3,600 mg daily in three divided doses) or placebo for 14 weeks. A significant reduction (p < 0.05) in the symptoms of social phobia was observed among patients on gabapentin compared with those on placebo as evaluated by clinician- and patient-rated scales. Results were similar for the intent-to-treat and week-2 completer populations. Adverse events were consistent with the known side effect profile of gabapentin. Dizziness (p = 0.05), dry mouth (p = 0.05), somnolence, nausea, flatulence, and decreased libido occurred at a higher frequency among patients receiving gabapentin than among those receiving placebo. No serious adverse events or deaths were reported. On the basis of these limited data, it seems that gabapentin offers a favorable risk-benefit ratio for the treatment of patients with social phobia. Further studies are required to confirm this effect and to determine whether a dose-response relationship exists.", "Seventy-seven patients with a primary diagnosis of social phobia (DSM-III-R) were randomized to treatment with the reversible and selective monoamine oxidase type A inhibitor brofaromine (n = 37) or placebo (n = 40) for 12 weeks in a double-blind trial. A fixed dose of 150 mg/day or a matching placebo was given after a 2-week dose titration phase. Patients with additional diagnoses of simple phobia, generalized anxiety disorder, dysthymia or major depressive disorder currently in remission were accepted. Patients with other Axis I mental disorders were excluded. In the brofaromine group, 78% of the patients scored much or very much improved on the Clinical Global Impression scale compared with 23% in the placebo group. The anxiety and avoidance scores on the Liebowitz Social Anxiety Scale (LSAS) were significantly reduced in favor of brofaromine. The clinical effects were not significantly correlated with the plasma concentration of brofaromine. After 12 weeks the brofaromine group scored significantly lower than the placebo group on a core depression part of the Montgomery-Asberg Depression Rating Scale. After 12 weeks of treatment the brofaromine group had significantly higher total scores on the LSAS than an age- and gender-matched group of healthy controls. The brofaromine group improved further during 9-month follow-up treatment period, whereas 60% of the placebo responders who continued long-term treatment relapsed. The most common side effects in the brofaromine group were sleep disturbances, dry mouth and nausea.", "The authors evaluated the efficacy, safety, and tolerability of sertraline, a selective serotonin reuptake inhibitor, in the treatment of generalized social phobia.\n Adult outpatients with generalized social phobia (N=204) from 10 Canadian centers were randomly assigned to receive sertraline or placebo in a 2:1 ratio for a 20-week double-blind study following a 1-week, single-blind, placebo run-in. The initial dose of sertraline was 50 mg/day with increases of 50 mg/day every 3 weeks permitted after the fourth week of treatment (dosing was flexible up to a maximum of 200 mg/day). Primary efficacy assessments were the percentage of patients rated much or very much improved on the Clinical Global Impression (CGI) improvement item and the mean changes from baseline to study endpoint in total score on the social phobia subscale of the Marks Fear Questionnaire and total score on the Brief Social Phobia Scale.\n In intent-to-treat endpoint analyses of 203 of the patients, significantly more of the 134 patients given sertraline (N=71 [53%]) than of the 69 patients receiving placebo (N=20 [29%]) were considered responders according to their CGI improvement scores at the end of treatment. The mean reductions in the social phobia subscale of the Marks Fear Questionnaire and in the total score on the Brief Social Phobia Scale were 32.6% and 34.3% in the sertraline group and 10.8% and 18.6% in the placebo group, respectively. Analysis of covariance showed superiority of sertraline over placebo on all primary and secondary efficacy measures. Sertraline was well tolerated: 103 (76%) of the 135 sertraline-treated patients and 54 (78%) of the 69 placebo-treated patients completed the study.\n Sertraline is an effective treatment for patients with generalized social phobia.", "The objective of the study was to examine the efficacy of fluoxetine in social phobia. Sixty subjects were randomly assigned to 14 weeks of double-blind therapy with either fluoxetine or placebo. Dose was fixed at 20 mg for fluoxetine during the first 8 weeks of double-blind treatment; during the final 6 weeks, the dose could be increased every two weeks by 20 mg to a maximum of 60 mg/day. An intentto-treat analysis was used. A significant change from baseline to endpoint was found for both fluoxetine and placebo on the Liebowitz Social Anxiety Scale. However, no significant difference was found between fluoxetine and placebo. The change for fluoxetine was somewhat lower than that found with other selective serotonin reuptake inhibitors, whereas the placebo response was greater. Fluoxetine failed to separate from placebo in this trial. It is unknown whether a larger dose for longer duration would have yielded separation from placebo. A higher than usual placebo response rate was found.", "Patients with social phobia who responded well to 6 months of open-label treatment with clonazepam were assigned to receive either continuation treatment (CT) with clonazepam for another 5 months, or to undergo discontinuation treatment (DT) using a clonazepam taper at the rate of 0.25 mg every 2 weeks, with double-blind placebo substitution. Clinical efficacy was compared between the CT and DT groups using three different social phobia scales. Benzodiazepine withdrawal symptoms were also measured. Relapse rates were 0 and 21.1% in the CT and DT groups, respectively. Subjects in the CT group generally showed a more favorable clinical response at midpoint and/or endpoint, although even in the DT group clinical response remained good. With respect to withdrawal symptoms, the rates were low in both groups (12.5% for CT and 27.7% for DT) with no real evidence suggesting significant withdrawal difficulties. At the end of 11 months of treatment with clonazepam, however, a more rapid withdrawal rate was associated with greater distress. This study offers preliminary evidence to suggest that continuation therapy with clonazepam in the treatment of social phobia is safe and effective, producing a somewhat greater clinical benefit than a slow-taper discontinuation regime. However, even in the DT group, withdrawal symptoms were not found to be a major problem. The study can be taken as supportive of benefit for longterm clonazepam treatment in social phobia, as well as being compatible with a reasonably good outcome after short-term treatment and slow taper.", "Performance anxiety in musicians may be severe enough to require intervention but has been the subject of relatively little clinical research. The authors' objectives were to describe the results of a comprehensive clinical and laboratory assessment and to perform a double-blind, placebo-controlled study comparing buspirone, cognitive-behavior therapy, and the combination of these treatments for performance anxiety.\n Ninety-four subjects were recruited by mass media announcements and were seen in a university-based outpatient psychiatric clinic. Assessments were 1) questionnaires for all 94 subjects, 2) diagnostic interview of 50 subjects, and 3) laboratory performance of 34 subjects. Treatment conditions were 1) 6 weeks of buspirone, 2) 6 weeks of placebo, 3) a five-session, group cognitive-behavior therapy program with buspirone, or 4) the cognitive-behavior therapy program with placebo. Treatment outcome measures included subjective anxiety ratings and heart rate measures during a laboratory performance, a questionnaire measure of performance confidence, and a blind rating of musical performance quality.\n All subjects fulfilled criteria for DSM-III-R social phobia. Of the 15 full-time professional musicians, ten had tried propranolol and three had stopped performing. Most of the subjects had substantial anxiety and heart rate increases during laboratory speech and musical performances. Cognitive-behavior therapy resulted in statistically significant reductions in subjective anxiety, improved quality of musical performance, and improved performance confidence. Buspirone was not an effective treatment.\n Cognitive-behavior therapy is a viable treatment approach for performance anxiety in musicians.", "The primary objectives of this large multicenter study (n = 578) were to determine the efficacy and safety of moclobemide, 300 or 600 mg per day, for the treatment of social phobia. A double-blind fixed-dose parallel group study was conducted to compare the two different doses of moclobemide to placebo. After a 1-week placebo run-in period, patients were randomly assigned to one of the three treatment groups to receive the test compound for a 12-week period. Assessments were performed at screen, on baseline and on weeks 1, 2, 3, 4, 6, 8, 10, and 12. There were consistent, reliable and clinically meaningful drug effects and indications of a dose-response relationship. Statistical analysis of the results at both weeks 8 and 12 showed that 600 mg of moclobemide was effective and statistically significantly superior to placebo. The 300 mg dose also showed better efficacy than placebo on all measures of efficacy, and about half of them were statistically significantly different from placebo. Moclobemide was well tolerated. Adverse events, except for insomnia, were neither dose-related nor were there significant drug-placebo differences. The results indicate that 600 mg of moclobemide per day given b.i.d. is effective in social phobia, reducing the symptoms and the impairment associated with the disorder. The compound is well tolerated and safe.", "Moclobemide, a reversible inhibitor of monoamine oxidase A, previously has been reported to have efficacy in the treatment of social phobia.\n Seventy-seven non-responders to one week of single-blind placebo were randomly assigned to moclobemide or placebo for eight weeks of double-blind treatment. Outcome was assessed by independent evaluator, treating psychiatrist and self-ratings. After eight weeks, patients who were at least minimally improved continued treatment for a further eight weeks.\n Intention-to-treat sample response rates at week 8 were 7/40 (17.5%) for the moclobemide group and 5/37 (13.5%) for placebo (NS). Moclobemide was significantly superior to placebo on 2 of 10 primary outcome measures. Moclobemide was well tolerated.\n Moclobemide may have efficacy in the treatment of social phobia, but absence of significant differences on most primary outcome measures and small effect sizes for all outcome measures suggest that the magnitude of its clinical effect is small.", "The authors examined the efficacy of sertraline in the treatment of social phobia.\n In a double-blind crossover study, 12 outpatients were randomly assigned to 10 weeks of sertraline (50-200 mg/day, flexible dosing) and 10 weeks of placebo.\n A statistically significant improvement in scores on the Liebowitz Social Anxiety Scale was found with sertraline but not with placebo. There was no significant difference between scores obtained with computer- and clinician-administered versions of the Liebowitz Social Anxiety Scale, and the majority of patients preferred to be interviewed by the computer.\n Sertraline seems a safe and effective treatment for social phobia, and computer administration may be a preferable mode of assessment with socially phobic patients.", "Clonazepam and placebo were administered in a double-blind pilot study to 75 outpatients with social phobia. The mean maximum dose of clonazepam was 2.4 mg/day at endpoint (range, 0.5 to 3 mg). Treatment was continued for up to 10 weeks. The results of an intent-to-treat analysis indicated superior effects of clonazepam on most measures. Response rates for clonazepam and placebo were 78.3 and 20.0%. Drug effects were apparent on performance and generalized social anxiety, on fear and phobic avoidance, on interpersonal sensitivity, on fears of negative evaluation, and on disability measures. Significant differences were evident by week 1, 2, or 6, depending upon the rating scale used. Clonazepam was well tolerated in general, although unsteadiness and dizziness were more severe and persistent than was the case for placebo subjects.", "Generalized social anxiety disorder is an early onset, highly chronic, frequently disabling disorder with a lifetime prevalence of approximately 13%. The goal of the current study was to evaluate the efficacy and tolerability of sertraline for the treatment of severe generalized social anxiety disorder in adults.\n After a 1-week single-blind placebo lead-in period, patients with DSM-IV generalized social phobia were randomly assigned to 12 weeks of double-blind treatment with flexible doses of sertraline (50-200 mg/day) or placebo. Primary efficacy outcomes were the mean change in the Liebowitz Social Anxiety Scale (LSAS) total score and the responder rate for the Clinical Global Impressions-Improvement scale (CGI-I), defined as a CGI-I score </= 2. Data were collected in 2000 and 2001.\n 211 patients were randomly assigned to sertraline (intent-to-treat [ITT] sample, 205), and 204 patients, to placebo (ITT sample, 196). At week 12, sertraline produced a significantly greater reduction in LSAS total score compared with placebo (mean last-observation-carried-forward [LOCF] change from baseline: -31.0 vs. -21.7; p =.001) and a greater proportion of responders (CGI-I score </= 2: 55.6% vs. 29% among week 12 completers and 46.8% vs. 25.5% in the ITT-LOCF sample; p <.001 for both comparisons). Sertraline was well tolerated, with 7.6% of patients discontinuing due to adverse events versus 2.9% of placebo-treated patients.\n The results of the current study confirm the efficacy of sertraline in the treatment of severe social anxiety disorder.", "Seventy-four patients who met DSM-III criteria for social phobia completed 8 weeks of double-blind, randomly assigned treatment with the monoamine oxidase inhibitor phenelzine sulfate, the cardioselective beta-adrenergic blocker atenolol, or placebo. The overall response rates were 64% for phenelzine, 30% for atenolol, and 23% for placebo. Phenelzine was widely superior to both atenolol and placebo on independent rater analyses and, to a lesser extent, on self-report, with no significant differences between atenolol and placebo. At the end of 16 weeks, phenelzine was still significantly superior to placebo, while atenolol showed an intermediate response that did not differ significantly from either of the other treatments. Patients with generalized social phobia constituted 76% of the sample, and they were preferentially responsive to phenelzine. The small size of the discrete social phobic sample precluded separate outcome analyses for this subtype. Overall, the findings support the responsivity of social phobia to monoamine oxidase inhibitors.", "The aim of this study was to evaluate the utility of paroxetine treatment in social anxiety disorder.\n Previously undiagnosed and untreated subjects with social anxiety disorder (generalized social phobia) were selected from among responders to a newspaper advertisement. They were randomized to double-blind treatment with paroxetine 20-50 mg daily or placebo for 3 months. Outcome measures were self-rated social anxiety and avoidance behaviour, and clinician-rated global assessment of improvement.\n Significant differences in efficacy between treatments (intent-to-treat analysis: 44 subjects on paroxetine and 48 subjects on placebo) were noted after 4-6 weeks, increasing through the treatment period in the paroxetine group. Nine subjects on paroxetine and 3 subjects on placebo discontinued the treatment due to adverse events. Sexual side-effects were noted by 18 subjects on paroxetine and 4 subjects on placebo.\n Paroxetine was effective in alleviating symptoms and avoidance behaviour in social anxiety disorder.", "The aim of this study was to evaluate the efficacy, tolerability, and effects on quality of life of sertraline, a selective serotonin reuptake inhibitor, in the prevention of relapse of generalized social phobia. Fifty adult outpatients with generalized social phobia who were rated much or very much improved on the Clinical Global Impression Scale of Improvement (CGI-I) after 20 weeks of sertraline treatment (50-200 mg/day) were randomly assigned in a one-to-one ratio to either continue double-blind treatment with sertraline or immediately switch to placebo for another 24 weeks. The initial 20-week study was placebo-controlled, and 15 responders to placebo also continued to receive double-blind placebo treatment in the continuation study. Eighty-eight percent of patients in the sertraline-continuation group and only 40% of patients in the placebo-switch and placebo-responder groups completed the study. In intent-to-treat endpoint analyses, 1 (4%) of 25 patients in the sertraline-continuation group and 9 (36%) of 25 patients in the placebo-switch group had relapsed at study endpoint (chi2 = 8.0, Fisher exact test, p = 0.01). The relative risk (hazards ratio) for relapse associated with placebo-switch relative to sertraline-continuation treatment was 10.2 (95% confidence interval, 1.3-80.7). Mean CGI-Severity, Marks Fear Questionnaire (MFQ) Social Phobia subscale, and Duke Brief Social Phobia Scale (BSPS) total scores were reduced by 0.07, 0.34, and 1.86 in the Sertraline-Continuation group and increased by 0.88, 4.09, and 5.99 in the Placebo-Switch group (all F > 5.3, p < 0.03), respectively. CGI-Severity, MFQ Social Phobia subscale, and BSPS scores also increased in the Placebo-Responder group. Discontinuations because of lack of efficacy were 4% in the sertraline-continuation group, 28% in the placebo-switch group (chi2 = 5.36, Fisher exact test, p = 0.049), relative to sertraline, and 27% in the placebo-responder group. Sertraline was effective in preventing relapse of generalized social phobia. Future research should assess whether improvements may be maintained or further increased by longer periods of treatment or through the addition of cognitive-behavioral techniques.", "Seventy-two social phobics were randomly assigned to behavioral (flooding) or drug treatment with atenolol or placebo. Treatment was administered over a 3-month period of time, and duration of treatment effects was determined at a 6-month follow-up assessment. Multiple measures of outcome were used, including self-report, clinician ratings (including assessment by independent evaluators), behavioral assessment, and performance on composite indexes. The results indicated that flooding consistently was superior to placebo, whereas atenolol was not. Flooding also was superior to atenolol on behavioral measures and composite indexes. Those subjects who improved during treatment maintained gains at the 6-month follow-up regardless of whether they received flooding or atenolol. The variability of outcome on different measures in social phobia research is discussed, and the need for broad-based treatment strategies to address the pervasive deficits associated with social phobia is noted.", "No controlled trial of treatment of generalised social phobia has been conducted in general practice.\n To examine the efficacy of sertraline or exposure therapy, administered alone or in combination in this setting.\n Study was of a randomised, double-blind design. Patients (n = 387) received sertraline 50-150 mg or placebo for 24 weeks. Patients were additionally randomised to exposure therapy or general medical care.\n Sertraline-treated patients were significantly more improved than non-sertraline-treated patients (chi(2)=12.53, P<0.001; odds ratio=0.534; 95% Cl 0.347-0.835). No significant difference was observed between exposure- and non-exposure-treated patients (chi(2)=2.18, P=0.140; odds ratio=0.732; 95% Cl 0.475-1.134). In the pairwise comparisons, combined sertraline and exposure (chi(2)=12.32; P<0.001) and sertraline (chi(2)=10.13; P=0.002) were significantly superior to placebo.\n Sertraline is an effective treatment for generalised social phobia. Combined treatment with sertraline and exposure therapy, conducted by the general practitioner, may enhance the treatment efficacy in primary care.", "The effect of 5 mg pindolol on stress-induced disturbances of performance were assessed in 30 professional musicians. An overall inverse relationship was found between anxiety and musical performance. Reduction in anxiety by administration of pindolol was associated with a subjective improvement in performance. A stress-related tachycardia and increase in systolic blood pressure were attenuated. Pindolol had no effect on peak flow measurements.", "Based on evidence suggesting anxiolytic properties of the atypical antipsychotic olanzapine, this study was conducted to evaluate whether olanzapine may be efficacious in treating social anxiety disorder (SAD). This study was an 8-week, double-blind, placebo-controlled evaluation of olanzapine as monotherapy in which 12 patients with the DSM-IV diagnosis of SAD were randomized to either olanzapine (n = 7) or placebo (n = 5). An initial dose of 5 mg/day was titrated to a maximum of 20 mg/day. Baseline to endpoint scores from the Brief Social Phobia Scale (BSPS), Social Phobia Inventory (SPIN), Liebowitz Social Anxiety Scale and Sheehan Disability Scale, as well as Clinical Global Impression-Improvement ratings, were compared for olanzapine versus placebo. Seven subjects completed all 8 weeks of the study, four in the olanzapine group and three in the placebo group. In the intent-to-treat analysis, olanzapine yielded greater improvement than placebo on the primary measures: BSPS (p = 0.02) and SPIN (p = 0.01). Both treatments were well tolerated, although the olanzapine group had more drowsiness and dry mouth. Olanzapine and placebo were both associated with negligible weight gain. Olanzapine was superior to placebo on the primary outcome measures in this preliminary study of SAD. Additional studies of olanzapine as a treatment for SAD are warranted.", "The safety and efficacy of brofaromine, a reversible and selective monoamine oxidase inhibitor, were examined in a multicenter trial of 102 outpatients with social phobia. After a 1-week placebo washout, subjects were randomly assigned to 10 weeks of treatment with either brofaromine (N = 52) or placebo (N = 50). Brofaromine dosage began at 50 mg/day and was titrated to a maximum of 150 mg/day, depending on treatment response. Brofaromine produced a significantly greater change from baseline in Liebowitz Social Anxiety Scale (LSAS) scores compared with placebo, F(1) = 6.01, p < 0.016. Mean LSAS scores decreased from 81.8 at baseline to 62.6 at endpoint for brofaromine, t = 5.41,p < 0.001, and from 79.8 to 70.7 for placebo, t = 3.66, p < 0.001. Eleven of the 14 brofaromine early terminators discontinued because of adverse experiences, as did 4 of the 17 placebo early terminators. Side effects more common with brofaromine than placebo included insomnia, dizziness, dry mouth, anorexia, tinnitus, and tremor. No clinically significant variations in vital signs or laboratory values were found. The findings are consistent with the clinical efficacy for the treatment of social phobia." ]

[ "8596594", "16801465", "12692572", "10437863" ]

[ "Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group.", "Renal function and effectiveness of angiotensin-converting enzyme inhibitor therapy in patients with chronic stable coronary disease in the Prevention of Events with ACE inhibition (PEACE) trial.", "Distinct time courses of renal protective action of angiotensin receptor antagonists and ACE inhibitors in chronic renal disease.", "Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria." ]

[ "Drugs that inhibit angiotensin-converting enzyme slow the progression of renal insufficiency in patients with diabetic neuropathy. Whether these drugs have a similar action in patients with other renal diseases is not known. We conducted a study to determine the effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of renal insufficiency in patients with various underlying renal diseases.\n In a three-year trial involving 583 patients with renal insufficiency caused by various disorders, 300 patients received benazepril and 283 received placebo. The underlying diseases included glomerulopathies (in 192 patients), interstitial nephritis (in 105), nephrosclerosis (in 97), polycystic kidney disease (in 64), diabetic nephropathy (in 21), and miscellaneous or unknown disorders (in 104). The severity of renal insufficiency was classified according to the base-line creatinine clearance: 227 patients had mild insufficiency (creatinine clearance, 46 TO 60 ml per minute), and 356 had moderate insufficiency (creatinine clearance, 30 to 45 ml per minute). The primary end point was a doubling of the base-line serum creatine concentration or the need for dialysis.\n At three years. 31 patients in the benazepril group and 57 in the placebo group had reached the primary end point (P<0.001). In the benazepril group, the reduction in the risk of reaching the end point was 53 percent overall (95 percent confidence interval, 27 to 70 percent), 71 percent (95 percent confidence interval, 21 to 90 percent) among the patients with mild renal insufficiency, and 46 percent (95 percent confidence interval, 12 to 67 percent) among those with moderate renal insufficiency. The reduction in risk was greatest among the male patients; those with glomerular diseases, diabetic nephropathy, or miscellaneous or unknown causes of renal disease; and those with base-line urinary protein excretion above 1 g per 24 hours. Benazepril was not effective in patients with polycystic disease. Diastolic pressure decreased by 3.5 to 5.0 mm Hg in the benazepril group and increased by 0.2 to 1.5 mm Hg in the placebo group.\n Benazepril provides protection against the progression of renal insufficiency in patients with various renal diseases.", "Patients with reduced renal function are at increased risk for adverse cardiovascular outcomes. In the post-myocardial infarction setting, angiotensin-converting enzyme (ACE) inhibitors have been shown to be as effective in patients with impaired renal function as in those with preserved renal function.\n We assessed the relation between renal function and outcomes, the influence of ACE inhibition on this relation, and whether renal function modifies the effectiveness of ACE inhibition in patients with stable coronary artery disease and preserved systolic function enrolled in the Prevention of Events with ACE inhibition trial (PEACE). Patients (n=8290) were randomly assigned to receive trandolapril (target, 4 mg/d) or placebo. Clinical creatinine measures were available for 8280 patients before randomization. The estimated glomerular filtration rate (eGFR) was calculated with the 4-point Modification of Diet in Renal Disease equation. Renal function was related to outcomes, and the influence of ACE-inhibitor therapy was assessed with formal interaction modeling. The mean eGFR in PEACE was 77.6+/-19.4, and 1355 (16.3%) patients had reduced renal function (eGFR <60 mg.mL(-1).1.73 m(-2)). We observed a significant interaction between eGFR and treatment group with respect to cardiovascular and all-cause mortality (P=0.02). Trandolapril was associated with a reduction in total mortality in patients with reduced renal function (adjusted HR, 0.73; 95% CI, 0.54 to 1.00) but not in patients with preserved renal function (adjusted HR, 0.94; 95% CI, 0.78 to 1.13).\n Although trandolapril did not improve survival in the overall PEACE cohort, in which mean eGFR was relatively high, trandolapril reduced mortality in patients with reduced eGFR. These data suggest that reduced renal function may define a subset of patients most likely to benefit from ACE-inhibitor therapy for cardiovascular protection.", "Although the angiotensin receptor antagonist (ARB) shares the angiotensin-II-blocking activity with the angiotensin-converting enzyme inhibitor (ACE-I), pharmacological mechanisms of action of these agents differ. We evaluated the temporal profiles of action of ACE-I and ARB on urinary protein excretion and nitrate/nitrate (NO(x)) excretion in hypertensive (140 and/or 90 mmHg) patients with chronic renal disease (serum creatinine < 265 (range, 44-265) micromol/l or creatinine clearance > 30 (range, 30-121) ml/min). Patients with mild (<1 g/day; range, 0.4-1.0) and moderate proteinuria (>1 g/day; range, 1.1-6.9) were randomly assigned to ACE-I- and ARB-treated groups, and were treated with ACE-I (trandolapril or perindopril) or ARB(losartan or candesartan) for 48 weeks. In all groups, treatment with ACE-I or ARB decreased blood pressure to the same level, but had no effect on creatinine clearance. In patients with mild proteinuria, neither ACE-I nor ARB altered urinary protein excretion. In patients with moderate proteinuria, ACE-I caused 44 +/- 6% reduction in proteinuria (from 2.7 +/- 0.5 to 1.5 +/- 0.4 g/day, n = 14) at 12 weeks, and this beneficial effect persisted throughout the protocol (48 weeks, 1.2 +/- 0.2 g/day). In contrast, ARB did not produce a significant decrease in proteinuria at 12 weeks (23 +/- 8%, n = 13), but a 41 +/- 6% reduction in proteinuria was observed at 48 weeks. Similarly, although early (12 weeks) increases in urinary NO(x) excretion were observed with ACE-I (from 257 +/- 70 to 1111 +/- 160 micromol/day) and ARB (from 280 +/- 82 to 723 +/- 86 micromol/day), the ARB-induced increase in NO(x) excretion was smaller than that by ACE-I (P < 0.05). In conclusion, although both ACE-I and ARB reduce blood pressure similarly, the effect of these agents on proteinuria differs in chronic renal disease with moderate proteinuria. Relatively early onset of the proteinuria-reducing effect was observed with ACE-I, which paralleled the increase in urinary NO(x) excretion. Conversely, ARB decreased proteinuria and increased urinary NO(x) excretion gradually. These time course-dependent changes in proteinuria and urinary NO(x) may reflect the pharmacological property of ACE-I and ARB, with regard to the action on bradykinin.", "Stratum 2 of the Ramipril Efficacy in Nephropathy (REIN) study has already shown that in patients with chronic nephropathies and proteinuria of 3 g or more per 24 h, angiotensin-converting enzyme (ACE) inhibition reduced the rate of decline in glomerular filtration and halved the combined risk of doubling of serum creatinine or end-stage renal failure (ESRF) found in controls on placebo plus conventional antihypertensives. In REIN stratum 1, reported here, 24 h proteinuria was 1 g or more but less than 3 g per 24 h.\n In stratum 1 of this double-blind trial 186 patients were randomised to a ramipril or a control (placebo plus conventional antihypertensive therapy) group targeted at achieving a diastolic blood pressure of less than 90 mm Hg. The primary endpoints were change in glomerular filtration rate (GFR) and time to ESRF or overt proteinuria (> or =53 g/24 h). Median follow-up was 31 months.\n The decline in GFR per month was not significantly different (ramipril 0.26 [SE 0.05] mL per min per 1.73m2, control 0.29 [0.06]). Progression to ESRF was significantly less common in the ramipril group (9/99 vs 18/87) for a relative risk (RR) of 2.72 (95% CI 1.22-6.08); so was progression to overt proteinuria (15/99 vs 27/87, RR 2.40 [1.27-4.52]). Patients with a baseline GFR of 45 mL/min/1.73 m2 or less and proteinuria of 1.5 g/24 h or more had more rapid progression and gained the most from ramipril treatment. Proteinuria decreased by 13% in the ramipril group and increased by 15% in the controls. Cardiovascular events were similar. As expected, the rate of decline in GFR and the frequency of ESRF were much lower in stratum 1 than they had been in stratum 2.\n In non-diabetic nephropathies, ACE inhibition confers renoprotection even to patients with non-nephrotic proteinuria." ]

[ "16594854", "15062908", "12915873", "16427245", "10944557", "16999640", "16055276", "17047645" ]

[ "Effects of counseling Ashkenazi Jewish women about breast cancer risk.", "Breast cancer risk counseling improves women's functioning.", "A randomised controlled trial of breast cancer genetics services in South East Scotland: psychological impact.", "Results of a randomized study of telephone versus in-person breast cancer risk counseling.", "Randomized trial of a specialist genetic assessment service for familial breast cancer.", "Healthy women with a family history of breast cancer: impact of a tailored genetic counseling intervention on risk perception, knowledge, and menopausal therapy decision making.", "Development of a risk assessment tool for women with a family history of breast cancer.", "Familial breast cancer: management of 'lower risk' referrals." ]

[ "The goal of this study was to determine whether genetic counseling or psychosocial group counseling provided to Ashkenazi women can reduce breast cancer worry, cancer risk perception, and interest in having genetic testing. Women (N=211) were randomized to receive individual genetic risk counseling, to receive a group psychosocial group counseling, or to serve as a control group. The authors found that both counseling methods reduced cancer worry, lowered perceptions of breast cancer risk, and decreased interest in having genetic testing. Counseling can help women gain a more accurate perception of their risk, expose them to the benefits and limitations of genetic testing, and reduce their worry about cancer.\n Copyright (c) 2006 APA, all rights reserved.", "Helping people cope with health risks is an important area for research and practice. Counseling offers people the opportunity to relieve their distress and improve the ways in which they manage their health issues. This study was a randomized test of two different counseling methods, genetic and psychosocial counseling, compared to a control group. Eligibility requirements included being between 18 and 74 years old, having at least one relative with breast cancer, not having a family history consistent with carrying a BRCA1/2 mutation for breast cancer risk, having no personal history of breast or ovarian cancer, living within 60 miles of the research institute, and willingness to complete the research requirements of the project. Perceived risk decreased by 50% for participants in the two counseling groups relative to comparison participants. Cancer worry decreased in both counseling groups by one scale point (P < 0.05). These results indicate that counseling can relieve women's negative reactions to breast cancer risk.", "This study compared the psychological impact of two models of breast cancer genetics services in South East Scotland. One hundred and seventy general practices were randomised to refer patients to the existing standard regional service or the novel community-based service. Participants completed postal questionnaires at baseline (n=373), 4 weeks (n=276) and 6 months (n=263) to assess perceived risk of breast cancer, subjective and objective understanding of genetics and screening issues, general psychological distress, cancer worry and health behaviours. For participants in both arms of the trial, there were improvements in subjective and objective understanding up to 4 weeks which were generally sustained up to 6 months. However, improvements in subjective understanding for the women at low risk of breast cancer (i.e. not at significantly increased risk) in the standard service arm did not reach statistical significance. Cancer worry was significantly reduced at 6 months for participants in both arms of the trial. The two models of cancer genetics services tested were generally comparable in terms of the participants' psychological outcomes. Therefore, decisions regarding the implementation of the novel community-based service should be based on the resources required and client satisfaction with the service.", "Women of all risk levels have reported high interest in obtaining genetic testing for breast cancer risk. Breast cancer risk counseling may help women to learn about their risk and appropriate options of testing. This study measured the effects of an intervention in-person and by telephone, compared to a control group.\n Participants were 340 women, recruited through a network of primary care physicians. They received a baseline questionnaire in the mail, were randomized to one of the three study arms, and completed a follow-up survey 3 months later.\n Both types of counseling were very well received. The counseling decreased women's cancer worry, risk perceptions, and intentions to pursue genetic testing. There were similar effects for both in-person and telephone counseling.\n Genetic counseling can be used to inform women at all risk levels about their breast cancer risk.\n Breast cancer risk counseling can be done in-person and by telephone--thereby reaching women in remote areas.", "Because of the growing demand for genetic assessment, there is an urgent need for information about what services are appropriate for women with a family history of breast cancer. Our purpose was to compare the psychologic impact and costs of a multidisciplinary genetic and surgical assessment service with those of current service provisions.\n We carried out a prospective randomized trial of surgical consultation with (the trial group) and without (the control group) genetic assessment in 1000 women with a family history of breast cancer. All P: values are from two-sided tests.\n Although statistically significantly greater improvement in knowledge about breast cancer was found in the trial group (P: =.05), differences between groups in other psychologic outcomes were not statistically significant. Women in both groups experienced statistically significant reductions in anxiety and found attending the clinics to be highly satisfying. An initial specialist genetic assessment cost pound 14.27 (U.S. $22.55) more than a consultation with a breast surgeon. Counseling and genetic testing of affected relatives, plus subsequent testing of family members of affected relatives identified as mutation carriers, raised the total extra direct and indirect costs per woman in the trial group to pound 60.98 (U.S. $96.35) over costs for the control subjects.\n There may be little benefit in providing specialist genetics services to all women with a family history of breast cancer. Further investigation of factors that may mediate the impact of genetic assessment is in progress and may reveal subgroups of women who would benefit from specialist genetics services.", "Women with a family history of breast cancer have several menopausal therapy options, including tamoxifen, hormone therapy (HT), alternative medications, or no treatment. This complex decision should be based on each woman's risk to develop breast cancer, menopausal symptoms, preferences, and risks for other conditions. The authors determined the effects of a personalized risk assessment and genetic counseling intervention on knowledge, risk perception, and decision making in a group of healthy women who had a first-degree relative with breast cancer.\n Forty-eight cancer-free menopausal women age > or =40 years who had at least one first-degree relative with breast cancer were randomized to a genetic counseling intervention or control. Intervention participants were given a personalized risk assessment for breast cancer, heart disease, osteoporosis, and uterine cancer based on family history and personal health data. Knowledge, risk perception, and medication usage were measured at baseline, 1 month, and 6 months.\n Knowledge was higher in the intervention group at both follow-up time points postintervention. Perceived risk for developing breast cancer was significantly lower and more accurate in the intervention group at 1 and 6 months postintervention than at baseline, as was perceived risk of developing heart disease. Although the counseling intervention did affect both knowledge and risk perception, overall, both groups were reluctant to take any form of menopausal therapy.\n A personalized risk assessment and genetic counseling intervention improves patient knowledge and risk perception; however, it is unclear that the intervention influenced menopausal treatment decisions.", "Innovative technologies that enable the collection of family history information and the assessment of breast cancer risk have a potential to enhance the quality of preventive care. We developed a computerized tool that supports stratification of breast cancer risk, genetic risk assessment in the clinical environment (GRACE).\n In a preliminary evaluation of the tool's impact, we randomized women with a family history of breast cancer (n=72) to either use the GRACE tool or undergo risk counseling by a nurse specialist.\n There was no statistically significant differences between the GRACE and nurse counselling groups in risk perceptions (F=.03, P>.05) and cancer-related worries (F=.80, P>.05). However, patients reported more positive attitudes toward working with the nurse.\n It was feasible to use GRACE in a Clinic. Additional research is required to identify solutions for providing emotional support in conjunction with the tool.", "Up to 40% of referrals from primary care to 'breast cancer family clinics' prove to be of women whose assessed risk falls below the guidelines' threshold for management in secondary or tertiary care, despite recommendations that they should be screened out at primary care level. A randomised trial, involving 87 such women referred to the Tayside Familial Breast Cancer Service compared two ways of communicating risk information, letter or personal interview. Both were found to be acceptable to referred women and to their family doctors, although the former expressed a slight preference for interview. Only four women returned to their family doctors with continuing concerns about breast cancer. Nevertheless, understanding of information provided by either route was unsatisfactory, with apparent confusion about both absolute and relative risks of breast cancer. Substantial minorities appear to believe that they are at no increased risk at all, or even below the population level of risk, while others remain convinced that their personal risk has been underestimated. Family history record forms, completed by the referred women, preferably with the assistance of relatives, are crucial to full assessment of familial risk but one quarter of women referred to the Tayside Familial Breast Cancer Service currently do not complete and return these forms ahead of their clinic appointment. Further collaboration between primary care and the Breast Cancer Family Service is required to improve provision for concerned women whose risks fall below the threshold for special surveillance and to maximise effective use of the family history record form." ]

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[ "Randomized controlled trial between perineal and anal repairs of rectocele in obstructed defecation.", "Randomized prospective comparison of needle colposuspension versus endopelvic fascia plication for potential stress incontinence prophylaxis in women undergoing vaginal reconstruction for stage III or IV pelvic organ prolapse. The Continence Program for Women Research Group.", "Vaginal versus abdominal reconstructive surgery for the treatment of pelvic support defects: a prospective randomized study with long-term outcome evaluation.", "Transanal or vaginal approach to rectocele repair: a prospective, randomized pilot study.", "Abdominal sacral colpopexy or vaginal sacrospinous colpopexy for vaginal vault prolapse: a prospective randomized study.", "Two-year outcomes after sacrocolpopexy with and without burch to prevent stress urinary incontinence.", "Laparoscopic compared with robotic sacrocolpopexy for vaginal prolapse: a randomized controlled trial.", "Prospective randomized trial of polyglactin 910 mesh to prevent recurrence of cystoceles and rectoceles.", "Porcine skin collagen implants for anterior vaginal wall prolapse: a randomised prospective controlled study.", "A prospective randomized trial using solvent dehydrated fascia lata for the prevention of recurrent anterior vaginal wall prolapse.", "A randomized comparison of polypropylene mesh surgery with site-specific surgery in the treatment of cystocoele.", "Trocar-guided mesh compared with conventional vaginal repair in recurrent prolapse: a randomized controlled trial.", "Anterior colporrhaphy versus repair with mesh for anterior vaginal wall prolapse: a comparative clinical study.", "Anterior vaginal wall prolapse: a randomized controlled trial of SIS graft versus traditional colporrhaphy.", "One-year follow-up after sacrospinous hysteropexy and vaginal hysterectomy for uterine descent: a randomized study.", "A prospective, randomized, controlled study comparing Gynemesh, a synthetic mesh, and Pelvicol, a biologic graft, in the surgical treatment of recurrent cystocele.", "A randomised controlled trial of abdominal versus laparoscopic sacrocolpopexy for the treatment of post-hysterectomy vaginal vault prolapse: LAS study.", "A randomised controlled trial evaluating the use of polyglactin mesh, polydioxanone and polyglactin sutures for pelvic organ prolapse surgery.", "Vaginal mesh for prolapse: a randomized controlled trial.", "Porcine subintestinal submucosal graft augmentation for rectocele repair: a randomized controlled trial.", "A randomised controlled trial comparing abdominal and vaginal prolapse surgery: effects on urogenital function.", "Anterior colporrhaphy versus transvaginal mesh for pelvic-organ prolapse.", "Laparoscopic sacral colpopexy versus total vaginal mesh for vaginal vault prolapse: a randomized trial.", "Primary surgical repair of anterior vaginal prolapse: a randomised trial comparing anatomical and functional outcome between anterior colporrhaphy and trocar-guided transobturator anterior mesh.", "Surgery for genitourinary prolapse and stress incontinence: a randomized trial of posterior pubourethral ligament plication and Pereyra suspension.", "Prevention of postoperative urinary stress incontinence after surgery for genitourinary prolapse.", "Symptom resolution and sexual function after anterior vaginal wall repair with or without polypropylene mesh.", "A randomized comparison of tension-free vaginal tape and endopelvic fascia plication in women with genital prolapse and occult stress urinary incontinence.", "Porcine skin collagen implants to prevent anterior vaginal wall prolapse recurrence: a multicenter, randomized study.", "Surgical strategies for women with pelvic organ prolapse and urinary stress incontinence.", "Randomised comparison of Burch colposuspension versus anterior colporrhaphy in women with stress urinary incontinence and anterior vaginal wall prolapse.", "A randomized controlled trial comparing fascia lata and synthetic mesh for sacral colpopexy.", "Vaginal repair with mesh versus colporrhaphy for prolapse: a randomised controlled trial.", "Outcome after anterior vaginal prolapse repair: a randomized controlled trial.", "Infracoccygeal sacropexy or sacrospinous suspension for uterine or vaginal vault prolapse.", "Sexual functioning after vaginal hysterectomy or transvaginal sacrospinous uterine suspension for uterine prolapse: a comparison.", "Anterior repair with or without collagen matrix reinforcement: a randomized controlled trial.", "Rectocele repair: a randomized trial of three surgical techniques including graft augmentation.", "A midurethral sling to reduce incontinence after vaginal prolapse repair.", "Colporrhaphy compared with mesh or graft-reinforced vaginal paravaginal repair for anterior vaginal wall prolapse: a randomized controlled trial.", "Must colposuspension be associated with sacropexy to prevent postoperative urinary incontinence?", "Burch colposuspension does not provide any additional benefit to pelvic organ prolapse repair in patients with urinary incontinence: a randomized surgical trial.", "Anterior colporrhaphy: a randomized trial of three surgical techniques.", "High levator myorraphy versus uterosacral ligament suspension for vaginal vault fixation: a prospective, randomized study." ]

[ "The present study was designed to evaluate functional outcome of perineal repair with and without levatorplasty versus transanal repair of rectocele in obstructed defecation.\n A total of 48 multiparous women with obstructed defecation caused by a rectocele were randomly allocated to three groups: transperineal repair with levatorplasty (TPR-LP; n = 16); transperineal repair without levatorplasty (TPR; n = 16); and transanal repair (TAR; n = 16). The study included defecographic assessment, anal manometry, symptom improvement, sexual function, and score on a function questionnaire. Assessments were done preoperatively and 6 months postoperatively.\n Defecography showed significant reduction in size of rectocele in all groups. Constipation improved significantly in both groups with transperineal repair but not in the group with transanal repair. Significant reductions in mean anal resting pressure, maximum reflex volume, and urge-to-defecate volume were observed only with the transperineal approach (with and without levatorplasty). Functional score improved significantly in the transperineal groups (with levatorplasty, P < 0.001; without levatorplasty, P < 0.01), but not in the transanal group (P = 0.142). Levatorplasty added to transperineal repair significantly improved the overall functional score compared with transperineal repair alone (P < 0.01) and transanal repair TAR (P < 0.001).\n Rectocele repair appears to improve anorectal function by improving rectal urge sensitivity. Transperineal repair of rectocele is superior to transanal repair in both structural and functional outcome. Levatorplasty improves functional outcome, but potential effects on dyspareunia should be discussed with the patient.", "Severe prolapse may mask potential genuine stress urinary incontinence in women. Some have suggested that a suspending urethropexy be performed in women who have potential genuine stress incontinence demonstrated by barrier reduction of the prolapse preoperatively. Our aim was to compare outcomes after prolapse surgery that included a formal bladder neck suspension with those operations that did not.\n This prospective randomized clinical trial assigned 32 women with bladder neck hypermobility and stage III or IV pelvic organ prolapse to receive either a needle colposuspension or bladder neck endopelvic fascia plication as part of the vaginal reconstructive surgery. Twenty-nine subjects underwent detailed clinical, anatomic, urodynamic, and quality-of-life evaluations before and 6 weeks and 6 months after surgery; 23 completed urinary diary and quality-of-life evaluations after a mean of 2.9 years.\n Needle colposuspension increased short-term complications without providing additional protection from de novo stress incontinence. Barrier testing before surgery predicted urethral sphincteric resistance after surgery; however, such testing neither predicted a patient's function after surgery nor indicated the need for a suspending urethropexy. The combination of a needle colposuspension with a sacrospinous ligament suspension predisposed to the early development of support defects of the upper anterior vaginal segment and to failure of bladder neck support.\n Preoperative barrier testing in women with severe prolapse is not useful in identifying individuals who require a suspending urethropexy. Needle colposuspension increases short-term complications, lacks durability, and may predispose to early and severe recurrent anterior prolapse when performed with a sacrospinous ligament vault suspension.", "Our purpose was to determine whether a vaginal or abdominal approach is more effective in correcting uterovaginal prolapse.\n Eighty-eight women with cervical prolapse to or beyond the hymen or with vaginal vault inversion > 50% of its length and anterior vaginal wall descent to or beyond the hymen were randomized to a vaginal versus abdominal surgical approach. Forty-eight women underwent a vaginal approach with bilateral sacrospinous vault suspension and paravaginal repair, and 40 women underwent an abdominal approach with colposacral suspension and paravaginal repair. Ancillary procedures were performed as indicated. Detailed pelvic examination was performed postoperatively by the nonsurgeon coauthor yearly up to 5 years. The women were examined while standing during maximum strain. Surgery was classified as optimally effective if the woman remained asymptomatic, the vaginal apex was supported above the levator plate, and no protrusion of any vaginal tissue beyond the hymen occurred. Surgical effectiveness was considered unsatisfactory if the woman was symptomatic, the apex descended > 50% of its length, or the vaginal wall protruded beyond the hymen.\n Eighty women (vaginal 42, abdominal 38) were available for evaluation at 1 to 5.5 years (mean 2.5 years). The groups were similar in age, weight, parity, and estrogen status, and 56% had undergone prior pelvic surgery. There was no significant difference between the groups in morbidity, complications, hemoglobin change, dyspareunia, pain, or hospital stay. The vaginal group had longer catheter use, more urinary tract infections, more incontinence, decreased operative time, and lower hospital charge. Surgical effectiveness was optimal in 29% of the vaginal group and 58% of the abdominal group and was unsatisfactory leading to reoperation in 33% of the vaginal group and 16% of the abdominal group. The reoperations included procedures for recurrent incontinence in 12% of the vaginal and 2% of the abdominal groups. The relative risk of optimal effectiveness by the abdominal route is 2.03 (95% confidence interval 1.22 to 9.83), and the relative risk of unsatisfactory outcome using the vaginal route is 2.11 (95% confidence interval 0.90 to 4.94).\n Reconstructive pelvic surgery for correction of significant pelvic support defects was more effective with an abdominal approach.", "This study was designed to compare outcomes of transanal and vaginal techniques for rectocele repair.\n Thirty females with symptomatic rectocele were enrolled in a prospective, randomized study. Fifteen underwent transanal rectoceleplasty, the other 15 underwent vaginal posterior colporrhaphy. Patients were assessed by clinical interview and examination, defecography, colon transit study, and anorectal manometry before randomization and 12 months postoperatively. Patients with compromised anal sphincter function or other symptomatic prolapse were excluded.\n The study groups were comparable in terms of demographic factors and rectocelerelated symptoms and signs. Eleven (73 percent) patients in the vaginal group and 10 (66 percent) in the transanal group digitally assisted rectal emptying preoperatively. The mean depth of the rectocele was 6.0 +/- 1.6 cm vs. 5.6 +/- 1.8 cm (P = 0.53) in the respective groups. At follow-up, 14 (93 percent) patients in the vaginal group and 11 (73 percent) in the transanal group reported improvement in symptoms (P = 0.08). Need to digitally assist rectal emptying decreased significantly in both groups, to one (7 percent) for the vaginal group and four (27 percent) for the transanal group (P = 0.17 between groups). The respective recurrence rates of rectocele were one (7 percent) vs. six (40 percent) (P = 0.04), and enterocele rates were zero vs. four (P = 0.05). In the vaginal group defecography showed a significant decrease in rectocele depth whereas in the transanal group the difference did not reach statistical significance. None of the patients reported de novo dyspareunia, but 27 percent reported improvement.\n Patients' symptoms were significantly alleviated by both operative techniques. The transanal technique was associated with more clinically diagnosed recurrences of rectocele and/or enterocele. Adverse effects on sexual life were avoided by use of both techniques.", "The purpose of this study was to compare the abdominal sacral colpopexy and vaginal sacrospinous colpopexy in the treatment of vaginal vault prolapse.\n Ninety-five women with vaginal vault prolapse were allocated randomly to sacral colpopexy (47 women) or sacrospinous colpopexy (48 women). Primary outcome measurements include subjective, objective, and patient-determined success rates. Secondary outcomes include the impact on bowel, bladder, and sexual function, cost, and quality of life.\n Two years after the operation (range, 6-60 months), the subjective success rate was 94% in the abdominal and 91% in the vaginal group (P=.19). The objective success rate was 76% in the abdominal group and 69% in the vaginal group (P=.48). The abdominal approach was associated with a longer operating time, a slower return to activities of daily living, and a greater cost than the sacrospinous colpopexy (P<.01). Both surgeries significantly improved the patient's quality of life (P<.05).\n Abdominal sacral colpopexy and vaginal sacrospinous colpopexy are both highly effective in the treatment of vaginal vault prolapse.", "To report anatomic and functional outcomes 2 years after sacrocolpopexy in stress-continent women with or without prophylactic Burch colposuspension.\n In the Colpopexy and Urinary Reduction Efforts (CARE) trial, stress-continent women undergoing sacrocolpopexy were randomized to receive or not receive a Burch colposuspension. Outcomes included urinary symptoms, other pelvic symptoms, and pelvic support. Standardized pelvic organ prolapse quantification examinations and validated outcome measures including the Pelvic Floor Distress Inventory and the Pelvic Floor Impact Questionnaire were completed before surgery and at several postoperative intervals, including at 2 years.\n This analysis is based on 302 of 322 randomized participants. Most were Caucasian (94%), with a mean age of 62+/-10 years (mean+/-standard deviation). Two years after surgery, 32.0% and 45.2% of women in the Burch and control groups, respectively, met the stress incontinence endpoint (presence of symptoms or positive cough stress test or interval treatment for stress incontinence, P=.026). The apex was well supported (point C within 2 cm of total vaginal length) in 95% of women, and this was not affected by concomitant Burch (P=.18). There was a trend toward fewer urgency symptoms in the Burch group (32.0% versus 44.5% no Burch, P=.085). Twenty participants experienced mesh or suture erosions.\n The early advantage of prophylactic Burch colposuspension for stress incontinence that was seen at 3 months remains at 2 years. Apical anatomic success rates are high and not affected by concomitant Burch.\n (www.clinicaltrials.gov), ClinicalTrials.gov, NCT00065845.\n I.", "To compare conventional laparoscopic and robotic-assisted laparoscopic sacrocolpopexy for vaginal apex prolapse.\n This single-center, blinded randomized trial included participants with stage 2-4 posthysterectomy vaginal prolapse. Participants were randomized to laparoscopic or robotic sacrocolpopexy. The primary outcome was total operative time from incision to closure. Secondary outcomes were postoperative pain, functional activity, bowel and bladder symptoms, quality of life, anatomic vaginal support, and cost from a health care system perspective.\n A total of 78 patients enrolled and were randomized (laparoscopic n=38; robotic n=40). Total operative time was significantly longer in the robotic group compared with the laparoscopic group (+67-minute difference; 95% confidence interval [CI] 43-89; P<.001). Anesthesia time, total time in the operating room, total sacrocolpopexy time, and total suturing time were all significantly longer in the robotic group. Participants in the robotic group also had significantly higher pain at rest and with activity during weeks 3 through 5 after surgery and required longer use of nonsteroidal anti-inflammatory drugs (median, 20 compared with 11 days, P<.005). The robotic group incurred greater cost than the laparoscopic group (mean difference +$1,936; 95% CI $417-$3,454; P=.008). Both groups demonstrated significant improvement in vaginal support and functional outcomes 1 year after surgery with no differences between groups.\n Robotic-assisted sacrocolpopexy results in longer operating time and increased pain and cost compared with the conventional laparoscopic approach.", "Our aim was to evaluate the efficacy of polyglactin 910 mesh in preventing recurrent cystoceles and rectoceles.\n In a prospective, randomized, controlled trial, patients undergoing vaginal reconstructive surgery with cystoceles to the hymenal ring and beyond were randomly selected to undergo anterior and posterior colporrhaphy with or without polyglactin 910 mesh reinforcement. Results were evaluated preoperatively and at 2, 6, 12, and 52 weeks postoperatively.\n A total of 161 women were randomly selected for this study. One woman was excluded at the time of surgery, and 17 women were lost to follow-up. Eighty women received mesh, and 80 did not. Both groups were found to be equivalent with respect to age, parity, concomitant surgery, and menopausal and hormone replacement status. Preoperatively 49 women had a central cystocele to the hymenal ring and 111 women had cystoceles beyond the introitus; 91 women had a rectocele to the mid-vaginal plane, 31 to the hymenal ring, and 22 beyond the introitus. After 1 year, 30 (43%) of 70 subjects without mesh and 18 (25%) of 73 subjects with mesh had recurrent cystoceles beyond the mid-vaginal plane (P =.02). Eight women without mesh and 2 women with mesh had recurrent cystoceles to the hymenal ring (P =.04). No recurrent cystoceles beyond the hymenal ring occurred in either group. Multivariate logistic regression analysis showed concurrent slings to be associated with significantly fewer recurrent cystoceles (odds ratio, 0.32; P =.005), whereas the presence of mesh remained significantly predictive of fewer cystocele recurrences in this analysis. Thirteen recurrent rectoceles were noted 1 year postoperatively, with no differences between groups.\n Polyglactin 910 mesh was found to be useful in the prevention of recurrent cystoceles.", "The effect of a Pelvicol graft compared with a conventional anterior vaginal repair was evaluated in this randomised controlled study.\n Only patients with a stage II or higher (Ba >or= -1) defect were included.\n Thirty-one patients were allocated to a conventional anterior repair; 30 to Pelvicol graft. At 12 months follow-up, four patients among controls (15%) and two in the graft group (7%) had objective recurrence. Among controls, the difference at 3 months follow-up in Ba was 6.0 cm when compared with the position of Ba prior to surgery. In the graft group, the difference was 7.0 cm (P < 0.05). This difference was still present at 12 months follow-up (6.0 vs. 7.0 cm; P < 0.05).\n The implantation of a Pelvicol graft does not improve the POP-Q stage.", "This study was undertaken to compare outcomes after anterior colporrhaphy with and without a solvent dehydrated cadaveric fascia lata graft.\n A total of 162 women were enrolled in a prospective, randomized trial that evaluated the impact of a solvent dehydrated cadaveric fascia lata patch on recurrent anterior vaginal prolapse. Subjects were randomly assigned to standard colporrhaphy with or without a patch. Before and after surgery, subjects were evaluated by both the Baden-Walker and pelvic organ prolapse quantification systems. \"Failure\" was defined as stage II anterior wall prolapse or worse.\n Of 154 women randomly assigned (76 patch: 78 no patch), all underwent surgery and 153 (99%) returned for follow-up. Sixteen women (21%) in the patch group and 23 (29%) in the control group experienced recurrent anterior vaginal wall prolapse (P = .229). Only 26% of all recurrences were symptomatic. Concomitant transvaginal Cooper's ligament sling procedures were associated with a dramatic decrease in recurrent prolapse (odds ratio [OR] 0.105 , P < .0001).\n Solvent dehydrated fascia lata as a barrier does not decrease recurrent prolapse after anterior colporrhaphy. Transvaginal bladder neck slings were associated with a significant reduction in the risk of recurrent anterior wall prolapse.", "The aim of this study was to compare the efficiency of polypropylene mesh surgery with the site-specific repair surgeries in the treatment of cystocoeles. We randomized 90 patients into two groups according to a computer-based program. After a 12-month (mean) follow up, we noticed that the polypropylene mesh surgery yielded good anatomical results. Acceptable anatomical cure rates were 91 and 72% in the mesh surgery group and site-specific surgery group, respectively. There were three cases (6.9%) of mesh erosion. One case of urinary retention and two cases of de novo dyspareunia were seen in the mesh surgery group. De novo stress urinary incontinence developed in three patients in the site-specific surgery group. We concluded that surgery with light polypropylene mesh (Sofradim, Parietene) is superior to the site-specific surgery in the treatment of cystocoeles.", "To compare efficacy and safety of trocar-guided tension-free vaginal mesh insertion with conventional vaginal prolapse repair in patients with recurrent pelvic organ prolapse.\n Patients with recurrent pelvic organ prolapse stage II or higher were randomly assigned to either conventional vaginal prolapse surgery or polypropylene mesh insertion. Primary outcome was anatomic failure (pelvic organ prolapse stage II or higher) in the treated vaginal compartments. Secondary outcomes were subjective improvement, effects on bother, quality of life, and adverse events. Questionnaires such as the Incontinence Impact Questionnaire and Urogenital Distress Inventory were administered at baseline, 6 months, and 12 months. Anatomic outcomes were assessed by an unblinded surgeon. Power calculation with α=0.05 and β=0.80 indicated that 194 patients were needed.\n Ninety-seven women underwent conventional repair and 93 mesh repair. The follow-up rate after 12 months was 186 of 190 patients (98%). Twelve months postsurgery, anatomic failure in the treated compartment was observed in 38 of 84 patients (45.2%) in the conventional group and in eight of 83 patients (9.6%) in the mesh group (P<.001; odds ratio, 7.7; 95% confidence interval, 3.3-18). Patients in either group reported less bulge and overactive bladder symptoms. Subjective improvement was reported by 64 of 80 patients (80%) in the conventional group compared with 63 of 78 patients (81%) in the mesh group. Mesh exposure was detected in 14 of 83 patients (16.9%).\n At 12 months, the number of anatomic failures observed after tension-free vaginal mesh insertion was less than after conventional vaginal prolapse repair. Symptom decrease and improvement of quality of life were equal in both groups.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT00372190.\n I.", "To compare the clinical effectiveness of anterior colporrhaphy versus mesh repair as surgical management of anterior vaginal prolapse.\n Of 50 patients with ≥stage II anterior vaginal prolapse on Pelvic Organ Prolapse Quantification (POPQ) system who were initially approached, 44 consented and underwent surgery. They were randomly recruited into two groups. Group I (23 patients) received anterior colporrhaphy, while group II (21 patients) received soft polypropylene mesh (GYNEMESH*PS, Gynecare, Ethicon, France). Clinical assessment took place preoperatively and postoperatively at definite intervals. Functional and anatomical comparisons were based on comparison between preoperative and 24 months postoperative assessments of symptoms and POPQ stages, respectively. Four patients in total did not complete the follow-up assessments and were excluded.\n Both groups showed clinical improvement in their symptoms and POPQ staging at the end of the postoperative follow-up period. Improvement, however, was more significant in the repair with mesh group, as patients in this group reported better improvement of their prolapse symptoms, mainly vaginal bulge/pressure sensation (P < 0.05), and showed better improvement in the anatomical staging, individual POP-Q points Aa and Ba (P < 0.01), than the anterior colporrhaphy group. Group II also showed more satisfactory outcome with the general POP-Q staging (P < 0.05) than group I, reflecting a better quality of life of the patients in the repair with mesh group.\n Our data shows that repair with mesh is superior to anterior colporrhaphy with more satisfactory outcome to the patients. Due to the small size of our study and uncertainty of the long-term safety and resilience of the mesh, we recommend larger studies to confirm our preliminary results.", "This study seeks to compare the small intestine submucosa (SIS) graft with traditional colporrhaphy (TC) for surgical treatment of anterior vaginal prolapse.\n Subjects were randomly assigned to SIS (n = 29) or to TC (n = 27) preoperatively and outcomes analyzed at 12 months postoperatively. The primary outcome was the absence of POP-Q stage >or= II prolapse, and secondary outcome was improvement in quality of life. Data were compared with independent samples or paired Student's t test.\n SIS group had 86.2% anatomic cure compared to 59.3% in TC (p = 0.03). SIS improved point Ba measurement significantly (-1.93 cm versus -1.37 cm, p = 0.02). Both operations significantly improved quality of life, although there were no differences between the groups. We observed a greater number of complications in the SIS group, with no infections or erosion.\n SIS repair improved point Ba significantly. However, there were no differences observed in quality of life between the techniques.", "In a retrospective study, the sacrospinous hysteropexy was associated with a shorter recovery time compared to a vaginal hysterectomy with no differences in anatomical outcomes. No randomized trials are performed.\n Sixty-six women with stage 2-4 uterine descent were randomized for vaginal hysterectomy(31) or sacrospinous hysteropexy(35). Recovery time, anatomical outcomes, functional outcomes, and quality of life were measured.\n Length of time to return to work was shorter after a sacrospinous hysteropexy (43 versus 66 days, p = 0.02). The difference in risk for recurrent prolapse stage 2 or more of the apical compartment at 1-year follow-up was 17% (95% confidence interval, 2 to 30) in favor of the vaginal hysterectomy. No differences in quality of life and urogenital symptoms were found.\n The sacrospinous hysteropexy for uterine descent is associated with an earlier recovery time, more recurrent apical prolapses but no differences in functional outcomes, and quality of life.", "We compared safety and efficacy of Gynemesh PS and Pelvicol for recurrent cystocele repair. One hundred ninety patients were randomly divided into Gynemesh PS and Pelvicol groups and underwent tension-free cystocele repair. The Chi-square test was used to compare categorical variables, the paired t test for continuous parametric variables, and the Mann-Whitney test for continuous nonparametric variables. Ninety-six Gynemesh PS patients and 94 Pelvicol patients were studied. Mesh erosions occurred in 6.3% of Gynemesh PS patients. No erosions were observed in Pelvicol patients (p = 0.02). Objective cure was 71.9% for Gynemesh PS and 56.4% for Pelvicol (p = 0.06). Subjective cure was the same in both groups except for better sexuality in the Pelvicol group. At 24 months follow-up, only Gynemesh PS patients had mesh erosions. Anatomical outcome was similar in the two groups. Pelvicol gave a better impact on voiding and sexuality.", "This prospective multi-centre true two-sided equivalence trial was designed to test the clinical equivalence of open (ASCP) and laparoscopic (LSCP) sacrocolpopexy using objective and subjective outcomes\n The study was carried out in three urogynaecology units in England, UK and the patient population consisted of women referred with symptomatic and bothersome post-hysterectomy vaginal vault prolapse at least 1 cm above or beyond the hymeneal remnants. The interventions were either abdominal or laparoscopic sacrocolpopexy following randomisation to one of the types of surgery.\n For the primary outcome (point C on the POP-Q) the results at 1 year were -6.63 cm for the open ASCP and -6.67 cm for the LSCP respectively. Subjective outcomes at 1 year showed that 90% of the ASCP group and 80% of the LSCP group were \"much better\". There were improvements with regard to blood loss, haemoglobin and shorter length of stay in the LSCP group compared with the ASCP group.\n This fully powered randomised controlled trial comparing open and laparoscopic sacrocolpopexy has shown clinical equivalence.", "To compare the effectiveness of polyglactin mesh, and polydioxanone or polyglactin sutures in women having pelvic organ prolapse surgery. Randomised controlled trial with a factorial 2(2 design of polyglactin mesh or not, and polydioxanone or polyglactin suture. Outcomes were assessed using questionnaires at baseline and on the third day and at 6 months after surgery. Women were also examined clinically 3 months after surgery. The primary outcome was the subjective improvement in prolapse symptoms and quality of life scores from baseline to 6 months. There was a subjective improvement in the prolapse symptom score from baseline to 6 months after surgery (mean difference of 9.2 (95% CI for difference 7.2-11.2, p < 0.001) and an improvement in the mean quality of life score over the same period with a reduction of 3.4 (95% CI for difference 2.4-4.3, p < 0.001). However, there were no significant differences in the mean difference in prolapse symptoms and quality of life (QoL) scores according to the randomised groups. The majority (86%) of women were satisfied with their surgery. Our study demonstrated that at short-term follow-up, there was no significant difference in the mean differences in prolapse symptoms and QoL scores after surgery using polyglactin mesh or not, polyglactin or polyglactin sutures, but the numbers were too small for a definitive conclusion. Longer-term follow-up and/or a larger trial are required.", "To present 3-month outcomes of a double-blind, multicenter randomized controlled trial comparing traditional vaginal prolapse surgery without mesh with vaginal surgery with mesh.\n Women with pelvic organ prolapse quantification prolapse stages 2-4 were randomized to vaginal colpopexy repair with mesh or traditional vaginal colpopexy without mesh. The primary outcome measure was objective treatment success (pelvic organ prolapse quantification stage 1 or lower) at 3 months. Secondary outcome measures included quality-of-life variables and complication rates.\n Sixty-five women were recruited from January 2007 to August 2009, when the study was halted due to predetermined stopping criteria for vaginal mesh erosion at a median follow-up of 9.7 months (range, 2.4-26.7 months). Thirty-two women underwent mesh colpopexy (24 anterior mesh, eight total mesh), and 33 women had vaginal colpopexies without mesh (primarily uterosacral ligament suspension) and concurrent colporrhaphy. There were no statistically significant baseline differences between the mesh and no-mesh groups with respect to demographics, menopausal status, and race. Analysis of the mesh and no-mesh women found no difference with respect to overall recurrence (mesh: 19 [59.4%] compared with no mesh: 24 [70.4%], P=.28). There were five (15.6%) vaginal mesh erosions. Two cystotomies and one blood transfusion occurred in the mesh group only. Subjective cure of bulge symptoms was noted in 93.3% of mesh patients and 100% of no-mesh patients. Furthermore, subjective quality-of-life measurements did not differ between the two groups at baseline or 3 months postoperatively.\n At 3 months, there is a high vaginal mesh erosion rate (15.6%) with no difference in overall objective and subjective cure rates. This study questions the value of additive synthetic polypropylene mesh for vaginal prolapse repairs.\n Clinicaltrials.gov, www.clinicaltrials.gov, NCT00475540.\n I.", "To estimate the effect of porcine subintestinal submucosal graft augmentation on improving anatomic and subjective rectocele repair outcomes compared with native tissue repair.\n We conducted a randomized controlled trial at two sites, including women with at least stage 2 symptomatic rectocele. Anatomic and subjective outcomes (vaginal bulge and defecatory) were collected 12 months postoperatively, including blinded Pelvic Organ Prolapse Quantification (POP-Q) examinations. Anatomic failure was defined as points Ap or Bp -1 or greater on POP-Q. Subjective failure was defined as no improvement or worsening of symptoms. We estimated number needed to treat and adjusted odds ratios (ORs). Assuming graft use is associated with 93% anatomic success, 63 women per group would be needed to detect a 20% difference at α=.05 and β=.20.\n One hundred sixty women were randomized; 137 had 12-month anatomic data (67 graft; 70 control). There was no difference in anatomic failure (12% compared with 9%, P=.5), vaginal bulge symptom failure (3% compared with 7%, P=.4, number needed to treat=26) or defecatory symptom failure (44% compared with 45%, P=.9, number needed to treat=91) for graft compared with control, respectively. Both groups reported improvement in vaginal bulge and defecatory symptoms (P<.05 for all). On multiple logistic regression, graft use was not associated with a decreased odds of anatomic failure (adjusted OR 1.36, 95% confidence interval [CI] 0.44-4.25), vaginal bulge symptoms (adjusted OR 0.46, 95% CI 0.08-2.68), or defecatory symptoms (adjusted OR 0.98, 95% CI 0.48-2.03).\n Although rectocele repair by either approach is associated with improved symptoms, subintestinal submucosal graft augmentation was not superior to native tissue for anatomic or subjective outcomes at 12 months.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT00321867.", "To compare the effects of vaginal hysterectomy (combined with anterior and/or posterior colporraphy) and abdominal sacro-colpopexy (with preservation of the uterus) on urogenital function.\n Randomised trial.\n Three teaching hospitals in The Netherlands.\n Eighty-two patients undergoing surgical correction of uterine prolapse stages II-IV.\n Participating patients completed the urogenital distress inventory (UDI), before and at six weeks, six months and one year after surgery, to measure discomfort of prolapse and micturition symptoms. Domain scores of the UDI (ranging from 0 to 100, higher scores indicating more discomfort) were compared between groups at all time points. Findings at pelvic examination, number of doctor visits within the first year after surgery because of pelvic floor symptoms and performed or planned surgery of recurrent genital prolapse were also compared.\n Domain scores of the UDI at one year after surgery.\n At one year after surgery, scores on the discomfort/pain domain (mean difference 7.1, 95% confidence interval [CI] 1.1-13.2), overactive bladder domain (mean difference 8.7, 95% CI 0.5-16.9) and obstructive micturition domain (mean difference 10.3, 95% CI 0.6-20.1) of the UDI were significantly higher in the abdominal group than in the vaginal group. Findings at pelvic examination were similar in both groups. Doctor visits because of pelvic floor symptoms were more frequent in the abdominal group than in the vaginal group. Re-operation was performed or planned in 9 of the 41 patients who underwent abdominal surgery and in 1 of the 41 patients who underwent vaginal surgery (odds ratio [OR] = 11.2, 95% CI 1.4-90.0).\n Our findings suggest that vaginal hysterectomy with anterior and/or posterior colporraphy is preferable to abdominal sacro-colpopexy with preservation of the uterus as surgical correction in patients with uterine prolapse stages II-IV.", "The use of standardized mesh kits for repair of pelvic-organ prolapse has spread rapidly in recent years, but it is unclear whether this approach results in better outcomes than traditional colporrhaphy.\n In this multicenter, parallel-group, randomized, controlled trial, we compared the use of a trocar-guided, transvaginal polypropylene-mesh repair kit with traditional colporrhaphy in women with prolapse of the anterior vaginal wall (cystocele). The primary outcome was a composite of the objective anatomical designation of stage 0 (no prolapse) or 1 (position of the anterior vaginal wall more than 1 cm above the hymen), according to the Pelvic Organ Prolapse Quantification system, and the subjective absence of symptoms of vaginal bulging 12 months after the surgery.\n Of 389 women who were randomly assigned to a study treatment, 200 underwent prolapse repair with the transvaginal mesh kit and 189 underwent traditional colporrhaphy. At 1 year, the primary outcome was significantly more common in the women treated with transvaginal mesh repair (60.8%) than in those who underwent colporrhaphy (34.5%) (absolute difference, 26.3 percentage points; 95% confidence interval, 15.6 to 37.0). The surgery lasted longer and the rates of intraoperative hemorrhage were higher in the mesh-repair group than in the colporrhaphy group (P<0.001 for both comparisons). Rates of bladder perforation were 3.5% in the mesh-repair group and 0.5% in the colporrhaphy group (P=0.07), and the respective rates of new stress urinary incontinence after surgery were 12.3% and 6.3% (P=0.05). Surgical reintervention to correct mesh exposure during follow-up occurred in 3.2% of 186 patients in the mesh-repair group.\n As compared with anterior colporrhaphy, use of a standardized, trocar-guided mesh kit for cystocele repair resulted in higher short-term rates of successful treatment but also in higher rates of surgical complications and postoperative adverse events. (Funded by the Karolinska Institutet and Ethicon; ClinicalTrials.gov number, NCT00566917.).", "To compare the laparoscopic sacral colpopexy and total vaginal mesh for vaginal vault prolapse.\n Women with symptomatic stage ≥2 vault prolapse were randomly allocated the laparoscopic sacral colpopexy (53) or total vaginal mesh (55). Primary outcome measures were objective success rates at pelvic organ prolapse quantification sites individually and collectively. Secondary outcome measures included perioperative outcomes, patient satisfaction, quality of life outcomes, complications, and reoperations.\n The laparoscopic sacral colpopexy group had a longer operating time, reduced inpatient days, and quicker return to activities of daily living as compared with the total vaginal mesh group. At the 2-year review, the total objective success rate at all vaginal sites was 41 of 53 (77%) for laparoscopic sacral colpopexy as compared with 23 of 55 (43%) in total vaginal mesh (P < .001). Reoperation rate was significantly higher after the vaginal mesh surgery 12 of 55 (22%) as compared with laparoscopic sacral colpopexy 3 of 53 (5%) (P = .006).\n At 2 years, the laparoscopic sacral colpopexy had a higher satisfaction rate and objective success rate than the total vaginal mesh with lower perioperative morbidity and reoperation rate.\n Crown Copyright © 2011. Published by Mosby, Inc. All rights reserved.", "To compare anterior colporrhaphy with a trocar-guided transobturator mesh procedure (Avaulta(®) anterior).\n Randomised, controlled trial.\n Three teaching hospitals.\n Women with a symptomatic cystocele at least stage II requiring primary surgical correction.\n A total of 125 women were assessed at baseline and 1-year follow up. A sacrospinous hysteropexy or posterior colporrhaphy was performed when indicated.\n The primary outcome was the difference in anatomical cure (defined as Pelvic Organ Prolapse-Quantification <stage II cystocele). Secondary outcomes were complications, self-reported urogenital symptom severity, and quality of life, as measured with validated questionnaires.\n In all, 64 women were allocated to the anterior colporrhaphy group and 61 to the mesh group; 58/64 women versus 56/61 completed 12 months of follow-up analysis. Compared with the anterior colporrhaphy group, the mesh reduced the risk of anatomical failure at 12 months follow up from 59 to 9% (risk reduction 50.3%, 95% CI 35.5-65.1). Only three (5%) re-operations for anatomical failure in the anterior colporrhaphy group were performed versus 0% in the mesh group. Functional outcome improved significantly at 12 months on almost all domains, with similar results between groups. Mesh exposure occurred in two (4%) women. Baseline dyspareunia disappeared significantly more often after an anterior colporrhaphy (80%) than in the mesh group (20%). There was a trend towards more de novo dyspareunia in the mesh group (15% versus 9%).\n Primary cystocele repair with trocar-guided transobturator mesh resulted in a statistically significant better anatomical outcome compared with the anterior colporrhaphy. However, functional outcome was similar between groups.\n © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.", "Our purpose was to compare two antiincontinence procedures in patients with severe genitourinary prolapse and coexisting clinical or potential stress incontinence.\n In addition to cystopexy, 109 patients with a urethrocystocele of grade 2 or more and a positive stress test result with prolapse reduction received posterior pubourethral ligament plication or Pereyra suspension.\n Of 55 patients undergoing posterior pubourethral ligament plication, 15 were clinically and 40 potentially incontinent; the same figures were 21 and 33, respectively, among 54 patients undergoing the Pereyra procedure. Follow-up was for 3 to 9 years. Subjective (60% vs 71%, p = 0.72) and objective (27% vs 57%, p = 0.14) cure rates were not statistically different among patients who were clinically incontinent (posterior pubourethral ligament plication vs Pereyra suspension). Among potentially incontinent patients, subjective (85% vs 100%, p = 0.03) and objective (50% vs 76%, p = 0.04) continence rates were higher after the Pereyra procedure. Overall, the cotton swab test had negative results (maximum straining angle < or = 30 degrees) after successful surgery in 79% and 96%, respectively, of patients (p = 0.03). Four subjects (7%) underwent removal of one Pereyra suture because of urinary retention or suprapubic wound infection.\n Cystopexy with Pereyra suspension is recommended, particularly for patients with prolapse and potential stress incontinence.", "To compare cystopexy alone versus cystopexy with posterior pubourethral ligaments plication for the occurrence of postoperative stress incontinence after prolapse surgery, and to compare the two surgical series in terms of complications and urodynamic effects.\n One hundred two continent patients randomly underwent cystopexy alone (N = 52) or cystopexy with posterior pubourethral ligaments plication (N = 50). All had a urethrocystocele grade 2 or greater and a negative stress test with the prolapse repositioned. A full urodynamic investigation was repeated 6 months after surgery.\n Twelve (23%) and 14 (28%) patients (P = .73) required intermittent self-catheterization for 11.1 +/- 5.1 and 16.5 +/- 11.1 days, respectively (cystopexy alone versus cystopexy with posterior pubourethral ligaments plication, P = .002). Long-lasting difficulties in voiding were present in zero and five (10%) patients (P = .02). One subject receiving posterior pubourethral ligaments plication underwent urethral dilation for complete urinary retention. At 1 year follow-up, four patients (8%) in each series developed postoperative stress incontinence (P = .62). Symptomatic detrusor instability complicated the postoperative course in one patient (2%) of each group.\n Cystopexy alone implied lower morbidity in terms of resumption of spontaneous voiding and long-lasting difficulties in voiding. The procedure could be recommended as an effective and safe treatment for continent patients with severe urethrocystocele. Additional plication of the posterior pubourethral ligaments did not seem superior to cystopexy alone in preventing the postoperative occurrence of stress incontinence.", "To evaluate whether symptom resolution and sexual function is better after reinforcement with polypropylene mesh than with traditional anterior repair. Ninety-seven patients were randomized to anterior colporrhaphy and 105 to an operation with mesh. Participants were evaluated up to 24 months by physical examination, standard questions, and questionnaire. The overall symptom rate did not differ between the groups, but a sensation of vaginal bulge was reported less frequently in the mesh group, the figures being 17 versus 5 (p = 0.003). The recurrence rate for the no-mesh group was 41% and for the mesh group 11% (p < 0.001). The dyspareunia score was statistically significantly lower in the mesh group (p = 0.015). The mesh exposure rate was 8%. Sensation of vaginal bulge was relieved more efficiently by the mesh technique without causing dyspareunia.", "The purpose of this study was to compare 2 anti-incontinence procedures in women who had severe genital prolapse and potential stress incontinence.\n In addition to vaginal reconstructive surgery, 50 patients with stage II or higher anterior defect and a positive stress test result with prolapse reduction received either tension-free vaginal tape or plication of the endopelvic fascia. Preoperative evaluation included history, physical examination, stress test, and urodynamic assessment. Data were analyzed with the Student t test, the Fisher's exact test, and the Wilcoxon signed-rank test.\n The median follow-up time was similar for both groups, 26 and 24 months. Subjective (96% vs 64%; P=.01) and objective (92% vs 56%; P<.01) continence rates were higher after the tension-free vaginal tape procedure. Time for the resumption of spontaneous voiding, rates of urinary retention, or de novo urge incontinence were similar in the 2 groups.\n Tension-free vaginal tape can be recommended for patients with prolapse and occult stress incontinence.", "We evaluated the efficacy of the Pelvicol porcine collagen implant for preventing recurrent anterior vaginal wall prolapse in women undergoing primary surgery for pelvic organ prolapse.\n This was a prospective, randomized, multicenter trial in 206 women with stage II or greater anterior vaginal wall prolapse (point Ba -1 or greater) according to the pelvic organ prolapse quantification system. The patients were randomly assigned to undergo anterior vaginal repair or the same procedure with Pelvicol implant reinforcement. SPSS software was used for data analysis.\n A total of 201 women were available for surgical outcome analysis, including 98 and 103 in the implant and no implant groups, respectively. All completed the 1-year followup visit. Most women were satisfied with the postoperative condition with a significant decrease in the visual analog scale score in each group (p <0.001). Anatomical anterior recurrence (point Ba greater than -1) was observed in 7 women (7%) in the implant group and in 20 (19%) in the other groups (OR 3.13, 95% CI 1.26-7.78, p = 0.019). Additionally, there were 11 women (3 and 8, respectively, or 5%) with posterior recurrence and 6 (3 per group or 3%) with unsatisfactory results at the upper vaginal segment. One patient who received a porcine implant had vaginal extrusion of the mesh 1 month after surgery.\n Our data show that the Pelvicol implant can be easily and readily used to augment and reinforce anterior colporrhaphy. The prolapse recurrence rate was considerably lower in the implant group compared with outcomes in patients treated with simple anterior repair.", "This study aims to compare the result of an incontinence procedure performed at the time of prolapse repair or 3 months later in women with pelvic organ prolapse (POP) and stress urinary incontinence (SUI).\n In a multicenter prospective randomized trial, women with POP and SUI were randomized to have a tension-free vaginal tape (TVT) at the time of prolapse repair (n = 87; group I) or 3 months later (n = 94; group II). Women in group II were evaluated for SUI 3 months after the prolapse repair. Those with confirmed SUI had a TVT performed (n = 53). The main evaluation of all women was 1 year after the last surgery.\n On-treatment analysis resulted in 95% cure of SUI in group I and 89% in group II (p = 0.12). Twenty-seven percent were cured after prolapse surgery alone.\n No differences were found between the two treatment strategies, but almost one third of women were cured of SUI by prolapse surgery alone.", "To compare the Burch colposuspension and the anterior colporrhaphy in women with both stress urinary incontinence and advanced anterior vaginal wall prolapse (cystocele).\n Prospective randomised study.\n Secondary referral centre, Urogynaecology Unit, San Gerardo Hospital, Monza, Italy.\n Seventy-one women undergoing surgery for primary genuine stress incontinence and concurrent grade 2 or 3 cystocele (descending at or outside the vaginal introitus).\n Full urodynamic investigation performed pre-operatively and repeated six months after surgery. Clinical follow up continued for 8 to 17 years.\n Subjective (patient history) and objective (negative stress test result) cure of stress incontinence. Assessment of cystocele recurrence.\n Thirty (86%) of the 35 evaluable women who had the Burch colposuspension and 17 (52%) of the 33 evaluable women who had the anterior colporrhaphy were subjectively cured (OR 5.6, 95% CI 1.6 to 21.6; P = 0.005). Objective cure rates were 74% (26 of 35) and 42% (14 of 33), respectively (OR 3.9, 95% CI 1.3 to 12.5; P = 0.02). A recurrent cystocele of grade 2 or 3 with or without prolapse at other vaginal sites was recorded in 34% (12 of 35) and 3% (1 of 33) of women, respectively (OR 16.7, 95% CI 2.0 to 368.1; P = 0.003).\n The Burch colposuspension was better in controlling stress incontinence but it lead to an unacceptable high rate of prolapse recurrence. The anterior colporrhaphy was more effective in restoring vaginal anatomy but it was accompanied by an unacceptable low cure rate of stress incontinence. Neither of the two operations is recommended for women who are suffering from a combination of stress incontinence and advanced cystocele.", "To compare the objective anatomic outcomes after sacral colpopexy performed with cadaveric fascia lata and polypropylene mesh.\n Patients undergoing a sacral colpopexy were randomized to receive either fascia lata or polypropylene mesh in a double-blinded fashion. Data were collected at 6 weeks, 3 months, 6 months, and 1 year postoperatively. The main outcome measures were pelvic organ prolapse quantification (POP-Q) system stage and individual POP-Q points over time. Objective anatomic failure was defined as POP-Q stage 2 or more at any point during the follow-up period. Proportions of patients with objective anatomic failure at 1 year in each group were compared using the chi(2) test. Mean POP-Q points and stage at 1 year were compared by using the independent samples t test.\n One hundred patients were randomized to receive either fascia (n = 46) or mesh (n = 54). Of the 89 patients returning for 1-year follow-up, 91% (41/45) of the mesh group and 68% (30/44) of the fascia group were classified as objectively cured (P = .007). We found significant differences between the mesh and fascia groups with respect to the 1-year postoperative comparisons of points Aa, C, and POP-Q stage. There were no differences between the 2 groups with respect to points TVL (total vaginal length), GH (genital hiatus), PB (perineal body), Ap or Bp (2 points along the posterior vaginal wall).\n Polypropylene mesh was superior to fascia lata in terms of POP-Q points, POP-Q stage, and objective anatomic failure rates.\n I.", "To compare vaginal repair augmented by mesh with traditional colporrhaphy for the treatment of pelvic organ prolapse.\n Prospective randomised controlled trial.\n Tertiary teaching hospital.\n One hundred and thirty-nine women with stage >or=2 prolapse according to the pelvic organ prolapse quantification (POP-Q) system requiring both anterior and posterior compartment repair.\n Subjects were randomised to anterior and posterior vaginal repair with mesh augmentation (mesh group, n = 69) or traditional anterior and posterior colporrhaphy (no mesh group, n = 70).\n The primary outcome was the absence of POP-Q stage >or=2 prolapse at 12 months. Secondary outcomes were symptoms, quality-of-life outcomes and satisfaction with surgery. Complications were also reported.\n For subjects attending the 12-month review, success in the mesh group was 81.0% (51 of 63 subjects) compared with 65.6% (40/61) in the no mesh group and was not significantly different (P-value = 0.07). A high level of satisfaction with surgery and improvements in symptoms and quality-of-life data were observed at 12 months compared to baseline in both groups, but there was no significant difference in these outcomes between the two groups. Vaginal mesh exposure occurred in four women in the mesh group (5.6%). De novo dyspareunia was reported by five of 30 (16.7%) sexually active women in the mesh group and five of 33 (15.2%) in the no mesh group at 12 months.\n In this study, vaginal surgery augmented by mesh did not result in significantly less recurrent prolapse than traditional colporrhaphy 12 months following surgery.", "To report 1-year outcomes of a randomized controlled trial comparing polypropylene mesh-reinforced anterior vaginal prolapse repair with anterior colporrhaphy.\n Seventy-six patients with stage II or greater anterior vaginal prolapse were randomly assigned to either colporrhaphy or polypropylene mesh repair. The primary outcome was recurrent stage II anterior vaginal prolapse, and secondary outcomes were effects on quality of life and sexual symptom scores, operative time, blood loss, length of hospitalization, and adverse events.\n Thirty-eight women had anterior colporrhaphy, and 37 had polypropylene mesh repair. One patient allocated to mesh repair withdrew from the study before surgery. Clinical and demographic data did not differ significantly between the two treatment groups. One year after surgery, optimal and satisfactory anterior vaginal support were obtained in 21 of 38 (55%) of the colporrhaphy group and 33 of 38 (87%) of the mesh group (P=.005). Patients in both groups reported less bother after surgery in both prolapse and urinary symptoms. The rates of de novo dyspareunia were 4 of 26 (16%) and 2 of 23 (9%) in the colporrhaphy and mesh groups, respectively. Two of 37 (5%) patients had vaginal mesh extrusion. Nine anterior colporrhaphy patients would have to have recurrent anterior vaginal prolapse to prevent one vaginal mesh extrusion. Neither serious adverse events nor deaths occurred in either group.\n Anterior vaginal prolapse repair with polypropylene mesh reinforcement offers lower anatomic recurrence than anterior colporrhaphy at one year. However, quality of life and sexual symptoms scores improved in both groups.", "To compare infracoccygeal sacropexy (IS) and sacrospinous suspension (SS) for the treatment of uterine or vault prolapse.\n A randomized trial of 49 women assigned to either the IS group using IVS tape (n=24) or SS group (n=25). Concomitant hysterectomy and repairs were performed as appropriate. Evaluations included prolapse staging using the POP-Q system and validated questionnaires for symptoms (PFDI), quality of life (PFIQ), and sexuality (PISQ-12). The primary outcome measure was postoperative pain.\n Patients' characteristics were similar in both groups. IS was quicker, easier, and less painful than SS (P<0.01). Hemorrhage or hematoma rates were similar. Neither rectal injury nor vaginal erosion occurred. Mean follow-up was 16.8 months. Prolapse cure rates, symptom scores, and quality of life were similar. Postoperative cystocele occurred in 4.8% of women after IS and 25% after SS (P>0.05).\n Infracoccygeal sacropexy is equivalent to sacrospinous suspension, with a decreased rate of postoperative pain and cystocele recurrence.", "To examine changes in sexuality after total vaginal hysterectomy (TVH) or transvaginal sacrospinous uterine suspension (SSUS)for uterine prolapse.\n One hundred fifty-eight women with moderate to severe uterine prolapse undergoing TVH (78) or SSUS (80) were included in a prospective study from January 2001 to June 2002. All women were <50 years old and sexually active within the last 6 months before surgical intervention. None had major medical disorders. Sexual functioning before and 6 months after surgery was examined via a face-to-face questionnaire. Sexual interest, sexual satisfaction, frequency of sexual intercourse and frequency of orgasm were measured using an analogue scale.\n Of women undergoing TVH, 5.1% had decreased sexual interest, and 21% had less frequent orgasms postoperatively. For women undergoing SSUS, 13% had decreased sexual interest, and 20% had less frequent orgasms postoperatively. Frequency of orgasm was the only parameter that changed significantly after surgery in the 2 groups. All women with less frequent orgasms said that they were afraid of wound disruption or disease recurrence and so refrained from vigorous or exciting sexual intercourse. About four-fifths of the women in both groups accepted or were satisfied with their sexuality after surgery. For women undergoing TVH, 2.6% had increased frequency of orgasm, and 5% had better overall sexual satisfaction postoperatively. For women undergoing SSUS, 10% had increased sexual satisfaction postoperatively. There was a 2.5% and 2.6% increase in postoperative sexual interest in the SSUS and TVH groups, respectively. The sexual functioning scores were not different before or after surgical intervention in either group.\n There is a decrease in thefrequency of orgasm after both TVH and SSUS. However, there is no significant difference in postoperative sexual functioning between women with and without preservation of the uterus in correcting uterine prolapse.", "To compare outcomes of anterior colporrhaphy alone to that reinforced with bovine pericardium graft.\n Women with anterior vaginal wall prolapse were enrolled in a randomized fashion in this grafted compared with nongrafted repair study. Outcome measures included pelvic organ prolapse quantification data, quality-of-life assessment, healing abnormalities, and complications.\n Ninety-four patients were enrolled. Seventy-two (77%) provided 1-year data, and 59 (63%) supplied 2-year data. Demographics and stage of prolapse were similar between groups at baseline. Postoperative complications consisted basically of low urinary tract infection and were low in both groups (10 in bovine pericardium graft and 16 in anterior colporrhaphy alone). One year after surgery, successful anterior vaginal wall support was obtained in 85.7% of the bovine pericardium graft group and 78.4% of anterior colporrhaphy-alone group (P=.544). For the cohort that comprised 2-year analyses, the success rate was 76.5% for the bovine pericardium graft group and 63% for anterior colporrhaphy-alone group (P=.509). Postoperative Urogenital Distress Inventory-6 and Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire-12 scores were uniformly improved over baseline in both groups.\n The use of bovine pericardium graft for anterior vaginal prolapse does not have higher complication rates or healing difficulties. At 1- and 2-year follow-up, anterior colporrhaphy with bovine pericardium reinforcement did not show a statistically significant improvement over colporrhaphy alone.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT00860912\n I.", "This study was undertaken to compare outcomes of 3 different rectocele repair techniques.\n One hundred six women with stage II or greater posterior vaginal wall prolapse were randomly assigned to either posterior colporrhaphy (n = 37), site-specific rectocele repair (n = 37), or site-specific rectocele repair augmented with a porcine small intestinal submucosa graft (Fortagen, Organogenesis, Inc, Canton, MA; n = 32). Subjects underwent a physical examination and completed 3 validated pelvic floor instruments at baseline and 6 months, 1 year, and 2 years after surgery. Anatomic failure was defined as pelvic organ prolapse quantitation system (POPQ) point Bp > or = -2 at 1 year.\n Of 106 subjects who enrolled, 105 underwent surgery and of those 105, 98 subjects returned (93%) with a mean follow-up of 17.5 +/- 7 months. After 1 year, those subjects who received graft augmentation had a significantly greater anatomic failure rate (12/26; 46%) than those who received site-specific repair alone (6/27; 22%) or posterior colporraphy (4/28; 14%), P = .02. There was a significant improvement in prolapse and colorectal scales and overall summary scores of the Pelvic Floor Distress Inventory short form 20 (PFDI-20), the Pelvic Floor Impact Questionnaire short form 7 (PFIQ-7) after surgery in all groups (P < .001 for each) with no differences between groups. The proportion of subjects with functional failures was 15% overall, and not significantly different between groups. There was no significant change in the rate of dyspareunia 1 year after surgery and there were no differences between groups. Overall sexual function as measured by the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form (PISQ-12) improved significantly in all groups postoperatively (P < . 001), with no differences between groups.\n Posterior colporraphy and site-specific rectocele repair result in similar anatomic and functional outcomes. The addition of a porcine-derived graft does not improve anatomic outcomes. All 3 methods of rectocele repair result in significant improvements in symptoms, quality of life, and sexual function.", "Women without stress urinary incontinence undergoing vaginal surgery for pelvic-organ prolapse are at risk for postoperative urinary incontinence. A midurethral sling may be placed at the time of prolapse repair to reduce this risk.\n We performed a multicenter trial involving women without symptoms of stress incontinence and with anterior prolapse (of stage 2 or higher on a Pelvic Organ Prolapse Quantification system examination) who were planning to undergo vaginal prolapse surgery. Women were randomly assigned to receive either a midurethral sling or sham incisions during surgery. One primary end point was urinary incontinence or treatment for this condition at 3 months. The second primary end point was the presence of incontinence at 12 months, allowing for subsequent treatment for incontinence.\n Of the 337 women who underwent randomization, 327 (97%) completed follow-up at 1 year. At 3 months, the rate of urinary incontinence (or treatment) was 23.6% in the sling group and 49.4% in the sham group (P<0.001). At 12 months, urinary incontinence (allowing for subsequent treatment of incontinence) was present in 27.3% and 43.0% of patients in the sling and sham groups, respectively (P=0.002). The number needed to treat with a sling to prevent one case of urinary incontinence at 12 months was 6.3. The rate of bladder perforation was higher in the sling group than in the sham group (6.7% vs. 0%), as were rates of urinary tract infection (31.0% vs. 18.3%), major bleeding complications (3.1% vs. 0%), and incomplete bladder emptying 6 weeks after surgery (3.7% vs. 0%) (P≤0.05 for all comparisons).\n A prophylactic midurethral sling inserted during vaginal prolapse surgery resulted in a lower rate of urinary incontinence at 3 and 12 months but higher rates of adverse events. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women's Health; OPUS ClinicalTrials.gov number, NCT00460434.).", "To report 2-year outcomes of a randomized controlled trial comparing standard anterior colporrhaphy with reinforced vaginal paravaginal repair using xenograft or synthetic mesh in women with symptomatic anterior vaginal wall prolapse.\n Women with stage II or greater anterior prolapse were randomly assigned to three groups: anterior colporrhaphy, paravaginal repair with porcine dermis, or polypropylene mesh. Outcomes of prolapse stage, quality of life, degree of bother, and sexual symptoms were assessed by blinded examiners and validated measures at 2 years. Anatomic failure was defined as anterior prolapse at stage II or greater. Composite failure was defined as symptoms of \"bulge\" and anterior prolapse at stage II or greater. Power calculations determined 33 participants per arm would detect a 40% difference in anatomic success between standard and grafted repair. χ, Mann-Whitney U, and Student's t tests were used for comparisons.\n Of the 99 participants enrolled, 78 (79%) completed a minimum of 2-year follow-up. Those with mesh had a significantly lower anatomic failure rate (18%) than both the porcine (46%, P=.015) and colporrhaphy groups (58%, P=.002). All groups had statistically similar reductions in their prolapse and urinary symptom subscale scores. Composite failure was not statistically different between groups: 13% colporrhaphy, 12% porcine, and 4% mesh. Two reoperations for anterior prolapse occurred in the porcine group. Mesh erosion rates were 14% for the mesh group.\n Vaginal paravaginal repair with polypropylene mesh has the lowest anatomic failure rate when compared with that with xenograft and anterior colporrhaphy without differences in composite failures.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT0139171.\n I.", "This prospective, randomised study investigated whether a prophylactic procedure, performed during colposacropexy for prolapse repair, prevents ex novo postoperative incontinence. Sixty-six consecutive continent patients with advanced prolapse were randomised into two groups: group A underwent sacropexy combined with a Burch colposuspension; no anti-incontinence procedure was performed in group B patients.\n Work-up included clinical assessment (Halfway System and International Continence Society [ICS] classification for prolapse and Ingelman Sunderberg scale for incontinence), the Urogenital Distress Inventory and Impact Incontinence Quality of Life questionnaires, urogynaecologic ultrasound scans, and complete urodynamic testing that included the urethral pressure profile and Valsalva leak point pressure with reduced prolapse. Check-ups were done at 3, 6, 12 mo postoperatively and then yearly. Mean follow-up time was 39.5 mo.\n The mean age (+/- standard deviation) was 62+/-9 yr. All patients presented with grade (G) 3-4 prolapse. Postoperative incontinence was present in 12 of the 34 patients in group A: 7 G1; 4 G2, and 1 G3. Postoperative incontinence was present in 3 of the 32 patients in group B: 2 G1, 1 G3. The frequency of postoperative incontinence was significantly greater in patients who had undergone colposuspension (p<0.05).\n These preliminary data cast doubt on whether colposuspension should be performed during sacropexy for severe urogenital prolapse as prophylaxis for postoperative incontinence because it seems to emerge as overtreatment. Incontinence developed ex novo in 35% of continent patients treated with colposuspension combined with sacropexy.", "We evaluated the impact of Burch colposuspension as an anti-incontinence measure in patients with urinary incontinence undergoing abdominal surgery for pelvic organ prolapse repair.\n A total of 47 women with pelvic organ prolapse and urinary incontinence were randomly assigned to abdominal pelvic organ prolapse repair and concomitant Burch colposuspension (24 patients, group A) or pelvic organ prolapse repair alone without an anti-incontinence procedure (23 patients, group B). They were followed up at 3, 6 and 9 months after surgery, and then annually. The primary outcome measures were anatomical outcome and changes in incontinence status as indicated by a bladder diary, the number of daily pads and the stress test. Secondary end points were changes in subjective symptoms and quality of life as measured by the Urogenital Distress Inventory and the Incontinence Impact Questionnaire.\n In group A 13 of 24 patients (54.2%) were still incontinent after surgery compared with 9 of 23 (39.1%) in group B. The intragroup difference was significant (group A p = 0.003, group B p = 0.0001), but there was no significant intergroup difference (p = 0.459 for A vs B). No significant intergroup difference emerged in anatomical outcome. Urogenital Distress Inventory and Incontinence Impact Questionnaire scores improved in both groups (p = 0.0001) but the intergroup difference was not significant in either questionnaire (p = 0.769 and p = 0.327, respectively).\n Burch colposuspension does not provide any additional benefit in pelvic organ prolapse repair in patients with urinary incontinence.", "The purpose of this study was to compare outcomes after anterior colporrhaphy with the use of 3 different surgical techniques.\n One hundred fourteen women with anterior vaginal prolapse were randomly assigned to undergo anterior repair by one of 3 techniques: standard, standard plus polyglactin 910 mesh, or ultralateral anterior colporrhaphy. Before and after operation, patients underwent physical examination staging of prolapse; the International Continence Society system was used. Symptoms were assessed by questionnaire and visual analog scales. We defined \"cure\" as satisfactory (stage I) or optimal (stage 0) outcome at points Aa and Ba.\n Of 114 patients who were originally enrolled, 109 patients underwent operation, and 83 patients (76%) returned for follow-up. Mean age (+/- SD) was 64.7 +/- 11.1 years. At entry, 7 patients (7%) had stage I anterior vaginal prolapse; 35 patients (37%) had stage II anterior vaginal prolapse; 51 patients (54%) had stage III anterior vaginal prolapse; and 2 patients (2%) had stage IV anterior vaginal prolapse. At a median length of follow-up of 23.3 months, 10 of 33 patients (30%) who were randomly assigned to the standard anterior colporrhaphy group experienced satisfactory or optimal anatomic results, compared with 11 of 26 patients (42%) with standard plus mesh and with 11 of 24 patients (46%) with ultralateral anterior colporrhaphy. The severity of symptoms that were related to prolapse improved markedly (preoperative score, 6.9 +/- 2.7; postoperative score, 1.1 +/- 0.8). Twenty-three of 24 patients (96%) no longer required manual pressure to void after operation.\n These 3 techniques of anterior colporrhaphy provided similar anatomic cure rates and symptom resolution for anterior vaginal prolapse repair. The addition of polyglactin 910 mesh did not improve the cure rate compared with standard anterior colporrhaphy.", "Our study compared high levator myorrhaphy (HLM) and uterosacral ligament suspension (USLS) for vaginal apex fixation from both an anatomical and functional point of view, and assessed the impact of surgery on quality of life (QoL) and sexuality.\n Two hundred twenty-nine patients with symptomatic stage >or=2 apical prolapse were randomized to USLS or HLM. Those patients who also needed cystocele repair additionally underwent an anterior prosthetic reinforcement. We defined as cure no prolapse of stage 2 or greater in any compartments according to the POP-Q system.\n Correction of apical prolapse was observed in 96.6% of the HLM group and 98.3% of the USLS group. However, a persistent anterior wall prolapse occurred in 29.2% of the HLM group and in 35.4% of the USLS group. Both groups reported improvement in storage, voiding, and prolapse-related symptoms. Urodynamics of patients in the HLM group showed post-operative reduction in detrusor pressure at maximum flow and an increase in maximum flow. Both groups saw similar improvement in QoL. We did not encounter any serious side effects, except for nine cases of intraoperative ureteral occlusion following USLS.\n This study demonstrates similar efficacy of HLM and USLS for vaginal apex suspension; however, USLS has a higher incidence of complications involving the upper urinary tract." ]

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[ "A controlled trial of cyclosporine in patients with progressive membranous nephropathy. Canadian Glomerulonephritis Study Group.", "The Medical Research Council trial of short-term high-dose alternate day prednisolone in idiopathic membranous nephropathy with nephrotic syndrome in adults. The MRC Glomerulonephritis Working Party.", "A randomized controlled trial of prednisone in patients with idiopathic membranous nephropathy.", "Controlled trial of cyclophosphamide in idiopathic membranous nephropathy.", "Controlled trial of azathioprine in the nephrotic syndrome secondary to idiopathic membranous glomerulonephritis.", "Cyclosporine in patients with steroid-resistant membranous nephropathy: a randomized trial.", "Oral cyclophosphamide versus chlorambucil in the treatment of patients with membranous nephropathy and renal insufficiency.", "Treatment of progressive membranous glomerulopathy. A randomized trial comparing cyclophosphamide and corticosteroids with corticosteroids alone. The Glomerular Disease Collaborative Network.", "A randomized trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy.", "Prognosis and management of membraneous nephropathy.", "A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy.", "Methylprednisolone plus chlorambucil as compared with methylprednisolone alone for the treatment of idiopathic membranous nephropathy. The Italian Idiopathic Membranous Nephropathy Treatment Study Group.", "Preserving renal function in patients with membranous nephropathy: daily oral chlorambucil compared with intermittent monthly pulses of cyclophosphamide.", "Randomized controlled trial of cyclophosphamide, warfarin and dipyridamole in idiopathic membranous glomerulonephritis." ]

[ "A controlled trial of cyclosporine in patients diagnosed with progressive membranous nephropathy (MGN) was carried out to determine whether cyclosporine (D) would be more effective than placebo (P) in reducing the rate of deterioration in renal function. Patients (N = 64) with MGN were placed on a restricted protein diet (< or = 0.9 g/kg) and followed closely for 12 months (Part 1). Patients at high risk of progression based on an absolute loss in creatinine clearance (CCr) of > or = 8 ml/min and persistent nephrotic range proteinuria (Pr) were selected and randomly assigned to either (D) (N = 9) or (P) (N = 8) for 12 months (Part 2). No differences in the two groups were noted at entry. After 12 months, the improvement in CCr slope in ml/min/month was significantly greater in the D patients (D + 2.1 vs. P + 0.5, mean difference 1.6; 95% CI 0.3 to 3.0, P < 0.02). This improvement was maintained in six of eight D (75%) over a mean follow-up period of 21 months. Daily Pr also improved with D (by month 3, D - 4.5 g/day vs. P + 0.7 g/day, P = 0.02) and was sustained in six of eight (75%) D patients. When Pr was expressed as a function of their concurrent CCr, the D versus P patients' time to halving was faster (P = 0.02) and absolute number higher (4/9 D vs 0/8 P). In the D group a trend towards worse hypertension and an increase in the number of transient rises in serum creatinine were noted.(ABSTRACT TRUNCATED AT 250 WORDS)", "We have assessed the medium-term effect of a short course of high-dose, alternate-day prednisolone on adult nephrotic patients with membranous nephropathy, using a randomized, prospective, double-blind, controlled trial. Patients were entered over the period 1981 to 1984 and were observed for a minimum of three years. One hundred and seven adult patients who had not previously received immunosuppressive treatment were included in the trial. One hundred and sixty further patients, excluded from the trial, but with membranous nephropathy were identified, followed and assessed retrospectively at the end of the trial. At 36 months there was no significant difference between control and treatment groups in plasma creatinine, creatinine clearance or 24-h excretion of protein. At between three and six months serum albumin concentrations were higher and protein excretions lower in the treatment group compared to controls. No significant benefit was therefore observed on renal function in the medium term.", "We conducted a prospective randomized study in which patients with biopsy-confirmed idiopathic membranous nephropathy were assigned to receive either a six-month course of prednisone given on alternate days (45 mg per square meter of body-surface area; n = 81) or no specific treatment (n = 77). The mean duration of follow-up was 48 months. Patients in the prednisone group (median age, 46 years) entered with a mean disease duration of 15 months, a median creatinine clearance of 1.2 ml per second per 1.73 m2 (range, 0.25 to 2.6), and a median rate of urinary protein excretion of 6.8 g per day (0.3 to 26). The annual change in the corrected creatinine clearance at six months did not differ between the prednisone group and the control group (0.10 vs. 0.06 ml per second; P = 0.8), or at the last follow-up evaluation (-0.07 vs. -0.02 ml per second; P = 0.2; 95 percent confidence interval on the difference, -0.03 to 0.13). The proportion of patients with complete remission of proteinuria was also similar in the groups at 6 and 12 months and after a mean of 48 months. Outcomes were similar in the two groups with respect to progression to renal failure (3 vs. 4 patients), death (3 vs. 1 patient), complete remission of proteinuria at 36 months (16 vs. 19 patients), and a decline of 25 percent or more in the creatinine clearance at 60 months (32 vs. 25 percent of patients). A multivariate analysis, which adjusted for differences at entry in sex distribution, urinary protein excretion, and creatinine concentration, as well as other prognostic variables, failed to provide an explanation for the lack of effect of prednisone. We conclude that a six-month course of therapy in which prednisone is given on alternate days is of no benefit to patients with idiopathic membranous nephropathy.", "nan", "In a controlled double-blind trial five patients with the nephrotic syndrome due to idiopathic membranous glomerulonephritis received azathioprine, 2.5 mg/kg-d, while four others received placebo. After 1 year of treatment there was no significant difference between the two groups with regard to the changes in leukocyte count, values for hemoglobin, serum creatinine, blood urea nitrogen or serum albumin, 24-hour excretion of protein in the urine, or creatinine clearance. In this study azathiprine appeared not to be useful in the treatment of idiopathic membranous glomerulonephritis.", "A clinical trial of cyclosporine in patients with steroid-resistant membranous nephropathy (MGN) was conducted. Although MGN remains the most common cause of adult-onset nephrotic syndrome, its management is still controversial. Cyclosporine has been shown to be effective in cases of progressive MGN, but it has not been used in controlled studies at an early stage of the disease.\n We conducted a randomized trial in 51 biopsy-proven idiopathic MGN patients with nephrotic-range proteinuria comparing 26 weeks of cyclosporine treatment plus low-dose prednisone to placebo plus prednisone. All patients were followed for an average of 78 weeks, and the short- and long-term effects on renal function were assessed.\n Seventy-five percent of the treatment group versus 22% of the control group (P < 0.001) had a partial or complete remission of their proteinuria by 26 weeks. Relapse occurred in 43% (N = 9) of the cyclosporine remission group and 40% (N = 2) of the placebo group by week 52. The fraction of the total population in remission then remained almost unchanged and significant different between the groups until the end of the study (cyclosporine 39%, placebo 13%, P = 0.007). Renal function was unchanged and equal in the two groups over the test medication period. In the subsequent follow-up, renal insufficiency, defined as doubling of baseline creatinine, was seen in two patients in each group, but remained equal and stable in all of the other patients.\n This study suggests that cyclosporine is an effective therapeutic agent in the treatment of steroid-resistant cases of MGN. Although a high relapse does occur, 39% of the treated patients remained in remission and were subnephrotic for at least one-year post-treatment, with no adverse effect on filtration function.", "We treated patients with idiopathic membranous nephropathy (iMGN) and renal insufficiency, using: (i) (n = 15) monthly cycles of steroids (1 g methyl-prednisolone i.v. on three consecutive days, followed by oral prednisone 0.5 mg/kg/day months 1, 3 and 5) and chlorambucil (0.15 mg/kg/day months 2, 4 and 6); or (ii) (n = 17) oral cyclophosphamide (1.5-2.0 mg/kg/day for 1 year) and steroids in a comparable dose. The groups were comparable in age, renal function and levels of proteinuria. During the 6 months preceding treatment, serum creatinine levels increased from 148 +/- 50 to 219 +/- 73 mumol/l in the chlorambucil group and from 164 +/- 86 to 274 +/- 126 mumol/l in the cyclophosphamide group. Median (range) follow-ups were: chlorambucil 38 months (8-71); cyclophosphamide 26 months (5-68) (NS). Renal function improved in both groups, but the improvement was short-lived in the chlorambucil group; 12 months after starting treatment, mean serum creatinine was 6.3 mumol/l lower in the chlorambucil group and 121 mumol/l lower in the cyclophosphamide group (p < 0.01). Four chlorambucil-treated patients developed ESRD, and five needed a second course of therapy, whereas only one cyclophosphamide-treated patient developed ESRD (p < 0.05). Remissions of proteinuria occurred more frequently after cyclophosphamide treatment (15/17 vs. 5/15; p < 0.01). Side-effects necessitated interruption of treatment in six patients on cyclophosphamide and in 11 on chlorambucil (p < 0.05). In our patients, oral cyclophosphamide was better tolerated than oral chlorambucil. The suggested greater efficacy of the oral cyclophosphamide regimen needs to be ascertained by longer follow-up.", "To determine if deterioration in renal function could be ameliorated by adding cyclophosphamide to corticosteroid therapy in patients with progressive membranous glomerulopathy.\n Randomized, controlled treatment trial. Patients were followed for a mean of 29.2 +/- 17.1 months.\n Collaborative network of 120 university and private-practice nephrologists.\n Patients with membranous glomerulopathy whose renal function deteriorated (as evidenced by doubling of the serum creatinine level, a 50% fall in the glomerular filtration rate, or a sustained serum creatinine level of greater than 2.0 mg/dL [reciprocal creatinine value, 0.5], or whose nephrotic range proteinuria persisted in association with morbid complications. Of 156 patients with biopsy-proven membranous glomerulopathy, 36 became eligible for randomization. Twenty-six of these 36 patients were randomly assigned to receive one of the two treatments.\n Pulse methylprednisolone, oral corticosteroids, and 6 months of intravenous cyclophosphamide or alternate-day corticosteroid therapy alone.\n At entry, no statistical differences were found between the treatment groups in duration of renal disease, age, gender, serum creatinine level, 24-hour urine protein excretion, or biopsy stage. The groups showed no difference in mean arterial blood pressure during follow-up. Four of the 13 patients receiving corticosteroids alone and 4 of the 13 patients receiving corticosteroids plus intravenous cyclophosphamide progressed to end-stage renal disease during follow-up. Reciprocal creatinine values tested at 6-month intervals showed no statistical differences between treatment groups at any time point. The log of the 24-hour protein excretion values showed no statistical differences between treatment groups after treatment. The power to detect a substantial improvement in renal function, defined as a doubling of the reciprocal of the serum creatinine, at the 0.05 significance level was 0.92.\n Combination therapy with intravenous cyclophosphamide and corticosteroids, when compared with corticosteroid therapy alone, does not improve renal function in patients with progressive membranous glomerulopathy.", "We conducted a controlled trial to investigate the long-term effects of treatment with methylprednisolone and chlorambucil in patients with idiopathic membranous nephropathy. We have previously reported that after a mean of 31 months, treated patients did better. We now report the results of a longer follow-up. Eighty-one patients with proteinuria (greater than or equal to 3.5 g per day) and biopsy-proved membranous nephropathy were randomly assigned to receive either supportive therapy alone or a six-month course of corticosteroids alternated with chlorambucil (0.2 mg per kilogram of body weight per day) every other month. Methylprednisolone was first given intravenously in three pulses (1 g per day) and was then given orally (0.4 mg per kilogram per day) for 27 days. The patients were followed for 2 to 11 years (median, 5). Two patients in the control group and one in the treatment group died. At the last follow-up visit, 9 of 39 patients assigned to the control group (23 percent) and 28 of 42 patients assigned to the treatment group (67 percent) did not have the nephrotic syndrome. At five years there were more remissions of the nephrotic syndrome in treated patients than in controls (22 of 30 vs. 10 of 25; P = 0.026). Compared with base-line values, the mean reciprocal of the plasma creatinine level declined significantly in the control group (33 percent; P = 0.0002) but not in the treatment group (6 percent; P not significant). Plasma creatinine increased by 50 percent or more in 19 controls (49 percent) and in 4 treated patients (10 percent). We conclude that a six-month course of methylprednisolone and chlorambucil can bring about sustained remission of the nephrotic syndrome and help to preserve renal function in patients with idiopathic membranous nephropathy.", "Patients of idiopathic membranous nephropathy (MGN) were randomly assigned to received steroid and cyclophosphamide every other month (Gr-I) and steroid alone (Gr-II). Of 36 patients in Gr.I, 33 patients achieved complete remissions, 2 had relapsing course with remission on further courses of therapy and only one has reached end stage renal failure. In contrast, of the 35 patients in Gr. II, 15 (P < 0.001) achieved complete remission, 7 are in partial remission, 5 have no response, another 5 have deterioration of renal function of which two required dialysis, and 3 have relapsing course after the initial remission. Mean follow up period was 46 +/- 10.2 months. We conclude that steroid and cyclophosphamide every other month is highly effective in achieving remission in patients with membranous nephropathy.", "To assess whether chlorambucil or cyclophosphamide may have a better therapeutic index in patients with idiopathic membranous nephropathy, we compared two regimens based on a 6-mo treatment, alternating every other month methylprednisolone with chlorambucil or methylprednisolone with cyclophosphamide. Patients with biopsy-proven membranous nephropathy and with a nephrotic syndrome were randomized to be given methylprednisolone (1 g intravenously for 3 consecutive days followed by oral methylprednisolone, 0.4 mg/kg per d for 27 d) alternated every other month either with chlorambucil (0.2 mg/kg per d for 30 d) or cyclophosphamide (2.5 mg/kg per d for 30 d). The whole treatment lasted 6 mo; 3 mo with corticosteroids and 3 mo with one cytotoxic drug. Among 87 patients followed for at least 1 yr, 36 of 44 (82%; 95% confidence interval [CI], 67.3 to 91.8%) assigned to methylprednisolone and chlorambucil entered complete or partial remission of the nephrotic syndrome, versus 40 of 43 (93%; 95% CI, 80.9 to 98.5%) assigned to methylprednisolone and cyclophosphamide (P = 0.116). Of patients who attained remission of the nephrotic syndrome, 11 of 36 in the chlorambucil group (30.5%) and 10 of 40 in the cyclophosphamide group (25%) had a relapse of the nephrotic syndrome between 6 and 30 mo. The reciprocal of plasma creatinine improved in the cohort groups followed for 1 yr for both treatment groups (P < 0.01) and remained unchanged when compared with basal values in the cohort groups followed for 2 and 3 yr. Six patients in the chlorambucil group and two in the cyclophosphamide group did not complete the treatment because of side effects. Four patients in the chlorambucil group but none in the cyclophosphamide group suffered from herpes zoster. One patient per group developed cancer. It is concluded that in nephrotic patients with idiopathic membranous nephropathy both treatments may be effective in favoring remission and in preserving renal function for at least 3 yr.", "Treatment with methylprednisolone and chlorambucil may protect renal function and increase the chance of remission of the nephrotic syndrome in patients with idiopathic membranous nephropathy. To determine whether similar results might be obtained with methylprednisolone alone, we compared the effects of methylprednisolone and chlorambucil with those of methylprednisolone alone in 92 patients with the nephrotic syndrome caused by idiopathic membranous nephropathy. The patients were randomly assigned to receive either alternating one-month courses of methylprednisolone and then chlorambucil for a total of six months (group 1) or methylprednisolone alone for six months at the same cumulative dosage (group 2).\n Four of the 45 patients in group 1 (9 percent) and 1 of the 47 in group 2 (2 percent) stopped treatment because of side effects. At one, two, and three years, the percentage of patients who did not have the nephrotic syndrome was significantly higher in group 1 than in group 2. It was 58, 54, and 66 percent, respectively, in group 1, as compared with 26, 32, and 40 percent in group 2 (P = 0.002, 0.029, and 0.011). By year 4, the difference was no longer statistically significant: 62 percent of the patients in group 1 and 42 percent of those in group 2 did not have the nephrotic syndrome (P = 0.102). The patients in group 1 were in remission longer than those in group 2 (P = 0.008).\n In patients with the nephrotic syndrome caused by idiopathic membranous nephropathy, treatment with methylprednisolone and chlorambucil for six months induces an earlier remission of the nephrotic syndrome than methylprednisolone alone, but the difference may diminish with time.", "To compare oral chlorambucil and intravenous cyclophosphamide-based drug regimens in the treatment of patients with membranous nephropathy and deteriorating renal function.\n Randomized study.\n University hospital and teaching hospitals.\n 18 patients with membranous nephropathy, a nephrotic syndrome, and deteriorating renal function.\n Chlorambucil (0.15 mg/kg body weight per day orally in months 2, 4, and 6) and prednisone (three intravenous pulses of 1 g of methylprednisolone followed by oral prednisone at 0.5 mg/kg per day in months 1, 3, and 5) or intravenous cyclophosphamide (750 mg/m2 body surface area once every month for 6 months) and methylprednisolone (three intravenous 1-g pulses in months 1, 3, and 5).\n Serum creatinine, serum cholesterol, serum albumin, and urinary protein levels.\n Before treatment, no statistical differences were found between the treatment groups. Six months after treatment was started, serum creatinine levels had decreased in the group treated with chlorambucil, methylprednisolone, and prednisone from a mean of 260 +/- 112 mumol/L to 186 +/- 74 mumol/L (P = 0.003) and had increased in the group treated with intravenous cyclophosphamide and methylprednisolone from 218 +/- 85 mumol/L to 297 +/- 143 mumol/L (P = 0.02; difference between both groups, P < 0.001). Serum albumin levels increased in both groups by 9 and 6 g/L, respectively, and the urinary protein/creatinine ratio decreased by 2.6 and 3.1 g/10 mmol, respectively. At the end of follow-up (median, 15 months; range, 6 to 36 months), one patient in the chlorambucil group and four patients in the cyclophosphamide group had reached end-stage renal failure after 36, 12, 12, 18, and 18 months of therapy, respectively. One patient in the intravenous cyclophosphamide group died after 6 months of therapy.\n Thus far, both oral chlorambucil and oral cyclophosphamide have been shown to be effective in the treatment of patients with membranous nephropathy and deteriorating renal function. Our study shows that intermittent monthly pulses of low-dose cyclophosphamide are ineffective in preserving renal function in such patients.", "40 patients with idiopathic membranous glomerulonephritis were randomized to receive either no treatment or a regime of cyclophosphamide for 6 months, and warfarin and dipyridamole for two years. During the two years of the trial there was no significant deterioration in renal function in either group. A significantly greater improvement in urinary protein excretion was, however, observed at all time points in the treatment group. Plasma albumin was also significantly higher in the treatment group at 18 and 24 months. As progressive deterioration in renal function in membranous glomerulonephritis is associated with persistent heavy proteinuria these results suggest a beneficial effect of treatment." ]

[ "11897644" ]

[ "Prospective, randomized, controlled pilot study of partial liquid ventilation in adult acute respiratory distress syndrome." ]

[ "We evaluated the safety and efficacy of partial liquid ventilation (PLV) with perflubron in adult patients with acute lung injury and the acute respiratory distress syndrome (ARDS) in a multicenter, prospective, controlled, randomized exploratory clinical trial. Ninety adult patients with PaO2/FIO2 ratios > 60 and < 300 with ARDS for no more than 24 hours were randomized to receive PLV (n = 65) with administration of perflubron through an endotracheal tube sideport or conventional mechanical ventilation (CMV, n = 25) for a maximum of five days. Although a significant reduction in progression to ARDS was noted among patients with PLV, no significant differences in the number of days free from the ventilator at 28 days (CMV = 6.7 +/- 1.8, PLV = 6.3 +/- 1.0 days, p = 0.85), the incidence of mortality (CMV = 36%, PLV = 42%, p = 0.63), or any pulmonary-related parameter were observed. During a post hoc subgroup analysis, significantly more rapid discontinuation of mechanical ventilation (p = 0.045) and a trend toward an increase in the number of days free from the ventilator at 28 days (CMV = 3.2 +/- 1.9, PLV = 8.0 +/- 2.2 days, p = 0.06) were observed during PLV among those patients under 55 years of age with acute lung injury or ARDS. Episodes of hypoxia, respiratory acidosis, and bradycardia occurred more frequently in the PLV group, but these were transient and self-limited. Further evaluation of PLV is warranted to further define beneficial effects in well-defined groups of patients and also to gain additional information regarding safety." ]

[ "10471432", "15680453", "9818860", "2222242", "2651586", "2926492", "15352598" ]

[ "Early surgical treatment for supratentorial intracerebral hemorrhage: a randomized feasibility study.", "Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial.", "Surgical treatment for intracerebral hemorrhage (STICH): a single-center, randomized clinical trial.", "Failure of surgery to improve outcome in hypertensive putaminal hemorrhage. A prospective randomized trial.", "The treatment of spontaneous intracerebral hemorrhage. A prospective randomized trial of surgical and conservative treatment.", "Endoscopic surgery versus medical treatment for spontaneous intracerebral hematoma: a randomized study.", "Impact of stereotactic hematoma evacuation on activities of daily living during the chronic period following spontaneous putaminal hemorrhage: a randomized study." ]

[ "The safety and the effectiveness of the surgical treatment of spontaneous intracerebral hemorrhage (ICH) remain controversial. To investigate the feasibility of urgent surgical evacuation of ICH, we conducted a small, randomized feasibility study of early surgical treatment versus current nonoperative management in patients with spontaneous supratentorial ICH.\n Patients with spontaneous supratentorial ICH who presented to 1 university and 2 community hospitals were randomized to surgical treatment or best medical treatment. Principal eligibility criteria were ICH volume >10 cm(3) on baseline CT scan with a focal neurological deficit, Glasgow Coma Scale score >4 at the time of enrollment, randomization and therapy within 24 hours of symptom onset, surgery within 3 hours of randomization, and no evidence for ruptured aneurysm or arteriovenous malformation. The primary end point was the 3-month Glasgow Outcome Scale (GOS). A good outcome was defined as a 3-month GOS score >3.\n Twenty patients were randomized over 24 months, 9 to surgical intervention and 11 to medical treatment. The median time from onset of symptoms to presentation at the treating hospitals was 3 hours and 17 minutes, the time from randomization to surgery was 1 hour and 20 minutes, and the time from onset of symptoms to surgery was 8 hours and 35 minutes. The likelihood of a good outcome (primary outcome measure: GOS score >3) for the surgical treatment group (56%) did not differ significantly from the medical treatment group (36%). There was no significant difference in mortality at 3 months. Analysis of the secondary 3-month outcome measures showed a nonsignificant trend toward a better outcome in the surgical treatment group versus the medical treatment group for the median GOS, Barthel Index, and Rankin Scale and a significant difference in the National Institutes of Health Stroke Scale score (4 versus 14; P=0.04).\n Very early surgical treatment for acute ICH is difficult to achieve but feasible at academic medical centers and community hospitals. The trend toward less 3-month morbidity with surgical intervention in patients with spontaneous supratentorial ICH warrants further investigation of very early clot removal in larger randomized clinical trials.", "Spontaneous supratentorial intracerebral haemorrhage accounts for 20% of all stroke-related sudden neurological deficits, has the highest morbidity and mortality of all stroke, and the role of surgery remains controversial. We undertook a prospective randomised trial to compare early surgery with initial conservative treatment for patients with intracerebral haemorrhage.\n A parallel-group trial design was used. Early surgery combined haematoma evacuation (within 24 h of randomisation) with medical treatment. Initial conservative treatment used medical treatment, although later evacuation was allowed if necessary. We used the eight-point Glasgow outcome scale obtained by postal questionnaires sent directly to patients at 6 months follow-up as the primary outcome measure. We divided the patients into good and poor prognosis groups on the basis of their clinical status at randomisation. For the good prognosis group, a favourable outcome was defined as good recovery or moderate disability on the Glasgow outcome scale. For the poor prognosis group, a favourable outcome also included the upper level of severe disability. Analysis was by intention to treat.\n 1033 patients from 83 centres in 27 countries were randomised to early surgery (503) or initial conservative treatment (530). At 6 months, 51 patients were lost to follow-up, and 17 were alive with unknown status. Of 468 patients randomised to early surgery, 122 (26%) had a favourable outcome compared with 118 (24%) of 496 randomised to initial conservative treatment (odds ratio 0.89 [95% CI 0.66-1.19], p=0.414); absolute benefit 2.3% (-3.2 to 7.7), relative benefit 10% (-13 to 33).\n Patients with spontaneous supratentorial intracerebral haemorrhage in neurosurgical units show no overall benefit from early surgery when compared with initial conservative treatment.", "To perform a single-center pilot investigation of early hematoma removal in patients with intracerebral hemorrhage (ICH).\n Considerable debate remains regarding the utility of surgical clot evacuation for ICH.\n This was a prospective trial of open craniotomy within 12 hours of ICH symptom onset versus best medical therapy. Patients were eligible if they had a nontraumatic ICH >9 mL with significant neurologic impairment and were prepared for surgery within 12 hours of symptom onset. The study included a prospective registry of patients and a randomized trial.\n The registry group included 34 medical and seven surgical patients. The surgical group had larger hemorrhages (median, 96 mL) and a lower Glasgow Coma Scale (GCS) score (median, 10) compared with the medical group (33 mL; GCS score, 13). Six-month mortality was less in the medical group (36%) compared with the surgical group (54%). In the randomized series, median ICH volumes were similar in the surgical group (n = 17; 49 mL) compared with the medical group (n = 17; 44 mL). Median GCS score was also similar (medical, 10; surgical, 11). Mortality was lower in the surgical group (6%) compared with the medical group (24%) at 1 month, but similar at 6 months (surgical group, 17%; medical group, 24%).\n A trial of early surgery for ICH is feasible. This study represents the largest prospective, randomized series of surgery for ICH. A modest early mortality benefit for surgery is possible, but long-term benefit for surgery was not established in this single-center pilot investigation.", "Hypertensive putaminal hemorrhage remains a major cause of hemorrhagic stroke carrying extremely high morbidity. Considerable controversy remains regarding the optimal form of therapy. Between 1983 and 1989 we conducted a prospective randomized trial with three treatment strategies: best medical management, best medical management plus intracranial pressure monitoring, and surgical evacuation. Only patients with significant deficit harboring a putaminal hematoma at least 3.0 cm in diameter were entered. The study was interrupted after 21 patients had been studied (9, best medical management; 4, intracranial pressure monitoring; and 8, surgical evacuation). No differences were found among groups for age, admission blood pressure, and time interval between onset of symptoms and arrival at hospital. None of the subjects were capable of returning to prestroke activity. Fifteen (71%) died or remained vegetative at 6 months, and only 4 (19%) were capable of independent life at home. Of the 9 patients in the best medical management arm, 7 were dead or vegetative. In the surgical group, 4 patients died and only 2 were capable of independent life. These results suggest that current medical and neurosurgical therapies remain ineffective in preventing the devastating neurologic consequences of hypertensive putaminal hemorrhage.", "In a prospective study, 52 patients with a spontaneous supratentorial intracerebral hematoma (ICH) were randomly assigned to receive emergency surgery or conservative treatment within 48 hours after the bleed. Patients with a decreased level of consciousness and/or a severe neurological deficit were admitted to the study. The overall mortality rate at 6 months was 42%: 10 (38%) of the 26 patients in the conservative group and 12 (46%) of the 26 in the surgical group. Six (20%) of the 30 survivors at 6 months were able to conduct their activities of daily living independently: five (31%) of the 16 patients in the conservative group and one (7%) of the 14 in the operative group. These differences are not statistically significant. The mortality rate of semicomatose or stuporous patients (Glasgow Coma Scale score 7 to 10) was statistically significantly lower in the surgical group (none of the four patients) than in the conservative group (four of five patients) (p less than 0.05); however, all surviving patients in this subgroup were severely disabled. The study suggests that surgical treatment of this category of patients with ICH does not offer any definite advantage over conservative treatment. In semicomatose or stuporous patients, surgery may improve the length of survival, but the quality of life remains poor.", "A controlled randomized study of endoscopic evacuation versus medical treatment was performed in 100 patients with spontaneous supratentorial intracerebral (subcortical, putaminal, and thalamic) hematomas. Patients with aneurysms, arteriovenous malformations, brain tumors, or head injuries were excluded. Criteria for inclusion were as follows: patients' age between 30 and 80 years; a hematoma volume of more than 10 cu cm; the presence of neurological or consciousness impairment; the appropriateness of surgery from a medical and anesthesiological point of view; and the initiation of treatment within 48 hours after hemorrhage. The criteria of randomization were the location, size, and side of the hematoma as well as the patient's age, state of consciousness, and history of hypertension. Evaluation of outcome was performed 6 months after hemorrhage. Surgical patients with subcortical hematomas showed a significantly lower mortality rate (30%) than their medically treated counterparts (70%, p less than 0.05). Moreover, 40% of these patients had a good outcome with no or only a minimal deficit versus 25% in the medically treated group; the difference was statistically significant for operated patients with no postoperative deficit (p less than 0.01). Surgical patients with hematomas smaller than 50 cu cm made a significantly better functional recovery than did patients of the medically treated group, but had a comparable mortality rate. By contrast, patients with larger hematomas showed significantly lower mortality rates after operation but had no better functional recovery than the medically treated group. This effect from surgery was limited to patients in a preoperatively alert or somnolent state; stuporous or comatose patients had no better outcome after surgery. The outcome of surgical patients with putaminal or thalamic hemorrhage was no better than for those with medical treatment; however, there was a trend toward better quality of survival and chance of survival in the operated group.", "Stereotactic evacuation of hematoma has been reported to reduce the incidence of mortality and to improve functional outcome in patients with spontaneous putaminal hemorrhage. Stereotactic evacuation of hematoma has not been widely accepted as a standard therapy, however, because its effect on functional outcome has been regarded as marginal and there have been no randomized trials with sufficient statistical power to quantify the benefits of this procedure. The authors reassessed the value of stereotactic evacuation of hematoma by analyzing its impact on activities of living during the chronic period following spontaneous putaminal hemorrhage in a randomized study.\n Four hundred ninety patients were entered into the study. The severity of their hemorrhages was graded neurologically on admission (neurological grades: 1, eyes are open; 2, eyes are closed but open to weak stimuli; 3, eyes are closed but open to strong stimuli; 4, eyes do not open but extremities move to stimuli; and 5, eyes do not open and extremities do not move to stimuli). Patients with Grade 2 and those with Grade 3 were randomized into two groups with different treatment protocols (Group I, stereotactic evacuation of the hematoma; and Group II, conservative treatment). Patients assigned neurological Grade 4 or 5 were excluded from the study because a large-scale retrospective study in Japan revealed that surgical treatment in patients assigned to these neurological grades does not improve functional outcome. Among the 490 patients, 242 were randomized strictly. This patient population comprised 148 men and 94 women ranging in age from 38 to 80 years (mean 60.5 years). Compared with Group II, Group I treatment resulted in a lower mortality rate and better recovery to functional independence in patients with neurological Grade 3. In patients with Grade 2, Group I treatment contributed to a better recovery of functional outcome and a lower mortality rate, but the difference was not significant. Multivariate analysis confirmed that stereotactic evacuation of the hematoma was contributory to a better recovery in functional outcome.\n Stereotactic evacuation of hematoma is clearly of value in selected patients with spontaneous putuminal hemorrhage, whose eyes are closed but will open in response to strong stimuli (neurological Grade 3) on admission." ]

[ "18836622", "19340730", "16128939" ]

[ "Propofol infusion versus intermittent meperidine and midazolam injection for conscious sedation in ERCP.", "Sedation with propofol for interventional endoscopy by trained nurses in high-risk octogenarians: a prospective, randomized, controlled study.", "Sedation with propofol for routine ERCP in high-risk octogenarians: a randomized, controlled study." ]

[ "ERCP generally requires longer time than standard endoscopy. Only few studies have shown benefit of intermittent propofol over conventional sedation. This study was conducted to compare satisfaction, recovery score, and recovery/safety profiles for ERCP sedation between continuous infusion of propofol and conventional sedation.\n One hundred thirty-four patients with ASA I-III underwent ERCP and were randomly assigned into two groups (n=67 each). Patients underwent propofol sedation or meperidine/midazolam sedation. Supplemental oxygen was offered only when oxygen saturation was lower than 90 %. Oxygen saturation, blood pressure, heart rate, recovery score, times for recovery and satisfaction score after procedure were recorded and analyzed.\n Average amount of meperidine, midazolam and propofol per each patient were 61.54 (+/- 27.29), 7.80 (+/- 3.73), 299.90 (+/- 146.15) mg, respectively. Time to regain full consciousness in the propofol arm was significantly shorter than in the conventional arm (17.24 +/- 5.99 versus 34.25 +/- 16.06 min, p<0.001). The rates of desaturation, bradycardia and hypotension in both arms were low and comparable. Propofol provided higher level of recovery scores at 15, 30, 45 and 60 min after the procedure (p < 0.001).\n Continuous infusion of propofol for ERCP by direction of gastroenterologist yields no difference in the completion rate and adverse profiles when compared with conventional technique but it provides a better recovery profile. The maintainance of appropriate level of sedation by well trained personnel is the key to achieve this success.", "Sedation with the short-acting anesthetic agent propofol has shown several advantages, particularly in interventional endoscopy. So far, however, there are no valid data on the safety of nurse-administered propofol sedation (NAPS) during interventional endoscopy in elderly high-risk patients.\n A total of 150 patients aged > 80 years with high comorbidity were randomized to receive midazolam plus meperidine (n = 75) or propofol alone (n = 76) for sedation during endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS), or double-balloon endoscopy (DBE). Sedation was supervised by a trained nurse and a trained physician both of whom were not involved in the endoscopic procedure. Vital signs were continuously monitored as well as patient cooperation and tolerance. Mortality and morbidity at 30 days was analyzed.\n The overall cardiopulmonary complication rate was 16 % in the midazolam group and 23.7 % in the propofol group ( P > 0.05). The mean decline in oxygen saturation (initial vs. lowest O (2) saturation) and the mean decline of blood pressure (initial vs. lowest blood pressure) were significantly greater with propofol (7 % +/- 3 % vs. 4 % +/- 2 % [ P < 0.05] and 10 % +/- 2 % vs. 8 % +/- 2 %, respectively [ P < 0.05]). No procedure had to be interrupted due to serious adverse events. Patient cooperation was statistically significantly better in the propofol group (7 +/- 2 vs. 5 +/- 2 points). Patients sedated with propofol showed a significantly lower oxygen saturation rate during recovery time (8 % vs. 28 %; P < or = 0.01).\n NAPS during interventional endoscopy is as safe as midazolam/pethidine sedation even in high-risk patients aged > 80 years.", "Adequate patient sedation is mandatory for diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). In this respect it is known that the short-acting anesthetic propofol offers certain potential advantages for sedation during ERCP, but there are no controlled studies concerning the feasibility and safety of propofol sedation in elderly, high-risk patients.\n One hundred and fifty consecutive patients aged >or=80 yr with high comorbidity (ASA score >or=III: 91 %), randomly received midazolam plus meperidine (n = 75) or propofol alone (n = 75) for sedation during ERCP. Vital signs were continuously monitored and procedure-related parameters, recovery time, and quality as well as patients' cooperation and tolerance of the procedure were assessed.\n Clinically relevant changes in vital signs were observed at comparable frequencies with a temporary oxygen desaturation (<90%) occurring in eight patients in the propofol-group and seven patients receiving midazolam/meperidine (n.s.). Hypotension was documented in two patients in the propofol group and one patient receiving midazolam/meperidine. Propofol provided a significantly better patient cooperation than midazolam/meperidine (p < 0.01), but the procedure tolerability was rated nearly the same by both groups. Mean recovery time was significantly shorter in the propofol group (22 +/- 7 min vs 31 +/- 8 min for midazolam/meperidine (p < 0.01)) while the recovery score was significantly higher under propofol (8.3 +/- 1.2 vs 6.1 +/- 1.1(p < 0.01)). During recovery a significant lower number of desaturation events (<90%) were observed in the propofol group (12%) than in the midazolam/meperidine group (26%, p < 0.01).\n Under careful monitoring the use of propofol for sedation during ERCP is superior to midazolam/meperidine even in high-risk octogenarians." ]

[ "20042424", "17572255", "19208649", "21167340", "18845667", "15219514", "21148540", "19508995", "16413875", "16520413", "17081355", "21127322", "19936457", "20826249", "16990384", "16820564", "17764767", "19420003", "16117862", "16796836", "17711705", "20211323", "20022872", "16822566", "16990383", "19892047", "17521544", "16775089" ]

[ "Bone marrow cell transplantation improves cardiac, autonomic, and functional indexes in acute anterior myocardial infarction patients (Cardiac Study).", "Intracoronary injection of autologous bone marrow-derived mononuclear cells in patients with large anterior acute myocardial infarction: a prematurely terminated randomized study.", "Intracoronary infusion of bone marrow-derived selected CD34+CXCR4+ cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial.", "CD34(+) cell infusion after ST elevation myocardial infarction is associated with improved perfusion and is dose dependent.", "Effects of intracoronary injection of mononuclear bone marrow cells on left ventricular function, arrhythmia risk profile, and restenosis after thrombolytic therapy of acute myocardial infarction.", "Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction.", "Intracoronary infusion of mononuclear cells from bone marrow or peripheral blood compared with standard therapy in patients after acute myocardial infarction treated by primary percutaneous coronary intervention: results of the randomized controlled HEBE trial.", "Long-term myocardial functional improvement after autologous bone marrow mononuclear cells transplantation in patients with ST-segment elevation myocardial infarction: 4 years follow-up.", "Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial.", "Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months' follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial.", "[Observation on the safety: clinical trail on intracoronary autologous bone marrow mononuclear cells transplantation for acute myocardial infarction].", "Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction: results of the randomized multicenter BONAMI trial.", "Systolic function of patients with myocardial infarction undergoing autologous bone marrow transplantation.", "Results of a phase 1, randomized, double-blind, placebo-controlled trial of bone marrow mononuclear stem cell administration in patients following ST-elevation myocardial infarction.", "Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction.", "Differential effect of intracoronary infusion of mobilized peripheral blood stem cells by granulocyte colony-stimulating factor on left ventricular function and remodeling in patients with acute myocardial infarction versus old myocardial infarction: the MAGIC Cell-3-DES randomized, controlled trial.", "Three-, 6-, and 12-month results of autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction.", "Repeated autologous bone marrow mononuclear cell therapy in patients with large myocardial infarction.", "Assessment of left ventricular segmental function after autologous bone marrow stem cells transplantation in patients with acute myocardial infarction by tissue tracking and strain imaging.", "[Long term follow-up on emergent intracoronary autologous bone marrow mononuclear cell transplantation for acute inferior-wall myocardial infarction].", "[Evaluation of myocardial viability with 201Tl/18F-FDG DISA-SPECT technique in patients with acute myocardial infarction after emergent intracoronary autologous bone marrow mononuclear cells transplantation].", "Results of intracoronary stem cell therapy after acute myocardial infarction.", "Influence of bone marrow stem cells on left ventricle perfusion and ejection fraction in patients with acute myocardial infarction of anterior wall: randomized clinical trial: Impact of bone marrow stem cell intracoronary infusion on improvement of microcirculation.", "The clinical study of autologous peripheral blood stem cell transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI).", "Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction.", "Effect of intracoronary injection of mononuclear bone marrow stem cells on left ventricular function in patients with acute myocardial infarction.", "[Regenerative therapy in patients with a revascularized acute anterior myocardial infarction and depressed ventricular function].", "Efficacy of emergent transcatheter transplantation of stem cells for treatment of acute myocardial infarction (TCT-STAMI)." ]

[ "Bone marrow (BM) stem cells improve cardiac function and outcome after acute ST-segment elevation myocardial infarction (MI). In this randomized controlled trial, the effects of intracoronary transfer of autologous BM cells on left ventricular ejection fraction (LVEF) and volumes (2D-echo and resting SPECT), stroke volume [impedance cardiography (ICG)], autonomic control [heart rate variability (HRV)], baroreflex sensitivity (BRS), and exercise tolerance (cardiopulmonary exercise test) were assessed in post-MI patients. Exercise stress SPECT was also performed.\n After percutaneous coronary intervention (PCI), 38 patients with residual LV dysfunction were randomized to either the BM group (optimized treatment plus intracoronary transfer of autologous BM cells 4 + or - 1 days after PCI, n = 19) or control (C) group (optimized treatment only, n = 19). After 12 months, mean LVEF (%) increased 13.1 + or - 1.9 in the BM patients vs. 5.3 + or - 2.0 in C, with an increase in stroke volume (mL, 14.5 + or - 4.0 in BM vs. 1.8 + or - 3.7 in C) associated with improved HRV [SD (ms) 62.4 + or - 8.3 in BM vs. 19.0 + or - 7.5 in C), higher BRS (ms/mmHg, 8.0 + or - 1.8 in BM vs. -1.9 + or - 1.7 in C), and peak VO(2) (mL/kg min(-1), 3.5 + or - 1.0 in BM vs. -0.4 + or - 0.5 in C). Stress SPECT showed improvements in perfusion, regional and global LV function scores (P < 0.05 BM vs. C groups for all comparisons). Cell transfer did not increase the risk of adverse clinical, in-stent restenosis, or proarrhythmic events.\n The beneficial effect of autologous BM cells in post-MI patients with depressed LV function may be mediated by restoration of autonomic control, and improved exercise tolerance.", "nan", "Comparison of intracoronary infusion of bone marrow (BM)-derived unselected mononuclear cells (UNSEL) and selected CD34(+)CXCR4(+) cells (SEL) in patients with acute myocardial infarction (AMI) and reduced <40% left ventricular ejection fraction (LVEF).\n Two hundred patients were randomized to intracoronary infusion of UNSEL (n = 80) or SEL (n = 80) BM cells or to the control (CTRL) group without BM cell treatment. Primary endpoint: change of LVEF and volumes measured by magnetic resonance imaging before and 6 months after the procedure. After 6 months, LVEF increased by 3% (P = 0.01) in patients treated with UNSEL, 3% in patients receiving SEL (P = 0.04) and remained unchanged in CTRL group (P = 0.73). There were no significant differences in absolute changes of LVEF between the groups. Absolute changes of left ventricular end-systolic volume and left ventricular end-diastolic volume were not significantly different in all groups. Significant increase of LVEF was observed only in patients treated with BM cells who had baseline LVEF < median (37%). Baseline LVEF < median and time from the onset of symptoms to primary percutaneous coronary intervention > or = median were predictors of LVEF improvement in patients receiving BM cells. There were no differences in major cardiovascular event (death, re-infarction, stroke, target vessel revascularization) between groups.\n In patients with AMI and impaired LVEF, treatment with BM cells does not lead to a significant improvement of LVEF or volumes. There was however a trend in favour of cell therapy in patients with most severely impaired LVEF and longer delay between the symptoms and revascularization.", "the objective of the study was to determine whether the effects of infarct-related artery (IRA) infusion of autologous bone marrow-derived CD34(+) cells after ST elevation myocardial infarction (STEMI) are dependent on the dose (quantity and mobility) of the cells infused. Beneficial effects of IRA infusion of mononuclear cells after STEMI have been inconsistent, possibly because of differences in timing, cell type, quantity, and mobility of infused cells.\n patients were randomized to bone marrow harvest (n = 16) or control (n = 15). At a median of 8.3 days after coronary stenting for STEMI, CD34(+) cells were infused via the IRA at 3 dose levels (5, 10, and 15 × 10(6)) in cohorts of 5 patients each. Baseline and follow-up imaging and ex vivo CD34(+) cell mobility were performed.\n Cell harvest and infusion were safe. Quantitative rest hypoperfusion score measured by single-photon emission computed tomography improved at 6 months in the ≥ 10 million cohorts compared with controls (-256 vs +14, P = .02). There was a trend toward improved ejection fraction at 6 months (+4.5%) in the ≥ 10 million cohorts compared with no change in the controls and 5 million cohort (+0.7%). Improved perfusion and infarct size reduction correlated with the quantity and mobility of the infused CD34(+) cells.\n the effects of CD34(+) cell IRA infusion during the repair phase after STEMI are dose dependent and, at a threshold dose of 10 million CD34(+) cells, associated with a significant improvement in perfusion that may limit deterioration in cardiac function (IRA infusion of CD34(+) cells in patients with acute myocardial infarction [AMR-01] NCT00313339).", "To assess the efficacy and safety of bone marrow cell (BMC) therapy after thrombolytic therapy of an acute ST-elevation myocardial infarction (STEMI).\n Patients with STEMI treated with thrombolysis followed by percutaneous coronary intervention (PCI) 2-6 days after STEMI were randomly assigned to receive intracoronary BMCs (n = 40) or placebo medium (n = 40), collected and prepared 3-6 h prior PCI and injected into the infarct artery immediately after stenting. Efficacy was assessed by the measurement of global left ventricular ejection fraction (LVEF) by left ventricular angiography and 2-D echocardiography, and safety by measuring arrhythmia risk variables and restenosis of the stented vessel by intravascular ultrasound. At 6 months, BMC group had a greater absolute increase of global LVEF than placebo group, measured either by angiography (mean +/- SD increase 7.1 +/- 12.3 vs. 1.2 +/- 11.5%, P = 0.05) or by 2-D echocardiography (mean +/- SD increase 4.0 +/- 11.2 vs. -1.4 +/- 10.2%, P = 0.03). No differences were observed between the groups in the adverse clinical events, arrhythmia risk variables, or the minimal lumen diameter of the stented coronary lesion.\n Intracoronary BMC therapy is associated with an improvement of global LVEF and neutral effects on arrhythmia risk profile and restenosis of the stented coronary lesions in patients after thrombolytic therapy of STEMI.", "Sixty-nine patients who underwent primary percutaneous coronary intervention within 12 hours after onset of acute myocardial infarction were randomized to receive intracoronary injection of autologous bone marrow mesenchymal stem cell or standard saline. Several imagining techniques demonstrated that bone marrow mesenchymal stem cells significantly improved left ventricular function.", "Previous trials that investigated cell therapy as an adjunctive therapy after acute myocardial infarction (AMI) have shown conflicting results. We designed a randomized controlled trial to determine the effect of intracoronary infusion of mononuclear cells from bone marrow (BM) or peripheral blood in patients with AMI.\n In a multicentre trial, 200 patients with large first AMI treated with primary percutaneous coronary intervention were randomly assigned to either intracoronary infusion of mononuclear BM cells (n = 69), mononuclear peripheral blood cells (n = 66), or standard therapy (without placebo infusion) (n = 65). Mononuclear cells were delivered intracoronary between 3 and 8 days after AMI. Regional and global left ventricular myocardial function and volumes were assessed by magnetic resonance imaging before randomization and at 4 months, and clinical events were reported. The primary endpoint of the percentage of dysfunctional left ventricular segments that improved during follow-up did not differ significantly between either of the treatment groups and control: 38.6 ± 24.7% in the BM group, 36.8 ± 20.9% in the peripheral blood group, and 42.4 ± 18.7% in the control group (P = 0.33 and P = 0.14). Improvement of left ventricular ejection fraction was 3.8 ± 7.4% in the BM group, 4.2 ± 6.2% in the peripheral blood group when compared with 4.0 ± 5.8% in the control group (P = 0.94 and P = 0.90). Furthermore, the three groups did not differ significantly in changes in left ventricular volumes, mass, and infarct size and had similar rates of clinical events.\n Intracoronary infusion of mononuclear cells from BM or peripheral blood following AMI does not improve regional or global systolic myocardial function in the HEBE trial.\n The Netherlands Trial Register #NTR166 (www.trialregister.nl) and the International Standard Randomised Controlled Trial, #ISRCTN95796863 (http://isrctn.org).", "To evaluate the safety profile and efficacy of bone marrow mononuclear cells (BMMNC) transplantation for ST-segment elevation myocardial infarction (STEMI) by assessing patients and their left ventricular function at up to 4 years follow-up.\n Eighty-six patients with STEMI who had successfully undergone percutaneous coronary intervention (PCI) were randomized to receive intracoronary injection of BMMNC (n = 41) or saline (n = 45). Left ventricular ejection fraction, as evaluated by UCG, was markedly improved at 6 months (0.484 +/- 0.5 vs. 0.457 +/- 0.6, P = 0.001), 1 year (0.482 +/- 0.7 vs. 0.446 +/- 0.6, P < 0.001), and 4 years (0.505 +/- 0.8 vs. 0.464 +/- 0.8, P < 0.001) after BMMNC transplant when compared with control group. However, the current cell therapy did not improve the myocardial viability of the infarcted area as assessed by single-photon emission computed tomography analysis at 4 years post-transplant (0.263 +/- 0.007 in BMMNC group vs. 0.281 +/- 0.008 in control group, P = 0.10). During the follow-up period, one control group case (2.2%) of in-stent restenosis was confirmed by coronary angiography and underwent repeat PCI. Also during follow-up, one death (2.2%) occurred in the control group, and one patient (2.4%) in the BMMNC group had transient acute heart failure.\n This study indicates that intracoronary delivery of autologous BMMNC is safe and feasible for STEMI patients who have undergone PCI, and can lead to long-term improvement in myocardial function.", "The benefit of reperfusion therapies for ST-elevation acute myocardial infarction (STEMI) is limited by post-infarction left-ventricular (LV) dysfunction. Our aim was to investigate the effect of autologous bone marrow-derived stem cell (BMSC) transfer in the infarct-related artery on LV function and structure.\n We did a randomised, double-blind, placebo-controlled study in 67 patients from whom we harvested bone marrow 1 day after successful percutaneous coronary intervention for STEMI. We assigned patients optimum medical treatment and infusion of placebo (n=34) or BMSC (n=33). Our primary endpoint was the increase in LV ejection fraction and our secondary endpoints were change in infarct size and regional LV function at 4 months' follow-up, all assessed by MRI. We assessed changes in myocardial perfusion and oxidative metabolism with serial 1-[11C]acetate PET. Analyses were per protocol. This study is registered with , number NCT00264316.\n Mean global LV ejection fraction 4 days after percutaneous coronary intervention was 46.9% (SD 8.2) in controls and 48.5% (7.2) in BMSC patients, and increased after 4 months to 49.1% (10.7) and 51.8% (8.8; OR for treatment effect 1.036, 95% CI 0.961-1.118, p=0.36). Compared with placebo infusion, BMSC transfer was associated with a significant reduction in myocardial infarct size (BMSC treatment effect 28%, p=0.036) and a better recovery of regional systolic function. Myocardial perfusion and metabolism increased similarly in both groups. We noted no complications associated with BMSC transfer and all but one patient in the BMSC group completed the 4 months' follow-up.\n Intracoronary transfer of autologous bone marrow cells within 24 h of optimum reperfusion therapy does not augment recovery of global LV function after myocardial infarction, but could favourably affect infarct remodelling.", "Intracoronary transfer of autologous bone marrow cells (BMCs) may enhance recovery of left ventricular (LV) function in patients after acute myocardial infarction (AMI). However, clinical studies addressing the effects of BMCs after AMI have covered only limited time frames ranging from 3 to 6 months. The critical question of whether BMC transfer can have a sustained impact on LV function remains unanswered.\n After percutaneous coronary intervention with stent implantation (PCI) of the infarct-related artery, 60 patients were randomized 1:1 to a control group with optimal postinfarction therapy and a BMC transfer group that also received an intracoronary BMC infusion 4.8+/-1.3 days after PCI. Cardiac MRI was performed 3.5+/-1.5 days, 6+/-1 months, and 18+/-6 months after PCI. BMC transfer was not associated with adverse clinical events. In the control group, mean global LV ejection fraction increased by 0.7 and 3.1 percentage points after 6 and 18 months, respectively. LV ejection fraction in the BMC transfer group increased by 6.7 and 5.9 percentage points. The difference in LVEF improvement between groups was significant after 6 months but not after 18 months (P=0.27). The speed of LV ejection fraction recovery over the course of 18 months was significantly higher in the BMC transfer group (P=0.001).\n In this study, a single dose of intracoronary BMCs did not provide long-term benefit on LV systolic function after AMI compared with a randomized control group; however, the study suggests an acceleration of LV ejection fraction recovery after AMI by BMC therapy.", "To investigate the safety of autologous bone marrow mononuclear cell (BM-MNCs) transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI).\n One hundred and eighty-four patients with AMI treated with percutaneous coronary intervention (PCI) were randomized in a 1:1 way to either intracoronary transplantation of autologous BM-MNCs (n = 92) right after PCI or to sodium chloride concluding heparin (controlled, n = 92) via a micro infusion catheter. In the process of the intracoronary infusion of BM-MNCs, the complications should be recorded, which were aberration reflect (including of pale, syncope, nausea, hypotension and shock), deterioration of angina or heart failure, arrhythmias (including of bradycardia, sinus arrest or atrial ventricular block or ventricular fibrillation), embolism etc. Body temperature, blood pressure and heart rates should be monitored during the first week after transplantation. Holter, coronary angiography and ultrasonic cardiography were performed at the designed time points. Main heart accidents, restenosis and tumor were recorded during 2-years follow up.\n During the period of bone marrow puncture and intracoronary infusion of BM-MNCs, few patients occurred pale, dizziness, bradycardia and hypotension, which were transient and due to vagus reflect. No stem cell-related arrhythmias, deterioration of angina were noted. In BM-MNCs group one patient developed in-stent reocclusion in one week after transplantation, five developed in-stent restenosis during further follow-up 30 months, which were similar with control group. There were no deaths, major adverse cardiac events, tumor and other late adverse events during follow-up period in both groups.\n Intracoronary transplantation of autologous BM-MNCs in the acute phase after AMI is feasible and seems safe in the 30 months of follow-up.", "Intracoronary administration of autologous bone marrow cells (BMCs) leads to a modest improvement in cardiac function, but the effect on myocardial viability is unknown. The aim of this randomized multicentre study was to evaluate the effect of BMC therapy on myocardial viability in patients with decreased left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI) and to identify predictive factors for improvement of myocardial viability.\n One hundred and one patients with AMI and successful reperfusion, LVEF ≤45%, and decreased myocardial viability (resting Tl201-SPECT) were randomized to either a control group (n = 49) or a BMC group (n = 52). Primary endpoint was improvement of myocardial viability 3 months after AMI. Baseline mean LVEF measured by radionuclide angiography was 36.3 ± 6.9%. Bone marrow cell infusion was performed 9.3 ± 1.7 days after AMI. Myocardial viability improved in 16/47 (34%) patients in the BMC group compared with 7/43 (16%) in the control group (P = 0.06). The number of non-viable segments becoming viable was 0.8 ± 1.1 in the control group and 1.2 ± 1.5 in the BMC group (P = 0.13). Multivariate analysis including major post-AMI prognostic factors showed a significant improvement of myocardial viability in BMC vs. control group (P = 0.03). Moreover, a significant adverse role for active smoking (P = 0.04) and a positive trend for microvascular obstruction (P = 0.07) were observed.\n Intracoronary autologous BMC administration to patients with decreased LVEF after AMI was associated with improvement of myocardial viability in multivariate-but not in univariate-analysis. A large multicentre international trial is warranted to further document the efficacy of cardiac cell therapy and better define a group of patients that will benefit from this therapy. Clinical Trial Registration Information: URL: http://www.clinicaltrials.gov. Unique identifier NCT00200707.", "Several studies have been published on the effect of bone-marrow stem cells on the left ventricle when acting on post- acute myocardial infarction remodeling. However, the results have been controversial.\n To carry out an echocardiographic analysis of the systolic function of patients with acute myocardial infarction after autologous mononuclear bone marrow cell transplantation (AMBMCT) as performed via the intracoronary and intravenous routes.\n This is an open-label, prospective, randomized study. Inclusion criteria: patients admitted for ST-elevation acute myocardial infarction (MI) who had undergone mechanical or chemical reperfusion within 24 hours of the onset of symptoms and whose echocardiogram showed decreased segmental wall motion and fixed perfusion defect related to the culprit artery. Autologous bone marrow was aspirated from the posterior iliac crest under sedation and analgesia of the patients randomly assigned for the treatment group. After laboratory manipulation, intracoronary or intravenous injection of 100 x 106 mononuclear cells was performed. Echocardiography (Vivid 7) was used to assess ventricular function before and three and six months after cell infusion.\n A total of 30 patients were included, 14 in the arterial group (AG), 10 in the venous group (VG), and six in the control group (CG). No statistical difference was found between the groups for the echocardiographic parameters studied.\n Autologous mononuclear bone marrow cell transplantation did not improve the echocardiographic parameters of systolic function.", "Initial clinical trials from Europe have demonstrated that the administration of bone marrow-derived mononuclear cells (BMCs) may improve left ventricular (LV) function in patients following ST-elevation myocardial infarction (STEMI). However, results from trials performed in the United States have not yet been presented.\n We developed a phase 1, randomized, placebo-controlled, double-blind trial to investigate the effects of BMC administration in patients following STEMI on recovery of LV function using cardiac magnetic resonance imaging (cMRI). Forty patients with moderate to large anterior STEMIs were randomized to 100 million intracoronary BMCs versus placebo 3 to 10 days following successful primary angioplasty and stenting (percutaneous coronary intervention) of the left anterior descending coronary artery.\n Administration of BMC was safely performed in a high-risk cohort with minimal major adverse clinical event rates, and all patients remain alive to date. Left ventricular ejection fraction increased from 49.0% +/- 9.5% at baseline to 55.2% +/- 9.8% at 6 months by cMRI in the BMC group (P < .05), which was not different from the increase in the placebo group (48.6% +/- 8.5% to 57.0% +/- 13.4%, P < .05). Left ventricular end-diastolic volume decreased by 4 mL/m(2) in the BMC group at 6 months but increased significantly in the placebo group (17 mL/m(2), P < .01).\n This phase 1 study from the United States confirms the ongoing safety profile of BMC administration in patients following STEMI. The improvement in LV ejection fraction at 6 months by cMRI in the cell therapy group was not different than the placebo group. However, BMC administration had a favorable effect on LV remodeling at 6 months.\n 2010 Mosby, Inc. All rights reserved.", "Pilot trials suggest that the intracoronary administration of autologous progenitor cells may improve left ventricular function after acute myocardial infarction.\n In a multicenter trial, we randomly assigned 204 patients with acute myocardial infarction to receive an intracoronary infusion of progenitor cells derived from bone marrow (BMC) or placebo medium into the infarct artery 3 to 7 days after successful reperfusion therapy.\n At 4 months, the absolute improvement in the global left ventricular ejection fraction (LVEF) was significantly greater in the BMC group than in the placebo group (mean [+/-SD] increase, 5.5+/-7.3% vs. 3.0+/-6.5%; P=0.01). Patients with a baseline LVEF at or below the median value of 48.9% derived the most benefit (absolute improvement in LVEF, 5.0%; 95% confidence interval, 2.0 to 8.1). At 1 year, intracoronary infusion of BMC was associated with a reduction in the prespecified combined clinical end point of death, recurrence of myocardial infarction, and any revascularization procedure (P=0.01).\n Intracoronary administration of BMC is associated with improved recovery of left ventricular contractile function in patients with acute myocardial infarction. Large-scale studies are warranted to examine the potential effects of progenitor-cell administration on morbidity and mortality.\n 2006 Massachusetts Medical Society", "The efficacy of intracoronary infusion of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSCs) has not been compared between patients with acute (AMI) versus old myocardial infarction (OMI). In addition, the potential risk of restenosis associated with G-CSF-based stem cell therapy has not been evaluated in the setting of drug eluting stent (DES) implantation.\n We randomly allocated 96 patients with myocardial infarction who underwent coronary revascularization with DES for the culprit lesion into 4 groups. Eighty-two patients completed 6-month follow-up; AMI cell infusion (n=25), AMI control (n=25), OMI cell infusion (n=16), and OMI control group (n=16). In cell infusion groups, PBSCs were mobilized by G-CSF for 3 days and delivered to infarcted myocardium via intracoronary infusion. The AMI cell infusion group showed a significant additive improvement in left ventricular ejection fraction (LVEF) and remodeling compared with controls (change of LVEF: +5.1+/-9.1% versus -0.2+/-8.6%, P<0.05; change of end-systolic volume: -5.4+/-17.0 mL versus 6.5+/-21.9 mL, P<0.05). In OMI patients, however, there was no significant change of LVEF and ventricular remodeling in spite of significant improvement of coronary flow reserve after cell infusion. G-CSF-based cell therapy did not aggravate neointimal growth with DES implantation.\n Intracoronary infusion of mobilized PBSCs with G-CSF improves LVEF and remodeling in patients with AMI but is less definite in patients with OMI. G-CSF-based stem cell therapy with DES implantation is both feasible and safe, eliminating any potential for restenosis.", "There are only few data on long-term effectiveness of the stem cell therapy.\n We studied the time course of global and regional left ventricular function in patients with acute myocardial infarction within 1 year after the autologous mononuclear bone marrow cell transplantation.\n Sixty patients with a first acute myocardial infarction, who had been randomized into 3 groups, completed a 12-month protocol. Two groups were intracoronarily given bone marrow cells in either higher (10(8) cells, HD group, n=20) or lower (10(7) cells, LD group, n=20) doses. Twenty patients without cell transplantation served as a control (C) group. Doppler tissue imaging and the gated technetium-99m sestamibi single photon emission computed tomography were performed before cell transplantation and at 3, 6, and 12 months later.\n The baseline peak systolic velocities of longitudinal contraction of the infarcted wall (S(infarct)) of 5.2 cm/s, 4.6 cm/s, and 4.4 cm/s in C, LD, and HD groups increased by 0.0 cm/s, 0.3 cm/s (p=NS vs. C group), and by 0.7 cm/s (p<0.05 vs. C group), respectively, at 3 months. At 12 months, however, the corresponding changes from baseline values of 0.1 cm/s, 0.2 cm/s, and 0.6 cm/s did not differ significantly (all p=NS). In contrast, the post-transplant improvements in the left ventricular ejection fraction by 6%, 7%, and 7% at months 3, 6, and 12, respectively, were preserved in HD group patients during the whole 12-month follow-up and remained significantly better as compared to controls.\n In our study, the autologous mononuclear bone marrow cell transplantation provided sustained improvement in global left ventricular systolic function in patients with acute myocardial infarction. However, when evaluating regional systolic function of the infarcted wall, the short-term benefit was partially lost during the 12-month follow-up.", "We sought to determine whether repeat administration of bone marrow mononuclear cells (BMC) can improve left ventricular function compared with a single infusion in patients with large acute myocardial infarction (AMI).\n Thirty-nine patients with a ST-elevation AMI of the anterior wall and a significantly decreased left ventricular ejection fraction (LVEF 20-39%) were randomly assigned to three groups following primary percutaneous coronary intervention: Group A (n = 12) received a single intracoronary infusion of BMC (1.9 +/- 1.2 x 10(8)) at 3-7 days after AMI; Group B (n = 15) received BMC administration both at 3-7 days (2.0 +/- 1.4 x 10(8)) and at 3 months (2.1 +/- 1.7 x 10(8)); and the control group (CON, n = 12) received one placebo injection at 3-7 days. We noted no severe complications associated with the BMC transfer. The increase in LVEF evaluated by magnetic resonance imaging (MRI) after 12 months in Group B (11.7 +/- 2.6%) was significantly greater than that in Group A (7.2 +/- 1.6%, P < 0.001) or in CON (2.9 +/- 2.0%, P < 0.001). Magnetic resonance imaging-derived myocardial infarct size decreased significantly in Group B compared with Group A (11.3 +/- 2.7% vs. 6.3 +/- 1.6%, P < 0.001).\n Data from this preliminary study suggest that repeated BMC administration might be a safe and feasible therapeutic strategy for patients with large AMI.", "Emerging evidence suggests that stem cells can be used to improve cardiac function in patients after acute myocardial infarction. In this randomized trial, we aimed to use Doppler tissue tracking and strain imaging to assess left ventricular segmental function after intracoronary transfer of autologous bone-marrow stem cells (BMCs) for 6 months' follow up.\n Twenty patients with acute myocardial infarction and anterior descending coronary artery occlusion proven by angiography were [corrected] randomized into intracoronary injection of bone-marrow cell (treated, n = 9) or diluted serum (control, n = 11) groups. GE vivid 7 and Q-analyze software were used to perform echocardiogram in both groups 1 week, 3 months and 6 months after treatment. Three apical views of tissue Doppler imaging were acquired to measure peak systolic displacement (Ds) and peak systolic strain (epsilonpeak) from 12 segments of LV walls. Left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and end-systolic volume (ESV) were obtained by Simposon's biplane method.\n (1) 3 months later, Ds and epsilonpeak over the infract-related region clearly increased in the BMCs group [Ds: (4.49 +/- 2.71) mm vs (7.56 +/- 2.95) mm, P < 0.01; epsilonpeak: (-13.40 +/- 6.00)% vs (-17.06 +/- 6.05)%, P < 0.01], but not in the control group [Ds: (4.74 +/- 2.67) mm vs (5.01 +/- 3.23) mm, P > 0.05; epsilonpeak: (-13.84 +/- 6.05)% vs (-15.04 +/- 6.75)%, P > 0.05]. At the same time, Ds over the normal region also increased, but the Ds enhancement was markedly higher in the BMCs group than that in the control group [(3.21 +/- 3.17) mm vs (0.76 +/- 1.94) mm, P < 0.01]. Parameters remained steady from the 3rd to 6th month in either group (P > 0.05). (2) LVEF in treated and control groups were almost the same at baseline (1st week after PCI) [(53.37 +/- 8.92)% vs (53.51 +/- 5.84)%, P > 0.05]. But 6 months later, LVEF in the BMCs group were clearly higher than that in the control group [(59.33 +/- 12.91)% vs (50.30 +/- 8.30)%, P < 0.05]. (3) There were no evident difference in EDV or ESV between two groups at baseline [EDV: (113.74 +/- 23.24) ml vs (129.94 +/- 32.72) ml, P > 0.05; ESV: (57.12 +/- 18.66) ml vs (62.09 +/- 17.68) ml, P > 0.05]. Three months later, EDV and ESV in the control group were markedly greater than those in the BMCs group [EDV: (154.89 +/- 46.34) ml vs (104.85 +/- 33.21) ml, P < 0.05; ESV: (82.91 +/- 35.79) ml vs (49.54 +/- 23.32) ml, P < 0.05]. But EDV and ESV did not change much from 3rd to 6th month in either group (P > 0.05).\n Emergency transplantation of autologous BMCs in patients with acute myocardial infarction helps to improve global and regional contractility and attenuate post-infarction left ventricular remodeling. Tissue tracking and strain imaging provide quick, simple and noninvasive methods for quantifying left ventricular segmental function in humans.", "To investigate the effects of emergent intracoronary autologous bone marrow mononuclear cell (BM-MNC) transplantation on left ventricular function and myocardium lesion area in patients with first acute inferior-wall myocardial infarction.\n Forty patients with first onset of acute inferior-wall myocardial infarction, 28 males and 12 females, aged < or = 75, treated with emergent percutaneous coronary intervention (PCI) were randomly divided into 2 equal groups: group undergoing intracoronary transplantation of autologous BM-MNC via a micro-catheter right after PCI (BM-MNC group), and control group receiving normal saline and heparin. Blood routine examination, myocardium zymogram, and serum high sensitive C reactive protein (hsCRP) were detected, and 24-hour dynamic electrocardiography, delayed-enhancement myocardial magnetic resonance imaging (CMR), and angiography of the coronary artery and left ventricle were conducted before the transplantation and immediately, 1 week, and 6 months after transplantation.\n CMR showed that 6 months later the left ventricular ejection fraction (LVEF) of the control group was 47.9% +/- 6.7%, significantly higher than that 1 week later (43.4% +/- 6.7%, P = 0.001), and the LVEF of the BM-MNC group 6 months later was 51.5% +/- 5.2%, significantly higher than that 1 week later (44.5% +/- 7.1%, P = 0.001; however, the absolute change of LVEF (DeltaLVEF) of the BM-MNC group was 6.95% +/- 3.33%, significantly higher than that of the control group (4.05% +/- 1.68%, P = 0.047). Six months later the myocardial lesion area of the BM-MNC group decreased more significantly in comparison with the control group. Nevertheless, there was no difference in change of left ventricular end diastolic volume (LVEDV) between these two groups. The serum hsCRP 48 h after transplantation of the BM-MNC group was 2.8 g/L +/- 0.8 g/L, significantly lower than that before transplantation (13.4 g/L +/- 3.6 g/L, P < 0.001). No severe clinical events, such death, recurrent cardiac infarction, malignant arrhythmia, occur in these 2 groups.\n Emergent intracoronary transplantation of autologous BM-MNC in patients with acute inferior-wall myocardial infarction improves the left ventricular function and myocardial infusion, minimizes the myocardial lesion area significantly.", "To evaluate the myocardial viability with (201)Tl/(18)F-FDG DISA-SPECT technique in patients with acute myocardial infarction underwent emergent intracoronary autologous bone marrow mononuclear cells (BM-MNC) transplantation.\n Patients with first acute myocardial infarction underwent emergent percutaneous coronary intervention (PCI) were randomized in a 1:1 ratio to either intracoronary transplantation of autologous BM-MNC (n = 20) or to sodium chloride concluding heparin (control, n = 20) via a micro infusion catheter group immediately after PCI. Change in global left ventricular function (LVEF measured by echocardiography) and the myocardial viability detected by (201)Tl/(18)F-FDG DISA-SPECT from baseline and 6-months post transplantation were analyzed.\n Left ventricular ejection fraction (LVEF) was improved in both groups and the absolute increase (DeltaLVEF) in BM-MNC group was significantly higher than that in control group (7.6% +/- 2.8% vs. 3.0% +/- 2.8%, P < 0.001). In addition, the absolute decrease of myocardial infusion defect detected by (201)Tl SPECT was more significant in BM-MNC group than that in control group (6.7% +/- 3.0% vs. 2.6% +/- 2.6%, P < 0.001) and the number of mismatched segments (indicating viable myocardium) detected by (18)F-FDG SPECT in border zone was also significantly higher in BM-MNC group than that in control group.\n Improved myocardial viability and reduced myocardial infusion defect post emergent intracoronary transplantation of autologous BM-MNC in patients with acute myocardial infarction could be detected by (201)Tl/(18)F-FDG DISA-SPECT technique.", "To assess the effect of autologous bone-marrow cell (BMC) therapy in patients with acute myocardial infarction in a rigorous double-blind, randomized, placebo-controlled trial. Patients with reperfusion >6 hours after symptom onset were randomly assigned in a 2:1 ratio to receive intracoronary BMC or placebo therapy 5 to 7 days after symptom onset. The patients were stratified according to age, acute myocardial infarction localization, and left ventricular (LV) function. Rigorous double-blinding was ensured using autologous erythrocytes for the placebo preparation that was visually indistinguishable from the active treatment. Serial cardiac magnetic resonance imaging studies were performed before study therapy and after 1, 3, and 6 months. The primary end point was the difference in the LV ejection fraction from baseline to 6 months. The secondary end points included changes in the LV end-diastolic and end-systolic volume indexes and infarct size. A total of 42 patients were enrolled (29 in the BMC group and 13 in the placebo group) in the integrated pilot phase. A mean of 381 x 10(6) mononuclear BMCs were administered. The baseline clinical and cardiac magnetic resonance imaging parameters did not differ. Compared to baseline, the difference in LV ejection fraction for the placebo group versus BMC group was 1.7 +/- 6.4% versus -0.9 +/- 5.5% at 1 month, 3.1 +/- 6.0% versus 1.9 +/- 4.3% at 3 months, and 5.7 +/- 8.4% versus 1.8 +/- 5.3% at 6 months (primary end point; not significant). No difference was found in the secondary end points between the 2 groups, including changes in infarct size or LV end-diastolic and end-systolic volume indexes. In conclusion, in this rigorous double-blind, randomized, placebo-controlled trial, we did not observe an evidence for a positive effect for intracoronary BMC versus placebo therapy with respect to LV ejection fraction, LV volume indexes, or infarct size.\n Copyright 2010 Elsevier Inc. All rights reserved.", "Randomized trial to assess change in left ventricle ejection fraction (LVEF) and myocardial perfusion in patients with acute myocardial infarction (AMI) of anterior wall treated with bone marrow stem cells (BMSCs), compared with control group-from baseline in the acute phase up to 12 months of follow-up.\n Forty-five patients were randomized 2:1 to BMSC group (n= 31) or to control group (n = 14). Bone marrow stem cells were administered into infarct-related artery (IRA) at 4-6 day after primary PCI. Groups were followed up with Tc-99m-MIBI SPECT, radionuclide ventriculography (EF-RNV), echocardiography (ECHO), and spiroergometric stress test. Coronary angiography was repeated after 6 months. EF-RNV did not differ significantly in both groups, but trend towards increase in EF at 6 months and its maintenance after 12 months was noticed in the BMSC group. At rest study, perfusion index (PI) of region supplied with blood by IRA distal to its previous occlusion (PI-IRA) improved significantly in the BMSC group at 6 months: PI-IRA at 4-6 days vs. PI-IRA at 6 months (3.00 +/- 0.97 vs. 2.65 +/- 0.64; P = 0.017). At 12 months, PI-IRA at rest was 2.66 +/- 0.55; P = 0.07. The difference between BMSC and control groups at rest study in PI-IRA was not observed. At dipyridamole study (PI-dip), perfusion in the BMSC group was better compared with controls at 6 months (2.26 +/- 0.44 vs. 2.47 +/- 0.40; P = 0.033) and at 12 months (2.34 +/- 0.55 vs. 2.52 +/- 0.42; P = 0.014), also for region supplied with blood by IRA (PI-IRA-dip; at 6 months 2.63 +/- 0.77 vs. 3.06 +/- 0.46; P = 0.021 and at 12 months 2.71 +/- 0.63 vs. 3.15 +/- 0.51; P = 0.001). Results of LVEF, LVEDV, LVESV in ECHO and results of spiroergometric stress test did not differ significantly between groups. Major adverse cardiac events occurred more often in the control group (P = 0.027).\n In our study, BMSC intracoronary transplantation in patients with anterior AMI did not result in increase in EF. Slight improvement of myocardial perfusion was noticed in the BMSC group. This finding may indicate better microcirculation enhanced by BMSCs, but small number of patients allow for hypothesis rather than final statement.", "To investigate the effects and safety of autologous peripheral blood stem cell (PBSCs) transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI).\n 70 patients with AMI were allocated to two groups, one was PBSCs transplantation group (n=35) that received optimal post-infarction medical treatment (standard drug and coronary artery intervention therapy) and intracoronary transplantation of PBSCs; the other was control group (n=35) that received optimum post-infarction medical treatment (standard drug and coronary artery intervention therapy). The PBSCs transplantation group received granulocyte colony-stimulating factor (G-CSF: Filgrastim, 300 microg) with the dose of 300-600 microg/day to mobilize the stem cell, and the duration of administration G-CSF was 5 days. On the sixth day, PBSCs were separated by Baxter CS 3000 blood cell separator into suspend liquid 57 ml. Then, the suspend liquid was transferred into the infarct-related artery (IRA) by occluding the over-the-wire balloon and infusing artery through balloon center lumen. In the process of the mobilization, separation and intracoronary infusion of PBSCs, the complications have been investigated. Changes in left ventricular function were assessed at 6-month follow-up.\n 35 cases had finished follow-up in the treated group, while 23 cases in control group. After 6 months, within the treated group, there was a significant improvement in global left ventricular function ejection fraction (EF) from a baseline of 50.0+/-8.2% to 57.1+/-7.8% (P<0.0001), wall motion score index (WMSI) from 1.219+/-0.190 to 1.101+/-0.118 (P<0.0001), left end-systolic volume (ESV) from 63.8+/-23.9 ml to 52.6+/-20.3 ml (P=0.01) and left end-diastolic volume (EDV) from 134.2+/-36.7 ml to 119.2+/-30.3 ml (P=0.07); in the control group, there was no significant improvement in EF, WISM, EDV and ESV (P=0.490, 0.259, 0.117, 0.395). After 6-month follow-up, according to treatment group vs. control group, there was a significant improvement in EF from 57.1+/-7.8 to 52.6+/-5.7 (P=0.041) and WISM from 1.101+/-0.118 to 1.184+/-0.138 (P=0.034). There were a total of 25 cases with complications during the mobilization, separating and infusion of PBSC. The incidence of complications relating to mobilization was 37.1% (13/35), relating to separating was 14.3% (5/35) and relating to intracoronary infusion was 20.0% (7/35). No death was observed.\n Autologous PBSCs transplantation by intracoronary infusion is feasible and safe, and it can improve left ventricular function in the 6-month follow-up.", "Previous studies have shown improvement in left ventricular function after intracoronary injection of autologous cells derived from bone marrow (BMC) in the acute phase of myocardial infarction. We designed a randomized, controlled trial to further investigate the effects of this treatment.\n Patients with acute ST-elevation myocardial infarction of the anterior wall treated with percutaneous coronary intervention were randomly assigned to the group that underwent intracoronary injection of autologous mononuclear BMC or to the control group, in which neither aspiration nor sham injection was performed. Left ventricular function was assessed with the use of electrocardiogram-gated single-photon-emission computed tomography (SPECT) and echocardiography at baseline and magnetic resonance imaging (MRI) 2 to 3 weeks after the infarction. These procedures were repeated 6 months after the infarction. End points were changes in the left ventricular ejection fraction (LVEF), end-diastolic volume, and infarct size.\n Of the 50 patients assigned to treatment with mononuclear BMC, 47 underwent intracoronary injection of the cells at a median of 6 days after myocardial infarction. There were 50 patients in the control group. The mean (+/-SD) change in LVEF, measured with the use of SPECT, between baseline and 6 months after infarction for all patients was 7.6+/-10.4 percentage points. The effect of BMC treatment on the change in LVEF was an increase of 0.6 percentage point (95% confidence interval [CI], -3.4 to 4.6; P=0.77) on SPECT, an increase of 0.6 percentage point (95% CI, -2.6 to 3.8; P=0.70) on echocardiography, and a decrease of 3.0 percentage points (95% CI, 0.1 to -6.1; P=0.054) on MRI. The two groups did not differ significantly in changes in left ventricular end-diastolic volume or infarct size and had similar rates of adverse events.\n With the methods used, we found no effects of intracoronary injection of autologous mononuclear BMC on global left ventricular function.\n 2006 Massachusetts Medical Society", "To investigate the effect of intracoronary injection of autologous mononuclear bone marrow stem cells (BMSCs) in patients with ST-elevation myocardial infarction (STEMI) on left ventricular (LV) systolic and diastolic function using standard echocardiography and 2-dimensional systolic strain. A total of 60 patients with first anterior wall STEMI and LV ejection fraction of <40%, treated with successful primary percutaneous coronary intervention were randomly assigned to the treatment group (BMSC group) or the control group in a 2:1 ratio. Transcatheter intracoronary injection of BMSCs into the infarct-related artery was performed 7 days after STEMI. Standard echocardiography and speckle tracking analysis was performed at baseline and 6 months after STEMI. No differences were found in the baseline echocardiographic parameters of LV systolic and diastolic dysfunction--the LV ejection fraction was 35 +/- 6% in the BMSC group, similar to that in the control group (33 +/- 7%, p = 0.42). After 6 months, the absolute change in the LV ejection fraction was significantly greater in the BMSC group than in the control group (10 +/- 9% versus 5 +/- 8%, p = 0.04). Significant improvement was seen in 2-dimensional systolic strain in all segments (12 +/- 4 vs 14 +/- 4; p = 0.0009) and in the infarcted area (5 +/- 2 vs 6 +/- 2; p = 0.0038) only in the BMSC group. Of the diastolic function parameters, we observed improvement in the early filling propagation velocity (30 +/- 8 cm/s vs 37 +/- 13 cm/s; p = 0.0008), early diastolic velocity - E' (4.5 +/- 1.5 vs 5.0 +/- 1.3, p = 0.02), and the E/E' ratio (17 +/- 7 vs 14 +/- 5; p = 0.03) in the BMSC group. In conclusion, intracoronary injection of unselected BMSCs in patients with STEMI improved both LV systolic and diastolic function at 6 months of follow-up.", "It is difficult to distinguish the effects early revascularization and regenerative therapy have on left ventricular function in patients with acute myocardial infarction (AMI). This study was an investigation into three groups of patients who had a revascularized anterior wall AMI and depressed left ventricular function (i.e., ejection fraction < 45%). The aim was to compare changes in left ventricular function between patients who received regenerative therapy and those who did not.\n Patients were randomly assigned to receive either an intracoronary infusion of autologous mononuclear bone marrow cells (Group I; n=10) or systemic administration of granulocyte colony-stimulating factor (G-CSF) (Group II; n=10), or to a control group (Group III; n=10). In Group I, intracoronary infusion was carried out 7(2) days after AMI. Group-II patients received a 10-day course of subcutaneous G-CSF injections, 10 .g/kg per day starting 5 days after AMI. Ventricular function was assessed at baseline and 3-month follow-up.\n A 20% increase in mean ejection fraction was observed in Group I, compared with increases of 4% (P<.01) and 6% (P<.05) in Groups II and III, respectively.\n Intracoronary infusion of mononuclear bone marrow cells in patients with AMI and poor ventricular function was associated with better short-term functional recovery than previously reported. However, mobilization of stem cells by G-CSF did not have a significant influence on functional recovery.", "To study whether emergent intracoronary autologous bone marrow cell transplantation (BMT) is applicable for the treatment of acute myocardial infarction (AMI).\n 20 patients admitted within 24 h after the onset of a first AMI were randomly allocated to receive intracoronary autologous BMT (n = 10) or bone marrow supernatant (controls, n = 10) immediately after primary percutaneous coronary intervention. Left ventricular ejection fraction (LVEF), left ventricular end diastolic internal diameter (LVDd) and myocardial perfusion defect scores were examined respectively by echocardiography and single-photon emission computed tomography at one week and six months after AMI.\n From one week to six months after AMI, LVEF was enhanced from mean 53.8 (SD 9.2)% to 58.6 (9.9)% (p < 0.05) in the BMT group but was unchanged in the control group (58.2 (7.5)% v 56.3 (3.5)%, p > 0.05); LVDd remained unchanged (52.5 (2.8) v 52.1 (3.2) mm, p > 0.05) in the BMT group but was significantly enlarged in the control group (50.4 (6.0) v 55.2 (7.1) mm, p < 0.05). Additionally, myocardial perfusion defect scores decreased from 21 (11) to 13 (10) (p < 0.01) in the BMT group but were unchanged in the control group (20 (14) v 17 (15), p > 0.05).\n Emergent intracoronary transplantation of bone marrow mononuclear cells after AMI is practicable, and it improved cardiac function, prevented myocardial remodelling and increased myocardial perfusion at six months' follow up." ]

[ "12403858", "20061311", "19948623", "16892780", "3545094", "10705068", "16754825", "20528605", "19119703", "19255389", "16777828" ]

[ "Home-based asthma education of young low-income children and their families.", "Problem-solving skills training for vulnerable families of children with persistent asthma: report of a randomized trial on health-related quality of life outcomes.", "Adherence feedback to improve asthma outcomes among inner-city children: a randomized trial.", "Randomized trial of a comprehensive asthma education program after an emergency department visit.", "Asthma education by community child health nurses.", "Pilot study of a home-based asthma health education program.", "Effectiveness of nebulizer use-targeted asthma education on underserved children with asthma.", "Influence of caregiver and provider communication on symptom days and medication use for inner-city children with asthma.", "Assessing the value of disease management: impact of 2 disease management strategies in an underserved asthma population.", "A randomized controlled evaluation of the effect of community health workers on hospitalization for asthma: the asthma coach.", "Emergency department allies: a controlled trial of two emergency department-based follow-up interventions to improve asthma outcomes in children." ]

[ "To conduct a controlled trial of a home-based education program for low-income caregivers of young children with asthma.\n Participants were randomized to treatment-eight weekly asthma education sessions adapted from the Wee Wheezers program (n = 49)-or usual care (n = 46). Baseline and 3- and 12-month follow-up data were gathered from caregivers and from children's medical records.\n Treatment was associated with less bother from asthma symptoms, more symptom-free days, and better caregiver quality of life at follow-up for children 1-3, but not those 4-6, years of age. Treatment and control groups did not differ in caregiver asthma management behavior or children's acute care utilization.\n This home-based asthma education program was most effective with younger children; perhaps their caregivers were more motivated to learn about asthma management. Targeting psychosocial factors associated with asthma morbidity might also enhance the efficacy of asthma education for these families.", "To test the efficacy of problem-solving skill training (PST) in improving health-related quality of life (HRQOL) of children with persistent asthma from predominantly lower socioeconomic status (SES) Spanish-speaking Hispanic families.\n Randomized controlled trial comparing standard care waitlist (SC) control, home-visiting asthma education/care coordination (CC), and combined intervention (CC + PST) at baseline, after intervention, and 6-month follow-up. The primary outcome was parent proxy-report child HRQOL (PedsQL).\n Participants (n = 252) were 83.3% Hispanic and 56.3% monolingual Spanish speakers, and 72.6% of mothers had not graduated high school. We found a significant (P = 0.05) intervention effect for parent proxy-reported child generic (but not asthma-specific) HRQOL, with CC + PST superior to SC [83.8 vs 79.8; adjusted mean difference of 4.05 points (95% confidence interval 0.63-7.4], but no difference between the CC and SC groups.\n In this sample of vulnerable families of children with persistent asthma, a CC + PST intervention was efficacious in improving children's generic HRQOL.", "We evaluated the longitudinal effects of home-based asthma education combined with medication adherence feedback (adherence monitoring with feedback [AMF]) and asthma education alone (asthma basic care [ABC]) on asthma outcomes, relative to a usual-care (UC) control group.\n A total of 250 inner-city children with asthma (mean age: 7 years; 62% male; 98% black) were recruited from a pediatric emergency department (ED). Health-outcome measures included caregiver-frequency of asthma symptoms, ED visits, hospitalizations, and courses of oral corticosteroids at baseline and 6-, 12-, and 18-month assessments. Adherence measures included caregiver-reported adherence to inhaled corticosteroid (ICS) therapy and pharmacy records of ICS refills. Multilevel modeling was used to examine the differential effects of AMF and ABC compared with UC.\n ED visits decreased more rapidly for the AMF group than for the UC group, but no difference was found between the ABC and UC groups. The AMF intervention led to short-term improvements in ICS adherence during the active-intervention phase relative to UC, but this improvement decreased over time. Asthma symptoms and courses of corticosteroids decreased more rapidly for the ABC group than for the UC group. Hospitalization rates did not differ between either intervention group and the UC group. No differences were found between the ABC and AMF groups on any outcome.\n Asthma education led to improved adherence and decreased morbidity compared with UC. Home-based educational interventions may lead to modest short-term improvements in asthma outcomes among inner-city children. Adherence feedback did not improve outcomes over education alone.", "Patients with asthma who visit the emergency department (ED) may benefit from education that optimizes self-management and treatment.\n To conduct a randomized trial of asthma education (AE) after an ED visit.\n Patients who present with acute asthma and history consistent with moderate to severe persistent asthma or recent ED visits were stratified by age (adult, child) and randomly assigned to intervention or usual care during the ED visit. The intervention was conducted by trained asthma educators and included a facilitated office visit with the primary care physician followed by a home visit. Intention-to-treat analysis was conducted, with time to first asthma relapse (either ED or unscheduled urgent office visit) during the 6-month follow-up period used as the primary outcome.\n Of the 239 patients analyzed, 46% were adults, 46% were male, 30% were African American, and 56% had moderate to severe persistent asthma. Follow-up information was obtained on 191 patients (80%) at 6 months; 23.1% of the intervention group vs 31.1% of the usual care group had an urgent asthma visit (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.48-1.29). Overall, 39% of the 117 patients assigned to the intervention group did not comply with any of the post-ED activities. Subgroup analysis suggested greater benefit among children (HR, 0.62; 95% CI, 0.33-1.19) than adults (HR, 1.08; 95% CI, 0.50-2.33).\n Delivery of a comprehensive AE program after an ED visit was ineffective in adult patients; however, it may be effective in children. Further research on alternative AE delivery strategies appears warranted to reduce the burden of asthma visits to the ED.", "A randomised controlled study of an educational programme for children with asthma and their families was carried out by community child health nurses. Three hundred and sixty eight children aged 2 to 14 years were enrolled in the study after admission to hospital for asthma. The intervention group was visited monthly by a nurse for six months. The subjects were assessed six months later by a postal, self administered questionnaire. European children in the intervention group were taking significantly more drugs for the treatment of asthma six months after the index admission to hospital than those in the control group (mean (SD) intake 2.7 (1.1) v 2.1 (1.0), respectively). In particular, they were using more theophylline (56.6% v 37.0%) and inhaled steroids (34.9% v 21.0%). There was no difference between the groups for parental reports of improvement, of missed schooling, and in severe attacks of asthma of not responding to the usual treatment at home. European children in the intervention group used the hospital services for severe attacks of asthma more than controls (34.2% v 10.5%). There were more re-admissions in the European intervention group in the subsequent six months after the index admission than in the control group (mean (SD) 0.51 (0.97) v 0.29 (0.65). Re-admission continued to be higher in the 12 months after the nurse had stopped visiting (0.81 (1.65) v 0.25 (0.65]. There was no difference in the duration of hospital stay between the intervention and control groups. For Polynesian children there was no difference between the groups for any outcome measures.", "Caring for a child with asthma can affect the parent's coping and well-being and coping strategies. This study examined the influence of a home-based asthma health education program on parental coping and quality of life.\n Randomized controlled non-blinded clinical trial.\n Northern community pediatrician's office.\n Families whose children, under the age of 11, had chronic stable asthma, and who presented to the pediatrician's office for continuing care; those with an acute exacerbation of asthma were excluded.\n Families were randomly assigned to receive either a single two-hour, standardized home-based asthma health education session or a booklet representing conventional care.\n One and three-months following the intervention, assessments were obtained for coping measured by Hymovich's Parent Perception Inventory (PPI), quality of life measured by the Pediatric Asthma Caregiver Quality of Life Questionnaire (PACQLQ) and change in asthma measured by the Caregiver Perception of Change (CPC) survey.\n Forty families were recruited and randomized; baseline characteristics were similar between groups. At the final follow-up, reduction in parental need for asthma information (p = 0.04), reduction in parental concerns (p = 0.02) and increased use of coping strategies (p = 0.04) were observed in the home-based care group. Improvement was noted in the parent's perception of their child's asthma in the home-based asthma education group (p = 0.01). Quality of life as measured by the PACQLQ remained unchanged over the intervention period (p > 0.05).\n These results suggest the use of a one-time, flexible, home-based intervention to assist families caring for children with asthma should be considered and appears effective.", "To determine the effectiveness of a home-based asthma education intervention in increasing appropriate nebulizer use and reducing symptom frequency, emergency department (ED) visits, and hospitalizations over 12 months.\n A randomized clinical trial. Settings Pediatric primary care, pulmonary/allergy, and ED practices associated with the University of Maryland Medical System and The Johns Hopkins Hospital, Baltimore.\n Children with persistent asthma, aged 2 to 9 years, with regular nebulizer use and an ED visit or hospitalization within the past 12 months. Children were randomized into the intervention (n = 110) or control (n = 111) group. Follow-up data were available for 95 intervention and 86 control children.\n Home-based asthma education, including symptom recognition, home treatment of acute symptoms, appropriate asthma medication, and nebulizer practice.\n Estimates of mean differences in asthma symptom frequency, number of ED visits and hospitalizations and appropriate quick relief, controller medication, and nebulizer practice over 12 months.\n Of the 221 children, 181 (81.9%) completed the study. There were no significant differences in home nebulizer practice, asthma morbidity, ED visits, or hospitalizations between groups (P range, .11-.79). Although most children received appropriate nonurgent asthma care (mean, 2 visits per 6 months), more than one third of all children received at least 6 quick-relief medication prescriptions during 12 months, with no difference by group.\n A nebulizer education intervention had no effect on asthma severity or health care use. Of concern is the high quick-relief and low controller medication use in young children with asthma seen nearly every 3 months for nonurgent care.", "Effective pediatric guideline-based asthma care requires the caregiver to accurately relay the child's symptom frequency, pattern of rescue and controller medication use, and level of asthma control to the child's primary care clinician.\n This study evaluated the longitudinal effects of a caregiver-clinician asthma communication education intervention (ACE) relative to an asthma education control group (CON) on symptom days and controller medication use in inner-city children with asthma. Participants and\n 231 inner-city children with asthma, recruited from urban pediatric emergency departments (EDs) and community practices, were followed for 12 months. Data included number of symptom days and nights, ED visits, hospitalizations, presence of limited activity, and controller medication use over 12 months. Pharmacy records were used to calculate controller to total asthma medication ratios as a proxy of appropriate controller medication use. Multivariate logistic regression models were used to identify factors associated with number of symptom days and nights over the past 30 days at the 12-month follow-up.\n Most caregivers rated the communication with their child's clinician as high. Unadjusted and adjusted rates of symptom days and nights did not differ by group at follow-up. ACE children tended towards a higher controller to total medication ratio at 12 months as compared to CON children (mean ratio: ACE: 0.54, SD 0.3; CON, 0.45, SD 0.4; p = .07). Activity limitation due to asthma and persistent asthma severity were the only factors significantly associated with reporting any symptom day within the past 30 days, adjusting for treatment group, number of oral corticosteroid courses and number of clinician visits in the last 6 months, seasonality, insurance type, and controller to total asthma medication ratio covariates.\n A home-based caregiver asthma communication educational intervention was not associated with decreased symptom days. However, a trend was noted in higher controller to total medication ratios in the intervention group. Inner-city caregivers of children with asthma may require a health systems approach to help convey the child's asthma health information to their clinician.", "The goal of disease management (DM) is to improve health outcomes and reduce cost through decreasing health care utilization. Although some studies have shown that DM improves asthma outcomes, these interventions have not been examined in a large randomized controlled trial.\n To compare the effectiveness of 2 previously successful DM programs with that of traditional care.\n Nine hundred two individuals with asthma (429 adults; 473 children) were randomly assigned to telephonic DM, augmented DM (ADM; DM plus in-home visits by a respiratory therapist), or traditional care. Data were collected at enrollment and at 6 and 12 months. Primary outcomes were time to first asthma-related event, quality of life (QOL), and rates of asthma-related health care utilization. Secondary outcomes included rate of controller medication initiation, number of oral corticosteroid bursts, asthma symptom scores, and number of school days missed.\n There were no significant differences between groups in time to first asthma-related event or health care utilization. Adult participants in the ADM group had greater improvement in QOL (P = .04) and a decrease in asthma symptoms (P = .001) compared with other groups. Of children not receiving controller medications at enrollment (13%), those in the intervention groups were more likely to have controller medications initiated than the control group (P = .01). Otherwise, there were no differences in outcomes.\n Overall, participation in asthma DM did not result in significant differences in utilization or clinical outcomes. The only significant impact was a higher rate of controllermedication initiation in children and improvement in asthma symptoms and QOL in adults who received ADM.", "To test whether community health workers are able to reach low-income parents of African American children hospitalized for asthma and to reduce rehospitalization among them.\n A randomized controlled evaluation of usual care vs 2-year asthma coach intervention.\n An urban children's hospital and the surrounding community.\n A population-based sample of 306 children hospitalized for asthma met the inclusion criteria of being 2 to 8 years of age, of African American ethnicity, and having Medicaid coverage. Of these, 200 were contacted and 191 recruited with commitment to evaluation activities but, in order to assess reach, no commitment to participating in intervention.\n Coaches reinforced basic asthma education and encouraged key management behaviors through home visits and phone calls tailored to parent's readiness to adopt management practices and emphasizing a nondirective supportive style (cooperative and accepting of feelings and choices).\n The reach of intervention to parents, contacts with coaches, and rehospitalization over 2 years based on hospital records.\n Within 3 months of randomization to the asthma coach group, 89.6% of parents had at least 1 substantive contact with the coach, with an average of 21.1 contacts per parent over the 24-month intervention. The proportion of children rehospitalized was 35 of 96 (36.5%) in the asthma coach group and 55 of 93 (59.1%) in the usual care group (P < .01), controlling for parental education and child age, sex, and hospitalization in the year prior to the index hospitalization. In surveys, parents indicated the importance of the nondirective approach to support.\n An asthma coach can reach low-income parents of African American children hospitalized for asthma and reduce rehospitalization among the children.", "We sought to study the impact of emergency department (ED)-based intensive primary care linkage and initiation of asthma case management on long-term, patient-oriented outcomes for children with an asthma exacerbation.\n Our study was a randomized, 3-arm, parallel-group, single-blind clinical trial. Children aged 2 through 17 years treated in a pediatric ED for acute asthma were randomly assigned to standard care (group 1), including patient education, a written care plan, and instructions to follow up with the primary care provider within 7 days, or 1 of 2 interventions. Group 2 received standard care plus assistance with scheduling follow-up, while group 3 received the above interventions, plus enrollment in a case management program.\n The primary outcome was the proportion of children having an ED visit for asthma within 6 months. Other outcomes included change in quality-of-life score and controller-medication use.\n Three hundred fifty-two children were enrolled; 78% completed follow-up, 69% were black, and 70% had persistent asthma. Of the children, 37.8% had a subsequent ED visit for asthma, with no difference among the treatment groups (group 1: 38.4%; group 2, 39.2%; group 3, 35.8%). Children in all groups had a substantial, but similar, increase in their quality-of-life score. Controller-medication use increased from 69.4% to 81.4%, with no difference among the groups.\n ED-based attempts to improve primary care linkage or initiate case management are no more effective than our standard ED care in improving subsequent asthma outcomes over a 6-month period." ]

[ "14695409", "17485707" ]

[ "Single versus double autologous stem-cell transplantation for multiple myeloma.", "Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study." ]

[ "We conducted a randomized trial of the treatment of multiple myeloma with high-dose chemotherapy followed by either one or two successive autologous stem-cell transplantations.\n At the time of diagnosis, 399 previously untreated patients under the age of 60 years were randomly assigned to receive a single or double transplant.\n A complete or a very good partial response was achieved by 42 percent of patients in the single-transplant group and 50 percent of patients in the double-transplant group (P=0.10). The probability of surviving event-free for seven years after the diagnosis was 10 percent in the single-transplant group and 20 percent in the double-transplant group (P=0.03). The estimated overall seven-year survival rate was 21 percent in the single-transplant group and 42 percent in the double-transplant group (P=0.01). Among patients who did not have a very good partial response within three months after one transplantation, the probability of surviving seven years was 11 percent in the single-transplant group and 43 percent in the double-transplant group (P<0.001). Four factors were significantly related to survival: base-line serum levels of beta2-microglobulin (P<0.01) and lactate dehydrogenase (P<0.01), age (P<0.05), and treatment group (P<0.01).\n As compared with a single autologous stem-cell transplantation after high-dose chemotherapy, double transplantation improves overall survival among patients with myeloma, especially those who do not have a very good partial response after undergoing one transplantation.\n Copyright 2003 Massachusetts Medical Society", "We performed a prospective, randomized study of single (arm A) versus double (arm B) autologous stem-cell transplantation (ASCT) for younger patients with newly diagnosed multiple myeloma (MM).\n A total of 321 patients were enrolled onto the study and were randomly assigned to receive either a single course of high-dose melphalan at 200 mg/m2 (arm A) or melphalan at 200 mg/m2 followed, after 3 to 6 months, by melphalan at 120 mg/m2 and busulfan at 12 mg/kilogram (arm B).\n As compared with assignment to the single-transplantation group (n = 163 patients), random assignment to receive double ASCT (n = 158 patients) significantly increased the probability to attain at least a near complete response (nCR; 33% v 47%, respectively; P = .008), prolonged relapse-free survival (RFS) duration of 18 months (median, 24 v 42 months, respectively; P < .001), and significantly extended event-free survival (EFS; median, 23 v 35 months, respectively; P = .001). Administration of a second transplantation and of novel agents for treating sequential relapses in up to 50% of patients randomly assigned to receive a single ASCT likely contributed to prolong the survival duration of the whole group, whose 7-year rate (46%) was similar to that of the double-transplantation group (43%; P = .90). Transplantation-related mortality was 3% in arm A and 4% in arm B (P = .70).\n In comparison with a single ASCT as up-front therapy for newly diagnosed MM, double ASCT effected superior CR or nCR rate, RFS, and EFS, but failed to significantly prolong overall survival. Benefits offered by double ASCT were particularly evident among patients who failed at least nCR after one autotransplantation." ]

[ "224831", "3789208", "482458" ]

[ "Day treatment and psychotropic drugs in the aftercare of schizophrenic patients. A Veterans Administration cooperative study.", "A controlled study of transitional day care for non-chronically-ill patients.", "Day hospital versus outpatient treatment: a controlled study." ]

[ "Schizophrenic patients referred for day treatment at the time of discharge from ten hospitals were randomly assigned to receive day treatment plus drugs or to receive drugs alone. They were tested before assignment and at 6, 12, 18, and 24 months on social functioning, symptoms, and attitudes. Community tenure and costs were also measured. The ten day centers were described on process variables every six months for the four years of the study. Some centers were found to be effective in treating chronic schizophrenic patients and others were not. All centers improved the patients' social functioning. Six of the centers were found to significantly delay relapse, reduce sumptoms, and change some attitudes. Costs for patients in these centers were not significantly different from the group receiving only drugs. More professional staff hours, group therapy, and a high patient turnover treatment philosophy were associated with poor-result centers. More occupational therapy and a sustained nonthreatening environment were more characteristic of successful outcome centers.", "The authors randomly assigned 79 inpatients with nonchronic schizophrenia or affective disorder to either an intensive experimental day program called \"transitional treatment\" or a control treatment--weekly clinically believed to require intensive posthospital treatment to make the transition to the community. Although initially there was a significantly higher dropout rate from the control condition, at the point of discharge from the two programs as well as at 6- and 12-month follow-up there was no difference in outcome. Direct costs for the transitional treatment, however, were much higher.", "This study compares day hospitalization with traditional outpatient treatment effecting rehospitalization, symptomatology, mood, community, and vocational adjustment for 30 recently discharged schizophrenic patients. Results indicate day hospital patients were significantly more involved in work and training activities, but had no significant difference in the other areas of measurement." ]

[ "18055725", "19205272", "16202734", "299462", "8191328", "15878927", "20101858", "15327617", "16037110", "358728", "9292644", "16101611", "18366490", "19049993", "10686224", "3240887", "18794161", "8688400", "8842586", "12452468", "7769082", "11006200", "8883754", "9866000", "15042010", "4533699", "9397098", "8300840", "16817081", "18412782", "2515847", "9351755", "7724098", "8724617", "12388963", "6586395", "12881083", "2075246" ]

[ "Mifepristone in second-trimester medical abortion: a randomized controlled trial.", "Vaginal versus oral misoprostol for second-trimester pregnancy termination: a randomized trial.", "A prospective, randomized comparison of vaginal misoprostol versus intra-amniotic prostaglandins for midtrimester termination of pregnancy.", "Use of prostaglandin, hypertonic saline and oxytocin for second-trimester abortion.", "Mid-trimester termination of pregnancy--a randomised controlled trial of two prostaglandin regimens.", "A randomized trial of mifepristone in combination with misoprostol administered sublingually or vaginally for medical abortion at 13-20 weeks gestation.", "A comparison of low-dose and high-dose protocols of vaginal misoprostol for second trimester termination of pregnancy.", "A prospective randomised comparison of sublingual and vaginal misoprostol in second trimester termination of pregnancy.", "A prospective randomized comparison of sublingual and oral misoprostol when combined with mifepristone for medical abortion at 12-20 weeks gestation.", "Comparison of extra-amniotic instillation of rivanol and PGF2alpha either separately or in combination followed by oxytocin for second trimester abortion.", "Comparison of ethacridine lactate and prostaglandin E2 in second trimester medical abortion.", "A randomised controlled trial of 6 and 12 hourly administration of vaginal misoprostol for second trimester pregnancy termination.", "A randomised comparative study on sublingual versus vaginal administration of misoprostol for termination of pregnancy between 13 to 20 weeks.", "A randomized trial to compare two dosing intervals of misoprostol following mifepristone administration in second trimester medical abortion.", "A comparison of two regimens of intravaginal misoprostol for termination of second trimester pregnancy: a randomized comparative trial.", "Intra-amniotic injection of oxytetracycline hydrochloride for termination of mid-trimester pregnancy.", "Comparison of vaginal and sublingual misoprostol for second trimester abortion: randomized controlled equivalence trial.", "A comparison of 600 and 200 mg mifepristone prior to second trimester abortion with the prostaglandin misoprostol.", "A randomised study of two doses of gemeprost in combination with mifepristone for induction of abortion in the second trimester of pregnancy.", "A randomised study of misoprostol and gemeprost in combination with mifepristone for induction of abortion in the second trimester of pregnancy.", "Induction of abortion in the second trimester by a combination of misoprostol and mifepristone: a randomized comparison between two misoprostol regimens.", "Randomized comparison of vaginal (200 microg every 3 h) and oral (400 microg every 3 h) misoprostol when combined with mifepristone in termination of second trimester pregnancy.", "A randomized trial of 2 regimens for the administration of vaginal prostaglandins (gemeprost) for the induction of midtrimester abortion.", "Vaginal misoprostol compared with vaginal gemeprost in termination of second trimester pregnancy. A randomized trial.", "Randomized controlled trial of misoprostol for second-trimester pregnancy termination associated with fetal malformation.", "Prostaglandin F2alpha and oxytocin compared with hypertonic saline and oxytocin for the induction of second trimester abortion.", "A comparison between two doses of intravaginal misoprostol and gemeprost for induction of second-trimester abortion.", "The abortifacient effect of misoprostol in the second trimester. A randomized comparison with gemeprost in patients pre-treated with mifepristone (RU486).", "Randomized study on the effect of adding oxytocin to ethacridine lactate or misoprostol for second-trimester termination of pregnancy.", "Randomized comparison of dry tablet insertion versus gel form of vaginal misoprostol for second trimester pregnancy termination.", "Mid-trimester abortion by extraamniotic Emcredil versus normal saline.", "Vaginal misoprostol compared with oral misoprostol in termination of second-trimester pregnancy.", "Second-trimester abortion by intramuscular 15-methyl-prostaglandin F2 alpha or intravaginal prostaglandin E2 suppositories: a randomized trial.", "Misoprostol is as effective as gemeprost in termination of second trimester pregnancy when combined with mifepristone: a randomised comparative trial.", "A randomized controlled trial comparing two protocols for the use of misoprostol in midtrimester pregnancy termination.", "Randomized trial of intracervical prostaglandin E2 gel and intraamniotic prostaglandin F2 alpha for induction of second trimester abortion.", "Second-trimester pregnancy termination: comparison of three different methods.", "Second-trimester termination with 16,16 dimethyl-PGE1-methyl ester (gemeprost), compared with a regimen that included intra-amniotic PGF2 alpha and hypertonic saline." ]

[ "To investigate the adjunctive use of mifepristone in second-trimester induction abortions using misoprostol 1 day after feticidal digoxin.\n This is a randomized, placebo-controlled, double-blind trial of mifepristone in second-trimester induction termination using misoprostol after feticidal digoxin. Women seeking abortion between 18 and 23 weeks of gestation were offered enrollment. At the time of digoxin amnioinfusion, participants received a randomly allocated, identical-appearing capsule containing either mifepristone, 200 mg, or placebo. Patients returned the following day for induction with buccal misoprostol. The primary outcome was the time interval from the first misoprostol dose to abortion. Analysis utilized survival curves with log-rank testing.\n Of 64 women, 32 received mifepristone and 32 received placebo. The groups did not differ by ethnicity, age, parity, reason for termination, or gestational age. Median procedure time was significantly shorter for those who received mifepristone, 10 hours (95% confidence interval [CI] 8-12), than those who did not, 18 hours (95% CI 15-22), P<.01, and those parous, 10 hours (95% CI 9-14), compared with nulliparous, 16 hours (95% CI 12-22, P=.02). Other findings in the mifepristone compared with placebo group included rates of placental retention, 3.1% compared with 6.3% (P=.61), length of hospitalization, 0.66 days compared with 0.8 days (P=.23), and analgesic requirements, 27.2 mg compared with 39.3 mg morphine (P=.22). Side effects during induction were similar between groups.\n Addition of mifepristone in second-trimester termination inductions using misoprostol significantly reduces the abortion time interval.\n Clinicaltrials.gov, www.clinicaltrials.gov, NCT00382538\n I.", "The purpose of this study was to compare the efficacy and side effects of two different misoprostol regimens for second-trimester pregnancy termination. Sixty women in second trimester of gestation with indications for pregnancy termination were randomly assigned in two equal groups to receive either vaginal or oral misoprostol. The dosing regimen was 400 microg as the initial dose followed by 400 microg up to 3 doses (1200 microg) if needed in each group. Efficacy and side effects were compared. The percentage of women who delivered was significantly higher in vaginal group than the oral group (86.7 vs. 43.3 p = 0.0006). No significant differences in complication rates and induction to delivery interval were noted between the two groups. Vaginal administration of misoprostol resulted in a higher success rate for second trimester pregnancy termination, whereas, no significant differences in induction to delivery time and complication rates were noted between vaginal and oral groups.", "The purpose of this study was to compare the efficacy and adverse effects of vaginal misoprostol and intra-amniotic PGF2alpha for midtrimester abortion.\n One hundred thirty-two women between 12 and 24 weeks' gestation, seeking abortion in a tertiary hospital, were randomized to receive vaginal misoprostol (400 microg every 3 hours) or intra-amniotic PGF2alpha (carboprost 1.5 mg). Main outcome measures were induction-to-abortion interval, success rates at 24 and 48 hours, and adverse effects.\n Successful abortion rates at 24 and 48 hours between intra-amniotic PGF2alpha and vaginal misoprostol were not statistically different. However, vaginal misoprostol results in a significantly shorter mean induction-to-abortion interval, compared with intra-amniotic PGF2alpha (misoprostol: 16.2 hours; intra-amniotic PGF2alpha: 20.8 hours; P = .006), particularly among multiparous women (misoprostol: 13.1 hours; intra-amniotic PGF2alpha 18.3 hours; P = .011) and for gestation below 130 days (misoprostol: 14.6 hours; intra-amniotic PGF2alpha: 20.2 hours; P = .015). Fever and shivering were commoner with vaginal misoprostol.\n Vaginal misoprostol should be the regimen of choice for midtrimester abortion, particularly for multiparous women and women in the early second trimester.", "The management of second-trimester abortion is still not satisfactory with respect to safety and side-effects; it is considered to be in a state of evolution. The goal of this investigation has been to combine, in reduced quantity, prostaglandin and hypertonic saline in order to minimize the complications and side-effects associated with the separate administration of each component. This study documents the results of a random sample of 385 abortions performed in the second trimester, induced by intra-amniotic instillation of prostaglandin (20 mg) and NaCl 5 and 10 g in different volumes and concentrations augmented with oxytocin. In a series of 20 patients, the coagulation profile is presented and the clinical characteristics of 4 groups are compared. This study demonstrated no coagulation defects. The gastrointestinal side-effects were reduced. In spite of the reduced dosage of each component, the instillation abortion interval still remained 17.08 h on the average. Incomplete abortion ranged from 32% to 48.78%. The data presented in this report suggests that combination of prostaglandin, hypertonic saline and oxytocin is feasible for midtrimester abortion.", "To determine the more applicable of two ways of prostaglandin induction currently in use in second trimester induced abortions for congenital or chromosomal abnormalities.\n A prospective randomised controlled trial.\n Department of Obstetrics and Gynaecology, Tygerberg Hospital, CP.\n Twenty consecutive patients admitted for termination of pregnancy for congenital or chromosomal abnormalities between 14 and 26 weeks' pregnancy duration.\n Patients were randomly selected to receive either 1.5 mg prostaglandin E2 (PGE2) gel extra-amniotically or 25 mg prostaglandin F2 alpha (PGF2 alpha) intra-amniotically. Patients in both groups received oxytocin to a maximum dosage of 120 mU per minute if they had not aborted 18 hours after the original administration of either prostaglandin regimen. If abortion had not taken place 36 hours after commencement of treatment, management was considered unsuccessful.\n Proportion of successful inductions and complications.\n Complications of management were rare and did not differ between the two management groups. However, there were significantly more failures in the group who received intra-amniotic PGF2 alpha (7 v. 2 patients) as well as a significantly higher need for oxytocin in this group (10 v. 4 patients).\n With promising drugs such as prostaglandin analogues and anti-progesterones not universally available, methods of induction suitable to the local situation should be sought. Extra-amniotic PGE2 seems more suitable than intra-amniotic PGF2 alpha because of a shorter induction-to-delivery time without increased morbidity.", "Several studies have now reported the successful use of the sublingual administration of misoprostol for medical abortion in the first trimester. The objective of this study was to assess the acceptability to women, the efficacy of the regimen, as well as the acceptability to staff of sublingual versus vaginal administration of misoprostol following mifepristone for medical abortion at 13-20 weeks gestation.\n Women were randomized by opening consecutive sealed envelopes generated using random number tables. Mifepristone (200 mg) was followed 36-48 h later by sublingual administration of misoprostol 600 microg or vaginal misoprostol 800 microg. This was followed by 3 hourly doses of misoprostol 400 microg administered sublingually or vaginally.\n A total of 76 women were randomized. Of women in the sublingual group, 24 (66.7%) expressed satisfaction with the route of misoprostol administration compared with 25 (62.5%) in the vaginal group. A higher proportion in the sublingual group used intramuscular opiates. There was no significant difference in the surgical evacuation rate between the sublingual (three out of 36 women, 8.3%) and vaginal groups (one out of 40, 2.5%), (P=0.26) and acceptability to staff was the same for both methods.\n Sublingual administration of misoprostol following mifepristone is an acceptable and effective alternative to vaginal administration for medical abortion at 13-20 weeks gestation. However, women should be advised about the greater likelihood of requiring stronger analgesia.", "Sixty patients were randomized to low-dose and high-dose groups, receiving a maximum total dose 1400 g of misoprostol by the vaginal route to compare the efficacy of the protocols for second trimester termination of pregnancy. Outcome measures to be compared between the groups were success rates, time to termination, blood loss, complications and side-effects. Yet time to termination was significantly shorter in the high-dose than in the low-dose group (923 +/- 571 vs 1307 +/- 828 min; p < 0.05). The distance between the internal cervical os and the placenta was positively correlated with the duration of the termination process (r = 0.508, p < 0.001). Induction to the fetal expulsion period is shorter with the higher dose without any significant increase in morbidity. A shorter distance between the internal cervical os and the placenta may forecast a shorter termination process.", "To compare the efficacy, side effects and acceptability of sublingual and vaginal misoprostol for second trimester medical abortion.\n Prospective randomised controlled trial.\n Tertiary referral unit and a teaching hospital.\n Two hundred and twenty-four women at 12 to 20 weeks of gestation.\n The women were randomised to receive either sublingual or vaginal misoprostol 400 microg every 3 hours for a maximum of five doses. The course of misoprostol was repeated if the woman did not abort within 24 hours.\n The success rate at 48 hours, induction-to-abortion interval and the side effects.\n There was no significant difference in the success rate at 48 hours (sublingual: 91%; vaginal: 95%). However, the success rate at 24 hours was significantly higher in the vaginal group (85%) compared with the sublingual group (64%). There was no difference in the median induction-to-abortion interval (sublingual: 13.8 hours; vaginal: 12.0 hours). Significantly more women in the sublingual group preferred the route to which they were assigned when compared with the vaginal group. The incidence of fever was also less in the sublingual group.\n The use of vaginal misoprostol for second trimester medical abortion resulted in a higher success rate than sublingual misoprostol at 24 hours but the abortion rate was similar at 48 hours. Vaginal misoprostol should be the regimen of choice but sublingual misoprostol is also an effective alternative.", "Sublingual misoprostol has been shown to be effective in medical abortion. A prospective double-blinded placebo-controlled trial was done to compare the efficacy and side-effects of sublingual to oral misoprostol when used with mifepristone for medical abortion from 12 to 20 weeks gestation.\n A total of 120 women at 12-20 weeks of gestation were randomized to receive 200 mg oral mifepristone followed by either sublingual or oral misoprostol 400 mg every 3 h for a maximum of five doses 36-48 h later. The course of misoprostol was repeated if the woman did not abort within 24 h.\n There was no significant difference (P = 0.43) in the success rate at 24 h [relative risk = 1.075; 95% confidence interval (CI): 0.94-1.19]. Abortion occurred in 91.4% in the sublingual group (95% CI: 81.0-96.7%) as compared to 85.0% (95% CI: 73.7-92.1%) in the oral group. The median induction-to-abortion interval was significantly shorter (P = 0.009) in the sublingual group (5.5 h) as compared to the oral group (7.5 h). The incidence of fever was higher in the sublingual group (P < 0.0001). The incidences of other side-effects were similar.\n Sublingual misoprostol, when combined with mifepristone, is effective for medical abortion in the second trimester. The induction-to-abortion interval is shorter when sublingual misoprostol is used when compared to oral misoprostol.", "Second trimester abortion was induced in 92 women by extra-amniotic instillation of Rivanol and/or PGF2alpha followed by intravenous oxytocin after 24 hours. All instillations were made via a catheter with a balloon filled with 30 ml and left in place until abortion, but never for more than 24 hours. Induction was started by Rivanol alone (n = 23), PGF2alpha alone (n = 23), Rivanol combined with PGF2alpha (n = 23), or Rivanol combined with half dose PGF2alpha (n = 23) and the patients were allotted to the different groups in a random manner. The Rivanol solution was instilled as a single dose but PGF2alpha was instilled every 2nd hour for 24 hours. The mean induction-abortion time was similar in all 4 groups but a number of patients given PGF2alpha alone or in combination with Rivanol aborted earlier than patients induced by Rivanol alone, during the period before intravenous oxytocin was administered. Gastrointestinal side effects were equally common after Rivanol as after PGF2alpha. With the methods and doses used in the present investigation PGF2alpha alone or combined with Rivanol with subsequent oxytocin had no over-all advantage over Rivanol.", "A comparison of ethacridine lactate and prostaglandin E2 (PGE2) with or without oxytocin infusion in second trimester medical abortion cases.\n A prospective study was performed on 151 women requiring second trimester medical abortions between 1989 and 1995. Patients were randomly assigned to PGE2 group (n = 30), ethacridine lactate group (n = 48), ethacridine lactate combined with oxytocin infusion group (n = 49) and PGE2 combined with oxytocin infusion group (n = 24). Rates of successful abortion (i.e., complete evacuation of fetal and placental tissues from the uterus) within 24 hours for each group were determined and compared by chi2 and the Student t-test.\n Statistically significant difference concerning successful abortion rates was observed between ethacridine lactate and PGE2 groups, PGE2 and PGE2+oxytocin infusion groups, and ethacridine lactate+oxytocin infusion and PGE2 groups, while there was no significant difference between ethacridine lactate and ethacridine lactate+oxytocin infusion groups, ethacridine lactate and PGE2+oxytocin infusion groups, and PGE2+oxytocin infusion and ethacridine lactate+oxytocin infusion groups.\n Extra-amniotic ethacridine lactate instillation alone and intracervical PGE2 gel application are effective and safe methods for second trimester abortion.", "To compare the effectiveness of vaginal misoprostol administered 6 or 12 hourly for second trimester pregnancy termination.\n A randomised controlled trial.\n University teaching hospital.\n Two hundred and seventy-nine pregnant women at gestations between 14 and 26 weeks undergoing pregnancy termination.\n Women were randomised to receive 600-microg misoprostol tablets vaginally either every 6 hours or every 12 hours until abortion occurred.\n Induction-abortion interval, success rate within 24 and 48 hours and adverse effects.\n There was no significant difference in the median induction to abortion interval 6 hours (16 hours) and 12 hours (16 hours; P= 0.80). The total dose of misoprostol was higher in the 6-hour group (1800 vs 1200 microg). The cumulative abortion rates within 24 hours were 74% and 67% and within 48 hours 94% and 92%, in the 6- and 12-hour groups, respectively. Fever was more common in the 6-hour group (53%) versus the 12-hour group (31%; P < 0.001). The incidence of nausea, vomiting, diarrhoea, severe bleeding and abdominal pain were similar.\n Misoprostol (600 microg) administered at 12-hour intervals was associated with fewer adverse effects and was as effective as a 6-hour interval.", "Misoprostol is the drug of choice for medical abortion worldwide but consensus is yet to be reached regarding its preferred route of administration.\n To compare the outcome of sublingual with vaginal administrations of misoprostol for induction of second trimester abortion.\n A randomised comparative trial where 300 women at 13-20 weeks gestation, requiring medical abortion, were randomly assigned to sublingual or vaginal route for misoprostol administration with a dose schedule of 400 microg three-hourly, up to a maximum five doses over 24 h. The same doses were repeated for another 24 h in non-responders. Primary outcome measure was complete abortion rate at 24 and 48 h, and the secondary outcome measures were induction-abortion interval, failure rate, side-effects and patients' preference to the route.\n No statistically significant differences in the complete abortion rates were observed at 24 h (64.03% vs 61.59%, P = 0.767) and at 48 h (79.14% vs 82.01%, P = 0.651) when sublingual and vaginal groups were compared. Mean induction-abortion intervals in sublingual and vaginal groups were 14.1 and 14.5 h, respectively (P = 0.066). Other outcome measures were also more or less similar in both groups. Differences in the incidence of side-effects were also statistically insignificant when both groups were compared. Sublingual administration of the drug was preferred by most of the women as compared to vaginal administration (P < 0.0001).\n Both sublingual and vaginal administrations of misoprostol are equally effective in inducing medical abortion during second trimester but sublingual route was preferred by the patients.", "The conventional timing of misoprostol administration after mifepristone for second trimester medical abortion is 36-48 h, but simultaneous administration, which may make the regimen more convenient, has not been studied. The objective of this randomized comparison study is to compare two intervals of administration of misoprostol after pretreatment with mifepristone for second trimester medical abortion.\n Eligible women with gestational age between 12 and 20 weeks were randomized to receive mifepristone 200 mg orally followed by 600 microg misoprostol vaginally either immediately or 36-38 h later, followed by 400 microg vaginal misoprostol every 3 h for a maximum of four doses. The primary outcome measure was the success rate at 24 h after the start of misoprostol treatment and the secondary outcome measures were the induction-to-abortion interval and the frequency of side effects.\n There was a significant difference in the success rate at 24 h (36-38 h: 100%; immediate: 91.5%). The median induction-to-abortion interval was significantly shorter in the 36-38 h regimen (4.9 h) compared with the immediate regimen (10 h). Side effects in terms of febrile episodes and chills/rigors were significantly higher in the immediate administration group.\n Simultaneous use of mifepristone and misoprostol for second trimester medical abortion is not as effective as the regimen using a 36-38 h dosing interval.", "A prospective randomized trial was conducted in 148 women to compare the efficacy of two regimens of vaginal misoprostol for termination of second trimester pregnancy. Women aged 16-40 years requesting termination of second trimester pregnancy were randomized into two groups. Women in group 1 were given vaginal misoprostol 400 microg every 3 h for a maximum of five doses in 24 h. Women in group 2 were given vaginal misoprostol 400 microg every 6 h for a maximum of three doses in 24 h. If women did not abort in 24 h, the same regimen was repeated. The median induction-abortion interval in group 1 (15.2 h) was significantly shorter (P < 0.01) than that in the group 2 (19.0 h). The percentage of women who achieved successful abortion within 48 h in group 1 (90.5%) was also significantly higher (P < 0.02) than that in group 2 (75.7%). The incidence of fever was more common in group 1 (P = 0.01). It is concluded that the regimen of vaginal misoprostol 400 microg every 3 h with maximum of five doses in 24 h was more effective than the regimen of misoprostol every 6 h in termination of second trimester pregnancy.", "Seventy-eight women underwent induced mid-trimester abortion. Fifty-two women aborted after an intra-amniotic injection of 1 g oxytetracycline hydrochloride. The control group comprised 16 women who received an intra-amniotic injection of hypertonic saline and 9 women with prostaglandin F2 alpha. All but 2 women aborted after one injection. Thirty-five women of the oxytetracycline hydrochloride group received intravenous oxytocin after the appearance of uterine contractions, 17 did not. The mean injection abortion interval in the women who received intravenous oxytocin was 38.6 +/- 2.7 h, whereas in the group without oxytocin it was 31.3 +/- 2.3 h. There is no statistically significant difference between these two groups (p less than 0.2). The mean injection abortion interval in the hypertonic saline group was 18.4 +/- 2.2 h. In the F2 alpha group it was 13.2 +/- 1.3 h. There is no statistically significant difference between hypertonic saline and prostaglandins (p less than 0.2). The mean injection abortion interval is significantly shorter in the F2 alpha and hypertonic saline groups as compared to the oxytetracycline hydrochloride group (p less than 0.001). It is advisable therefore to use oxytetracycline hydrochloride only in cases when the use of F2 alpha or hypertonic saline is contraindicated.", "To identify an effective misoprostol-only regimen for the termination of second trimester pregnancy, we compared sublingual and vaginal administration of multiple doses of misoprostol in a randomized, placebo-controlled equivalence trial.\n Six hundred and eighty-one healthy pregnant women requesting medical abortion at 13-20 weeks' gestation were randomly assigned within 11 gynaecological centres in seven countries into two treatment groups: 400 microg of misoprostol administered either sublingually or vaginally every 3 h up to five doses, followed by sublingual administration of 400 microg misoprostol every 3 h up to five doses if abortion had not occurred at 24 h after the start of treatment. We chose 10% as the margin of equivalence. The primary end-point was the efficacy of the treatments to terminate pregnancy in 24 h. Successful abortion within 48 h was also considered as an outcome along with the induction-to-abortion-interval, side effects and women's perceptions on these treatments.\n At 24 h, the success (complete or incomplete abortion) rate was 85.9% in the vaginal administration group and 79.8% in the sublingual group (difference: 6.1%, 95% CI: 0.5 to 11.8). Thus, equivalence could not be concluded overall; the difference, however, was driven by the nulliparous women, among whom vaginal administration was clearly superior to sublingual administration (87.3% versus 68.5%), whereas no significant difference was observed between vaginal and sublingual treatments among parous women (84.7% versus 88.5%). The rates of side effects were similar in both groups except for fever, which was more common in the vaginal group. About 70% of women in both groups preferred sublingual administration.\n Equivalence between vaginal and sublingual administration could not be demonstrated overall. Vaginal administration showed a higher effectiveness than sublingual administration in terminating second trimester pregnancies, but this result was mainly driven by nulliparous women. Fever was more prevalent with vaginal administration. Registered with International Standard Randomized Controlled Trial number ISRCTN72965671.", "To compare the use of 600 and 200 mg mifepristone prior to second trimester termination of pregnancy with the prostaglandin misoprostol.\n A randomised study.\n A Scottish teaching hospital.\n Seventy women undergoing legal induced abortion between 13 and 20 weeks of gestation.\n Administration of either 600 or 200 mg mifepristone 36 to 48 hours prior to prostaglandin.\n Induction-abortion interval.\n The geometric mean induction abortion interval was 6.9 (95% CI 5.8-8.4) h and 6.9 (95% CI 5.8-8.2) h in the 600 and 200 mg groups, respectively (no significant difference). The median dose of misoprostol was 1600 micrograms (three doses) in each group. Analgesic requirements and prostaglandin-related side effects were similar between groups. Overall, 11.4% of women required surgical evacuation of the uterus as a result of retained placenta.\n The dose of mifepristone used in second trimester abortion can be reduced from 600 to 200 mg.", "Two regimens of the prostaglandin E1 analogue, gemeprost, in combination with mifepristone were compared in a randomised trial for termination of pregnancy between 12-19 weeks. Thirty-six hours after treatment with 200 mg mifepristone, women were allocated at random to receive either 4 x 1 mg (Group I) or 4 x 0.5 mg (Group II) gemeprost by vaginal pessary every 6 hours (n = 50 in each group). If abortion had not occurred after 24 h, 5 x 1 mg of gemeprost was administered every 3 h to both groups of women. Although the median abortion interval was slightly shorter in the 1 mg group (7.8 h vs. 8.4 h, p = 0.5), the cumulative abortion rates at 24 h were similar (98% vs. 96%). Women in Group I required significantly more gemeprost to induce abortion than Group II (p < 0.0001). Parous women in both groups required significantly less of the prostaglandin to induce abortion. In Group II, the median abortion interval was significantly longer in primigravidae than multigravidae (9.5 h vs. 6.1 h; p < 0.02). There were no significant differences between the groups in the incidence of vomiting, diarrhoea or the request for analgesia. The results suggest that in parous women, the dose of gemeprost can be reduced to 0.5 mg every 6 h within the first 24 h without loss of clinical efficacy.", "To compare the effectiveness of gemeprost and misoprostol as prostaglandins used in combination with mifepristone for induction of mid-trimester termination.\n Randomised trial.\n Scottish teaching hospital.\n One hundred women undergoing abortion between 12 and 20 weeks.\n Each woman received 200 mg mifepristone and 36-48 hours later either 1 mg gemeprost vaginal pessary every 6 hours for 18 hours or 4 x 200 microg misoprostol tablets vaginally followed by 2 x 200 microg misoprostol tablets orally every 3 hours for 12 hours. Success was defined as the percentage of women aborted within 24 hours of the first administration of prostaglandin.\n Prostaglandin-abortion interval and side effects.\n There were no significant differences in median prostaglandin-abortion interval between gemeprost (6.6 hours 95% CI 6.0-10.7) and misoprostol (6.1 hours 95% CI 5.5-7.5) (P = 0.22). The cumulative abortion rates at 24 hours (96% vs 94%, respectively), the surgical evacuation rates (12% and 10%) and the incidence of vomiting, diarrhoea and pain were similar.\n Two hundred milligrammes of mifepristone followed 36-48 hours later by either vaginal gemeprost or misoprostol is a highly effective way of inducing abortion in the second trimester of pregnancy.", "The combination of mifepristone (RU486) and prostaglandin is effective in the induction of abortion in the second trimester. The optimal regimen is still under development, but is likely to be characterized by a short induction-to-abortion interval, low incidence of side-effects and high acceptability. We have investigated further whether misoprostol, a synthetic prostaglandin E1 analogue, can reliably induce second trimester abortion in 70 women pre-treated with mifepristone, and whether different routes of administration affect the induction-to-abortion interval. Abortion was achieved in 97% [95% confidence interval (CI) 90-100%] of cases without resort to other prostaglandin agents. The mean induction abortion time for the studied population was 6.4 h (95% CI 5.6-7.0 h). No significant difference was found between two different routes of administration, namely vaginal versus a combination of vaginal and oral. Misoprostol has a number of advantages over other prostaglandin preparations. We recommend that, following pre-treatment with mifepristone, misoprostol is used as the prostaglandin of choice to induce abortion in the second trimester.", "It is known that when misoprostol is given at 200 microg every 3 h after mifepristone pretreatment, the vaginal route is more effective than the oral route. However, women prefer the oral route. This randomized study was to test our hypothesis that oral misoprostol 400 microg is as effective as vaginal misoprostol 200 microg when given every 3 h in termination of second trimester pregnancy after priming with mifepristone. A total of 142 patients was randomly assigned to group 1 (200 mg mifepristone + 400 microg oral misoprostol every 3 h up to five doses) or group 2 (200 mg mifepristone + 200 microg vaginal misoprostol every 3 h up to five doses). The incidence of side-effects and the preference study were assessed through a standardized questionnaire during and after the abortion. For the oral group, both the incidence of diarrhoea (40.0 versus 23.2%, P = 0.03) and the amount of drug used (1734 compared with 812 microg, P < 0.0001) were significantly higher than that of the vaginal group but the incidence of fever appeared to be lower (not significant). There was no significant difference in complete abortion rate: 81.4% in the oral group and 75.4% in the vaginal group. The median induction-abortion interval was similar in the two groups (10.4 versus 10.0 h). The percentage of women who aborted in 24 h was also similar: 57/70 (81.4%) in the oral group and 58/69 (87.0%) in the vaginal group. Overall, 82.0% of women preferred the oral route. Oral misoprostol (400 microg) given every 3 h up to five doses, when combined with mifepristone, was as effective as the vaginal (200 microg) route in second trimester termination of pregnancy. This regimen could also be offered to those women who found repeated vaginal administration unacceptable.", "The most frequently used method for second trimester termination of pregnancy is administration of gemeprost (16, 16-dimethyl-trans delta 2-prostaglandin E1methyl ester) as a vaginal pessary. This provides a safe and effective method for achieving abortion. The current prescribing advice is to insert the pessaries into the posterior vaginal fornix every 3 hours. This study compares this to a 6-hourly regimen. The median abortion interval in the 6-hour group was shorter than the 3-hour group (15 versus 16 hours respectively) but the cumulative abortion rates were similar (98% in the 3-hour group and 91.8% in the 6-hour group). The 6-hour group required a significantly lower total dose of gemeprost to induce abortion. There was no difference in the rates of side-effects in the 2 groups but those receiving pessaries every 6 hours required less analgesia. This study finds no advantage in giving gemeprost every 3 hours.", "A prospective randomized trial was conducted in 140 women to compare the efficacy of vaginal gemeprost with vaginal misoprostol for termination of second trimester pregnancy. Women requesting termination of second trimester pregnancy were randomized into two groups. Group A women were given 1 mg vaginal gemeprost every 3 h for a maximum of five doses in the first 24 h, whereas group B women were given 400 micrograms vaginal misoprostol every 3 h for a maximum of five doses in 24 h. The median induction-abortion interval in the vaginal misoprostol group (14.1 h) was significantly shorter than that in the gemeprost group (19.5 h). The percentage of women who achieved successful abortion within 24 h in the misoprostol group (80.0%) was significantly higher than that in the gemeprost group (58.6%). There was no significant difference in the incidence of side effects between the two groups except for diarrhea, which was more common in the gemeprost group. The incidence of fever was more common in the misoprostol group. It is concluded that vaginal misoprostol is more effective than gemeprost in termination of second trimester pregnancy.", "Our purpose was to compare the effectiveness, women's views of the termination procedure, and success of umbilical cord culture for vaginal and oral misoprostol versus intra-amniotic prostaglandin PGF(2alpha) for second-trimester pregnancy termination (STPT).\n We randomized 217 women, 15 to 24 weeks' gestation, into 3 groups. Oral (OM) and vaginal (VM) misoprostol groups received 400 microg of misoprostol every 4 hours for 24 hours. The intra-amniotic PGF(2alpha) (IAPG) group received 40 mg of PGF(2alpha) followed by oxytocin infusion. Women completed self-administered questionnaires 3 weeks after the termination procedure. Umbilical cord samples were collected at delivery for karyotype analysis. The primary outcome was the time from start of the procedure to placental delivery. Secondary outcomes were maternal complications, women's acceptance of the termination procedure, and success rates of umbilical cord culture.\n The time was longer for the OM group (30.5+/-14.4 hours) compared with the VM group (18.3+/-8.2 hours) and the IAPG group (21.1+/-10.2 hours), P<.001 for both comparisons. Women in the VM group reported being more willing to repeat the termination method in the future and reported fewer side effects than those in the other groups, P<.001. Failure rates for umbilical cord cultures were 9.6%, 17.0%, and 45.6% for the VM, OM, and IAPG groups, respectively.\n Oral misoprostol is less effective than intra-amniotic PGF(2alpha) or vaginal misoprostol for STPT. Women report vaginal misoprostol more acceptable than other methods. Umbilical cord culture failure rate is highest in the IAPG group.", "Second trimester abortion was induced in a randomized investigation using a single dose of prostaglandin F2alpha (PGF2alpha) in combination with oxytocin in one group of patients, and hypertonic saline (20%) in combination with oxytocin in another group of patients. Oxytocin was administered in order to induce a rapid abortion, and was given intravenously in a glucose drip (100 I.U. oxytocin added to 1 litre of 5% glucose). Administration rate was 10 I.U./hour. The PG-group consisted of 16 patients. The mean induction-abortion interval for this group was 14.2 hours, and all patients aborted within 24 hours. In three cases the bleeding exceeded 200 ml. In one of these cases infection occurred. Only mild side effects occurred. The saline group also consisted of 16 patients. The mean induction-abortion interval in this group was 21.5 hours. Eleven patients aborted within 24 hours. In two cases the bleeding exceeded 200 ml. No side effects occurred. Intraamniotic instillation of PGF2alpha seems to be a good alternative to hypertonic saline for termination of second trimester pregnancies.", "To compare the abortifacient efficacies of two intravaginally administered misoprostol doses and gemeprost in termination of second-trimester pregnancy.\n Eighty-one women between 12 and 24 weeks' gestation requesting abortion were randomized to receive intravaginally either 100 micrograms of misoprostol at 6-hour intervals (n = 27), 200 micrograms of misoprostol at 12-hour intervals (n = 26), or 1.0 mg of gemeprost at 3-hour intervals (n = 28). The regimen was continued until abortion, or for 36 hours, with assessment of the rate of complete and incomplete abortions as well as side effects within 48 hours from the start of the treatment.\n The final rates of terminations were 74% in the 100-microgram misoprostol group, 92% in the 200-microgram misoprostol group, and 89% in the gemeprost group. Abortion was complete in 37%, 61%, and 32% in each group, respectively (P = .03, when the 200-microgram misoprostol group was compared with the two other groups). The induction-to-abortion interval was longer (P = .001) in the misoprostol groups (mean 23.1 hours for the 100-microgram and 27.8 hours for the 200-microgram dose) than in the gemeprost group (14.5 hours). There was less pain (P = .01), diarrhea (P = .001), and vomiting (P = .01) in the misoprostol groups than in the gemeprost group. The mean blood loss in the misoprostol groups was lower than in the gemeprost group (P = .001).\n Intravaginal application of 200 micrograms of misoprostol at 12-hour intervals in induction of second-trimester abortion is equally effective to a standard gemeprost regimen. Misoprostol causes fewer side effects and is cheaper and more practical to use.", "The objective of this work was to study the abortifacient effects of misoprostol, an orally active prostaglandin E1 (PGE1) analogue, in the second trimester. A randomized study of two prostaglandin regimens in women pre-treated with the antiprogesterone mifepristone was carried out in the gynaecological wards of Aberdeen Royal Hospitals, NHS Trust, and included 60 women at 13-20 weeks' gestation, in whom termination of pregnancy had been agreed. Following pre-treatment with mifepristone 600 mg women were randomly allocated to one of two prostaglandin regimens which started 36-48 h later. The first misoprostol 400 micrograms orally (up to three doses) followed by gemeprost vaginal pessary 1 mg up to two doses. The second was gemeprost vaginal pessary 1 mg up to five doses. The main outcome measures were success rate induction-to-abortion interval and side-effects. There were no significant differences between the two groups in any of the main outcome measures. We conclude that misoprostol is a stable, cheap PGE1 analogue with demonstrable efficacy and acceptable side-effects in the management of second trimester abortion. Further work is needed to establish the optimum dose and regimen.", "To compare effectiveness of misoprostol and ethacridine lactate with or without oxytocin in second-trimester medical abortions.\n A randomized prospective study. A total of 388 women with genetic indications for termination of pregnancy at 13-24 weeks of gestation were recruited. Group I (n=85) were treated with extra-amniotic ethacridine lactate, 10 ml instilled per gestational week, to a maximum of 200 ml. Group II (n=93) were treated with misoprostol administered intravaginally (200 microg), followed by 100 microg of oral misoprostol 4 hourly for 24 h. Group III (n=102) were treated with a combination of ethacrine lactate and oxytocin. An initial dose of 6 mU/min oxytocin was given, followed by additional 6 mU/min doses every 20 min. Group IV (n=96) were treated with a combination of misoprostol and oxytocin administered in a similar way as in group III. The main outcome measures were time to induce abortion, side effects, and failure/success rates.\n The mean time to induce abortion was 14.2+/-3.6, 13.2+/-3.4, 10.8+/-2.6, and 9.9+/-2.4 h in groups I, II, III, and IV, respectively (p<0.001). Addition of oxytocin to ethacridine lactate did not decrease the risk of prolongation of induction beyond 24 h but use of oxytocin with misoprostol did reduce the risk of induction beyond 24 h (OR: 0.46, 95%CI: 0.21-1, p<0.05). The occurrence of minor side effects was similar in all groups.\n Addition of oxytocin to ethacridine lactate or misoprostol significantly decreases the length of time to induce abortion without supplementary side effects.", "To compare the effectiveness of vaginal misoprostol between dry tablet insertion and gel form for second trimester pregnancy termination.\n A non-blinded block randomized controlled trial was conducted on 148 pregnant women with live fetuses in the second trimester undergoing pregnancy termination. They were randomly allocated to receive vaginal misoprostol (400 microg) either dry tablet insertion (n=72) or gel form (n=76). The same dose was then repeated every 3 h if adequate uterine contraction was not achieved until 48 h after the initiation of misoprostol. If abortion did not occur within this period, the treatment was considered a failure and other technique of termination was then given based on the decision of the attending physicians and the cervical status.\n The mean induction-abortion interval in group 1 (20.9+/-12.3 h) was not significantly different from that in group 2 (17.7+/-10.2 h). The mean total dose of misoprostol was also not significantly different between the two groups (group 1, 1556.9 microg; group 2, 1350.9 microg), but the adverse effects of misoprostol (chill and diarrhoea) were more common in the gel group.\n Tablet insertion or gel form of vaginal misoprostol have similar effectiveness but the gel form was associated with more common adverse effects.", "Data is presented for 40 mid-trimester abortions, induced by 0.1% Emcredil (Group 1--20 cases) and normal saline (Group 2--20 cases) by instillation in the extraamniotic space. It was observed that the 2 groups were comparable for age, parity and period of gestation. The mean induction-abortion interval was 18 hours 9 minutes in Group 1 and 19 hours 19 minutes in Group 2. Abortion was complete in 45% and 65% in Group 1 and Group 2, respectively. With a cutoff time of 30 hours, there were 3 failures, 1 in Group 1 and 2 in Group 2. The induction-abortion interval was significantly less in the more advanced pregnancies in the saline group. There was no complication in either of the 2 groups. It is hypothesized that normal saline also acts by damage of the decidual cells with liberation of prostaglandins locally. Also since normal saline is a cheap and easily available commodity with no contraindication for its use and no side-effects, it seems to hold a lot of promise for induction of mid-trimester abortion.", "To compare the efficacy of vaginal with oral misoprostol in termination of second-trimester pregnancy after pretreatment with mifepristone.\n Women requesting termination of second-trimester pregnancy were randomized into two groups. Thirty-six to 48 hours after oral administration of 200 mg of mifepristone, women were given either oral or vaginal misoprostol 200 microg every 3 hours for a maximum of five doses in the first 24 hours. Women receiving oral misoprostol also were given a vaginal placebo (vitamin B6), whereas those receiving vaginal misoprostol were given an oral placebo. If they failed to abort, a second course was given by the same route.\n The median induction-abortion interval in the vaginal group (9 hours) was significantly shorter than that in the oral group (13 hours). The percentage of women aborting within 24 hours in the vaginal group (90%) was significantly higher than that in the oral group (69%). The median amount of misoprostol used in the vaginal group (600 microg) also was significantly less than that in the oral group (1000 microg). There was no significant difference in the incidence of side effects between the two groups except for fatigue and breast tenderness, which were more common in the oral group. Seventy-six percent of the women preferred the oral route, and 24.5% of the women preferred the vaginal route.\n Vaginal misoprostol is more effective than oral misoprostol in termination of second-trimester pregnancy after pretreatment with mifepristone, but more women preferred the oral route.", "To compare intramuscular (IM) prostaglandin 15 methyl-F2 alpha (15M-PGF2 alpha) with prostaglandin E2 (PGE2) vaginal suppositories for second-trimester abortion in terms of efficacy and side effects.\n Fifty-one women were randomized to receive either 15M-PGF2 alpha IM injections or PGE2 intravaginal suppositories for second-trimester abortion. Efficacy and side effects of the two agents were analyzed by two-tailed t tests, chi 2 analysis with Fisher exact test, and survival analysis.\n The mean times to rupture of membranes, delivery of fetus, and delivery of placenta were significantly less for women receiving PGE2 vaginal suppositories. The cumulative abortion rate after 24 hours for the PGE2 group was 96%, compared with 69% for the 15M-PGF2 alpha group. Although there were few differences in side effects, the 15M-PGF2 alpha group had significantly fewer headaches, fevers, and chills.\n Intravaginal PGE2 is superior to IM 15M-PGF2 alpha for second-trimester abortion.", "A prospective randomized study was conducted to compare the efficacy of misoprostol with gemeprost when combined with mifepristone for termination of second trimester pregnancy. Patients requesting termination of second trimester pregnancy were randomized into two groups. In both groups of patients, 200 mg of mifepristone was given 36 to 48 hours before the administration of prostaglandins. In Group 1, the women were given 400 micrograms of oral misoprostol every 3 hours up to 5 doses. In Group 2, patients were given 1 mg of vaginal gemeprost every 6 hours up to 4 doses. The main outcomes measured were the induction-abortion intervals (the interval between the first dose of prostaglandin and abortion) and the incidence of side effects. Altogether, 50 subjects were recruited with 25 women in each group. The mean age and parity of the women and the mean gestational age of the two groups of women were comparable. There was no significant difference in the median induction-abortion intervals (8.7 hours in Group 1 and 10.8 hours in Group 2) or the incidence of side effects between the two groups of patients. We conclude that misoprostol is as effective as gemeprost in termination of second trimester pregnancy when combined with mifepristone.", "Our purpose was to compare the efficacy of oral misoprostol with that of vaginal misoprostol for midtrimester termination of pregnancy.\n Women seen for midtrimester pregnancy termination were randomly assigned to receive either misoprostol orally in a dose of 200 microg every hour for 3 hours followed by 400 microg every 4 hours or vaginally in a dose of 400 microg every 4 hours. The protocol was followed for 24 hours, after which time further management was at the discretion of the attending physician. The primary outcome measure was the induction-to-delivery interval. Sample size was calculated a priori. Statistical analysis was performed with the t test for continuous variables and the chi(2) test for categorical variables. P <.05 was considered significant.\n One hundred fourteen women were randomized, with 49 receiving vaginal misoprostol and 65 receiving oral misoprostol. The two groups were comparable with respect to maternal age, parity, indication for pregnancy termination, gestational age, and maternal weight. The mean induction-to-delivery interval was significantly shorter for the vaginal group (19.6 +/- 17.5 hours vs 34.5 +/- 28.2 hours, P <.01). Length of stay was also shorter in the vaginal group (32.3 +/- 17.3 hours vs 50.9 +/- 27.9 hours, P <.01). Significantly more patients in the vaginal group were delivered within 24 hours (85.1% vs 39.5%, P <.01), and more patients in the oral group required changes in the method of induction when they were undelivered after 24 hours (38.2% vs 7%, P <.01). The only complication was an increase in febrile morbidity in the vaginal group (25% vs 6.7%, P =.046). This did not result in an increased use of antibiotics, and all the fevers resolved post partum without further complications.\n Vaginal administration of misoprostol resulted in a shorter induction-to-delivery interval. The shorter length of stay should result in improved patient care.", "For the purpose of reducing the side effects and complication rate when inducing second trimester abortion, intracervically administered PGE2 gel was tested for the first time and compared with a single intraamniotic instillation of PGF2 alpha by a randomized allocation of 41 consecutive patients in the 13th to 24th week of gestation. In both groups the treatment was supplemented with oxytocin 5 - 6 hours after starting the induction. The methods proved of equal value as regards the abortion success rate and the induction-abortion interval, whereas the incidence of gastrointestinal side effects on intracervical application of PGE2 gel was only half as high and the occurrence of diarrhea significantly lower (p less than 0.05) with this non-invasive method than with intraamniotic PGF2 alpha. Intracervical PGE2 gel also possessed other advantages, being int. al. more acceptable by the patients and technically easier to administer.", "The object of this study was to compare intravaginal misoprostol and dinoprostone (prostaglandin E2) for second-trimester pregnancy termination, and to examine the role of the nitric oxide donor, glyceryl trinitrate, as a possible alternative to prostaglandins to induce cervical ripening in second-trimester pregnancy termination. This was a randomised clinical trial. The trial involved pregnant women between 13 and 28 weeks' gestation admitted with clear medical or obstetric indications for pregnancy termination, and was carried out in the department of obstetrics and gynecology, Assiut University Hospital, Egypt. Patients were classified into Group A, where pregnancy termination was induced by vaginal misoprostol 100 micrograms every 4 hours with a maximum dose of 500 micrograms; Group B, where induction was by vaginal dinoprostone 6 mg every 6 hours with a maximum dose of 24 mg; and Group C, where induction involved vaginal glyceryl trinitrate 500 micrograms every 6 hours with a maximum dose of 2.5 mg. Twenty-four hours after the start of induction, the rate of complete abortion in the three groups was 100%, 66.67% and 0%, respectively. The rate of complete abortion was 100% in the nitric oxide (glyceryl trinitrate)-induced group after introducing a complementary procedure. The induction-abortion interval was significantly shorter, the number of doses needed was less and the maximum Bishop score reached was greater with misoprostol than with dinoprostone. A higher rate of side effects occurred with the misoprostol-induced group (74%) compared with the other two groups (46.6% and 0%). Misoprostol is a cheap, effective drug for second-trimester pregnancy termination with short induction abortion intervals but a higher rate of side effects. Prostin E2 is also effective in termination of second-trimester pregnancy but is expensive and may require high doses to be administered. Glyceryl trinitrate is an effective drug for cervical ripening (softening) but it has no role in the stimulation of uterine contractions.", "The use of gemeprost (16,16 dimethyl-PGE1-methyl ester) pessaries was compared in an open, randomized single-centre trial with the intra-amniotic injection of PGF2 alpha combined with hypertonic saline, intravenous oxytocin and a hygroscopic cervical dilator (Dilapan) for the termination of pregnancy between 14 and 20 weeks. There was no significant difference in the induction-delivery interval for the two groups. With the exception of an increased incidence of diarrhoea in the gemeprost group, there was no significant difference in other side effects, analgesic requirements or retained placentae. Gemeprost pessaries are an effective alternative to the more invasive methods previously used for the induction of second-trimester termination." ]

[ "12775730", "10213009", "9807986", "12610178", "15284252" ]

[ "Superiority of oxaliplatin and fluorouracil-leucovorin compared with either therapy alone in patients with progressive colorectal cancer after irinotecan and fluorouracil-leucovorin: interim results of a phase III trial.", "A phase III study of irinotecan (CPT-11) versus best supportive care in patients with metastatic colorectal cancer who have failed 5-fluorouracil therapy. V301 Study Group.", "Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer.", "Phase III comparison of two irinotecan dosing regimens in second-line therapy of metastatic colorectal cancer.", "A randomized trial comparing defined-duration with continuous irinotecan until disease progression in fluoropyrimidine and thymidylate synthase inhibitor-resistant advanced colorectal cancer." ]

[ "In North America, no effective therapy has been available for patients with progressive metastatic colorectal cancer after front-line treatment with irinotecan, bolus fluorouracil (FU), and leucovorin (IFL).\n Patients with metastatic colorectal cancer who progressed after IFL therapy were randomly assigned to bolus and infusional FU and leucovorin (LV5FU2), single-agent oxaliplatin, or the combination (FOLFOX4). This planned interim analysis evaluated objective response rate (RR), time to tumor progression (TTP), and alleviation of tumor-related symptoms (TRS) in an initial cohort of patients.\n Between November 2000 and September 2001, 463 patients from 120 sites in North America were randomly assigned to treatment. FOLFOX4 proved superior to LV5FU2 in all measures of clinical efficacy. Objective RRs determined by an independent radiology panel were 9.9% for FOLFOX4 versus 0% for LV5FU2 (Fisher's exact test, P <.0001). Median TTP was 4.6 months for FOLFOX4 versus 2.7 months for LV5FU2 (two-sided, stratified log-rank test, P <.0001). Relief of TRS occurred in 33% of patients treated with FOLFOX4 versus 12% of patients treated with LVFU2 (chi2 test, P <.001). Single-agent oxaliplatin was not superior to LV5FU2 in any measure of efficacy. Patients treated with FOLFOX4 experienced a higher incidence of clinically significant toxicities than patients treated with LV5FU2, but these toxicities were predictable and did not result in a higher rate of treatment discontinuation or 60-day mortality rate.\n For patients with metastatic colorectal cancer, second-line treatment with FOLFOX4 is superior to treatment with LVFU2 in terms of RR, TTP, and relief of TRS.", "In a prospective multicenter trial, 279 patients with metastatic colorectal cancer who had failed 5-fluorouracil therapy were randomized 2:1 to receive either best supportive care (BSC) plus treatment with the topoisomerase I inhibitor, irinotecan (CPT-11; Rhône-Poulenc Rorer, Antony, France), at a dose of 350 mg/m2 every 3 weeks or BSC alone. Overall survival, the primary end point of the study, was significantly improved in patients receiving the irinotecan treatment. Only 14% of patients receiving BSC alone were alive at 1 year compared with 36% in the irinotecan group. After adjustment for prognostic factors such as performance status, the difference in survival favoring irinotecan remained highly significant (P = .001). The benefit of irinotecan was also observed through significantly longer survival without performance status deterioration, longer survival without more than 5% weight loss, and longer duration of pain-free survival. Appreciable deterioration in global quality of life (50% reduction from baseline) occurred significantly later in the irinotecan-treated patients than in the controls. Additionally, quality of life analyses of all symptoms, except diarrhea, mean scores were significantly in favor of patients assigned to irinotecan treatment than those assigned to BSC. This is the first time that the benefit of second-line chemotherapy has been demonstrated by a randomized controlled trial in advanced colorectal cancer.", "In phase II trials, irinotecan is active in patients with advanced colorectal cancer, but the survival and clinical benefit of irinotecan compared with second-line fluorouracil by continuous infusion is not known.\n 267 patients who had failed to respond to first-line fluorouracil, or whose disease had progressed after treatment with first-line fluorouracil were randomly allocated irinotecan 300-350 mg/m2 infused once every 3 weeks or fluorouracil by continuous infusion. Treatment was given until disease progression, unacceptable toxic effects, or the patient refused to continue treatment. The primary endpoint was survival, while progression-free survival, response rate, symptom-free survival, adverse events, and quality of life (QoL) were secondary endpoints.\n 133 patients were randomly allocated irinotecan and 134 were allocated fluorouracil by continuous infusion. Patients treated with irinotecan lived for significantly longer than patients on fluorouracil (p=0.035). Survival at 1 year was increased from 32% in the fluorouracil group to 45% in the irinotecan group. Median survival was 10.8 months in the irinotecan group and 8.5 months in the fluorouracil group. Median progression-free survival was longer with irinotecan (4.2 vs 2.9 months for irinotecan vs fluorouracil, respectively; p=0.030). The median pain-free survival was 10.3 months and 8.5 months (p=0.06) for irinotecan and fluorouracil, respectively. Both treatments were equally well tolerated. QoL was similar in both groups.\n Compared with fluorouracil by continuous infusion second-line irinotecan significantly improved survival in patients with advanced colorectal cancer.", "Randomized trials in fluorouracil (FU)-refractory colorectal cancer demonstrate significant survival advantages for patients receiving irinotecan. We prospectively compared the efficacy and tolerability of two irinotecan regimens (once a week for 4 weeks followed by a 2-week rest period [weekly] v once every 3 weeks) in such patients.\n This multicenter, open-label, phase III study randomly assigned patients in a 1:2 ratio to irinotecan given either weekly (125 mg/m(2)) or once every 3 weeks (350 mg/m(2), or 300 mg/m(2) in patients who were >/= 70 years of age, who had Eastern Cooperative Oncology Group performance status equal to 2, or who had prior pelvic irradiation).\n With median follow-up of 15.8 months, there was no significant difference in 1-year survival (46% v 41%, respectively; P =.42), median survival (9.9 v 9.9 months, respectively; P =.43), or median time to progression (4.0 v 3.0 months, respectively; P =.54) between the two regimens. Grade 3/4 diarrhea occurred in 36% of patients treated weekly and in 19% of those treated once every 3 weeks (P =.002). Grade 3/4 neutropenia occurred in 29% of patients treated weekly and 34% of those treated once every 3 weeks (P =.35). Treatment-related mortality occurred in five patients (5.3%) receiving irinotecan weekly and three patients (1.6%) given therapy once every 3 weeks (P =.12). Global quality of life was not statistically different between treatment groups.\n Irinotecan schedules of weekly and of once every 3 weeks demonstrated similar efficacy and quality of life in patients with FU-refractory, metastatic colorectal cancer. The regimen of once every 3 weeks was associated with a significantly lower incidence of severe diarrhea.", "Irinotecan given until disease progression is an accepted standard treatment for advanced colorectal cancer (CRC) resistant to fluoropyrimidines. It is not known whether a predefined period of irinotecan treatment would result in similar duration of disease control. We performed a multicenter phase III trial to compare the two policies of defined-duration versus continuous irinotecan treatment.\n Three hundred thirty-three eligible patients with advanced CRC progressing on or within 24 weeks of completing fluoropyrimidine-based chemotherapy were prospectively registered. After receiving eight cycles of irinotecan given at 350 mg/m2 once every 3 weeks, 55 patients with responding or stable disease were randomly assigned to stop irinotecan (n = 30) or continue until disease progression (n = 25). Registered patients were not randomly assigned predominantly due to disease progression (n = 236) and intolerable toxicity (n = 38).\n From the time of random assignment, there were no differences in failure-free survival (P = .999) or overall survival (P = .11) between the two arms. No difference was seen in mean global health status quality-of-life score between the two arms at 12 weeks after random assignment. No grade 3 diarrhea and febrile neutropenia was seen in the continue-irinotecan arm after random assignment.\n For most patients, the decision to continue on irinotecan beyond 24 weeks is influenced by disease progression or treatment-related toxicity. However, for 17% of patients in whom this decision is clinically relevant, there seems to be little benefit from continuing irinotecan, though the drug was well tolerated without any deterioration in quality of life.\n Copyright 2004 American Society of Clinical Onocology" ]

[ "10049962", "9877372", "15217172", "10713806", "1346956", "9715552", "12032787", "9255195", "11758844", "12858823" ]

[ "Once- versus twice-daily gentamicin dosing in neonates >/=34 Weeks' gestation: cost-effectiveness analyses.", "Once daily gentamicin dosing in neonates.", "Once versus twice daily dose of gentamicin therapy in Thai neonates.", "Randomized controlled trial of once vs. twice daily gentamicin therapy in newborn.", "Pharmacokinetics and antibacterial activity of daily gentamicin.", "Gentamicin therapy in preterms: a comparison of two dosage regimens.", "Comparison of once-daily versus twice-daily gentamicin dosing regimens in infants > or = 2500 g.", "Pharmacokinetics of once-daily dosing of gentamicin in neonates.", "Gentamicin in neonatal infection: once versus twice daily dosage.", "[Tolerability of once-daily-dosing of intravenous gentamicin in preterm neonates born at 32-37 weeks of gestation]." ]

[ "To compare performance and cost analysis of two gentamicin regimens in infants >/=34 weeks' gestation requiring antibiotics for a 72-hour rule-out sepsis evaluation. A once-daily dosing (ODD) regimen of 4 mg/kg was compared with a standard twice-daily dosing (TDD) regimen of 2.5 mg/kg every 12 hours.\n Infants at two university-affiliated Level III nurseries were prospectively temporally allocated to receive ODD (n = 27) or TDD (n = 28) as part of their 72-hour empirical antibiotic regimen. Performance of dosing regimens was based on target serum gentamicin concentrations (SGC) established prospectively as a peak of 5 to 10 microgram/mL and a trough of </=2 microgram/mL. SGC were determined by fluorescence polarization immunoassay on day 3 of therapy. Cost data were obtained by distributing a questionnaire to 15 pediatric pharmacy practice sites. Inquiries were made regarding hospital cost of drug acquisition, drug supplies, drug preparation and administration, and serum concentration analysis. Performance and cost data were then used to do a cost-effectiveness analysis.\n Mean peak concentrations were higher with ODD (7.9 +/- 0.2 microgram/mL) than TDD (6.7 +/- 0.3 microgram/mL). Half of the patients in the TDD group had trough concentrations >2 microgram/mL, compared with none in the ODD group. Overall, 57% of the SGCs in the TDD group were outside the target concentration range versus 7% in the ODD group. Based on questionnaire results, a total 72-hour process cost of ODD versus TDD was compared for regimens with and without use of SGC analysis. If SGCs are obtained, more than 75% of the cost associated with gentamicin therapy is attributable to SGC analysis. Based on a cost-effectiveness analysis, ODD was the dominant dosing strategy in all categories analyzed.\n ODD of gentamicin at 4 mg/kg in neonates >/=34 weeks' gestation is the preferable treatment strategy based on: 1) significantly improved SGC performance compared with TDD; 2) elimination of the need for routine SGC collection in infants on short courses of therapy; and 3) significant antibiotic-associated hospital cost savings when compared with conventional therapy of TDD and SGC analysis.", "nan", "To compare the peak and trough gentamicin concentrations in neonates after a once (ODD) vs. twice daily dosing (TDD) to establish the appropriate dosage for Thai neonates.\n Neonates of gestational age > or = 34 weeks, or body weight > or = 2000 g, suspected of having bacterial infection were randomized to receive gentamicin intravenously, either 5 mg/kg every 24 hours or 2.5 mg/kg every 12 hours. The peak and trough serum gentamicin levels (SGLs) were measured. Serum creatinine cued nephrotoxicity.\n Neonates were evaluated and baseline characteristics between the groups were compared. The ODD and TDD group had a mean gentamicin peak and trough concentration of 10.1 +/- 3.0 vs. 7.8 +/- 2.0 microg/ml (p < 0.05) and 1.6 +/- 1.1 vs. 2.6 +/- 1.2 microg/ml (p < 0.05), respectively. The peak SGL of > or = 4 microg/ml was achieved in 100% vs. 96% of the ODD vs. TDD group, respectively. SGL troughs > or = 2 microg/ml were detected less often in the ODD group (22% vs. 68%, p < 0.05). Abnormal change in serum creatinine was not observed in either group.\n A once daily dose of gentamicin 5 mg/kg achieved a significantly higher peak SGL and safer trough than a twice-daily dose of 2.5 mg/kg albeit about a quarter of the ODD group had high troughs. A single daily dose of gentamicin 3.5-4 mg/kg/d in Thai neonates should be tested.", "To compare the efficacy of once daily gentamicin administration to the conventional twice daily dosage schedule by estimation of serum gentamicin concentrations (SGC) in neonates.\n Randomized controlled trial.\n Medical college hospital.\n Seventy three neonates of gestational age>32 weeks at risk or with clinical features of sepsis.\n The subjects were divided into preterm and term groups. Babies in each of these groups were randomized to receive a single daily dose (4 mg/kg) or a twice daily dose (2.5 mg/kg) of injection gentamicin intravenously. Trough and peak SGC were estimated half an hour prior and one hour after the second dose. Statistical analysis was done using the equivalence method.\n In preterm as well as term babies, the mean peak and trough gentamicin levels were comparable in the two regimens. There is statistically significant evidence to show that the effect of once daily and twice daily dosage is similar.\n Once daily gentamicin administration is as effective as twice daily therapy and would be more cost effective.", "Twenty full term neonates with suspected bacterial infection were randomly assigned to a once daily or a twice daily dosage regimen with gentamicin (4 mg/kg/day). Concomitantly all patients were treated with ampicillin (200 mg/kg/day). The gentamicin concentration time curves were analysed by an open two compartment model under steady state conditions on day 4 of treatment. The mean theoretical maximum serum concentration in the group taking gentamicin once daily (10.9 micrograms/ml) was significantly higher than in the group taking it twice daily (7.4 micrograms/ml). Potentially toxic serum concentrations were never reached. Mean trough concentrations were comparable in both groups (once daily 0.8 micrograms/ml; twice daily 1.0 micrograms/ml). Urinary alanine aminopeptidase excretion increased during and even two days after end of treatment in both groups without any significant differences. The results of the dynamic in vitro model revealed that both dosage schedules showed comparable bactericidal effects on pathogens inhibited by low concentrations of gentamicin like Escherichia coli and Staphylococcus aureus. However the once daily regimen was significantly superior in isolates with high minimal inhibitory concentrations.", "To compare the pharmacokinetic profile of gentamicin given as a once daily dose as against the conventional twelve hourly dose in preterm neonates.\n Randomized double blind study.\n Tertiary level Neonatal Intensive Care Unit.\n Eighteen preterms admitted during the period January 1994 to May 1994.\n The babies were randomly assigned to receive either the once daily (plan O, 4 mg/kg Q 24 h) or the conventional (plan C, 2.5 mg/kg Q 12 h) gentamicin dosage regimen. Blood was collected for the first peak level one hour after the first dose of gentamicin. Trough and peak-2 levels were collected before and one hour after the dose due at 48 hours, respectively. Assays were done using fluorescence immunoassay and the pharmacokinetic estimations were calculated using the three measured levels on a simplified one-compartment open model. Serum concentration time curves were plotted using the computerized Bayesian forecasting. Student 't' and Mann-Whitney U tests were applied as required.\n Initial peak levels and steady state trough and peak levels in both groups.\n Optimum therapeutic peak level after the first dose was achieved only with the once daily gentamicin regimen (mean level 5.88 vs 3.88 micrograms/ml p = 0.000). Mean trough levels remained over 2 micrograms/ml in the conventional regimen (2.76 vs 1.96 micrograms/ml p = 0.019) group. Mean peak levels at the steady state were not significantly different in either regimen (6.65 vs 5.45 micrograms/ml in conventional p = 0.177). None of the neonates showed nephrotoxicity.\n Once daily dose (4 mg/kg) of gentamicin has logistic and monetary benefits in addition to the obvious pharmacokinetic advantage.", "There is no uniformity in the current recommendations of dosing regimen of gentamicin for neonates. We conducted a prospective, randomized, controlled trial to compare a once-daily dosing regimen to the twice-daily dosing regimen for neonates > or = 2500 g during the first 7 days after birth.\n Infants > or = 2500 g admitted to the Neonatal Intensive Care Unit and prescribed gentamicin for suspected bacterial infection were randomized to receive either 4 mg/kg every 24 hours, study group (n=20), or a standard regimen of 2.5 mg/kg every 12 hours, control group (n=21). Serum gentamicin concentrations (SGCs) were followed and gentamicin pharmacokinetics calculated on all infants.\n Peak SGC 30 minutes after the first dose was 8.2+/-1.7 microg/ml in the study group, compared to 6.4+/-1.5 microg/ml in the control group (p=0.001). Ninety-five percent of study group infants, compared to 81% of the control group, had peak SGCs in therapeutic range after the first dose. Peak SGC at 48 hours (steady state) was 8.9+/-1.5 in the study group and 6.8+/-1.1 in the control group (p=0.0001). On further analysis, a significantly higher percentage of infants in the study group, compared to the control group, had peak SGCs in higher therapeutic ranges of 6 to 12 microg/ml as well as 8 to 12 microg/ml. None of the study infants, compared to six control infants, had trough SGCs > or = 2 microg/ml at steady state. Thus, none of the study group infants, versus six of the control group infants, needed a dosing adjustment at 48 hours (p=0.02, Fisher's exact test).\n We found that 4 mg/kg gentamicin given every 24 hours achieved significantly higher peak SGCs and safe trough concentrations in all infants, compared to the twice-daily regimen of 2.5 mg/kg. We suggest that SGCs may not need to be followed in term infants prescribed a short course of this once-daily regimen for suspected early-onset sepsis if renal functions are normal.", "In a prospective, randomized trial of once-daily versus twice-daily intravenous or intramuscular dosing with gentamicin, 11 neonates received 5.0 mg/kg once daily and 15 received 2.5 mg/kg twice daily for 2 ro 3 days. The once-daily intravenous dosing group and the twice-daily intravenous or intramuscular dosing group, respectively, had mean steady-state gentamicin peak concentrations of 10.7 versus 6.6 micrograms/ml (p < 0.05), 6-hour postdosing concentrations of 4.7 versus 2.8 micrograms/ml (p < 0.05), trough concentrations of 1.7 versus 1.7 micrograms/ml, elimination half-life of 8.8 versus 5.4 hours (p < 0.05), and volume of distribution at steady state of 0.67 versus 0.46 L/kg. No nephrotoxic effects were identified in any group. Once-daily gentamicin therapy with 5.0 mg/kg in neonates achieves peak serum levels that are more suitable for optimal bacterial killing than those which traditional regimens achieve. Similar trough levels suggest that even larger doses and longer dosing intervals may be ideal in term neonates.", "Fifty-four neonates were included and completed the study. Twenty-seven neonates were given 2.0-2.5 mg/kg of gentamicin twice daily while 27 neonates were given 4.0-5.0 mg/kg of gentamicin once daily. The twice daily dose and the once daily dose group had mean steady state gentamicin peak concentrations of 5.94 +/- 1.57 mg/l and 8.92 +/- 1.59 mg/l, respectively (p<0.05) while their trough concentrations were 1.44 +/- 0.49 mg/l and 0.90 +/- 0.35 mg/l, respectively (p<0.05). There were 3 neonates (11.11%) in the twice daily dose group whose peak and trough level were not within the desirable therapeutic range, two patients with too high trough level (>2 mg/l) and one with subtherapeutic peak level (<4 mg/l). Only one patient in the once daily group had undesirable trough level that was higher than 1.5 mg/l but less than 2 mg/l. Treatment with a once daily dose did not present more nephrotoxity than a twice daily dose regimen and had the tendency to have less effect on renal function. Once daily dosage can achieve the equivalent efficacy compared to a twice-daily dosage regimen. All neonates in twice daily and once daily dosage groups showed improvement in clinical outcome. Therefore, a once daily dose of gentamicin with 4.0-5.0 mg/kg could be an appropriate regimen in term neonates during the first 7 days of life. This regimen produces peak concentration that may have greater clinical efficacy and trough concentration with less toxicity than conventional dosing regimen.", "Gentamicin is an important factor in the empiric therapy of premature babies with suspected invasive bacterial infection. The aims of the study were to assess the tolerability of short course of gentamicin in preterm neonates.\n Preterm neonates aged 24 hours or less who were born at 32-37 weeks of gestation and weighed over 1500 grams were included in the study. Those infants suspected of having invasive non-CNS bacterial infection were assigned to treatment with ampicillin 50 mg/kg twice daily and either ODD (once daily dosing) or twice daily dosing (TDD) of gentamicin 5 mg/kg/day (17 and 18 patients, respectively). Neonates with shock, impaired renal function and known kidney, ear, and heart malformations, and metabolic disease were excluded from the study. At 72 to 96 hours of therapy, serum and urine creatinine, and sodium concentrations, peak (PGt) and though (TGt) serum levels of gentamicin, and urinary lysosyme secretion were measured. Fractional excretion of sodium (FeNa), and glomerullar filtration rate (GFR) were calculated for each infant. Audiometric evaluation was performed at 1 to 2 months of age.\n For the ODD and TDD groups respectively, the values of serum creatinine, FENa, GFR, and urinary lyzozim were similar. The mean SD PGt levels were 9.9 +/- 4.6 vs 5.9 +/- 1.9 g/ml (p < 0.04), and that of the TGt levels was 1.55 +/- 0.55 vs 2.4 +/- 0.9 micrograms/ml (p = 0.028), Ten (55.6%) vs 3(23.1%) of the TDD and ODD groups respectively had TGt levels above 2 micrograms/ml (p = 0.035). Audiometric evaluation was normal in all infants.\n Short course of ODD of gentamicin could be safe and potentially more effective in preterm babies." ]

[ "15636857", "9113175", "8017669", "10511769", "15636813", "2407045", "9690596", "3176835" ]

[ "Anaesthetic technique for elective caesarean section and neurobehavioural status of newborns.", "Anesthetic quality during cesarean section following subarachnoid or epidural administration of bupivacaine with or without fentanyl.", "[Pharmacokinetics of epidural or intrathecal bupivacaine in elective cesarean section].", "Comparison of general and regional anesthesia for cesarean section: success rate, blood loss and satisfaction from a randomized trial.", "Spinal or epidural anaesthesia for elective caesarean section? A Swedish experience.", "Visceral pain during caesarean section under spinal and epidural anaesthesia with bupivacaine.", "Thermoregulatory effects of spinal and epidural anesthesia during cesarean delivery.", "Subarachnoid versus epidural bupivacaine 0.5% for caesarean section." ]

[ "Ninety healthy parturients undergoing elective caesarean section were randomly allocated to receive either general (n = 30), epidural (n = 30) or spinal (n = 30) anaesthesia. Acid-base status, Apgar score and neurobehavioural status, using the neurologic and adaptive capacity scoring (NACS) system, were studied in the newborn. Apgar scores and acid-base parameters were similar in all the three groups. NACS testing revealed significantly more vigorous babies in the spinal anaesthesia group than in the other two groups at 15 min and 2 h interval after delivery, despite a higher incidence of maternal hypotension. We conclude that newborns tend to have a better neurobehavioural status in the early post-delivery period if their mothers receive spinal anaesthesia rather than general or epidural anaesthesia for caesarean section.", "It is often assumed that subarachnoid administration of local anesthetics produces a more profound blockade than epidural anesthesia. Furthermore, the addition of fentanyl has been reported to increase preferentially intraoperative analgesia. In the present study we set out to study these two issues in a randomized and controlled study with respect to perceived pain and discomfort during surgery and postoperative pain.\n In the present study, 100 parturients subjected to elective cesarean section, 34 nullipara and 66 multipara, received one out of four combinations of the local anesthetic bupivacaine and the opioid fentanyl; group A--bupivacaine 12.5 mg + 10 micrograms fentanyl subarachnoidally, group B--bupivacaine 12.5 mg + saline subarachnoidally, group C--bupivacaine 100 mg + 100 micrograms fentanyl epidurally, group D--bupivacaine 100 mg + saline epidurally; N = 25 in each group. Pain intensity and discomfort during surgery was assessed with a visual analogue scale (VAS). Postoperative pain intensity and need for analgesics postoperatively, ketobemidone, was registered for 24 h following surgery.\n Intraoperative pain intensity and discomfort did not differ significantly between parturients in any of the four groups Postoperative pain was significantly more intense in parturients receiving local anesthetics subarachnoidally as compared to the epidural groups during the first 6-h period. This difference was also reflected in a significantly increased consumption of analgesics during this period. No significant differences between the groups were observed with regard to hemodynamics (blood pressure), respiration (oxygen saturation) or other effects such as nausea or itching. All neonates had normal Apgar and neonatal adaptive capacity scores (NACS).\n We conclude that subarachnoidal (12.5 mg) and epidural (100 mg) injections with bupivacaine both produced adequate anesthetic quality in women undergoing elective cesarean section. The addition of fentanyl (10 micrograms subarachnoidally or 100 micrograms epidurally) did not significantly improve the quality of these already profound blockades.", "Twenty ASA 1 pregnant women at term, undergoing elective Caesarean section were included in this study. They were randomly assigned to one of two groups, receiving either a spinal or an epidural anaesthesia. Before induction, in order to prevent hypotension, all patients were given an i.v. infusion of 1000 ml of Ringer-lactate and a subcutaneous injection of ephedrine 30 mg. They were positioned on the operating table with a 15 degrees left lateral tilt. Spinal anaesthesia was performed with hyperbaric bupivacaine 0.5 p. cent (0.08 mg.cm-1 of height). Epidural anaesthesia was obtained with a bolus dose of 0.5 p. cent plain bupivacaine, followed by a continuous infusion through the epidural catheter until the level of surgical block reached T6 bilaterally. Bupivacaine was assayed in plasma by high performance liquid chromatography (HPLC). Following pharmacokinetic parameters of bupivacaine were determined: Cmax (maximal concentration), Tmax (time to reach maximum), AUC (area under curve), Cl (total plasma clearance), Vz (volume of distribution during the elimination phase), T1/2 (elimination half-life). Bupivacaine concentration was also measured in samples obtained at birth from umbilical vein and umbilical artery. The mean dose of bupivacaine used was 12.8 +/- 0.6 mg in the spinal group and 118.6 +/- 17.8 mg in the epidural group. The time of onset of surgical anaesthesia was significantly shorter with spinal anaesthesia (7.6 +/- 4.4 vs 31 +/- 11.1 min; p < 0.01). The sensory block had a longer duration in epidural group (223.2 +/- 15 vs 291 +/- 13.8; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)", "A prospective randomized trial was organized to compare the effectiveness of general and regional anesthesia for cesarean section (C/S).\n Three hundred and forty-one patients were randomized into the general anesthesia group (GA), epidural anesthesia group (EA) and spinal anesthesia group (SA). The effectiveness of interest was success rate, blood loss and patient satisfaction.\n We found that the success rates of EA and SA were lower than GA. Success in EA should be improved by using an epidural catheter to add more local anesthetic drug instead of a single shot; and the surgeon should allow more time for the block to work adequately. Success in SA should be improved by using bupivacaine instead of lidocaine. GA resulted in significantly more blood loss, lower postoperative hematocrit, and higher proportion of patients who had postoperative hematocrit < 30 per cent than EA and SA. The patients' satisfaction scores were not different among the 3 techniques. This meant that, given adequate explanation and perioperative care, Thai women were satisfied with regional anesthesia.\n Regional anesthesia is a better choice of anesthesia for C/S than general anesthesia. However, the availability of different techniques and ability to change the technique when needed were very useful and important. If GA is chosen, all safety procedures must be followed. Oxygen supplement and endotracheal intubation facilities must be available in all techniques. Guidelines of anesthesia for C/S at a national level should be agreed upon, including the type of personnel, monitoring equipment and postoperative care.", "Ninety seven women undergoing elective lower segment caesarean section were randomly divided into two groups, group 1 received spinal anaesthesia with hyperbaric bupivacaine and group 2 received mepivacaine 20 mg/ml with adrenaline 5 microg/ml via an epidural catheter. All patients were given a preload of Ringer acetate and Macrodex prior to onset of anaesthesia. Ephedrine 5 mg was given if the systolic blood pressure fell below 100 mmHg. There was a small (<30%) but significant (P<0.01) fall in blood pressure in both groups of women. Six women in the epidural group required supplemental analgesics during the operation compared to only 1 patient in the spinal group (P<0.01). Muscle relaxation was judged to be inadequate in 3 patients in the spinal group and in 5 patients in the epidural group. One patient in the spinal group had a characteristic post-spinal headache lasting 3 days. The injection-delivery time was shorter (P<0.01) in the spinal group compared to the epidural group. The Apgar scores at 1 and 5 min were similar in both groups. The results from our study suggest that spinal anaesthesia is a good alternative to epidural anaesthesia for elective caesarean section. A fall in blood pressure, which is equally possible in both groups of patients, should be prevented by adequate fluid preload and treated immediately by intravenous ephedrine.", "In a randomized study, the incidence of visceral pain was evaluated in 46 patients undergoing elective caesarean section under spinal or epidural anaesthesia with 0.5% bupivacaine. If the patient experienced pain during the operation, a standard visual analogue scale ranging from 0 to 10 was used to assess the degree of pain. Visceral pain occurred in 12/23 patients in the spinal group and in 13/23 patients in the epidural group. In neither group was a correlation found between the cephalad level of analgesia or the intensity of cutaneous analgesia in the sacral region, and the presence of visceral pain.", "Hypothermia is likely to develop faster during spinal anesthesia than epidural anesthesia. A natural consequence of the rapid temperature decrease during spinal anesthesia is that the shivering threshold will be reached sooner and that more shivering will be required to prevent further hypothermia. We tested the hypotheses that the onset of hypothermia is more rapid and the onset and intensity of shivering earlier during spinal than epidural anesthesia.\n Patients undergoing cesarean delivery were randomly assigned to spinal anesthesia or epidural anesthesia. Spinal anesthesia was induced by injecting 2 mL 0.5% dibucaine into the L4-L5 interspace. Epidural anesthesia was induced with 20 mL 2% mepivacaine injected into the L2-L3 interspace. Thermal comfort and shivering were scored by a blinded observer.\n Fifteen patients given each type of anesthesia had upper sensory levels > or =T4 dermatome. Sensation was entirely absent from the leg during spinal anesthesia, but lower block levels were near S5 during epidural anesthesia. Tympanic membrane temperatures initially decreased faster during spinal anesthesia, but subsequently decreased at a rate of 0.5 degrees C/h in both groups. The onset and incidence of shivering (detected qualitatively) did not differ significantly between the two groups, but shivering intensity was significantly reduced during spinal anesthesia. Furthermore, the shivering thresholds were 36.4+/-0.3 degrees C (mean+/-SD) during spinal anesthesia versus 37.1+/-0.4 degrees C in those given epidural anesthesia (P=.006). There were no clinically important differences in thermal comfort with the two kinds of neuraxial anesthesia.\n We failed to confirm our hypothesis, but for an unexpected reason: Thermoregulation was impaired more by spinal anesthesia than epidural anesthesia. It seems likely that in our patients spinal anesthesia inhibited thermoregulatory control more than epidural anesthesia because it better blocked sensory input from the legs.", "In order to compare subarachnoid (spinal) and epidural block for caesarean section, 40 women were randomly allocated to spinal or epidural analgesia with bupivacaine. The median dose of bupivacaine was 13 mg in the spinal group versus 155 mg in the epidural group. The mean time from induction to delivery was 32 min shorter in the spinal group (P less than 0.001). In the spinal group one woman was excluded because of spontaneous labour. Three patients in the spinal and one in the epidural group failed to develop adequate analgesia to initiate surgery. For the remaining patients both techniques provided good analgesia during operation. Postoperatively, epidural block provided better pain relief. The patients in the epidural group had a lower pain score during the first 4 h after the operation (P less than 0.01). In spite of similar haemodynamic changes in the two groups, the mean base deficit in umbilical cord blood at delivery was higher in the spinal group (P less than 0.05)." ]

[ "1350804", "1320133", "2842403", "3033339", "2167008", "9709043" ]

[ "Use of nonoxynol-9 and reduction in rate of gonococcal and chlamydial cervical infections.", "Efficacy of nonoxynol 9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes.", "A clinical trial of nonoxynol-9 for preventing gonococcal and chlamydial infections.", "Effect of the contraceptive sponge on chlamydial infection, gonorrhea, and candidiasis. A comparative clinical trial.", "A follow-up study of methods of contraception, sexual activity, and rates of trichomoniasis, candidiasis, and bacterial vaginosis.", "A controlled trial of nonoxynol 9 film to reduce male-to-female transmission of sexually transmitted diseases." ]

[ "The spermicide nonoxynol-9 (N-9) has been used as a contraceptive for over 30 years, but the use of a vaginal spermicide and condoms for the prevention of sexually transmitted infections has not been examined in randomised studies. We report a single-blind randomised field trial to assess the effect of N-9 film on the rate of gonococcal and chlamydial cervical infection in women at high risk of these diseases. 343 women were randomly assigned to use either condoms and N-9 (186 women) or condoms and a placebo (157). Compliance with condom use was much the same in the two groups. Overall, N-9 reduced the rate of cervical infection by 25% (rate ratio [RR] 0.75, 95% confidence interval [Cl] 0.5-1.1); in women who used N-9 for more than 75% of their coital acts the infection rate was reduced by 40% (RR 95% Cl 0.3-1.0). The rate of yeast vulvovaginitis or genital ulcers was not higher in N-9 users than in placebo users, but the rate of symptomatic irritation was increased by 70% (RR 95% Cl 1.1-2.6) among N-9 users. Condom use was more protective against cervical infection than N-9 use. The rate of infection was 50% (RR 95% Cl 0.3-0.7) lower with 75% than with 0-50% condom compliance. The use of a vaginal N-9 spermicide with condoms whenever possible seems to be a better strategy than the use of condoms only for prevention of gonococcal and chlamydial cervical infection.", "To determine the efficacy of the nonoxynol 9 contraceptive sponge in preventing sexual acquisition of the human immunodeficiency virus (HIV).\n Prospective, randomized placebo-controlled trial.\n Research clinic for prostitutes in Nairobi, Kenya.\n One hundred thirty-eight HIV-seronegative women were enrolled, of whom 74 were assigned to nonoxynol 9 sponge use and 64 to placebo use. These two groups did not significantly differ with respect to demographic characteristics, sexual practices, or prevalence of genital infections at enrollment, except for a lower number of sex partners per week and a higher initial prevalence of genital ulcers among women assigned to nonoxynol 9 sponge use. Among the 116 women who returned for follow-up, the mean durations of follow-up were 14 and 17 months for the two groups, respectively.\n HIV seroconversion.\n Nonoxynol 9 sponge use was associated with an increased frequency of genital ulcers (relative risk [RR], 3.3; P less than .0001) and vulvitis (RR, 3.3; P less than .0001) and a reduced risk of gonococcal cervicitis (RR, 0.4; P less than .0001). Twenty-seven (45%) of 60 women in the nonoxynol 9 sponge group and 20 (36%) of 56 women in the placebo group developed HIV antibodies. The hazard ratio for the association between nonoxynol 9 sponge use and HIV seroconversion was 1.7 (95% confidence interval [CI], 0.9 to 3.0). Using multivariate analysis to control for the presence of genital ulcers at enrollment, the adjusted hazard ratio for the association between nonoxynol 9 sponge use and seroconversion was 1.6 (95% CI, 0.8 to 2.8).\n Genital ulcers and vulvitis occurred with increased frequency in nonoxynol 9 sponge users. We were unable to demonstrate that nonoxynol 9 sponge use was effective in reducing the risk of HIV infection among highly exposed women.", "A randomized, double-blind, placebo-controlled trial was conducted to evaluate the spermicidal agent nonoxynol-9 as prophylaxis for cervical infections caused by Chlamydia trachomatis and Neisseria gonorrhoeae. Eight hundred eighteen women were recruited from a sexually transmitted disease clinic. Only subjects who were using reliable birth control methods (oral contraceptives, intrauterine device, or sterilization) were eligible. Subjects were randomly assigned to use either a commercially available spermicidal agent containing nonoxynol-9 or a placebo preparation. Subjects were followed up for six months; specimens were collected monthly for culture of the two pathogens. Women assigned to the nonoxynol-9 group were less likely to become infected with N. gonorrhoeae (relative rate, 0.75; 90% confidence limits, 0.58 and 0.96) and C. trachomatis (relative rate, 0.79; 90% confidence limits, 0.64 and 0.97). Among women who used their assigned gel for the majority of coital episodes, a stronger protective effect was observed.", "To investigate the effect of the nonoxynol 9-impregnated contraceptive sponge on the incidence of chlamydial infection, gonorrhea, and candidiasis, we conducted a randomized comparative study among high-risk women in Bangkok, Thailand. The first (parallel) portion of the study covered 434 woman-weeks among sponge users and 494 woman-weeks among nonusers. As compared with women not using the sponge, sponge users were found to be less likely to become infected with chlamydia (relative rate, 0.67; 95% confidence interval, 0.42 to 1.07) and gonorrhea (relative rate, 0.31 [0.16 to 0.60]) but more likely to become infected with Candida (relative rate, 2.76 [0.96 to 7.98]). Women who continued in the study were crossed over to the alternate group, with former nonusers starting to employ the sponge and vice versa. The results of this second phase were similar to those of the larger parallel study. Overall, these results suggest that women using the sponge are protected against the two most common sexually transmitted pathogens, which are also those with the most serious health consequences. However, women using the sponge should be advised they may have an increased likelihood of a vaginal infection with Candida.", "A randomized, clinical trial was conducted to evaluate the spermicidal agent nonoxynol 9 as prophylaxis for sexually transmitted diseases. Eight hundred eighteen women using birth control who attended a sexually transmitted disease clinic were evaluated monthly for trichomoniasis, candidiasis, and bacterial vaginosis for 6 months. Women using the active spermicide experienced a somewhat lower incidence rate of trichomoniasis (relative rate 0.83; 95% confidence interval 0.61 to 1.12) and bacterial vaginosis (relative rate 0.86; 95% confidence interval 0.69 to 1.12) as compared with placebo users. The rate of candidiasis was nearly identical for spermicide and placebo users (relative rate 1.02; 95% confidence interval 0.77 to 1.35). The number of sexual partners during the preceding month was related directly to the occurrence of trichomoniasis (p = 0.047) and bacterial vaginosis (p = 0.009) but not candidiasis (p = 0.99). Subjects using oral contraceptives experienced a statistically significant lower rate of trichomoniasis than did women using an intrauterine contraceptive device or who had had a tubal ligation (relative rate 0.56; 95% confidence interval 0.39 to 0.81).", "Nonoxynol 9 is a proved spermicide, but whether it is also a microbicide is uncertain. A truly effective vaginal microbicide would reduce the susceptibility of women to sexually transmitted diseases, including infection with the human immunodeficiency virus (HIV).\n We enrolled 1292 HIV-negative female sex workers in Cameroon and enrolled them in a double-blind, placebo-controlled study in which the participants were randomly assigned to use either a film containing 70 mg of nonoxynol 9 or a placebo film, inserted into the vagina before intercourse. All of the women were provided with latex condoms and were instructed to have their male sexual partners use them. At monthly follow-up visits, we examined the women with a colposcope for genital lesions, tested endocervical specimens for gonorrhea and chlamydia infection with DNA probes, tested for HIV infection, and treated the women for curable sexually transmitted diseases.\n The rates of HIV infection (cases per 100 woman-years) were 6.7 in the nonoxynol 9 group and 6.6 in the placebo group (rate ratio, 1.0; 95 percent confidence interval, 0.7 to 1.5). The rates of genital lesions were 42.2 cases per 100 woman-years in the nonoxynol 9 group and 33.5 in the placebo group (rate ratio, 1.3; 95 percent confidence interval, 1.0 to 1.6). The rates of gonorrhea were 33.3 and 31.1 cases per 100 woman-years in the nonoxynol 9 and placebo groups, respectively (rate ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4). The corresponding rates of chlamydia infection in the nonoxynol 9 group and the placebo group were 20.6 and 22.2 per 100 woman-years (rate ratio, 0.9; 95 percent confidence interval, 0.7 to 1.3). The women reported that condoms were used during 90 percent of sexual acts.\n The use of a nonoxynol 9 vaginal film did not reduce the rate of new HIV, gonorrhea, or chlamydia infection in this group of sex workers who used condoms and received treatment for sexually transmitted diseases." ]

[ "15288403", "12707429", "17959981", "18524684", "17703885", "19076108", "18278830", "11465977", "18640074", "18796160", "15818684", "18400400", "17631400", "15820913", "18716003", "15596757", "17507163", "15911152", "18448418", "15082123", "16466610", "17130411" ]

[ "Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial.", "Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial.", "A randomized, placebo-controlled trial of preoperative oral pregabalin for postoperative pain relief after minor gynecological surgery.", "A 14-week, randomized, double-blinded, placebo-controlled monotherapy trial of pregabalin in patients with fibromyalgia.", "Pregabalin in patients with central neuropathic pain: a randomized, double-blind, placebo-controlled trial of a flexible-dose regimen.", "Pregabalin and dexamethasone in combination with paracetamol for postoperative pain control after abdominal hysterectomy. A randomized clinical trial.", "A randomized, double-blind, placebo-controlled, phase III trial of pregabalin in the treatment of patients with fibromyalgia.", "Pregabalin in patients with postoperative dental pain.", "Pregabalin for postherpetic neuralgia: placebo-controlled trial of fixed and flexible dosing regimens on allodynia and time to onset of pain relief.", "Efficacy and safety of pregabalin 600 mg/d for treating painful diabetic peripheral neuropathy: a double-blind placebo-controlled trial.", "Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial.", "Fibromyalgia relapse evaluation and efficacy for durability of meaningful relief (FREEDOM): a 6-month, double-blind, placebo-controlled trial with pregabalin.", "Pregabalin for relief of neuropathic pain associated with diabetic neuropathy: a randomized, double-blind study.", "Relief of painful diabetic peripheral neuropathy with pregabalin: a randomized, placebo-controlled trial.", "Evaluation of a single preoperative dose of pregabalin for attenuation of postoperative pain after laparoscopic cholecystectomy.", "Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial.", "A randomized controlled trial of perioperative administration of pregabalin for pain after laparoscopic hysterectomy.", "Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens.", "Premedication with pregabalin 75 or 150 mg with ibuprofen to control pain after day-case gynaecological laparoscopic surgery.", "Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic neuralgia: results of a randomised, placebo-controlled clinical trial.", "Efficacy and tolerability of twice-daily pregabalin for treating pain and related sleep interference in postherpetic neuralgia: a 13-week, randomized trial.", "Pregabalin in central neuropathic pain associated with spinal cord injury: a placebo-controlled trial." ]

[ "A randomized, double-blind, placebo-controlled, parallel-group, multicenter, 8-week trial (with subsequent open-label phase) evaluated the effectiveness of pregabalin in alleviating pain associated with diabetic peripheral neuropathy (DPN). For enrollment, patients must have had at baseline: 1- to 5-year history of DPN pain; pain score > or =40 mm (Short-Form McGill Pain Questionnaire [SF-MPQ] visual analogue scale); average daily pain score of > or =4 (11-point numerical pain rating scale [0 = no pain, 10 = worst possible pain]). One hundred forty-six (146) patients were randomized to receive placebo (n = 70) or pregabalin 300 mg/day (n = 76). Primary efficacy measure was endpoint mean pain score from daily patient diaries (11-point numerical pain rating scale). Secondary measures included SF-MPQ scores; sleep interference scores; Patient and Clinical Global Impression of Change (PGIC and CGIC); Short Form-36 (SF-36) Health Survey scores; and Profile of Mood States (POMS) scores. Safety assessment included incidence and intensity of adverse events, physical and neurological examinations, and laboratory evaluations. Pregabalin produced significant improvements versus placebo for mean pain scores (P < 0.0001); mean sleep interference scores SF-36 Bodily Pain subscale (P < 0.0001); total SF-MPQ score (P < 0.01); SF-36 Bodily Pain subscale (P < 0.03); PGIC (P = 0.001); and Total Mood Disturbance and Tension-Anxiety components of POMS (P < 0.03). Pain relief and improved sleep began during week 1 and remained significant throughout the study (P < 0.01). Pregabalin was well tolerated despite a greater incidence of dizziness and somnolence than placebo. Most adverse events were mild to moderate and did not result in withdrawal. Pregabalin was safe and effective in decreasing pain associated with DPN, and also improved mood, sleep disturbance, and quality of life.", "To evaluate the efficacy and safety of pregabalin in the treatment of postherpetic neuralgia (PHN).\n The authors conducted a multicenter, parallel-group, double-blind, placebo-controlled, 8-week, randomized clinical trial in PHN, defined as pain for 3 or more months following herpes zoster rash healing. Patients (n = 173) were randomized to treatment with pregabalin or placebo. Patients randomized to pregabalin received either 600 mg/day (creatinine clearance > 60 mL/min) or 300 mg/day (creatinine clearance 30 to 60 mL/min). The primary efficacy measure was the mean of the last seven daily pain ratings. Secondary endpoints included additional pain ratings, sleep interference, quality of life, mood, and patient and clinician ratings of global improvement.\n Pregabalin-treated patients had greater decreases in pain than patients treated with placebo (endpoint mean scores 3.60 vs 5.29, p = 0.0001). Pain was significantly reduced in the pregabalin-treated patients after the first full day of treatment and throughout the study, and significant improvement on the McGill Pain Questionnaire total, sensory, and affective pain scores was also found. The proportions of patients with >or=30% and >or=50% decreases in mean pain scores were greater in the pregabalin than in the placebo group (63% vs 25% and 50% vs 20%, p = 0.001). Sleep also improved in patients treated with pregabalin compared to placebo (p = 0.0001). Both patients and clinicians were more likely to report global improvement with pregabalin than placebo (p = 0.001). Given the maximal dosage studied, pregabalin had acceptable tolerability compared to placebo despite a greater incidence of side effects, which were generally mild to moderate in intensity.\n Treatment of PHN with pregabalin is safe, efficacious in relieving pain and sleep interference, and associated with greater global improvement than treatment with placebo.", "Although pregabalin shows efficacy against neuropathic pain, very limited evidence supports postoperative analgesic efficacy. Our study objective was to investigate analgesic efficacy in an ambulatory day surgical population experiencing acute visceral pain. The null hypothesis was that there was no significant difference in pain relief between pregabalin and placebo.\n A randomized, double-blind, parallel-group, placebo-controlled trial was performed in 90 women having minor gynecological surgery involving the uterus. Patients received either oral pregabalin 100 mg (Group PG) or placebo (Group C) approximately 1 h before surgery. The primary outcome was pain score in the recovery unit and patients were followed for 24 h.\n There was no significant difference between groups for pain experienced in the recovery room (median, interquartile range 16, 0-36 vs 10, 6.5-36 for Groups PG and C, respectively, P = 0.80) or thereafter; nor for recovery room fentanyl requirement (42% Group PG versus 27% Group C, P = 0.12) or the quality of recovery at 24 h postoperatively (median, interquartile range score 17, 17-18 Group PG versus 18, 16.5-18 Group C, P = 0.75). The incidence of posthospital discharge light-headedness, visual disturbance, and difficulty with walking was significantly higher in the pregabalin group.\n A single preoperative dose of 100 mg pregabalin does not reduce acute pain or improve recovery after minor surgery involving only the uterus.", "The purpose of the study was to assess the efficacy and safety of pregabalin monotherapy in patients with fibromyalgia in a randomized, double-blinded, placebo-controlled trial. After 1 week of single-blinded administration of placebo, 750 patients meeting American College of Rheumatology criteria for fibromyalgia were randomly assigned to pregabalin (300 mg/d, 450 mg/d, 600 mg/d) or placebo, administered twice daily for 14 weeks. The primary outcome variable was comparison of end point mean pain scores, derived from daily diary ratings of pain intensity (0 to 10 scale), between each of the pregabalin groups and the placebo group. If positive, additional primary efficacy parameters included the Patient Global Impression of Change (PGIC) and the Fibromyalgia Impact Questionnaire (FIQ) total score. Compared with placebo-treated patients, mean changes in pain scores at the end point in pregabalin-treated patients were significantly greater (P < .001: 300 mg/d, -0.71; 450 mg/d, -0.98; 600 mg/d, -1.00). Compared with placebo, significantly more pregabalin-treated patients reported improvement on PGIC (P < .01 for all 3 pregabalin doses) and significant improvements in total FIQ score for the 450 mg/d (P = .004) and the 600 mg/d (P = .003) doses. Compared with placebo, all 3 doses of pregabalin were associated with significant improvement in sleep. The most commonly reported pregabalin-related adverse events were dizziness and somnolence, which tended to be dose-related.\n This randomized, placebo-controlled trial of 300, 450, and 600 mg/d of pregabalin monotherapy demonstrated that all 3 doses were efficacious for up to 14 weeks for the treatment of fibromyalgia and were well tolerated by most patients. These results provide evidence that pregabalin is an important treatment option for patients with fibromyalgia.", "The effective treatment of patients suffering from central neuropathic pain remains a clinical challenge, despite a standard pharmacological approach in combination with anticonvulsants and antidepressants. A randomized, double-blinded, placebo-controlled trial evaluated the effects of pregabalin on pain relief, tolerability, health status, and quality of life in patients with central neuropathic pain caused by brain or spinal cord injuries. At baseline and 4 weeks after the start of treatment subjects were evaluated with standard measures of efficacy: pain intensity measured by visual analog scale, health status (Pain Disability Index and EQ-5D) and quality of life (SF-36). Forty patients received escalating doses of either pregabalin (150, 300, and 600mg/day) or matching placebo capsules. In both groups, patients started with 1 capsule per day (either 150mg of pregabalin or placebo). If pain relief was insufficient, patients were titrated to a higher dose. There was a statistically significant decrease in mean pain score at endpoint for pregabalin treatment, compared with placebo (P=0.016). Follow-up observation showed no significant difference in Pain Disability Index scores between the two groups. The pregabalin group, however, showed a statistically significant improvement for the EQ-5D. Pregabalin treatment led to a significant improvement in the bodily pain domain of the SF36. In the other domains, more favorable scores were reported without reaching statistical significance. Pregabalin, in a flexible-dose regime, produced clinically significant reductions in pain, as well as improvements in health status in patients suffering from severe central neuropathic pain.", "Multimodal analgesia may be important for optimal postoperative pain treatment and facilitation of early mobilization and recovery. We investigated the analgesic effect of pregabalin and dexamethasone in combination with paracetamol after abdominal hysterectomy.\n One hundred and sixteen patients were randomly assigned to either group A (paracetamol+placebo x 2), group B (paracetamol+pregabalin+placebo) or group C (paracetamol+pregabalin+dexamethasone). According to randomization and preoperatively, patients received paracetamol 1000 mg, pregabalin 300 mg, dexamethasone 8 mg or placebo. General anaesthesia was performed. Postoperative pain treatment was paracetamol 1000 mg x 4 and patient-controlled intravenous morphine, 2.5 mg bolus. Nausea was treated with ondansetron. Morphine consumption, pain score (visual analogue scale) at rest and during mobilization, nausea, sedation, dizziness, number of vomits and consumption of ondansetron were recorded 2, 4 and 24 h after the operation. P<0.05 was considered statistically significant.\n The 24-h morphine consumption and pain score, both at rest and during mobilization, were not significantly different between treatment groups. The mean nausea score (P=0.002) was reduced in group C vs. A. The number of vomits was significantly reduced in both group B (P=0.041) and C (P=0.001) vs. A. Consumption of ondansetron was reduced in group C vs. A and B (P<0.001). Other side effects were not different between groups.\n Combinations of paracetamol and pregabalin, or paracetamol, pregabalin and dexamethasone did not reduce morphine consumption and pain score compared with paracetamol alone for patients undergoing abdominal hysterectomy. Dexamethasone reduced nausea, vomiting and use of ondansetron.", "To evaluate the efficacy and safety of pregabalin for symptomatic relief of pain associated with fibromyalgia (FM) and for management of FM.\n This multicenter, double-blind, placebo-controlled trial randomly assigned 748 patients with FM to receive placebo or pregabalin 300, 450, or 600 mg/day (dosed twice daily) for 13 weeks. The primary outcome variable for study objective 1, symptomatic relief of pain associated with FM, was comparison of endpoint mean pain scores between each pregabalin group and placebo. The outcome variable for study objective 2, management of FM, included endpoint mean pain scores, Patient Global Impression of Change (PGIC), and Fibromyalgia Impact Questionnaire (FIQ)-Total Score. Secondary outcomes included assessments of sleep, fatigue, and mood disturbance.\n Patients in all pregabalin groups showed statistically significant improvement in endpoint mean pain score and in PGIC response compared with placebo. Improvements in FIQ-Total Score for the pregabalin groups were numerically but not significantly greater than those for the placebo group. Compared with placebo, all pregabalin treatment groups showed statistically significant improvement in assessments of sleep and in patients' impressions of their global improvement. Dizziness and somnolence were the most frequently reported adverse events.\n Pregabalin at 300, 450, and 600 mg/day was efficacious and safe for treatment of pain associated with FM. Pregabalin monotherapy provides clinically meaningful benefit to patients with FM.", "Pregabalin is an analogue of the inhibitory neurotransmitter gamma-aminobutyric acid. In preclinical models, it has shown activity as an analgesic agent. A randomized, double-blind, placebo-controlled, parallel-group trial was undertaken to compare pregabalin to placebo and 400 mg of ibuprofen using a dental pain model. Study medication was administered postoperatively to patients who had undergone elective surgery to remove one or two third molars, at least one of which was mandibular and fully or partially impacted in bone. The study was conducted in the UK at a single centre and evaluated pregabalin at doses of 50 and 300 mg. Primary efficacy parameters included pain relief (PR), pain intensity difference (PID), pain relief intensity difference (PRID), time to onset of analgesia, and duration of analgesia. The patient's global impression of the study medication was used as a secondary efficacy parameter. Efficacy data were evaluated for the intent-to-treat (ITT) population, defined as all randomized patients who took study medication. Results showed that there were statistically significant differences in PR, PID, and PRID between the 300-mg pregabalin group and placebo. In addition, the 300-mg pregabalin group had a significantly longer duration of analgesia than the ibuprofen group and had the highest score on the patient global impression of study medication. Adverse events were reported more frequently in the pregabalin 300-mg group. Pregabalin appears to have significant analgesic properties in the third molar extraction model. Further research is needed to confirm these findings.\n Copyright 2001 European Federation of Chapters of the International Association for the study of pain.", "Time to onset of pain relief and improvement in allodynia in 269 patients with postherpetic neuralgia was examined in a 4-week randomized trial comparing flexibly dosed pregabalin (150-600 mg/d), fixed-dose pregabalin (300 mg/d), and placebo. For each patient with clinically meaningful pain reduction (>or=30%) at end point, onset of pain relief was defined as the first study day on which a patient reported >or=1-point reduction in pain relative to baseline. Average dose achieved was 396 mg/d in the flexible-dose group compared with 295 mg/d in the fixed-dose group. Median pain relief onset times were 3.5 days (flexible-dose), 1.5 days (fixed-dose), and >4 weeks (placebo). Compared with placebo, significantly more patients in both pregabalin treatment groups achieved >or=30% and >or=50% pain reduction at end point. Almost 95% of patients had brush-evoked allodynia, with 68% having moderate to severe allodynia (>or=40/100 mm). At baseline, pain and allodynia were highly correlated. Independent of treatment assignment, improvement in pain and improvement in allodynia were significantly correlated. Allodynia could serve as a useful surrogate outcome measure in future studies. Pregabalin was significantly better than placebo in alleviating allodynia (flexible-dose reduction, 26 mm; fixed-dose, 21 mm; placebo, 12 mm). Discontinuation rates due to adverse events were more frequent in the fixed-dose group.\n A flexible-dose regimen reduces discontinuations, facilitates higher final doses, and results in a slightly greater pain relief. Allodynia (touch-evoked pain) can be of disabling severity and is present in nearly all patients with postherpetic neuralgia. Allodynia severity is correlated with pain severity and improvement in allodynia is correlated with clinical response.", "Recent consensus guidelines recommend pregabalin as a first-tier treatment for painful diabetic peripheral neuropathy (DPN). We evaluated the efficacy of pregabalin 600 mg/d (300 mg dosed BID) versus placebo for relieving DPN-associated neuropathic pain, and assessed its safety using objective measures of nerve conduction (NC).\n In this randomized, double-blind, placebo-controlled trial, the primary efficacy measure was endpoint mean pain score (MPS) from daily pain diaries (11-point scale). NC velocity and sensory and motor amplitudes were assessed at baseline, endpoint, and end of follow-up (2 weeks post-treatment). At each timepoint, the median-motor, median-sensory, ulnar-sensory, and peroneal-motor nerves were evaluated. Secondary efficacy measures included weekly MPS and proportion of responders (patients achieving >or=50% reduction in MPS from baseline to endpoint). After 1-weeks' dosage escalation, pregabalin-treated patients received 300 mg BID for 12 weeks.\n Eighty-two patients received pregabalin and 85 placebo. Mean durations were 10 years for diabetes and approximately 5 years for painful DPN. Pregabalin-treated patients had lower MPS than controls (mean difference, -1.28; p <.001). For all four nerves, 95% CIs for median differences in amplitude and velocity from baseline to endpoint and baseline to follow-up included 0 (ie, no significant difference vs. placebo). Significant pain improvement among pregabalin-treated patients was evident at week 1 and sustained at every weekly timepoint. More pregabalin-treated patients (49%) than controls (23%) were responders (p <.001).\n Pregabalin 600 mg/d (300 mg BID) effectively reduced pain, was well tolerated, and had no statistically significant or clinically meaningful effect on NC in patients with painful DPN.", "Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain and lowered pain threshold. Other prominent symptoms include disordered sleep and fatigue. FMS affects an estimated 2% of the population, predominantly women. This trial was designed to evaluate the efficacy and safety of pregabalin, a novel alpha(2)-delta ligand, for treatment of symptoms associated with FMS.\n This multicenter, double-blind, 8-week, randomized clinical trial compared the effects of placebo with those of 150, 300, and 450 mg/day pregabalin on pain, sleep, fatigue, and health-related quality of life in 529 patients with FMS. The primary outcome variable was the comparison of end point mean pain scores, derived from daily diary ratings of pain intensity, between each of the pregabalin treatment groups and the placebo group.\n Pregabalin at 450 mg/day significantly reduced the average severity of pain in the primary analysis compared with placebo (-0.93 on a 0-10 scale) (P </= 0.001), and significantly more patients in this group had >/=50% improvement in pain at the end point (29%, versus 13% in the placebo group; P = 0.003). Pregabalin at 300 and 450 mg/day was associated with significant improvements in sleep quality, fatigue, and global measures of change. Pregabalin at 450 mg/day improved several domains of health-related quality of life. Dizziness and somnolence were the most frequent adverse events. Rates of discontinuation due to adverse events were similar across all 4 treatment groups.\n Pregabalin at 450 mg/day was efficacious for the treatment of FMS, reducing symptoms of pain, disturbed sleep, and fatigue compared with placebo. Pregabalin was well tolerated and improved global measures and health-related quality of life.", "This was a multicenter, double-blind (DB), placebo-controlled, randomized discontinuation trial to evaluate the efficacy of pregabalin monotherapy for durability of effect on fibromyalgia (FM) pain. The trial included a 6-week open-label (OL) pregabalin-treatment period followed by 26-week DB treatment with placebo or pregabalin. Adults with FM and 40-mm score on 100-mm pain visual analog scale (VAS) were eligible. During OL weeks 1-3, patients received escalating dosages of pregabalin to determine their optimal dosages. During OL weeks 4-6, patients received their optimal fixed dosages (300, 450, 600mg/d). To be randomized, patients must have had 50% decrease in pain VAS and a self-rating of \"much\" or \"very much\" improved on Patient Global Impression of Change (PGIC) at the end of OL. Double-blind treatment was with placebo or the patient's optimal fixed dosage of pregabalin. Primary outcome was time to loss of therapeutic response (LTR), defined as <30% reduction in pain (from OL baseline) or worsening of FM. A total of 1051 patients entered OL; 287 were randomized to placebo, 279 to pregabalin. Time to LTR was longer for pregabalin versus placebo (P<.0001). Kaplan-Meier estimates of time-to-event showed half the placebo group had LTR by Day 19; half the pregabalin group still had not lost response by trial end. At the end of DB, 174 (61%) placebo patients met LTR criteria versus 90 (32%) pregabalin patients. Pregabalin was well tolerated, though 178 (17%) discontinued during OL for treatment-related adverse events (AE), and more pregabalin than placebo patients discontinued for AEs during DB. In those who respond, pregabalin demonstrated durability of effect for relieving FM pain.", "Seven published, randomized, placebo-controlled clinical trials with pregabalin have shown robust efficacy for relief of neuropathic pain from DPN and PHN. An investigation of the efficacy and safety of twice daily pregabalin enrolled 395 adults with painful DPN for > or = 1 year in a 12-week, double-blind, placebo-controlled trial. Patients were randomized to placebo, 150, 300, or 600 mg/day pregabalin (n = 96, 99, 99, and 101). Primary efficacy measure was change from baseline in endpoint mean pain score from patients' daily pain diaries. Secondary efficacy measures included pain-related sleep-interference scores, Patient and Clinical Global Impressions of Change (PGIC, CGIC), and the EuroQOL Health Utilities Index (EQ-5D). Statistically significant reduction in pain was observed in patients receiving pregabalin 600 mg/day, and 46% of patients treated with 600 mg/day pregabalin reported > or = 50% improvement in mean pain scores from baseline (vs 30% of placebo patients, p = 0.036). Number needed to treat to achieve such response was 6.3. Pregabalin 600 mg/day was significantly superior to placebo in improving pain-related sleep-interference scores (p = 0.003), PGIC (p = 0.021), and CGIC (p = 0.009). (Neither pregabalin 150 nor 300 mg/day separated from placebo on these measures, largely because of an atypically large placebo response in one country representing 42% of patients.) All pregabalin dosages were superior to placebo in improving EQ-5D utility scores (all p > or = 0.0263 vs placebo). Pregabalin was well tolerated at all dosages; adverse events were generally mild to moderate. Number needed to harm (discontinuation because of adverse events) was 10.3 for pregabalin 600 mg/day.", "This was a 6-week, randomized, double-blind, multicenter study evaluating the efficacy of pregabalin in the treatment of painful diabetic neuropathy. Two hundred forty-six men and women with painful diabetic neuropathy received pregabalin (150 or 600 mg/day by mouth) or placebo. The primary efficacy variable was mean pain score at the end of treatment. Efficacy results indicate that pregabalin 600 mg/day significantly decreased mean pain score to 4.3 (vs 5.6 for placebo, P = .0002) and increased the proportion of patients who had a > or =50% decrease from baseline pain (39% vs 15% for placebo, P = .002). Pregabalin also significantly reduced sleep interference, past week and present pain intensity, sensory and affective pain scores, and bodily pain and decreased by > or =50% the number of patients describing their pain as gnawing, sickening, fearful, and punishing-cruel. More patients receiving pregabalin 600 mg/day than placebo showed improvement, as rated on the Clinical and Patient Global Impression of Change scales, 73% vs 45% and 85% vs 47%, respectively. Pregabalin 150 mg/day was essentially no different from placebo. Dizziness was the most common side effect. These study results show pregabalin 600 mg/day to be safe and effective in reducing the pain and other associated symptoms of painful diabetic neuropathy.\n Painful diabetic peripheral neuropathy is a challenging neuropathic pain syndrome. This randomized controlled trial demonstrates that pregabalin, a new drug that interacts with the alpha2-delta protein subunit of the voltage-gated calcium channel, is an efficacious and safe treatment for the pain of this condition.", "Postoperative pain is the dominating complaint and the primary reason for prolonged convalescence after laparoscopic cholecystectomy. We have evaluated the efficacy of a single preoperative dose of pregabalin for attenuating postoperative pain and fentanyl consumption after laparoscopic cholecystectomy.\n Sixty adults (16-60 yr), ASA physical status I and II, of either sex undergoing elective laparoscopic cholecystectomy were included in this prospective, randomized placebo controlled, double-blind study. Subjects were divided into two groups of 30 each to receive either a matching placebo or pregabalin 150 mg, administered orally 1 h before surgery. Postoperative pain (static and dynamic) was assessed by a 100 mm visual analogue scale, where 0, no pain; 100, worst imaginable pain. Subjects received patient-controlled i.v. fentanyl analgesia during the postoperative period. Results were analysed by Student's t-test, chi(2) test, Mann-Whitney U-test, and Fisher's exact test.\n Postoperative pain (static and dynamic) and postoperative patient-controlled fentanyl consumption were reduced in the pregabalin group compared with the placebo group (P<0.05). Side-effects were similar in both groups.\n A single preoperative oral dose of pregabalin 150 mg is an effective method for reducing postoperative pain and fentanyl consumption in patients undergoing laparoscopic cholecystectomy.", "Pregabalin, an alpha2-delta ligand with analgesic, anxiolytic, and anticonvulsant activity, has been evaluated for treatment of neuropathic pain. The authors assessed the efficacy and tolerability of pregabalin (75, 300, 600 mg/day) vs placebo in patients with diabetic peripheral neuropathy (DPN).\n Patients with a 1- to 5-year history of DPN and average weekly pain score of > or =4 on an 11-point numeric pain-rating scale were enrolled in a 5-week, double-blind, multicenter, placebo-controlled study. Patients (n = 338) were randomized to receive one of three doses of pregabalin or placebo TID. Pregabalin 600 mg/day was titrated over 6 days; lower doses were initiated on day 1.\n Patients in the 300- and 600-mg/day pregabalin groups showed improvements in endpoint mean pain score (primary efficacy measure) vs placebo (p = 0.0001). Improvements were also seen in weekly pain score, sleep interference score, patient global impression of change, clinical global impression of change, SF-McGill Pain Questionnaire, and multiple domains of the SF-36 Health Survey. Improvements in pain and sleep were seen as early as week 1 and were sustained throughout the 5 weeks. Responders (patients with > or =50% reduction in pain compared to baseline) were 46% (300 mg/day), 48% (600 mg/day), and 18% (placebo). Pregabalin was well tolerated with a low discontinuation rate. The most common adverse events were dizziness and somnolence.\n In patients with diabetic peripheral neuropathy, pregabalin demonstrated early and sustained improvement in pain and a beneficial effect on sleep, which were confirmed by positive patient global impression. Pregabalin was well tolerated at all doses.", "Pregabalin has anticonvulsant, antihyperalgesic, and anxiolytic properties. In this study we evaluated the control of pain after perioperative administration of pregabalin 300 or 600 mg, compared with diazepam 10mg. Altogether 91 women scheduled for laparoscopic hysterectomy were randomized to receive diazepam 10mg (D10), pregabalin 150 mg (P300) or 300 mg (P600) for premedication, and the dose was repeated after 12h, except for the D10 group, in which the patients received placebo. Up until the 1st postoperative morning, analgesia was provided by oxycodone using patient controlled analgesia. The visual analogue scale scores for pain and side effects, and the amounts of the analgesics were recorded for three days after surgery. The doses of oxycodone during hours 0-12 after surgery were similar in the three groups, whereas the dose of oxycodone during hours 12-24 after surgery was smaller in the P600 group than in the P300 group (0.09 vs. 0.16 mg kg(-1); P=0.025). The total dose of oxycodone (0-24h after surgery) was smaller in the P600 group than in the D10 group (0.34 vs. 0.45 mg kg(-1); P=0.046). The incidence of dizziness (70% vs. 35%; P=0.012), blurred vision (63% vs. 14%; P=0.002) and headache (31% vs. 7%; P=0.041) were higher in the P600 group than in the D10 group. In conclusion, perioperative administration of pregabalin 600 mg decreases oxycodone consumption compared with diazepam 10mg, but is associated with an increased incidence of adverse effects.", "Pregabalin binds with high affinity to the alpha2-delta subunit protein of voltage-gated calcium channels and, thereby, reduces release of excitatory neurotransmitters. This 12-week randomised, double-blind, multicentre, placebo-controlled, parallel-group study evaluated the efficacy and safety of pregabalin in patients with chronic postherpetic neuralgia (PHN) or painful diabetic peripheral neuropathy (DPN). Patients were randomised to placebo (n=65) or to one of two pregabalin regimens: a flexible schedule of 150, 300, 450, and 600 mg/day with weekly dose escalation based on patients' individual responses and tolerability (n=141) or a fixed schedule of 300 mg/day for 1 week followed by 600 mg/day for 11 weeks (n=132). Both flexible- and fixed-dose pregabalin significantly reduced endpoint mean pain score (primary outcome) versus placebo (P=0.002, P<0.001) and were significantly superior to placebo in improving pain-related sleep interference (P<0.001). The most common adverse events (AEs) for pregabalin-treated patients were dizziness, peripheral oedema, weight gain (not affecting diabetes control), and somnolence. These results are consistent with previous studies' demonstrating pregabalin's efficacy, tolerability, and safety for treatment of chronic neuropathic pain associated with DPN or PHN. Pregabalin dosing aimed at optimal balance of efficacy and tolerability provides significant pain relief and may reduce risks for AEs and therapy discontinuation.", "Multimodal pain management has been suggested to improve postoperative analgesia. In this study, we evaluated the quality of analgesia in women undergoing day-case gynaecological laparoscopic surgery, after premedication with pregabalin 75 mg (P75) or 150 mg (P150), compared with diazepam 5 mg (D5). All patients were given ibuprofen 800 mg orally.\n Altogether 90 consenting women were anaesthetized in a standardized fashion. Postoperative analgesia was provided by ibuprofen 800 mg twice a day with fentanyl i.v. on request in the recovery room (RR), and combination tablets with acetaminophen and codeine after the RR. The visual analogue scale (VAS) scores for pain and side-effects and the amounts of postoperative analgesics were recorded for 24 h after surgery. The areas under the curves (AUC) were calculated for the VAS scores for pain at rest, pain in motion, and pain at cough 1-8 and 1-24 h after surgery.\n The median AUC values for VAS scores for pain at rest (P=0.048) and in motion (P=0.046) 1-8 h after surgery were lower in the P150 group than that in the D5 group. The amounts of rescue analgesics or the degree of drowsiness did not differ in the three study groups.\n Analgesia was better after premedication with pregabalin 150 mg than after diazepam 5 mg, both with ibuprofen 800 mg, during the early recovery after day-case gynaecological laparoscopic surgery. Pregabalin 150 mg did not reduce the amount of postoperative analgesics required.", "This study was designed to assess the efficacy and safety of pregabalin-a novel alpha(2)-delta ligand with analgesic, anxiolytic, and anticonvulsant activity-for treating neuropathic pain in patients with post-herpetic neuralgia (PHN). Two hundred and thirty-eight patients were randomised into this multicentre, doubleblind, placebo-controlled trial to receive 150 (n=81), 300 mg/day (n=76) pregabalin, or placebo (n=81) for 8 weeks. Among the exclusion criteria was failure to respond to previous treatment for PHN with gabapentin at doses > or =1200 mg/day. Endpoint mean pain scores were significantly reduced in patients receiving 150 or 300 mg/day pregabalin compared with placebo. Efficacy was observed as early as week 1 and was maintained throughout the study. Significantly more patients in both pregabalin groups (150 mg, 26%; 300 mg, 28%) were responders (> or =50% decrease in mean pain score from baseline to endpoint) than in the placebo group (10%). Additionally, by week 1 and for the study's duration, 150 and 300 mg/day pregabalin significantly reduced weekly mean sleep interference scores. More pregabalin-treated patients than placebo-treated patients reported that they were 'much improved' or 'very much improved'. Health-related quality-of-life (HRQoL) measurements using the SF-36 Health Survey demonstrated improvement in the mental health domain for both pregabalin dosages, and bodily pain and vitality domains were improved in the 300 mg/day group. The most frequent adverse events were dizziness, somnolence, peripheral oedema, headache, and dry mouth. Pregabalin efficaciously treated the neuropathic pain of PHN. Additionally, pregabalin was associated with decreased sleep interference and significant improvements in HRQoL measures.", "This trial evaluated the efficacy and safety of pregabalin dosed twice daily (BID) for relief of neuro-pathic pain associated with postherpetic neuralgia (PHN).\n The 13-week, double-blind, placebo-controlled study randomized 370 patients with PHN to pregabalin (150, 300, or 600 mg/day BID) or placebo.\n Primary efficacy measure was endpoint mean pain score from daily pain diaries. Secondary efficacy measures included endpoint mean sleep-interference score from daily sleep diaries and Patient Global Impression of Change (PGIC). Safety evaluations included adverse events (AEs), physical and neurologic examinations, 12-lead ECG, vital signs, and laboratory testing.\n Pregabalin provided significant, dose-proportional pain relief at endpoint: difference from placebo in mean pain score, 150 mg/day, -0.88, p = 0.0077; 300 mg/day, -1.07, p = 0.0016; 600 mg/day, -1.79, p = 0.0003. Weekly mean pain scores significantly improved as early as week 1. Sleep interference in all pregabalin groups was also significantly improved at endpoint, compared with placebo (p < 0.001), beginning at week 1 (p < 0.01). At study termination, patients in the 150 (p = 0.02) and 600 mg/day (p = 0.003) groups were more likely to report global improvement than were those in the placebo group. Most AEs were mild or moderate. Among pregabalin-treated patients, 13.5% withdrew due to AEs, most commonly for dizziness (16 patients, 5.8%), somnolence (8, 2.9%), or ataxia (7, 2.5%).\n Pregabalin, dosed BID, reduced neuropathic pain associated with PHN and was well tolerated. It also reduced the extent to which pain interfered with sleep. Pregabalin's effects were seen as early as week 1 and were sustained throughout the 13-week study.", "To evaluate pregabalin in central neuropathic pain associated with spinal cord injury.\n A 12-week, multicenter study of patients randomized to either flexible-dose pregabalin 150 to 600 mg/day (n = 70) or placebo (n = 67), administered BID. Patients were allowed to remain on existing, stable pain therapy. The primary efficacy variable was the endpoint mean pain score, derived from patients' last 7 days daily pain diary entries. Key secondary endpoints included pain responder rates, the SF-MPQ, sleep interference, mood, and the patient global measure of change.\n The mean baseline pain score was 6.54 in the pregabalin group and 6.73 in the placebo group. The mean endpoint pain score was lower in the pregabalin group (4.62) than the placebo group (6.27; p < 0.001), with efficacy observed as early as week 1 and maintained for the duration of the study. The average pregabalin dose after the 3-week stabilization phase was 460 mg/day. Pregabalin was significantly superior to placebo in endpoint assessments on the SF-MPQ. The > or =30% and > or =50% pain responder rates were higher with pregabalin than placebo (p < 0.05). Pregabalin was associated with improvements in disturbed sleep (p < 0.001) and anxiety (p < 0.05), and more patients reported global improvement at endpoint in the pregabalin group (p < 0.001). Mild or moderate, typically transient, somnolence and dizziness were the most common adverse events.\n Pregabalin 150 to 600 mg/day was effective in relieving central neuropathic pain, improving sleep, anxiety, and overall patient status in patients with spinal cord injury." ]

[ "9141577", "8105165", "8116712", "8476803" ]

[ "A randomised controlled trial of Doppler ultrasound velocimetry of the umbilical artery in low risk pregnancies. Doppler French Study Group.", "Effects of frequent ultrasound during pregnancy: a randomised controlled trial.", "Screening for the compromised fetus: a randomized trial of umbilical artery velocimetry in unselected pregnancies.", "Randomised comparison of routine versus highly selective use of Doppler ultrasound in low risk pregnancies." ]

[ "To evaluate the effect on management and outcome of pregnancy of routine umbilical Doppler examination in low risk populations.\n Pragmatic randomised controlled trial.\n Twenty centres caring for low risk pregnant women.\n 4187 women were randomly assigned to umbilical Doppler between 28 and 34 weeks of gestation or no routine umbilical Doppler. The women included were at low risk at 28 weeks of gestation defined by a normal ultrasonographic examination at the time of randomisation and no obstetric or medical complications during the first two trimesters of the pregnancy.\n The general characteristics at inclusion were comparable for the two groups. Performance of umbilical Doppler led to a significant increase in the number of ultrasonographic and Doppler examinations subsequently conducted; there were no other effects on the management of the pregnancy. There was no significant difference in fetal distress during labour (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.70-1.33). There were three times fewer perinatal deaths in the Doppler group (three versus nine), but this difference was not significant (OR 0.33; 95% CI 0.06-1.33).\n Based on this trial routine use of umbilical doppler for low risk pregnancy cannot be recommended. More data are needed to reach a definite conclusion of the value of routine Doppler.", "Despite widespread application of ultrasound imaging and Doppler blood flow studies, the effects of their frequent and repeated use in pregnancy have not been evaluated in controlled trials. From 2834 women with single pregnancies at 16-20 weeks gestation, 1415 were selected at random to receive ultrasound imaging and continuous-wave Doppler flow studies at 18, 24, 28, 34, and 38 weeks gestation (the intensive group) and 1419 to receive single ultrasound imaging at 18 weeks (the regular group). Outcome data was obtained from 99% of women who entered the study. The only difference between the two groups was significantly higher intrauterine growth restriction in the intensive group, when expressed both as birthweight < 10th centile (relative risk 1.35; 95% confidence interval 1.09 to 1.67; p = 0.006) and birthweight < 3rd centile (relative risk 1.65; 95% confidence intervals 1.09 to 2.49; p = 0.020). While it is possible that this finding was a chance effect, it is also plausible that frequent exposure to ultrasound may have influenced fetal growth. Repeated prenatal ultrasound imaging and Doppler flow examinations should be restricted to those women to whom the information is likely to be of clinical benefit.", "Meta-analysis of randomized trials of Doppler ultrasonography in high-risk pregnancies has showed reduced mortality rates among normally formed fetuses. This trial addressed the impact on outcome of umbilical artery velocimetry in a nonselected population (i.e., as a screening test in low-risk and high-risk pregnancies).\n A randomized, controlled trial with Doppler ultrasonographic investigation was performed at two gestational age windows: 26 to 30 weeks and 34 to 36 weeks. The 2986 women were randomly allocated to revealed or concealed groups in which the Doppler results were either made available or not made available to clinicians; 1056 women were studied at only the first window, 544 at only the second, and 1386 at both.\n There were no significant differences between groups in antenatal admissions to hospital, preterm deliveries, rates of cesarean section, admission to the neonatal unit, and need for assisted ventilation. There was, however, a trend toward fewer stillbirths in the \"revealed\" group (three vs eight, odds ratio 0.34, confidence interval 0.10 to 1.07).\n The incidence of stillbirths was reduced by more than half in the Doppler-revealed group, but the confidence intervals were wide and these findings could be compatible with chance.", "To help answer the question: should Doppler ultrasound of the umbilical circulation be made available to all pregnant women as part of their routine antenatal care?\n A randomised trial.\n St James's University Hospital, Leeds.\n 2025 low risk primigravid women.\n Obstetric intervention rates and short term neonatal morbidity.\n The incidence of abnormal Doppler was low (1.7%) with complete absence of end diastolic flow in only 0.3% of cases. No significant differences could be demonstrated between control and study women in any of the outcomes measured.\n This study did not demonstrate any benefit or harm from Doppler ultrasound as a routine screening test for all low risk women, whereas our previous studies have suggested that it is useful in high risk pregnancies. Any marginal returns on extending access to Doppler ultrasound from high risk to all women must be small. Since this test has excellent performance characteristics (sensitivity and specificity) for the prediction of fetal hypoxia and acidosis our results call into question the cost to benefit ratio of all tests designed to predict these outcomes in low risk women." ]

[ "11000669", "15983143", "11167431", "9249106", "11103176", "7669314", "15109188", "10712710", "10866717", "9526937" ]

[ "Comparison of inhalation induction with 2%, 4%, 6%, and 8% sevoflurane in nitrous oxide for pediatric patients.", "Apnea during induction of anesthesia with sevoflurane is related to its mode of administration.", "Effect of smoking on induction of anaesthesia with sevoflurane.", "Immediate 8% sevoflurane induction in children: a comparison with incremental sevoflurane and incremental halothane.", "Nodal rhythm and bradycardia during inhalation induction with sevoflurane in infants: a comparison of incremental and high-concentration techniques.", "Efficient inspired concentration of sevoflurane for vital capacity rapid inhalation induction (VCRII) technique.", "Conventional stepwise vs. vital capacity rapid inhalation induction at two concentrations of sevoflurane.", "Comparison of three techniques for induction of anaesthesia with sevoflurane in children.", "Induction characteristics with 3% and 8% sevoflurane in adults: an evaluation of the second stage of anaesthesia and its haemodynamic consequences.", "High concentration versus incremental induction of anesthesia with sevoflurane in children: a comparison of induction times, vital signs, and complications." ]

[ "Sevoflurane is almost the idealest volatile anesthetic agent regarding inhalation induction of general anesthesia. Previous studies have established a role of sevoflurane in high concentration primed in the circuit for inhalation induction in pediatric patients. However, which concentration of sevoflurane is suitable has not yet been reported. This study was designed to compare the efficiency of different concentration of sevoflurane i.e. 2%, 4%, 6%, and 8% and with N2O in 50% oxygen for induction of anesthesia in pediatric patients and at the same time to evaluate the tolerance of patients.\n One hundred and twenty children who were 3 to 10 years old, of ASA class I, were randomly assigned to receive either 2%, 4%, 6%, and 8% sevoflurane and N2O in 50% O2 for induction of anesthesia. The time to loss of eyelash reflex, responses of airway reflex, involuntary movement, and hemodynamic responses were recorded.\n Ninety-nine children completed the study. The times to loss of eyelash reflex with 2% in sequence to 8% sevoflurane were 114 +/- 21 s, 87 +/- 11 s, 75 +/- 6 s, and 48 +/- 8 s respectively. Incidence of airway reflex response including coughing, laryngospasm, and breath holding was the highest in the 8% group (P < 0.05). Inhalation induction with sevoflurane significantly decreased systolic as well as diastolic blood pressure compared with baseline blood pressure in all the four groups. The extent of decrease of blood pressure was within 20% range of baseline blood pressure in all groups. Significant increase of heart rate was only observed in the 4% and 6% groups.\n Sevoflurane 6% for inhalation induction apparently caused low incidence of adverse effects and hastened induction. We suggest that 6% sevoflurene is a concentration more practical for inhalation induction in pediatric patients.", "The incidence and duration of apnea during sevoflurane anesthesia have not been fully characterized. We hypothesized that sevoflurane at slowly increasing concentrations reduces incidence and shortens the duration of apnea compared to administration of a highly concentrated anesthetic mixture.\n 131 women were randomly assigned to receive 35% oxygen in air and sevoflurane at: incremental concentrations of 1%, from 1% to 8% (group 1-8%, n = 42); decremental-incremental concentrations of 2%, from 8% to 4% and then from 4% to 8% (group 8-4-8%, n = 36); or fixed concentrations of 8% for induction of anesthesia (group 8%, n = 53). A blinded investigator observed whether and for how long patients stopped breathing.\n All groups reached 2.5 minimum alveolar concentration of end-tidal sevoflurane. Although apnea was observed in all groups, it was more frequent in the 8% group than in 1 to 8% (68% vs 21%, P < 0.05) or 8 to 4 to 8% groups (68% vs 20%, P < 0.05). Duration of apnea was also more pronounced in the 8% group than in 1 to 8% and 8 to 4 to 8% groups ( 58 +/- 25 s vs 32 +/- 18 sec, P < 0.05 and vs 35 +/- 16 sec, P < 0.05, respectively).\n Sevoflurane induces apnea more frequently and for longer duration at a fixed high concentration compared to incremental or decremental-incremental concentrations. Decremental-incremental concentrations offer the additional advantage of a speed of induction similar to that elicited by the 8% concentration.", "Inhalational induction with sevoflurane has been shown to be a viable alternative to intravenous induction; however, studies have focused mainly on healthy patients or volunteers. Airway complications in patients with potential airway irritability have not been studied. Sixty smokers undergoing general anaesthesia were randomly assigned to one of three groups: group 1, vital capacity breathing with 8% sevoflurane; group 2, tidal breathing with 8% sevoflurane; and group 3, tidal breathing with step-up of sevoflurane (sevoflurane concentration increased by increments of 2% every 10 s until 8%). Step-up induction was significantly slower to induce loss of consciousness than a vital capacity breath or tidal breathing at 8% (p < 0.05). Step-up induction produced more complications than tidal breathing at 8% (p = 0.05). All patients had acceptable induction of anaesthesia with no patient having an oxygen saturation below 96% at any time. Blood pressure and heart rate decreased gradually over time in all groups (p < 0.001), but there were no significant differences between groups. Patient satisfaction with the techniques was high with 59 of 60 patients willing to have the same technique again. Inhalational induction with sevoflurane can be used safely as an induction technique in smokers. In common with other patient groups, use of a high initial concentration reduces induction time without causing additional airway or cardiovascular complications.", "We compared the efficacy and tolerance of pediatric inductions with immediate 8% sevoflurane in 70% nitrous oxide with either incremental sevoflurane or incremental halothane in 70% nitrous oxide. Forty-six unpremedicated children had anesthesia induced by immediate 8% sevoflurane (high sevoflurane [HS]; circuit primed with 70% N2O and 8% sevoflurane before application of the face mask), gradual sevoflurane (GS; primed with 70% N2O with increments of sevoflurane), and gradual halothane (HAL; 70% N2O with incremental halothane). Blind video recordings were made, and each child's distress was rated prior to mask application, during mask application, and every 10 s thereafter using a behavioral rating scale. There were no complications. Of those subjects not quiet and cooperative throughout, times to complete quiet were significantly different (P = 0.001): HS 19.8 +/- 8 s (range 9-34); GS 52 +/- 17 s (range 8-73); HAL 43 +/- 22 s (range 13-73). Times to eye closure were also significantly different (P < 0.001): HS 37 +/- 10 s (range 15-56); GS 70 +/- 18 s (range 35-114); HAL 81 +/- 34 s (range 55-140). Distress scale scores showed more rapid decrement with HS than with GS or HAL. We conclude that 1) immediate 8% sevoflurane/N2O results in a significantly faster induction than GS or HAL;2) in children, HS in N2O will not result in a single-breath induction under the conditions of this study; 3) in this small group, HS was extremely well tolerated in ASA class I and II patients.", "We studied heart rate and rhythm changes during sevoflurane inhalation induction in 60 healthy, unpremedicated infants. Patients were allocated randomly to receive an incremental (2% sevoflurane, increased every four to six breaths by 2% increments, to 8%) or high-concentration induction technique (8% sevoflurane from the outset). The ECG was recorded for 330 s (30 s pre- and 300 s postinduction) using a mini-Holter device (Recollect Dual Channel, Hertford Medical) and later analysed by an independent observer. Twelve patients developed nodal rhythm (six in each group), but no other dysrhythmias were recorded. The onset of nodal rhythm was associated with bradycardia (< 80 bpm) in seven out of 12 cases, and occurred significantly earlier in the high-concentration group (median 123 (range 99-139) s versus 164 (127-138) s). Its duration was similar in both groups (62 (2-84) s versus 90 (20-167) s). These findings highlight the importance of using continuous ECG analysis when studying volatile anaesthetic agents in young children.", "To evaluate the efficient inspired concentration of sevoflurane for a vital capacity rapid inhalation induction (VCRII) technique with respect to induction time, characteristics, and acceptability.\n Prospective study.\n Medical college hospital.\n 68 unpremedicated healthy adult volunteers were assigned to one of four groups in order of sequential entry of informed consent.\n 3%, 4.5%, 6%, or 7.5% concentrations of sevoflurane were administered for 5 minutes (3% and 4.5%) or 3 minutes (6% and 7.5%) using a single breath technique.\n The mean induction time required with 3%, 4.5%, 6%, or 7.5% sevoflurane was 120 +/- 26 sec, 79 +/- 18 sec, 52 +/- 15 sec, or 47 +/- 17 seconds, respectively. Each induction time was significantly different from the others (p < 0.05) except for that between 6% and 7.5%. There appeared to be a direct inverse relationship between the mean induction time and the logarithm of inspired concentration of sevoflurane, but this relationship did not extend beyond concentrations above 6%. Blood pressure decreased by approximately 18% from baseline at the end of inhalation of the drug, and heart rate remained constant in all groups. Except of one subject in the 7.5% group, no coughing was observed and laryngospasm, breath-holding, and secretions were not seen in any subjects. Slight limb movement was observed in a few subjects in each group. All subjects except one in the 3% group would accept undergoing a similar procedure again.\n Sevoflurane 6% can be recommended for VCRII, but increasing the concentration higher than this does not markedly shorten the induction time and thus seems to add little benefit.", "A multicentre study was conducted to compare three methods of inhalation induction with sevoflurane in adult premedicated patients.\n One-hundred-and-twenty-five adult patients of ASA I-II were scheduled for short elective surgical procedures (< 90 min) under general anaesthesia with spontaneous ventilation of the lungs via a laryngeal mask airway. Patients were randomly assigned to one of three groups: conventional stepwise inhalation induction group (Group C) or vital capacity rapid inhalation induction groups at 4.5% (Group VC4.5) or at 8% sevoflurane (Group VC8). Before anaesthetic induction, fentanyl 1 micro kg(-1) was given and the face mask applied with the anaesthetic breathing system primed with sevoflurane 4.5% or 8% in the respective vital capacity groups. Loss of eyelash reflex, time to cessation of finger tapping, laryngeal mask insertion, side-effects and adequacy of induction were recorded.\n The time to loss of eyelash reflex was significantly shorter in both vital capacity groups vs. the control group: VC8: 68 +/- 7 s; and VC4.5: 94 +/- 6.5 s vs. C: 118 +/- 6.4s (P < 0.0001). Significant differences were found in all pairwise comparisons for time to cessation of tapping: Group VC8 (62 +/- 7 s), Group VC4.5 (85 +/- 6 s) and Group C (116 +/- 6 s; P < 0.0001). The time to laryngeal mask insertion was significantly shorter in the Group VC8 (176 +/- 13 s) compared with the other two groups, Group VC4.5 (219 +/- 13 s) and Group C (216 +/- 9 s). There were no significant differences in the incidence of side-effects between the three groups.\n Inhalation induction of anaesthesia with sevoflurane with the three techniques tested is safe, reliable and well accepted by the patients. The vital capacity rapid inhalation group primed with sevoflurane 8% was the fastest method with no relevant side-effects.", "This study was designed to evaluate the clinical characteristics of three induction techniques using sevoflurane in children scheduled for tonsillectomy: incremental induction with sevoflurane(2,4,6,7%) in 100% O2 (group IC-O2; n=23); induction with high concentration of sevoflurane in 100% O2 (group HC-O2; n=22); and induction with high concentration of sevoflurane in a mixture of O2:N2O(50:50) (group HC-N2O; n=20). Induction was well accepted and well tolerated in most children. The addition of nitrous oxide resulted in faster loss of consciousness (P< 0.001) compared to the other induction techniques and in a tendency for reduced excitement compared with the same rapid technique without nitrous oxide (P=0.053). Time to tracheal intubation was identical in the three groups and intubation conditions were scored as good in most children. During the early induction phase, an increase in SAP and HR was observed in the three groups. Changes were maximal at two min after the beginning of induction in the three groups. SAP and HR values were back to baseline values at the time of tracheal intubation. In conclusion, the addition of nitrous oxide to a high sevoflurane concentration decreases the time to loss of eyelash reflex, tends to reduce the incidence of excitement and is not associated with an increased incidence of respiratory complications even in patients with obstructive airway.", "The second stage of anaesthesia was examined during 3 and 8% sevoflurane induction to see if any shortening of its duration was at the expense of cardiovascular stability. Fourteen volunteers underwent consecutive, randomly ordered inductions. Pupil size, skin sympathetic activity, plasma catecholamines, blood pressure and heart rate were measured. Eight per cent sevoflurane produced significantly shorter times to loss of consciousness (mean 68 s (SD 18) vs. mean 150 s (SD38)) and durations of second stage (mean 58 s (SD 38) vs. mean 91 s (SD 46)). Blood pressure, heart rate and sympathetic nerve responses were the same in both groups. Compared with baseline, skin sympathetic activity was greatest during pre-oxygenation (not significant) and unaltered during second stage. Both groups showed significantly increased plasma norepinephrine and heart rate and decreased blood pressure from baseline. Eight per cent sevoflurane induction produced a shorter second stage than 3% with equal cardiovascular stability and the same sympathetic response.", "To compare sevoflurane induction times and complications in children during a high concentration, primed-circuit method and an incremental induction technique.\n Randomized, prospective open-label study.\n Academic university hospital.\n 40 unpremedicated ASA physical status I and II children age 4 months to 15 years undergoing elective surgical procedures with general anesthesia.\n Patients were randomized to one of two study groups. In the high concentration group, the anesthesia circuit was primed with 8% sevoflurane in a 2:1 nitrous oxide:oxygen (N2O:O2) mixture. Patients breathed this gas mixture spontaneously until loss of the eyelash reflex. In the incremental group, the face mask was applied and 1% sevoflurane in a 2:1 N2O:O2 mixture was administered. In this group, the sevoflurane concentration was increased by 1% every 2 to 3 breaths. Gas flows of 6 L/min were administered to both groups during the study period. Following loss of the eyelash reflex, the sevoflurane concentration was decreased to 5% until a depth of anesthesia sufficient to start an intravenous catheter was achieved.\n Induction cooperation, induction time (face mask application to loss of the eyelash reflex), one-minute vital signs [blood pressure, heart rate, oxygen saturation via pulse oximetry (SpO2)], induction complications. Induction of anesthesia was faster in the high concentration group than in the incremental group (mean (SD) 42 (9) sec vs. 66 (12) sec, respectively; p < 0.001). Induction complications were minor and occurred with similar frequencies (4/20 patients vs. 3/20 patients). There were no significant intergroup heart rate, blood pressure, or SpO2 differences during induction. No patients required treatment for hypotension or bradycardia.\n In healthy pediatric patients undergoing mask induction of general anesthesia with sevoflurane, the induction time can be significantly shortened without an increase in the frequency of airway or vital sign complications using a high concentration, primed circuit technique compared with a conventional, incremental induction method." ]

[ "7041788", "20133204" ]

[ "Prednisone improves chronic inflammatory demyelinating polyradiculoneuropathy more than no treatment.", "Pulsed high-dose dexamethasone versus standard prednisolone treatment for chronic inflammatory demyelinating polyradiculoneuropathy (PREDICT study): a double-blind, randomised, controlled trial." ]

[ "Of 40 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), 28 completed a controlled three-month trial of prednisone. Prednisone was shown to cause a small but significant improvement over no treatment in scored neurological disability, some measures of computer-assisted sensory detection threshold, graded muscle strength, and some attributes of nerve conduction. No subset of patients was more likely than another to be responsive to prednisone; those with a progressive course were as likely to be responsive as recurrent cases. This finding provides further justification for classifying progressive with recurrent cases as CIDP and demonstrates that prednisone treatment should not be withheld from patients with progressive disease.", "Pulsed high-dose dexamethasone induced long-lasting remission in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in a pilot study. The PREDICT study aimed to compare remission rates in patients with CIDP treated with high-dose dexamethasone with rates in patients treated with standard oral prednisolone.\n In eight neuromuscular centres in the Netherlands and one in the UK, patients aged 18 years or older who had newly diagnosed definite or probable CIDP were randomly assigned to a treatment regimen of either pulsed high-dose dexamethasone or standard oral prednisolone. Randomisation was done with a random number generator. The primary outcome measure was remission at 12 months, defined as improvement of at least three points on the Rivermead mobility index and improvement of at least one point on the inflammatory neuropathy cause and treatment disability scale. Analysis was by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN07779236.\n Between December, 2003, and December, 2008, 40 patients were treated: 24 received dexamethasone and 16 received prednisolone. At 12 months, 16 patients were in remission: ten in the dexamethasone group and six in the prednisolone group (odds ratio [OR] 1.2, 95% CI 0.3-4.4). Most adverse events were minor and did not differ substantially between treatment groups; however, sleeplessness and Cushing's face occurred more often in the prednisolone group.\n Pulsed high-dose dexamethasone treatment did not induce remission more often than prednisolone treatment. A substantial proportion of patients were in remission at 12 months in both treatment groups. High-dose dexamethasone could be considered as induction therapy in CIDP, but comparison with intravenous immunoglobulin treatment is needed.\n The Prinses Beatrix Fonds (MAR01-0213) and the Department of Neurology, Academic Medical Center.\n 2010 Elsevier Ltd. All rights reserved." ]

[ "11394463", "11493843", "15961625", "15706071", "17514726", "14501096", "16621849", "10877480", "18728907", "11276268", "17626135", "10450777" ]

[ "Computer terminal work and the benefit of microbreaks.", "A randomized controlled trial to prevent patient lift and transfer injuries of health care workers.", "A randomised controlled trial of postural interventions for prevention of musculoskeletal symptoms among computer users.", "Effects of an active ergonomics training program on risk exposure, worker beliefs, and symptoms in computer users.", "Supplementary breaks and stretching exercises for data entry operators: a follow-up field study.", "A comprehensive work injury prevention program with clerical and office workers: phase I.", "A randomised controlled trial evaluating the effects of two workstation interventions on upper body pain and incident musculoskeletal disorders among computer operators.", "A field study of supplementary rest breaks for data-entry operators.", "Health-related effects of worksite interventions involving physical exercise and reduced workhours.", "Effects of Ergorest arm supports on muscle strain and wrist positions during the use of the mouse and keyboard in work with visual display units: a work site intervention.", "A randomised controlled trial evaluating an alternative mouse and forearm support on upper body discomfort and musculoskeletal disorders among engineers.", "Effects of an ergonomic training program on workers with video display units." ]

[ "Microbreaks are scheduled rest breaks taken to prevent the onset or progression of cumulative trauma disorders in the computerized workstation environment. The authors examined the benefit of microbreaks by investigating myoelectric signal (MES) behavior, perceived discomfort, and worker productivity while individuals performed their usual keying work. Participants were randomly assigned to one of three experimental groups. Each participant provided data from working sessions where they took no breaks, and from working sessions where they took breaks according to their group assignment: microbreaks at their own discretion (control), microbreaks at 20 min intervals, and microbreaks at 40 min intervals. Four main muscle areas were studied: the cervical extensors, the lumbar erector spinae, the upper trapezius/supraspinatus, and the wrist and finger extensors. The authors have previously shown that when computer workers remained seated at their workstation, the muscles performing sustained postural contractions displayed a cyclic trend in the mean frequency (MNF) of the MES (McLean et al., J. Electrophysiol. Kinesiol. 10 (1) (2000) 33). The data provided evidence (p < 0.05) that all microbreak protocols were associated with a higher frequency of MNF cycling at the wrist extensors, at the neck when microbreaks were taken by the control and 40 min protocol groups, and at the back when breaks were taken by the 20 and 40 min protocol groups. No significant change in the frequency of MNF cycling was noted at the shoulder. It was determined (p < 0.05) that microbreaks had a positive effect on reducing discomfort in all areas studied during computer terminal work, particularly when breaks were taken at 20 min intervals. Finally, microbreaks showed no evidence of a detrimental effect on worker productivity. The underlying cause of MNF cycling, and its relationship to the development of discomfort or cumulative trauma disorders remains to be determined.", "Randomized controlled trial (RCT).\n To compare the effectiveness of training and equipment to reduce musculoskeletal injuries, increase comfort, and reduce physical demands on staff performing patient lifts and transfers at a large acute care hospital.\n Back injury to nursing staff during patient handling tasks is a major issue in health care. The value of mechanical assistive devices in reducing injuries to these workers is unclear.\n This three-armed RCT consisted of a \"control arm,\" a \"safe lifting\" arm, and a \"no strenuous lifting\" arm. A medical, surgical, and rehabilitation ward were each randomly assigned to each arm. Both intervention arms received intensive training in back care, patient assessment, and handling techniques. Hence, the \"safe lifting\" arm used improved patient handling techniques using manual equipment, whereas the \"no strenuous lifting\" arm aimed to eliminate manual patient handling through use of additional mechanical and other assistive equipment.\n Frequency of manual patient handling tasks was significantly decreased on the \"no strenuous lifting\" arm. Self-perceived work fatigue, back and shoulder pain, safety, and frequency and intensity of physical discomfort associated with patient handling tasks were improved on both intervention arms, but staff on the mechanical equipment arm showed greater improvements. Musculoskeletal injury rates were not significantly altered.\n The \"no strenuous lifting\" program, which combined training with assured availability of mechanical and other assistive patient handling equipment, most effectively improved comfort with patient handling, decreased staff fatigue, and decreased physical demands. The fact that injury rates were not statistically significantly reduced may reflect the less sensitive nature of this indicator compared with the subjective indicators.", "To examine the effect of two workstation and postural interventions on the incidence of musculoskeletal symptoms among computer users.\n Randomised controlled trial of two distinct workstation and postural interventions (an alternate intervention and a conventional intervention) among 376 persons using computer keyboards for more than 15 hours per week. The incidence of neck/shoulder symptoms and hand/arm symptoms during six months of follow up among individuals in the intervention groups was compared to the incidence in computer users who did not receive an intervention (comparison group). For individuals in the intervention groups, study staff adjusted workstations, where possible, and trained individuals to assume the intervention postures. Individuals reported musculoskeletal symptoms in a weekly diary. Participants who reported discomfort intensity of 6 or greater on a 0-10 visual analogue scale or who reported musculoskeletal symptoms requiring use of analgesic medication were considered symptomatic.\n There were no significant differences in the incidence of musculoskeletal symptoms among the three intervention groups. Twenty two (18.5%) participants in the alternate intervention group, 25 (20.2%) in the conventional intervention group, and 25 (21.7%) in the comparison group developed incident arm or hand symptoms. Thirty eight (33.3%) participants in the alternate intervention group, 36 (31.0%) in the conventional intervention group, and 33 (30.3%) in the comparison group developed incident neck or shoulder symptoms. Compliance with all components of the intervention was attained for only 25-38% of individuals, due mainly to the inflexibility of workstation configurations.\n This study provides evidence that two specific workplace postural interventions are unlikely to reduce the risk of upper extremity musculoskeletal symptoms among computer users.", "The purpose of this study was to evaluate the effectiveness of an active ergonomics training (AET) program in computer users. Two constructs from the social-cognitive theory were adopted to provide a more comprehensive assessment of the proximal markers of behavior change.\n Eighty-seven symptomatic and asymptomatic employees who worked at a computer for a minimum of 10 hours per week took part in a prospective randomized controlled study. Subjects participated in a six-hour training intervention at their workplace. Key elements of the AET intervention were skill development in workstation analysis, active participation, and implementation of multiple prevention strategies.\n After receiving AET, risk factor exposure was significantly reduced for participants at higher risk [F(1,82) = 6.42, p < 0.01]. Significant increases in knowledge [F(1,74) = 8.39, p < 0.01], self-efficacy [F(1,73) = 6.95, p < 0.01], and outcome expectations [F(1,75) = 8.75, p < 0.01] were found in the intervention group. When the participants were stratified according to the presence of symptoms at baseline, the group with pain that received the AET intervention had significantly less upper back pain intensity (z = -2.03, p < 0.05), pain frequency (z = -2.70, p < 0.01), and pain duration (z = -3.25, p < 0.01) post-intervention than the control group with pain.\n Results from this study provide evidence that participative training in workstation ergonomics can improve work postures, work practices, risk factor exposure, and pain.", "This study expanded previous NIOSH-IRS research examining the effects of rest breaks and stretching exercises on symptoms and performance in data-entry workers.\n All workers spent 4 weeks with conventional breaks (two 15 min breaks per day) and 4 weeks with supplementary breaks (two 15 min breaks plus four 5 min breaks per day). One-half were assigned at random to a group instructed to perform brief stretching exercises during breaks. The remainder comprised the \"no stretching\" (control) group.\n 51 workers (stretch group n = 21; no stretch group n = 30) completed the study symptom questionnaires. Discomfort and eyestrain were significantly lower with supplementary breaks, and supplementary breaks attenuated accumulation of discomfort and eyestrain during work sessions. Data-entry speed was significantly faster with supplementary breaks so that work output was maintained, despite replacing 20 min of work time with break time. In the stretch group, workers reported stretching during only 25% of conventional breaks and 39% of supplementary breaks, and no significant effects of stretching on discomfort or performance were observed.\n These results provide further converging evidence that supplementary breaks reliably minimize discomfort and eyestrain without impairing productivity. Low compliance in performing stretches prevented valid assessment of stretching effects. Further research on stretching exercises and exercise compliance is warranted.", "The risk for the development of musculoskeletal disorders and associated conditions in clerical and office workers is well documented. The majority of work injury prevention programs for this population were single-faceted (education, workstation redesign, or task modification) and yielded both positive and negative findings. This pilot study was conducted with 16 full-time clerical and office workers at a small private college. In a randomized control trial, the intervention group received four hours of individualized training through a multi-faceted injury prevention program. Between group differences in musculoskeletal symptom frequency and intensity and perceived stress and energy levels existed, although were statistically insignificant. There was a statistically significant decrease in Lower Back ache/pain from pre to post measures for the intervention group.", "Call centre work with computers is associated with increased rates of upper body pain and musculoskeletal disorders.\n This one year, randomised controlled intervention trial evaluated the effects of a wide forearm support surface and a trackball on upper body pain severity and incident musculoskeletal disorders among 182 call centre operators at a large healthcare company. Participants were randomised to receive (1) ergonomics training only, (2) training plus a trackball, (3) training plus a forearm support, or (4) training plus a trackball and forearm support. Outcome measures were weekly pain severity scores and diagnosis of incident musculoskeletal disorder in the upper extremities or the neck/shoulder region based on physical examination performed by a physician blinded to intervention. Analyses using Cox proportional hazard models and linear regression models adjusted for demographic factors, baseline pain levels, and psychosocial job factors.\n Post-intervention, 63 participants were diagnosed with one or more incident musculoskeletal disorders. Hazard rate ratios showed a protective effect of the armboard for neck/shoulder disorders (HR = 0.49, 95% CI 0.24 to 0.97) after adjusting for baseline pain levels and demographic and psychosocial factors. The armboard also significantly reduced neck/shoulder pain (p = 0.01) and right upper extremity pain (p = 0.002) in comparison to the control group. A return-on-investment model predicted a full return of armboard and installation costs within 10.6 months.\n Providing a large forearm support combined with ergonomic training is an effective intervention to prevent upper body musculoskeletal disorders and reduce upper body pain associated with computer work among call centre employees.", "This study examined the effects of supplementary rest breaks on musculoskeletal discomfort, eyestrain, mood, and performance in data-entry workers. Two rest break schedules were compared in a within-subjects design. Workers alternated between a 'conventional' and a 'supplementary' schedule in 4-week intervals. The conventional schedule contained a 15-min break during the first half of the work shift and a 15-min break during the second half of the shift. The supplementary schedule contained the same two 15-min breaks, and a 5-min break during each hour which otherwise did not contain a break, for a total of 20 extra minutes of break time. Results are based on data from 42 workers. They indicated that discomfort in several areas of the body, and eyestrain, were significantly lower under the supplementary than under the conventional schedule. While symptoms increased from pre- to post-work periods under both schedules, the magnitude of the increases was significantly less under the supplementary schedule. In addition, increases in discomfort of the right forearm, wrist and hand over the course of the work week under the conventional schedule were eliminated under the supplementary schedule. These beneficial effects were obtained without reductions in data-entry performance.", "This study examined the health-related effects of two worksite interventions, physical exercise and reduced workhours, on women employed in dentistry.\n Six workplaces were randomized to one of the following three conditions: (i) 2.5 hours of weekly, mandatory physical exercise of middle-to-high intensity to be performed during workhours (N=62), (ii) a reduction of full-time weekly workhours from 40 to 37.5 hours (N=50), and (iii) reference. In all, 177 women participated. Biomarkers and self-ratings in questionnaires were obtained before the intervention (T (1)), and six (T (2)) and 12 months (T (3)) after the intervention.\n The results showed increased levels of physical activity and exercise in all of the groups, the level of physical exercise being significantly greater in the physical exercise group. Repeated-measures analyses of variance using data from T (1)and T (3)for biological measures and all three time points for self-ratings produced significant interaction effects for glucose, waist-to-hip ratio, and work ability and clear trends for general symptoms and upper-extremity disorders. Posthoc analyses showed that the results of the health-related measures differed between the interventions, decreased glucose and upper-extremity disorders in the exercise group, and increased high-density lipoprotein and waist-to-hip ratio among those working reduced hours.\n These results show that the two interventions had small and varied effects on biomarkers and self-reports of different aspects of health among women. It is suggested that interventions involving a modest reduction in workhours seem to be more effective if these hours are used for physical exercise.", "The effects of Ergorest arm supports on wrist angles and musculoskeletal strain in the neck-shoulder-arm region and electrical activity in the shoulder and arm muscles were studied during typing or the use of the mouse in work with a visual display unit (VDU). Twenty-one women were randomized into 3 groups (1 arm support, 2 arm supports, and control). Measurements were carried out before and after the 6-week intervention. The wrist extension of the mouse hand, the muscle activity of the trapezius muscle, and the subjective discomfort ratings indicated that 2 arm supports were better than 1 in work with a mouse. The Ergorest arm support alleviates muscle and joint strain in VDU work when used for both arms.", "The aim of this intervention study was to determine the effects of an alternative mouse and/or a forearm support board on the change in upper body discomfort scores and the development of incident musculoskeletal disorders.\n This randomised controlled intervention trial followed 206 engineers for one year. Participants were randomised to receive (1) a conventional mouse only, (2) an alternative mouse only, (3) a forearm support board, or (4) an alternative mouse plus forearm support board. Outcome measures included weekly upper body discomfort scores and incident musculoskeletal disorders.\n During the study, 42 participants were diagnosed with an incident musculoskeletal disorder. The group that received the forearm support board experienced a reduction in their right upper extremity discomfort (beta-coefficient -0.35, 95% CI -0.67 to -0.03) in comparison to those who did not receive a forearm board. The group that received the alternative mouse had a protective, but non-significant (p = 0.20), effect on incident cases of right upper extremity musculoskeletal disorders (HR 0.57, 95% CI 0.24 to 1.34) and a non-significant reduction in neck/shoulder discomfort (beta-coefficient -0.23, 95% CI -0.056 to 0.10) in comparison to those who received a conventional mouse.\n In engineers who use a computer for more than 20 h per week, a forearm support board may reduce right upper extremity discomfort attributed to computer use.", "This study evaluated the effect of an ergonomic training program on workstation changes and on the prevalence of musculoskeletal disorders among video display unit (VDU) users at a large university.\n A pretest-posttest design with a reference group was used with random allocation of administrative and geographic units. In each group, the measurements involved direct observation of the workstations, a self-administered questionnaire, and a physical examination. The measurements were performed 2 weeks before and 6 months after the training in parallel in both groups. The study population was composed of 627 workers (81% of those eligible).\n The prevalence of all 3 of the postural stressors evaluated decreased in the experimental group after the training. In the reference group, 2 of the 3 stressors decreased in frequency but to a less extent. Some of these beneficial changes were more frequent in workers under 40 years of age. The prevalence of musculoskeletal disorders decreased among the workers under 40 years of age in the experimental group, from 29% to 13% determined by questionnaire and from 19% to 3% determined by physical examination. In other groups, there was no significant change in the prevalence of musculoskeletal disorders.\n Improvements in postural stressors occurred more frequently in the experimental group, and these beneficial changes tended to be more frequent in workers under 40 years of age. Improvements in musculoskeletal disorders occurred in the experimental group among the workers under 40 years of age." ]

[ "6352887", "364393", "3280773", "16204359", "3658526", "6384452" ]

[ "Diuresis and pulmonary function in premature infants with respiratory distress syndrome.", "Furosemide in hyaline membrane disease.", "Prophylactic furosemide in severe respiratory distress syndrome: blinded prospective study.", "A randomised, double blind, placebo controlled trial of the effect of theophylline in prevention of vasomotor nephropathy in very preterm neonates with respiratory distress syndrome.", "Effect of early furosemide administration in neonates with respiratory distress syndrome.", "Early furosemide therapy in premature infants (less than or equal to 2000 gm) with respiratory distress syndrome: a randomized controlled trial." ]

[ "A prospective study of 99 premature infants with severe respiratory distress syndrome who were randomly assigned to receive diuretic treatment with either furosemide or chlorothiazide was analyzed to examine the relationship of diuretic administration and diuresis to survival and to the duration and degree of mechanical ventilatory support. Subjects were given a diuretic, usually beginning on the second or third day of life, if they had not initiated the expected spontaneous diuresis and did not show pulmonary improvement. Infants given furosemide experienced a postnatal weight loss nearly identical to that in infants who were deemed not to need a diuretic; infants given chlorothiazide lost weight more slowly and had significantly greater body weight on postnatal days 4 and 5. Four factors were independently correlated with improved survival: furosemide usage, high birth weight, low initial mean airway pressure, and the absence of intraventricular hemorrhage. Ventilator mean airway pressure on the seventh day of life and duration of mechanical ventilation were both related to diuresis. These data provide additional evidence for the importance of water homeostasis in determining the course of respiratory distress syndrome in premature infants and indicate that furosemide administration is beneficial when spontaneous diuresis does not occur. Furosemide may be particularly effective if combined with early closure of the ductus arteriosus.", "In a randomized clinical trial designed to evaluate the effect of diuresis on infants with hyaline membrane disease, seven infants were treated with furosemide (2 mg/kg intravenously) and five received 5% dextrose water in 0.225% sodium chloride (control group). Arterial blood gas analyses performed before and during the six hours after treatment showed no significant difference between control and treated infants. Urine output and urine sodium and calcium loss were significantly increased (P less than .05) in the infants receiving furosemide. The diuresis seemed to have no effect on left atrial size determined echocardiographically, whereas measurements of dynamic skinfold thickness suggested mobilization of subcutaneous water. One infant became seriously dehydrated and hypotensive secondary to a massive diuresis. We concluded that furosemide had a potent diuretic effect in infants with hyaline membrane disease but does not improve cardiorespiratory function acutely. This may be because of failure to mobilize pulmonary interstitial fluid in the time period tested. It may also be possible that the presence of pulmonary interstitial fluid does not play an important role in the impairment of gas exchange in the acute stage of hyaline membrane disease.", "To further characterize the place for furosemide in the treatment of newborn infants with respiratory distress syndrome requiring mechanical ventilation, we conducted a blinded, prospective study comparing early prophylactic use (1 mg/kg every 12 hours for four doses beginning at 24 hours of age) with prn use of this drug. Prophylactic administration of furosemide produced no beneficial effect on any measure of pulmonary function compared with use of this drug as needed (prn). However, patients receiving the prophylactic furosemide regimen were found to have more rapid postnatal weight loss, higher pulse rate, and greater sympathomimetic drug requirement during the period of diuretic administration. Patients in the prophylactic group did not demonstrate the moderate expansion in plasma volume between 48 and 96 hours of age seen in the control group. These data suggest that the prophylactic regimen produced an undesirable degree of volume depletion. Further studies should be conducted to develop objective criteria for the selection of the subgroup of patients with respiratory distress syndrome who may benefit from furosemide.", "Vasomotor nephropathy is a common renal dysfunction in very preterm neonates.\n To determine whether theophylline could prevent vasomotor nephropathy in very preterm infants with respiratory distress syndrome.\n A randomised, double blind, placebo controlled trial of 50 preterm infants of gestational age < or = 32 weeks needing assisted ventilation. Infants received an intravenous dose of theophylline (1 mg/kg) or placebo for three days. The 24 hour urine volume was measured daily. On days 2, 5, and 11, blood samples and 12 hour urine collections were analysed for electrolytes, creatinine, and urea.\n On day 1, urine output was significantly higher in the theophylline (2.4 (0.9) ml/kg/h) than the placebo (1.6 (1.0) ml/kg/h; p = 0.023) group (values are mean (SD)). The incidence of oligoanuria was significantly lower in the theophylline treated (5%) than the placebo (33%) group. Twenty four hours after the first administration of theophylline/placebo, serum creatinine concentration was significantly lower in the theophylline (0.76 (0.23) mg/dl) than the placebo (1.0 (0.41) mg/dl; p = 0.025) group. On day 5 an increase in serum creatinine was observed in both groups. On day 11 a significant reduction in serum creatinine was observed, compared with day 5, with no difference between the two groups.\n The results suggest that, in very preterm infants with respiratory distress syndrome, early theophylline administration improves renal function during the first two days of life.", "The effect of early furosemide-induced diuresis was prospectively evaluated in 39 neonates less than 24 hr of age with clinical respiratory distress syndrome (RDS) who received either four doses of furosemide (1 mg/kg) or no diuretic. Measurements of FiO2 alveolar-arterial oxygen gradient (P[A-a]O2), peak inspiratory pressure (PIP), and urine output as a fraction of intake (O/I) were averaged for every 8 hr. The furosemide group overall showed a significant decrease (P less than 0.01) in FiO2, P[A-a]O2, and PIP with an earlier (32 hr vs 52 hr) and more pronounced diuresis (35% greater O/I) when compared to the controls. This effect was accentuated in the subgroup with 1,000-1,500 g birth weight (significantly lower FiO2 and P(A-a)O2 from 16 to 48 hours), while no increase in urine output was observed for the infants weighing less than 1,000 g. A significant reduction in supplemental oxygen and need for ventilatory support at 96 hr of age was observed in the furosemide-treated, less than 1,500-g infants. The incidence of patent ductus arteriosus was not increased following furosemide therapy, and no significant difference in echocardiographic parameters was observed in 21 infants from both groups, who were followed daily during the first week of life. This study suggests that early furosemide-induced diuresis, particularly in infants weighing 1,000-1,500 g at birth, promotes improvement in pulmonary functions in RDS and leads to faster reduction in oxygen and ventilatory support.", "Pulmonary edema has been demonstrated in the early stages of respiratory distress syndrome in premature infants. To evaluate whether early furosemide therapy (0 to 8 hours after birth) would affect the electrolyte balance, pulmonary status, and outcome, 57 infants (less than or equal to 2000 gm) with respiratory distress syndrome who required mechanical ventilation shortly after birth were randomized into two groups: 29 given furosemide (1 mg/kg/day intravenously for three doses) and 27 control. The clinical, biochemical, and laboratory characteristics of the groups were comparable before entry into the study. Administration of furosemide significantly enhanced the urinary excretion of Na and Cl at 0 to 24, 24 to 48 and 48 to 72 hours and of Ca at 24 to 48 and 48 to 72 hours after drug administration. There was no significant difference between the groups in urinary excretion of K and in serum Na, Cl, K, and Ca values. A spontaneous increase in urine output occurred in the control group at 48 to 72 hours after the initiation of the study (mean +/- SD 7.0 +/- 3.5 hours postnatal age), along with a decrease in mean airway pressure for mechanical ventilation. The use of furosemide (7.3 +/- 3.5 hours postnatal age) enhanced urine output at 24 to 48 and 48 to 72 hours after medication, resulting in further decrease in mean airway pressure and facilitating extubation. There was, however, no significant difference between the groups with respect to incidence of patent ductus arteriosus, morbidity from bronchopulmonary dysplasia, and mortality." ]

[ "8780093" ]

[ "Botulinum toxin versus trihexyphenidyl in cervical dystonia: a prospective, randomized, double-blind controlled trial." ]

[ "Botulinum toxin type A (BTA) is replacing trihexyphenidyl as the treatment of choice for idiopathic cervical dystonia (ICD), but there has never been a direct comparative study.\n This trial compares the effectiveness of BTA with that of trihexyphenidyl in a prospective, randomized, double-blind design. Sixty-six consecutive patients with ICD were randomized to treatment with trihexyphenidyl tablets plus placebo injection or placebo tablets plus BTA injections. Tablets were administered daily according to a fixed schedule. Dysport or saline was injected under EMG guidance at study entry and again after 8 weeks. Patients were assessed for efficacy at baseline and after 12 weeks by different clinical rating scales.\n Sixty-four patients completed the study, 32 in each group. Mean dose of BTA was 292 mouse units (first session) and 262 mouse units (second session). Mean dose of trihexyphenidyl was 16.25 mg. The changes on the Disability section of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-Disability) (primary outcome), Tsui Scale, and the General Health Perception Subscale were significantly in favor of BTA. More patients treated with BTA had an improvement of at least three points on the TWSTRS-Disability (14 versus 6) and on the Tsui Scale (23 versus 12). Adverse effects were significantly less frequent in the BTA group.\n BTA is significantly more effective in the treatment of ICD, with less adverse effects." ]

[ "9065962", "15162364", "14692723", "12131602", "1930344", "2029982", "14706720", "11605083" ]

[ "Kava-kava extract WS 1490 versus placebo in anxiety disorders--a randomized placebo-controlled 25-week outpatient trial.", "Kava treatment in patients with anxiety.", "Treatment of anxiety, tension and restlessness states with Kava special extract WS 1490 in general practice: a randomized placebo-controlled double-blind multicenter trial.", "A placebo-controlled study of Kava kava in generalized anxiety disorder.", "[Effect of a special kava extract in patients with anxiety-, tension-, and excitation states of non-psychotic genesis. Double blind study with placebos over 4 weeks].", "[Psychosomatic dysfunctions in the female climacteric. Clinical effectiveness and tolerance of Kava Extract WS 1490].", "Clinical efficacy of kava extract WS 1490 in sleep disturbances associated with anxiety disorders. Results of a multicenter, randomized, placebo-controlled, double-blind clinical trial.", "Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazepines." ]

[ "101 outpatients suffering from anxiety of non-psychotic origin (DSM-III-R criteria: agoraphobia, specific phobia, generalized anxiety disorder, and adjustment disorder with anxiety) were included in a 25-week multicenter randomized placebo-controlled double-blind trial with WS 1490, a special extract of kava-kava. In the main outcome criterion, the Hamilton Anxiety Scale (HAMA), there was a significant superiority of the test drug starting from week 8 on. WS 1490 was also found to be superior with respect to the secondary outcome variables. HAMA subscores somatic and psychic anxiety, Clinical Global Impression, Self-Report Symptom Inventory-90 Items revised, and Adjective Mood Scale. Adverse events were rare and distributed evenly in both groups. These results support WS 1490 as a treatment alternative to tricyclic antidepressants and benzodiazepines in anxiety disorders, with proven long-term efficacy and none of the tolerance problems associated with tricyclics and benzodiazepines.", "In several clinical trials, mainly conducted with a dose of 300 mg kava extract per day, kava has been employed successfully for the treatment of anxiety disorders. The goal of the placebo-controlled double-blind outpatient trial was to obtain more information on the dosage range and efficacy of a kava special extract WS 1490 in patients with non-psychotic anxiety. 50 patients were treated with a daily dose of 3 x 50 mg WS 1490 during a 4-week treatment period followed by a 2-week safety observation phase. In the active treatment group, the total score of the Hamilton anxiety scale (primary efficacy variable), showed a therapeutically relevant reduction in anxiety versus placebo (more than 4 points). In the secondary variables studied, HAMA 'somatic and psychic anxiety' subscales, the Erlangen anxiety, tension and aggression scale (EAAS), the brief personality structure scale (KEPS), the adjective checklist (EWL 60-S) and clinical global impressions scale (CGI), a trend in favour of the active treatment was detectable. WS 1490 was well tolerated and showed a safety profile with no drug-related adverse events or post-study withdrawal symptoms. It can be concluded that the applied 150 mg WS 1490 per day is an effective and safe treatment of non-psychotic anxiety syndromes in the described population.\n Copyright 2004 John Wiley & Sons, Ltd.", "The efficacy and tolerability of 150 mg/d Kava special extract WS 1490 were investigated in a randomized, placebo-controlled, double-blind multicenter study in patients suffering from neurotic anxiety (DSM-III-R diagnoses 300.02, 300.22, 300.23, 300.29, or 309.24). 141 adult, male and female out-patients received 3 x 1 capsule of 50 mg/d WS 1490 or placebo for four weeks, followed by two weeks of observation without study-specific treatment. During randomized treatment the total score of the Anxiety Status Inventory (ASI) observer rating scale showed more pronounced decreases in the WS 1490 group than in the placebo group. Although a treatment group comparison of the post-treatment ASI scores was not significant (p > 0.05), an exploratory analysis of variance across the differences between treatment end and baseline, with center as a second factor, showed superiority of the herbal extract over placebo (p < 0.01, two-sided). 73% of the patients treated with WS 1490 exhibited ASI score decreases > 5 points versus baseline, compared to 56% for placebo. Significant advantages for WS 1490 were also evident in a structured well-being self-rating scale (Bf-S) and the Clinical Global Impressions (CGI), while the Erlangen Anxiety, Tension and Aggression Scale (EAAS) and the Brief Test of Personality Structure (KEPS) showed only minor treatment group differences. Although the results show consistent advantages for WS 1490 over placebo in several psychiatric scales and indicate significant improvements in the patients' general well-being, the differences versus placebo were not as large as in previous trials which employed 300 mg/d of the same extract. WS 1490 was well tolerated, with no influence on liver function tests and only one trivial adverse event (tiredness) attributable to the study drug.", "We assessed the efficacy and safety of a botanical anxiolytic, Kava kava (Piper methysticum), in treating generalized anxiety disorder (GAD). Thirty-seven adults with DSM-IV GAD were randomly assigned to 4 weeks of double-blind treatment with kava or a matching placebo. Weekly efficacy assessments [Hamilton Anxiety Scale, Hospital Anxiety and Depression Scale (HADS), Self Assessment of Resilience and Anxiety (SARA)] and safety evaluations were conducted. Improvement was observed with both treatments but no differences were found in the principal analysis. Post-hoc analyses revealed significant differences based on baseline anxiety severity, whereby kava was superior on the SARA in low anxiety and placebo was superior on the HADS and SARA in high anxiety. Both treatments were well tolerated. Although kava was not superior to placebo, it would be premature to rule it out as efficacious in GAD.", "Clinical Efficacy of a Kava Extract in Patients with Anxiety Syndrome/Double-blind placebo controlled study over 4 weeks. In a randomized, placebo-controlled double-blind study two groups each containing 29 patients with anxiety syndrome not caused by psychotic disorders were treated for a period of 4 weeks with kava extract WS 1490 (Laitan) 3 x 100 mg/day or a placebo preparation. Therapeutic efficacy was assessed by the Hamilton-Anxiety-Scale (main target variable), the Adjectives-List and the Clinical-Global-Impression-Scale (secondary target variables) after 1, 2 and 4 weeks of treatment. The HAMA overall score of anxiety symptomatology revealed a significant reduction in the drug receiving group already after one week of treatment. This difference between the two groups of patients increased in the course of the study. The results of the secondary target variables were in agreement with the HAMA-score and demonstrate the efficacy of WS 1490 in patients with anxiety disorders. No adverse experiences caused by the medication were noted during the 4 week administration of WS 1490.", "Within the framework of a randomized, placebo-controlled double-blind study, two groups each containing 20 patients with climacteric-related symptomatology were treated for a period of 8 weeks with kava WS 1490 extract 3 X 100 mg/day or a placebo preparation. The target variable - the HAMA overall score of anxiety symptomatology - revealed a significant difference in the drug-receiving group vis-à-vis the placebo group already after only 1 week of treatment. The course of such further parameters as depressive mood (DSI), subjective well-being (patient diary), severity of the disease (CGI), and the climacteric symptomatology (Kuppermann Index and Schneider scale) over the overall period of treatment demonstrate a high level of efficacy of kava extract WS 1490 in neurovegetative and psychosomatic dysfunctions in the climacteric, associated with very good tolerance of the preparation.", "The aim of the present trial was to investigate the efficacy and safety of kava special extract WS 1490 in patients with sleep disturbances associated with anxiety, tension and restlessness states of non-psychotic origin.\n In a multicenter, randomized, double-blind clinical study, 61 patients received daily doses of 200 mg WS 1490 or placebo over a period of 4 weeks. Efficacy was measured by the sleep questionnaire SF-B, the Hamilton Anxiety Scale (HAMA), the Bf-S self-rating scale of well-being and the Clinical Global Impressions (CGI) scale.\n The confirmatory analysis of the two primary efficacy variables, the differences of sleep questionnaire SF-B sub-scores 'Quality of sleep' and 'Recuperative effect after sleep' after 4 weeks of double-blind treatment compared to baseline, demonstrated statistically significant group differences in favor of kava extract WS 1490 (P=0.007 and P=0.018, respectively). Superior effects of kava extract were also present in the HAMA psychic anxiety sub-score (P=0.002). More pronounced effects with respect to the self-rating of well-being and the global clinical evaluation also indicated superior therapeutic efficacy of kava extract. Safety and tolerability were good, with no drug-related adverse events or changes in clinical or laboratory parameters.\n We conclude that sleep disturbances associated with non-psychotic anxiety disorders can be effectively and safely treated with kava extract WS 1490.", "A 5-week randomized, placebo-controlled, double-blind study was carried out to investigate the efficacy of kava-kava special extract WS1490 in non-psychotic nervous anxiety, tension and restlessness states. During the first treatment week, the study dose drug was increased from 50 mg to 300 mg per day and pretreatment with benzodiazepines was tapered off over 2 weeks. These dosage adjustments were followed by 3 weeks of monotherapy with WS1490 or placebo. Outcome measures were the differences between baseline and end of treatment on the Hamilton Anxiety Scale (HAMA) and on a subjective well-being scale (Bf-S), as well as the benzodiazepine withdrawal symptoms. Changes in the Erlanger Anxiety, Tension and Aggression Scale (EAAS) and Clinical Global Impressions (CGI) were analyzed as secondary measures. Treatment safety was checked by interviews, adverse event reports and laboratory investigations. Forty patients (2x20) were included into the study. WS1490 was superior to placebo regarding the HAMA (P=0.01) and Bf-S (P=0.002) total scores and all secondary efficacy measures. The tolerance of WS1490 was not inferior to placebo. The study confirms the anxiolytic efficacy and good tolerance of WS1490 and shows that a further symptom reduction is possible after a change-over from benzodiazepine treatment." ]

[ "12716250", "11951146" ]

[ "Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial.", "Treatment of Tourette's syndrome with Delta 9-tetrahydrocannabinol (THC): a randomized crossover trial." ]

[ "Preliminary studies suggested that delta-9-tetrahydrocannabinol (THC), the major psychoactive ingredient of Cannabis sativa L., might be effective in the treatment of Tourette syndrome (TS). This study was performed to investigate for the first time under controlled conditions, over a longer-term treatment period, whether THC is effective and safe in reducing tics in TS.\n In this randomized, double-blind, placebo-controlled study, 24 patients with TS, according to DSM-III-R criteria, were treated over a 6-week period with up to 10 mg/day of THC. Tics were rated at 6 visits (visit 1, baseline; visits 2-4, during treatment period; visits 5-6, after withdrawal of medication) using the Tourette Syndrome Clinical Global Impressions scale (TS-CGI), the Shapiro Tourette-Syndrome Severity Scale (STSSS), the Yale Global Tic Severity Scale (YGTSS), the self-rated Tourette Syndrome Symptom List (TSSL), and a videotape-based rating scale.\n Seven patients dropped out of the study or had to be excluded, but only 1 due to side effects. Using the TS-CGI, STSSS, YGTSS, and video rating scale, we found a significant difference (p <.05) or a trend toward a significant difference (p <.10) between THC and placebo groups at visits 2, 3, and/or 4. Using the TSSL at 10 treatment days (between days 16 and 41) there was a significant difference (p <.05) between both groups. ANOVA as well demonstrated a significant difference (p =.037). No serious adverse effects occurred.\n Our results provide more evidence that THC is effective and safe in the treatment of tics. It, therefore, can be hypothesized that the central cannabinoid receptor system might play a role in TS pathology.", "Anecdotal reports in Tourette's syndrome (TS) have suggested that marijuana (cannabis sativa) and delta-9-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive ingredient of marijuana, reduce tics and associated behavioral disorders. We performed a randomized double-blind placebo-controlled crossover single-dose trial of Delta(9)-THC (5.0, 7.5 or 10.0 mg) in 12 adult TS patients. Tic severity was assessed using a self-rating scale (Tourette's syndrome Symptom List, TSSL) and examiner ratings (Shapiro Tourette's syndrome Severity Scale, Yale Global Tic Severity Scale, Tourette's syndrome Global Scale). Using the TSSL, patients also rated the severity of associated behavioral disorders. Clinical changes were correlated to maximum plasma levels of THC and its metabolites 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) and 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). Using the TSSL, there was a significant improvement of tics (p=0.015) and obsessive-compulsive behavior (OCB) (p = 0.041) after treatment with Delta(9)-THC compared to placebo. Examiner ratings demonstrated a significant difference for the subscore \"complex motor tics\" (p = 0.015) and a trend towards a significant improvement for the subscores \"motor tics\" (p = 0.065), \"simple motor tics\" (p = 0.093), and \"vocal tics\" (p = 0.093). No serious adverse reactions occurred. Five patients experienced mild, transient side effects. There was a significant correlation between tic improvement and maximum 11-OH-THC plasma concentration. Results obtained from this pilot study suggest that a single-dose treatment with Delta(9)-THC is effective and safe in treating tics and OCB in TS. It can be speculated that clinical effects may be caused by 11-OH-THC. A more long-term study is required to confirm these results." ]

[ "9973149" ]

[ "A randomized, double-blind, placebo-controlled study of moclobemide and amitriptyline in the treatment of fibromyalgia in females without psychiatric disorder." ]

[ "To study the usefulness of moclobemide and amitriptyline in the treatment of fibromyalgia (FM) in females without psychiatric disorder.\n In the present four centre, 12 week study, 130 female FM patients not suffering from psychiatric disorders were randomized to receive amitriptyline (AMI; 25 37.5 mg), moclobemide (MOCLO; 450-600 mg) or identical placebo.\n Seventy-four, 54 and 49 per cent of patients on AMI, MOCLO and placebo, respectively, were judged as responders. The patients on AMI also managed best regarding the respective improvements during the trial in general health, pain, sleep quality and quantity, and fatigue on visual analogue scales (VAS), the areas of the Nottingham Health Profile (NHP), as well as in the three Sheehan's functional disability scales. In the within-group comparisons, MOCLO also improved pain assessed both on VAS and on the NHP pain dimension, but the improvement was invalidated by the poor success of the drug with regard to sleep. The tolerabilities of all three drugs were comparable.\n The study indicates that MOCLO may not be helpful in FM patients free from clinically meaningful psychiatric problems." ]

[ "8132436", "371339", "16643581", "11014390", "7137561", "4560963", "7323625", "6140128", "2673161", "1771090" ]

[ "Sulpiride and paroxetine in the treatment of chronic tension-type headache. An explanatory double-blind trial.", "Analgesic treatment with levomepromazine in acute myocardial infarction. A randomized clinical trial.", "Haloperidol in the acute treatment of migraine: a randomized, double-blind, placebo-controlled study.", "Amitriptyline and fluphenazine in the treatment of postherpetic neuralgia.", "Haloperidol as an adjunct analgesic in the management of postoperative pain.", "Relief of mixed anxiety-depression in terminal cancer patients. Effect of thioridazine.", "[Tiapride in the treatment of chronic headache (author's transl)].", "Tiapride versus glafenine: a double-blind comparative study in the management of acute rheumatic pain.", "Pimozide therapy for trigeminal neuralgia.", "Does addition of low-dose flupentixol enhance the analgetic effects of low-dose amitriptyline in somatoform pain disorder?" ]

[ "Drugs influencing monoaminergic pathways are of potential use in the treatment of pain. A serotonin re-uptake inhibitor, paroxetine (20-30 mg daily), and a dopamine antagonist, sulpiride (200-400 mg daily) were compared in a randomized, double-blind, response-conditional cross-over pilot study in 50 non-depressed patients with chronic tension-type headache. Headache was scored daily on a 5-point verbal scale during 4-weeks baseline and during 8 weeks of treatment for each drug. A 5-point 'Global' assessment was obtained for each drug. In both treatment groups headache score decreased compared to baseline. Group comparison of 24 patients first treated with paroxetine and 24 patients first treated with sulpiride showed a non-significant trend in favor of sulpiride by 'Global' evaluation and by evaluation of the available diary records (18 paroxetine-treated and 19 sulpiride-treated). Cross-over analysis of 'Global' records from 20 patients treated with paroxetine followed by sulpiride and 17 patients treated in the reverse order showed better relief from sulpiride compared to paroxetine in patients having tested both drugs (P = .03). A similar difference was reflected in available headache scores (13 and 10 patients respectively; P = .03). Predominant side effects were sedation and depression, for paroxetine also nausea and head pain. None of the drugs improved headache more than one score-point on average. A placebo controlled trial of sulpiride may be warranted.", "The efficacy of a non-narcotic analgesic is evaluated in a double-blind randomized series of patients with acute myocardial infarction (AMI). Levomepromazine or pethidine were given in 328 consecutive cases to 316 patients within 24 hours after the onset of symptoms. Levomepromazine, 12.5 mg, appeared as effective as pethidine, 50 mg, in the alleviation of pain, though the initial dose had to be higher. Nausea and vomiting were half as frequent in the levomepromazine group as in the pethidine group (p less than 0.001). The incidences of arrhythmias, lung oedema, hypotension and thromboembolic complications did not differ between the groups. The mortality rate in the first 4 weeks was 22% in the levomepromazine group and 37% in the pethidine group (p less than 0.005), and after one year 39 and 50% (p less than 0.05), respectively. It is concluded that levomepromazine is better tolerated than pethidine in AMI. This suggests that the present management of pain in AMI should be reconsidered.", "To assess the efficacy and safety of i.v. haloperidol in treatment of acute migraine headache in a double-blind, randomized, placebo-controlled study design.\n Neuroleptics are mainly used as antiemetics in acute migraine. In a previous open trial haloperidol was effective in relieving migraine pain.\n Patients were randomized into 2 groups receiving intravenously either 5 mg haloperidol in 500 mL of normal saline or 500 mL of normal saline alone. Pain was assessed by visual analogue scale (VAS) before and 1 to 3 hours after the infusion. If the patient felt no relief in pain intensity 1 to 3 hours after the infusion and had received placebo, he/she then received haloperidol infusion as an open trial. The open trial also included 7 patients who refused from the placebo-controlled trial. About 1 month after the infusion the patients were contacted by telephone and interviewed about the side effects of the treatment.\n Forty patients were enrolled into the double-blind, placebo-controlled study. Before the infusion the VAS values were 7.7 in the haloperidol and 7.2 in the placebo group. After the infusion the VAS values were 2.2 in the haloperidol and 6.3 in the placebo group (P < .0001). Significant pain relief was achieved in 80% of the patients treated with haloperidol, whereas only 3 patients (15%) responded to placebo (P < .0001). Seventeen patients treated with placebo without response together with 7 patients who refused from the placebo-controlled study participated in the open trial. In this group VAS declined from 6.7 to 2.4 and 79% of these patients felt significant pain relief. The most common side effects caused by haloperidol were sedation and akathisia, the latter being more troublesome. These effects were very common in patients participating in the double-blind (80%) and open (88%) trials. Sixteen percent of the patients considered the side effects intolerable and would not like the migraine attacks to be treated with haloperidol in the future. Three patients (7%) returned to the emergency ward because of a relapse.\n This study shows that i.v. haloperidol is very effective in relieving migraine-associated pain. Because the majority of the patients had taken other medication without response, haloperidol appears to be an effective rescue medication even when other types of treatment have failed. Relapses are rare, but side effects are common, limiting the use of haloperidol in some patients.", "Postherpetic neuralgia (PHN) is a vexing problem occurring in 10 to 20 percent of people with from herpes zoster (shingles). Anecdotal reports show that fluphenazine enhances the effects of amitriptyline for the treatment of PHN. The aim of this study was to determine, in a controlled manner, whether this was the case.\n In a double-blind placebo-controlled study, 49 patients with PHN were randomly assigned to four treatment groups: Group 1, amitriptyline; Group 2, amitriptyline and fluphenazine; Group 3, fluphenazine; Group 4, a placebo. An active placebo was used to mimic the anticholinergic side effects of dry mouth. The study lasted 8 weeks, with weekly progress evaluations with use of visual analog scales (VAS), the McGill Pain Questionnaire (MPQ), and a side-effects scale.\n A statistically significant decrease was seen in pain in Groups 1 and 2, and no significant changes were seen in Groups 3 and 4. There was no significant difference when fluphenazine was added to amitriptyline.\n These data support the effectiveness of amitriptyline in treatment of PHN, but do not support the addition of fluphenazine.", "nan", "nan", "The therapeutic efficacy of tiapride in chronic headache (300 mg/day orally during 30 days) was studied in a doubleblind trial in a group of 50 patients, 40 of them with so-called \"mixed headache\", and 10 with classical migraine. The results were subjected to statistical analysis. 65% of treated patients had clinical benefit in the intensity and frequency of headaches. The mode of action of this drug is discussed, together with the involvement of several monoaminergic systems in the genesis of headache. The action of tiapride appears to be indirectly dopaminomimetic as it operates by a blockade of dopaminergic inhibitors receptors.", "A double-blind study was carried out in 42 patients suffering from acute rheumatic pain to compare the analgesic effectiveness and tolerance of tiapride with that of glafenine, a widely used analgesic in Europe. Patients were allocated at random to receive either 100 mg tiapride or 200 mg glafenine 3-times daily over a period of 14 days. Pain intensity was rated daily by the patients using a visual analogue scale and an overall assessment of response to treatment was made by both patients and physician at the end of the study. The results showed that, whilst both treatments resulted in a marked reduction in mean pain scores, pain disappeared completely in 16 (76%) of the 21 patients treated with tiapride compared with 9 (43%) of the 21 receiving glafenine. There was also a significant difference in favour of tiapride in the physician's overall assessment of response which was considered as excellent in 71% of the patients on tiapride compared with 31% receiving glafenine. Both treatments were well tolerated and few side-effects were reported. Drowsiness occurred in 6 patients on tiapride but this was only mild in 5 and moderate in the other patient.", "Pimozide was compared with carbamazepine in a double-blind crossover trial in 48 patients with trigeminal neuralgia who were refractory to medical therapy. Pimozide treatment produced greater reduction in trigeminal neuralgia symptoms than carbamazepine treatment. All of the pimozide-treated patients improved, while only 56% of carbamazepine-treated patients were relieved of their pain. Although both drugs provoked some adverse effects, it was not necessary to interrupt the trial in any case. After this 24-week trial, all patients began receiving pimozide and were followed up according to an open-label study design. In all cases, the pimozide dosage was progressively reduced until the minimal effective dose was reached. Central and peripheral mechanisms that may underlie pimozide-induced improvement are discussed.", "In a double-blind, crossover study, the effects of 75 mg amitriptyline alone during 5 weeks on pain intensity were compared with the effects of a combination of 75 mg amitriptyline and 3 mg flupentixol during 5 weeks in 34 patients with somatoform pain disorder. Both treatments resulted in a statistically significant reduction in pain. However, pain reduction in the combined treatment did not differ from that in the treatment with amitriptyline as a single drug. Neither tardive dyskinesias nor other serious side effects were observed. The results do not support the clinical practice of adding low-dose neuroleptics to low-dose antidepressants in the treatment of somatoform pain disorder." ]

[ "5780499", "2093085", "10458472", "5488906", "603481", "9933064", "3429403", "7216401", "10828674" ]

[ "Symptom treatment and symptom substitution in enuresis.", "Enuresis: an analysis of 82 cases.", "Treatment of nocturnal enuresis with an ultrasound bladder volume controlled alarm device.", "Treatment of nocturnal enuresis by conditioning techniques.", "Bladder training and enuresis: a controlled trial.", "Primary nocturnal enuresis: a new approach to conditioning treatment.", "Pharmacological and behavioral management of enuresis.", "Evaluation of various methods in treatment of enuresis.", "Functional bladder capacity as predictor of response to desmopressin and retention control training in monosymptomatic nocturnal enuresis." ]

[ "nan", "Of 400 children over the age of four years, 82 (20.5%) were found to be enuretics. Enuresis was found to be statistically higher (p less than 0.001) in lower social class and between the age group 3 to 5 years. Enuresis was found to be significantly more among boys as compared to girls (p less than 0.001). Various stress factors (e.g. negligence, overprotection, strictness of parents etc) and other associated habit disorders (e.g. fear reactions, nailbiting, temper-tantrums etc) were significantly higher (p less than 0.001) in enuretics as compared to control group. The group who was put on combined drug (imipramine) and psychological treatment showed a better long term response than the patients who were put only on drug or psychological treatment (p less than 0.001).", "Current treatment regimens for nocturnal enuresis are suboptimal. Medications such as desmopressin are efficacious for preventing the enuretic event but they offer little potential for a permanent cure and have side effects. Although the moisture alarm has good potential for a permanent cure, the child is mostly wet during treatment. Furthermore, the moisture alarm requires that the child make the somewhat remote association between the alarm event and a full bladder after the bladder has emptied. In this exploratory study bladder volume alarming, a new approach to treating nocturnal enuresis, was investigated.\n A total of 40 sequential children 6 to 16 years old with nonorganic nocturnal enuresis who had had at least 1 wetting episode weekly for greater than a year were divided into 2 groups. Each child wore a modified PCI 5000 miniature bladder volume measurement instrument during sleep. An alarm sounded when bladder volume reached 80% of the typical daytime voided volume in group 1 and at 80% of the typical enuretic volume in group 2. Group 2 patients also performed daytime bladder retention exercises in regard to instrument measured bladder volume versus a progressing target volume.\n In groups 1 and 2 the mean dryness rate before study initiation versus during the study was 32.9 and 9.3 versus 88.7 and 82.1%, respectively. Nighttime bladder capacity increased 69% in group 1 and 78% in group 2, while the cure rate was 55% (mean treatment period 10.5 months) and 60% (mean treatment period 7.2 months), respectively.\n Bladder volume tracking seems to approach the goals of ideal treatment for nocturnal enuresis in that it prevents the enuretic event, appears to facilitate a permanent cure and is noninvasive.", "nan", "nan", "Conditioning treatment is the most effective therapy for nocturnal enuresis, precluding the use of drugs. An ordinary alarm clock can be used as an enuresis alarm. We sought to assess its clinical utility as a new means of conditioning treatment.\n Using the ordinary home alarm clock, 125 enuretic children were enrolled into two treatment groups. Group I included 70 children who set the alarm so as to get up and void in the toilet at a critical time when the bladder was full and they were still dry. Group II included 55 children who used the alarm to be awakened for voiding after 2 to 3 hours of sleep regardless of whether they were dry or wet. All children were motivated to use the alarm clock continuously for 4 months.\n Initial success was achieved in 54 (77.1%) of 70 group I and 34 (61.8%) of 55 group II children. Three months after treatment was stopped, success was still maintained in 46 (65.7%) and 31 (56.4%) children in groups I and II, respectively, but dropped to 41 (58.6%) and 29 (52.7%), respectively, after 6 months. The relapse rate after 3 and 6 months was 14.8% and 24.1% for group I and 8.8% and 14.7% for group II, respectively.\n The ordinary alarm clock performs as well as currently used enuresis alarms. It is an effective, elective, noncontact alarm that does not wait for bedwetting to initiate a conditioning reflex. It is both reliable and safe.", "nan", "nan", "To evaluate the efficacy of intranasal desmopressin (DDAVP) and retention control training (RCT) for monosymptomatic nocturnal enuresis in childhood and to assess the predictive value of daytime functional bladder capacity for both methods.\n A total of 114 children with monosymptomatic nocturnal enuresis, of whom 99 (86.8%) wetted the bed every night, were treated with 1 of the 2 methods: intranasal DDAVP in 54 and RCT in 60 subjects.\n Twenty-one of 54 patients (38.9%) and 14 of 60 patients (23.3%) in the DDAVP group and the RCT group, respectively, achieved strong improvement (p = 0.061). Forty-five of 54 (90.0%) in the DDAVP and 35 of 60 (58.3%) in the RCT group had a more than 50% decrease in wet nights (p = 0.004). In the DDAVP group, the functional bladder capacities at baseline in responders and nonresponders were 82+/-22% and 56+/-20% of the predicted bladder capacity for their age (p<0.001). In the RCT group, responders and nonresponders did not differ in functional bladder capacity at baseline.\n DDAVP treatment is more effective than RCT in decreasing the number of wet nights in childhood nocturnal enuresis, but not so effective in children with a low functional bladder capacity. Daytime functional bladder capacity is a valuable predictor of response to DDAVP, but not so to RCT." ]

[ "7010763", "19230168" ]

[ "VACURG randomised trial of radical prostatectomy for stages I and II prostatic cancer. Veterans Administration Cooperative Urological Research Group.", "Experiences of randomization: interviews with patients and clinicians in the SPCG-IV trial." ]

[ "nan", "Recruitment of both patients and clinicians to randomized trials is difficult. Low participation carries the risk of terminating studies early and making them invalid owing to insufficient statistical power. This study investigated patients' and clinicians' experiences of randomization with the aim of facilitating trial participation in the future.\n This was a qualitative study using content analysis. Patients offered to participate in a randomized trial and randomizing clinicians were interviewed. Five participants, four non-participants and five randomizing clinicians were interviewed, 2-8 years from randomization.\n Clinicians used strategies in interaction with the patients to facilitate decision making. Patients' attitudes differed and experiences of relatives or friends were often stated as reasons for treatment preferences. Patients described that letting chance decide treatment was a difficult barrier to overcome for randomization. The clinicians used a number of different strategies perceived to make randomization more acceptable to their patients. The clinicians' own motivation for randomizing patients for trials depended on the medical relevance of the study question and the clinicians' major obstacle was to maintain equipoise over time. Regular meetings with the study group helped to maintain equipoise and motivation.\n To establish a good platform for randomization the clinician needs to know about the patient's treatment preferences and the patient's attitude concerning the role of the clinician to facilitate decision making. The strategies used by the clinicians were perceived as helpful and could be tested in an intervention study." ]

[ "8973666" ]

[ "A double-blind, placebo-controlled evaluation of the erectile response to transurethral alprostadil." ]

[ "Previous studies have indicated that the urethra may provide an effective route for administering vasoactive medication for the treatment of erectile dysfunction. We evaluated the safety and efficacy of alprostadil administered intraurethrally at home for the treatment of this disorder.\n This prospective, multicenter, double-blind, placebo-controlled study evaluated the erectile response to randomly assigned doses of transurethral alprostadil at home in 68 men with long-standing (mean 41 months) erectile dysfunction of primarily organic etiology. Patients completing the study each administered a random sequence of four different doses (125, 250, 500, and 1000 micrograms) and placebo over a 2 to 4-week period. Assessments included the couples' ability to have intercourse, patient ratings of erectile response by both categorical and visual analogue scales, penile volume measurements, and overall assessments of comfort and ease of administration.\n Overall, 75.4% (49 of 65) of study patients achieved full enlargement of the penis and 49.2% (32 of 65) achieved an erection judged by the patient to be sufficient for intercourse. In addition, 63.6% (42 of 66) of patients reported intercourse. Efficacy was similar across etiologies. The most common side effect was penile pain, which occurred in association with 9.1% to 18.3% of alprostadil administrations, depending on dose. Mean comfort ratings ranged from 79 to 87, depending on dose, where 0 = severe discomfort and 100 = comfortable; ease of administration scores were above 90 for each dose, where 0 = difficult and 100 = easy. There were no episodes of priapism in this study.\n Short-term treatment with transurethral alprostadil produced erections resulting in sexual intercourse in most patients with chronic erectile dysfunction. This therapy may be a useful treatment option for patients with erectile dysfunction." ]

[ "9457094" ]

[ "Randomised study of influence of two-dimensional versus three-dimensional imaging on performance of laparoscopic cholecystectomy." ]

[ "Several three-dimensional video-endoscopic systems have been introduced to enhance depth perception during minimum-access surgery. However, there is no conclusive evidence of benefit, and these systems are more expensive than conventional two-dimensional systems. We undertook a prospective randomised comparison of two-dimensional and three-dimensional imaging in elective laparoscopic cholecystectomy for symptomatic gallstone disease.\n The operations were done by four specialist registrars as part of their higher surgical training. 60 operations were randomised for execution by either two-dimensional or three-dimensional imaging display (30 by each method). The degree of difficulty of the operation was graded by a consultant surgeon on a standard grading system. The primary endpoints were execution time and the errors made during the procedure. The secondary endpoints were subjective assessment of the image quality and adverse effects on the surgeon.\n There was no difference between the two-dimensional and three-dimensional display groups in median execution time (3160 [IQR 2735-4335 vs 3100 [2379-3710] s; p = 0.2) or error rate (six vs six). Surgeons reported adverse symptoms immediately after the operations with both systems. The scores for visual strain, headache, and facial discomfort were higher with the three-dimensional system.\n With the current technology, three-dimensional systems based on sequential imaging show no advantage over two-dimensional systems in the conduct of laparoscopic cholecystectomy." ]

[ "9524826", "10803938", "10473925", "16517540", "3279774", "1739355", "9007599", "14752869", "12447952", "8608520", "23100925", "11389117", "11260566", "12942573", "19744230", "2403484", "11303851", "8894569", "15370671", "16838234", "16029455", "18203711", "9818751", "16400334", "12005083", "11054442", "20427546", "19484759", "8537265", "8983283", "11412645", "7799016", "9790130", "9682028", "2201252", "10981242", "16517534" ]

[ "Randomized comparison of sulbactam/cefoperazone with imipenem as empirical monotherapy for febrile granulocytopenic patients.", "Meropenem versus ceftazidime as empirical monotherapy for febrile neutropenic cancer patients.", "A comparative study of cefepime versus ceftazidime as empiric therapy of febrile episodes in neutropenic patients.", "Experience with cefepime versus meropenem as empiric monotherapy for neutropenia and fever in pediatric patients with solid tumors.", "Randomized trial of beta-lactam regimens in febrile neutropenic cancer patients.", "A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients.", "Empirical monotherapy with meropenem versus imipenem/cilastatin for febrile episodes in neutropenic patients.", "Cefepime vs. Meropenem as empirical therapy for neutropenic fever in children with lymphoma and solid tumours.", "Cefepime or carbapenem treatment for febrile neutropenia as a single agent is as effective as a combination of 4th-generation cephalosporin + aminoglycosides: comparative study.", "A comparison of aztreonam plus vancomycin and imipenem plus vancomycin as initial therapy for febrile neutropenic cancer patients.", "Cefepime versus ceftazidime as empirical therapy for fever in neutropenic patients with haematological malignancies.", "Meropenem versus ceftazidime as empirical monotherapy in febrile neutropenia of paediatric patients with cancer.", "Randomized comparison of cefepime versus ceftazidime monotherapy for fever and neutropenia in children with solid tumors.", "Treatment of febrile neutropenic patients with cancer who require hospitalization: a prospective randomized study comparing imipenem and cefepime.", "Imipenem-cilastatin versus piperacillin-tazobactam as monotherapy in febrile neutropenia.", "Beta-lactam regimens for the febrile neutropenic patient.", "Comparative study of cefepime versus ceftazidime in the empiric treatment of pediatric cancer patients with fever and neutropenia.", "Imipenem or cefoperazone-sulbactam combined with vancomycin for therapy of presumed or proven infection in neutropenic cancer patients.", "A prospective, randomized study comparing cefepime and imipenem-cilastatin in the empirical treatment of febrile neutropenia in patients treated for haematological malignancies.", "A randomized, open-label, multicenter comparative study of the efficacy and safety of piperacillin-tazobactam and cefepime for the empirical treatment of febrile neutropenic episodes in patients with hematologic malignancies.", "Empirical antimicrobial monotherapy in patients after high-dose chemotherapy and autologous stem cell transplantation: a randomised, multicentre trial.", "Panipenem versus cefepime as empirical monotherapy in adult cancer patients with febrile neutropenia: a prospective randomized trial.", "Cefepime versus imipenem-cilastatin as empirical monotherapy in 400 febrile patients with short duration neutropenia. CEMIC (Study Group of Infectious Diseases in Cancer).", "Piperacillin/tazobactam vs ceftazidime in the treatment of neutropenic fever in patients with acute leukemia or following autologous peripheral blood stem cell transplantation: a prospective randomized trial.", "Cefepime versus ceftazidime as empiric monotherapy for fever and neutropenia in children with cancer.", "Meropenem versus ceftazidime in the treatment of cancer patients with febrile neutropenia: a randomized, double-blind trial.", "Piperacillin-tazobactam versus carbapenem therapy with and without amikacin as empirical treatment of febrile neutropenia in cancer patients: results of an open randomized trial at a university hospital.", "Piperacillin/tazobactam versus cefepime for the empirical treatment of pediatric cancer patients with neutropenia and fever: a randomized and open-label study.", "Equivalent efficacies of meropenem and ceftazidime as empirical monotherapy of febrile neutropenic patients. The Meropenem Study Group of Leuven, London and Nijmegen.", "Randomised comparison of ceftazidime and imipenem as initial monotherapy for febrile episodes in neutropenic cancer patients.", "[Comparative study of piperacillin/tazobactam versus imipenem/cilastatin in febrile neutropenia (1994-1996)].", "Monotherapy for fever and neutropenia in cancer patients: a randomized comparison of ceftazidime versus imipenem.", "Empiric monotherapy for febrile neutropenia--a randomized study comparing meropenem with ceftazidime.", "Piperacillin/tazobactam versus cefepime as initial empirical antimicrobial therapy in febrile neutropenic patients: a prospective randomized pilot study.", "Ceftazidime versus imipenem-cilastatin as initial monotherapy for febrile neutropenic patients.", "Cefepime versus ceftazidime as empiric therapy for fever in neutropenic patients with cancer.", "Monotherapy with piperacillin/tazobactam versus cefepime as empirical therapy for febrile neutropenia in pediatric cancer patients: a randomized comparison." ]

[ "In a prospective, randomized, controlled trial, we compared sulbactam/cefoperazone with imipenem as empirical monotherapy for febrile, granulocytopenic patients; 101 patients received sulbactam/cefoperazone (2 g/4 g every 12 hours) and 102 patients received imipenem (500 mg every 6 hours). Documented infections were present in 40% of patients treated with sulbactam/cefoperazone (40 of 101) and in 39% of patients receiving imipenem (40 of 102). The number of pretherapy gram-positive pathogens (52 isolates) was twice the number of pretherapy gram-negative pathogens (26 isolates). The overall favorable clinical response rates for sulbactam/cefoperazone (91 of 103 patients, or 88%) and imipenem (84 of 104 patients, or 81%) were similar. Both drugs were generally well tolerated. However, diarrhea occurred more often in patients treated with sulbactam/cefoperazone (31 of 101 patients, or 31%, vs. 15 of 102 patients, or 15%; P = .007), while seizures developed only in patients receiving imipenem (0 of 101 patients vs. 3 of 102 patients, or 3%). Superinfections developed in 16% of patients in both study groups but were infrequently caused by beta-lactam-resistant gram-negative bacilli (two cases with sulbactam/cefoperazone therapy and six cases with imipenem). These results support the efficacy and safety of either sulbactam/cefoperazone or imipenem as empirical monotherapy for febrile granulocytopenic patients.", "A total of 101 cancer patients with 121 febrile neutropenia episodes were randomised to receive empirical treatment with i.v. meropenem (1g/8 h) or ceftazidime (2 g/8 h). After 3 days, 89% of patients were on unmodified therapy in the meropenem group, compared with 83% in the ceftazidime group. Of the evaluable episodes (n = 106), the success rate with unmodified empirical therapy until the end of the treatment course was slightly higher with meropenem than with ceftazidime (48% vs 38%, P=0.39). Furthermore, initial success with further infections was observed in 22% of episodes treated with meropenem and in 13% of episodes treated with ceftazidime. Glycopeptides were used as first modification in 28% and 39% of meropenem and ceftazidime recipients, respectively. Both treatments were well tolerated and there were no reports of drug-related nausea/vomiting or seizures. No significant differences in response rate or in tolerability were observed when analysing only the first febrile episodes. In conclusion, meropenem seems to be as efficacious and well tolerated as ceftazidime and may be associated with a lesser requirement for the addition of glycopeptides.", "An open-label, randomized comparative study was conducted to evaluate the efficacy and safety of cefepime (2.0 g q. 8 h) and ceftazidime (2.0 g q. 8 h) in the empiric therapy of febrile neutropenic patients. A total of 45 eligible febrile episodes were randomized (1:1) to be treated with the study regimen. Nineteen febrile episodes treated with cefepime and 22 febrile episodes treated with ceftazidime were evaluable for efficacy. The two groups were comparable in terms of age, sex, height, weight, underlying neoplasm, number of pretherapy neutrophil, duration of neutropenia and types of infections. The overall therapeutic success rate of the cefepime group (53%) was comparable to the ceftazidime group (50%). It did not differ significantly (95% confidence interval: -0.28 to 0. 34, p = 0.85). Eighty-eight percent of pathogens in each group were bacteriologically eradicated. The safety profile was similar in both groups. No patients in either group discontinued the therapy because of adverse events. None (0%) of the cefepime patients and 2 (9%) of the ceftazidime patients died of infection. The results of this study suggest that cefepime is an effective and safe agent in the empiric therapy of febrile episodes in neutropenic patients.", "A prospective, open-label, randomized, comparative study in pediatric cancer patients was conducted to evaluate the efficacy and safety of cefepime and meropenem in the empiric therapy of febrile neutropenic patients. Febrile episodes were classified as microbiologically documented infection, clinical documented infection, or fever of unknown origin. Clinical response to therapy was classified as success or failure. In this period 37 children with solid tumors including lymphoma, 25 males, 12 females, had neutropenia on 65 occasions. Microbiologically documented infections occurred in 21 episodes (32.31%). Frequency of positive bacteria isolated was higher than gram-negative bacteria. There was no infection-related death. There were no statistical differences between the cefepime and meropenem groups for duration of fever or neutropenia, response rate, and necessity for modification. Cefepime appears to be as effective and safe as meropenem for empiric treatment of febrile episodes in neutropenic pediatric cancer patients.", "A three-arm prospective randomized trial was designed to compare the efficacies of piperacillin plus vancomycin, ceftazidime plus vancomycin, or all three drugs as initial therapy for fever in neutropenic cancer patients. The objectives were to determine whether a broad-spectrum penicillin was as effective as a broad-spectrum cephalosporin and whether two beta-lactam antibiotics were more effective than one. Four hundred and seventy of the 519 febrile episodes entered in the study could be evaluated for response. Ceftazidime plus vancomycin was significantly more effective than piperacillin plus vancomycin, considering all febrile episodes (79 percent versus 61 percent, p = 0.001), documented infections (79 percent versus 57 percent, p = 0.004), gram-negative infections (88 percent versus 47 percent, p = 0.001), and bacteremias (81 percent versus 51 percent, p = 0.01). The addition of piperacillin to ceftazidime (piperacillin plus ceftazidime and vancomycin versus ceftazidime plus vancomycin) did not improve the response rate and was associated with a significantly higher incidence of skin rash. Vancomycin plus ceftazidime provides adequate antibiotic coverage for initial treatment of fever in neutropenic patients. This combination was equally effective, less expensive, and less toxic than the double beta-lactam combination used in this study.", "Neutropenic patients with cancer are traditionally treated with empiric antibiotic combinations when they become febrile. The availability of broad-spectrum antibiotics such as ceftazidime and imipenem has made it possible to initiate therapy with a single agent (monotherapy). The objectives of this trial were to compare ceftazidime and imipenem as single agents for the therapy of febrile episodes in neutropenic patients and to ascertain whether the addition of an aminoglycoside (amikacin) to either of these agents would provide an advantage.\n A prospective clinical trial was conducted in which eligible neutropenic patients with cancer were randomized to one of four treatment arms: ceftazidime alone; imipenem alone; ceftazidime plus amikacin; and imipenem plus amikacin. Efficacy analysis was done for 750 assessable episodes. A multivariate logistic-regression analysis was also performed to examine the unique contribution of various prognostic factors.\n The overall response rates were 76% with imipenem plus amikacin, 72% with imipenem, 71% with ceftazidime plus amikacin, and 59% with ceftazidime alone. Single-organism gram-positive infections occurred in 101 of 750 episodes. Without a change in antibiotics, the response rates were 50% with imipenem, 40% with imipenem plus amikacin, 39% with ceftazidime plus amikacin, and 38% with ceftazidime. Most responded to vancomycin or other antibiotics, and the mortality associated with gram-positive infections was only 5%. Regardless of the antibiotic regimen, the majority of uncomplicated gram-negative infections responded to therapy and the majority of complicated gram-negative infections failed to respond. Multivariate logistic-regression analysis showed that recovery of the neutrophil count was the most favorable prognostic factor in a patient's response to infection, whereas the presence of gram-positive infection, acute leukemia, pulmonary or enteric infection, and therapy with ceftazidime were unfavorable factors.\n Single-agent therapy with imipenem is as effective as more conventional combination antibiotic therapy for the empirical treatment of febrile episodes in neutropenic patients with cancer.", "In a nonblind, randomised, parallel-group study, initial empirical monotherapy with meropenem 1 g intravenously every 8 h was compared to an identical dosage of imipenem/cilastatin for the treatment of 66 febrile episodes in 61 adult neutropenic patients. 25/31 episodes treated with meropenem and 24/30 imipenem/cilastatin-treated episodes were still receiving unmodified therapy at 72 h (primary endpoint); this difference was not statistically significant. By the end of the treatment courses, 18/31 meropenem-treated episodes had responded clinically (cured or improved) compared with 18/30 episodes treated with imipenem/cilastatin. Another ten episodes initially treated with meropenem and six episodes treated with imipenem/cilastatia were cured after an additional antimicrobial agent had been administered (cured with modification). Satisfactory bacteriological responses (eradication plus presumed eradication) at the end of unmodified therapy was 9/11 in the meropenem group and 14/16 in the comparator group. Both regimes were well tolerated; however, there were more reports of nausea and/or vomiting in the impenem/cilastatin group (7/33 vs. 2/33 in the meropenem group). The carbapenems meropenem and imipenem/cilastatin appear to be suitable agents for empirical monotherapy of febrile episodes in neutropenic patients. Meropenem may be better tolerated than imipenem/cilastatin, allowing optimal dosing in this patient population.", "nan", "1998, a consensus meeting was held in Miyazaki, Japan, to develop an approach to management of febrile neutropenia (FN). The K-HOT study group decided to examine whether this proposal was applicable to clinical practice in a multicenter study. Patients who developed fever with neutrophil counts <1,000/microL were randomized to receive either a single antibiotic, cefepime or one of the carbapenems, or a combination of cefepime and an aminoglycoside. Patients who became afebrile within the first 3 days were continued on the same treatment. Patients who remained febrile were switched to a combination regimen if they were randomized to receive a single agent, and patients on combination medication were changed from cefepime to another cephalosporin. A total of 165 patients were entered into the trial. One hundred fifty-three patients were evaluable for response. The average age was 52 years, and 70% of the patients had acute leukemia. Severe neutropenia, defined as <100/microL at the time of FN, was seen in 62% of the patients on entry and during the course of treatment 71% of patients experienced neutrophil counts of <100/microL. Microbiologically documented infection was seen in 6.5% for monotherapy, and 10.5% for a combination treatment, and fever of unknown origin occurred in 75.3% and 59.2% of the patients in each regimen, respectively. Excellent to good response was seen in two-thirds of the patients in all treatment groups. Adverse events were minimal, and three early deaths were observed at days 9, 16, and 16 among patients treated with a single antibiotic and three in the combination regimen group at days 14, 15, and 20. These results indicate that cefepime or a carbapenem alone is as effective as a combination of cefepime and an aminoglycoside for treating FN.\n Copyright 2002 Wiley-Liss, Inc.", "The improved efficacy of imipenem over other beta-lactam antibiotics in the treatment of febrile neutropenic patients has been attributed to its broad spectrum of activity.\n A prospective, randomized, clinical trial was performed comparing vancomycin 1 g every 12 hours plus imipenem/cilassatin 500 mg every 6 hours and the same dose of vancomycin plus aztreonam 2 g every 6 hours for empiric treatment of febrile episodes in neutropenic patients with cancer.\n The imipenem regimen cured 76% of the 148 evaluable episodes compared with a 67% cure rate for the 152 episodes treated with the aztreonam regimen (p = 0.1). Most of the polymicrobial infections (77% or 10/13) treated with the imipenem responded, whereas only 38% (5/13) of these infections responded to the aztreonam regimen. Although the cost of the imipenem regimen was less than the cost of the aztreonam regimen, it was associated significantly more with skin rashes (12/194 vs 3/189, p = 0.02). In a multivariate analysis, a poor outcome was independently associated in both instances with the persistence of neutropenia and the presence of pneumonia (p < 0.001).\n Overall, in a multifactorial analysis that included efficacy, toxicity, and cost, the imipenem and aztreonam regimens were comparable.", "An open randomized comparative study was conducted to evaluate the efficacy of Cefepime (2 gm iv. 8 hr.) vs. ceftazidime (2 gm iv. every 8 hr.) in empirical therapy of febrile neutropenic patients. A total of 40 eligible febrile episodes were randomized to be treated with study regimen. Twenty febrile episodes were treated with cefepime and 20 were treated with ceftazidime. The two groups were comparable in terms of age, sex, height, underlying neoplasm, number of pretherapy neutrophils, duration of neutropenia. The overall therapeutic success rate of cetepime group (60%) was comparable to that of ceftazidime group (55%). The results of this study suggest that cefepime is an effective and safe agent in empirical therapy of febrile episode in neutropenic patient and its efficacy is comparable with that of ceftazidime.", "This trial assessed the efficacy and safety of meropenem versus ceftazidime as empirical monotherapy for febrile neutropenia in paediatric cancer patients. In a prospective randomized study, 172 evaluable febrile episodes in the meropenem arm and 170 episodes in the ceftazidime arm were analysed for the clinical and microbiological response dependent on the kind of infection. About half the episodes were classified as fever of unknown origin (FUO) and the remainder as microbiologically or clinically documented infections. The most frequently documented infections in both arms were bacteraemias (22.1 versus 26.5%), predominantly caused by Gram-positive organisms (57.9 versus 71.1%). The success rate of the initial monotherapy differed significantly between the two arms and was 55.8% in the meropenem and 40.0% in the ceftazidime arm (P = 0.003). In addition, a significantly longer duration of fever and of antimicrobial therapy was observed in the ceftazidime arm than in the meropenem arm (median 5 versus 4 days, P = 0.022, and 7 versus 6 days, P = 0.009, respectively). With respect to the kind of infection, differences between the two arms were significant only in episodes classified as FUO but not in documented infections. In both arms, side effects were minimal. Despite the greater response rate for meropenem in FUO, the fact that ceftazidime has been proven to be as effective as meropenem in documented infections in the present study suggests that both drugs are useful as empirical monotherapy in febrile paediatric cancer patients.", "With the availability of new broad-spectrum antibiotics, initial therapy with a single agent has become an alternative to classic combinations, especially beta-lactam antibiotics plus aminoglycosides, in the management of febrile neutropenic cancer patients.\n Since January 1994, monotherapy has been used for empiric initial treatment at our center. The aim of this prospective randomized study is to compare the efficacy of cefepime (CFP), a new fourth-generation cephalosporin, and ceftazidime (CFZ) as empirical monotherapy of febrile neutropenic patients with solid tumors. From January 1998 to November 1998, 63 episodes of fever and neutropenia occurring in 33 children with solid tumors including lymphomas, were randomized to receive treatment with either CFP or CFZ. The patients were analyzed for leukocyte count and absolute neutrophil count (ANC) at entry, days in fever, neutropenia and hospitalization, and side effects of drugs. Success with or without modifications of the initial antibiotic was defined as survival through neutropenia; failure was death due to infection.\n In our study group, with a median age of 7 [(1/12)-14] years, CFP was administered in 32, and CFZ in 31 episodes. An infection was documented microbiologically in eight episodes (25%) in the CFP arm and in nine episodes (29%) in the CFZ arm. The success rate with initial empiric monotherapy was 62.5% in the CFP arm and 61.3% in the CFZ arm respectively (P > 0.05). The total success rate (success with or without modification) was 100% in both arms. No major adverse effects were observed in either groups.\n CFP is as effective and safe as CFZ for the empirical treatment of febrile episodes in neutropenic patients with solid tumors.\n Copyright 2001 Wiley-Liss, Inc.", "The objective of the current study was to compare the efficacy and safety of imipenem and cefepime in the treatment of adult patients with cancer who had fever and neutropenia requiring hospitalization according to Infectious Disease Society of America criteria.\n In the current prospective randomized clinical trial at a university-affiliated tertiary cancer center, adult patients with cancer who had fever (> or = 38.3 degrees C or > or = 38.0 degrees C for > 2 hours) and neutropenia (< or = 500/mm(3) or < 1000/mm(3) but declining) requiring hospitalization were randomized to receive either cefepime or imipenem. Vancomycin or amikacin was added on suspicion of gram-positive or gram-negative bacterial infection, respectively.\n Patients who received an imipenem regimen or a cefepime regimen were comparable in terms of age, gender, underlying malignancy, prior transplantation, degree and trend of neutropenia, and presence of central venous catheters (P > or = 0.3). An intent-to-treat analysis showed a 68% response rate to the imipenem regimen, compared with a 75% response rate to the cefepime regimen (P = 0.2). The rates of antibiotic-related adverse events and superinfections also were comparable (P = 0.6). There was no difference in response among patients who received imipenem or cefepime alone compared with patients who also received vancomycin or amikacin (P = 1.0). Leukemia was the only independent risk factor associated with a poor outcome (odds ratio, 4.6; 95% confidence interval, 1.9-10.7; P < 0.0001).\n Imipenem and cefepime had similar efficacy and safety profiles in the treatment of adult cancer patients with fever and neutropenia who required hospitalization. The addition of either vancomycin or amikacin may not be necessary.\n Copyright 2003 American Cancer Society.", "In view of the recent trend toward monotherapy in the treatment of febrile neutropenia, we evaluated the clinical efficacy and safety of imipenem-cilastatin versus piperacillin-tazobactam as an empiric therapy for febrile neutropenia in children with malignant diseases.\n Febrile neutropenic patients received either imipenem-cilastatin or piperacillin-tazobactam randomly. Improvement without any changes in the initial antibiotic treatment was defined as \"success\" and improvement with modification of the initial treatment and death was defined as \"failure\".\n Over 12 months, 99 febrile neutropenic episodes were treated with monotherapy in 63 patients with a median age of 5 years. At admission, median absolute neutrophil count was 50/mm(3) and in 67% of episodes, neutrophil count was under 100/mm(3). Median duration of neutropenia was 5 days. In 22% of episodes, neutropenia persisted for more than 10 days. Piperacillin-tazobactam was used in 52 episodes and imipenem-cilastatin was used in 47 episodes. There was no difference between groups in terms of age, sex, primary diseases, neutrophil count or duration of neutropenia. In the whole group, the success rate was 67% and the failure rate was 33%, whereas in the piperacillin-tazobactam group, the rates were 71% and 29%; and in the imipenem-cilastatin group they were 62% and 38%, respectively (P > 0.05). There were no deaths. No major adverse effects were seen in either group.\n Although failure was slightly higher in the imipenem-cilastatin group, this was statistically insignificant. Both of these antibiotics can be used safely for initial empirical monotherapy of febrile neutropenia.", "A total of 535 evaluable febrile episodes in neutropenic patients were randomly assigned to treatment with ticarcillin-clavulanate plus vancomycin (TV), ceftazidime plus vancomycin (CV), or all three antibiotics (TCV). The TCV regimen was significantly more effective than TV, considering all evaluable episodes, documented infections, gram-negative infections, and infections in patients with persistent severe neutropenia (less than 100 neutrophils/mm3). The results with CV were intermediate between TV and TCV. The toxicities were similar with all three regimens and consisted primarily of skin rashes. The TCV regimen is effective for empiric therapy of fever in neutropenic patients and probably should be utilized in preference to CV or TV, although its superiority over CV in this study was inconclusive.", "In view of the recent trend toward monotherapy in the treatment of bacterial infection, we evaluate the clinical efficacy and safety of cefepime vs. ceftazidime for the empiric treatment of febrile episodes in neutropenic pediatric cancer patients.\n In a single site, open label study, 104 neutropenic pediatric cancer patients [96% with absolute neutrophil count (ANC) of <500 neutrophils/mm3] with a median age of 6 years were randomized (1:1) to receive either intravenous cefepime or ceftazidime (50 mg/kg/dose every 8 h; < or = 6 g/day) for empiric treatment of fever (temperature >38.0 degrees C occurring at least twice in 24 h, or single >38.5 degrees C). Febrile episodes were classified as either microbiologically or clinically documented infection or fever of unknown origin. Therapy continued until the ANC was > or = 1,000 neutrophils/mm3 or there was an increasing ANC in low risk patients (maximum duration of treatment, 8 weeks). The primary efficacy endpoints assessed were clinical and microbiologic response to assigned drug therapy. Secondary outcome measures were rate of early discontinuation of study drug and use of concomitant antibiotic therapy to modify initial study drug regimen.\n Of 68 patients who could be evaluated for efficacy, 74% (26 of 35) of cefepime-treated patients and 70% (23 of 33) of ceftazidime-treated patients responded to treatment. The small number of study patients precluded statistical analysis of results. In a modified intent-to-treat analysis, 59% of the patients treated with cefepime and 47% of ceftazidime-treated patients responded to therapy. Cefepime patients developed fewer new infections than ceftazidime patients (9% vs. 21%, respectively) and early discontinuation of study drug therapy occurred slightly more often in the ceftazidime group. Further, the use of concomitant systemic antimicrobial therapy (mostly vancomycin) occurred less often in the cefepime-treated patients, as compared with the ceftazidime group [35% [17 of 49] vs. 44% (24 of 55), respectively]. No deaths or serious adverse events were considered to be related to study therapy. The most frequent adverse event was rash that was moderate in severity, and it occurred equally in both groups.\n Cefepime appears to be safe and effective compared with ceftazidime for initial empiric therapy of febrile episodes in neutropenic pediatric cancer patients.", "The purpose of this prospective randomized study was to compare the efficacy and safety of imipenem and cefoperazone-sulbactam combined with vancomycin for the treatment of fever in neutropenic cancer patients. Patients were assigned to either imipenem 500 mg/m2 (500 mg for bone marrow transplant recipients) every 6 h or cefoperazone (2 g)-sulbactam (1 g) every 8 h All patients received vancomycin 1 g every 12 h. A total of 457 febrile or infectious episodes occurring in 407 patients were entered in the study. The response rate was 73% for imipenem plus vancomycin and 74% for cefoperazone-sulbactam plus vancomycin among the 369 episodes that could be evaluated. Response rates were comparable for the two regimens with regard to infecting organism, administration of antimicrobial prophylaxis, and neutrophil count and trend. The frequency of side-effects was significantly higher for imipenem plus vancomycin (11% vs.5%, p = 0.02), due to therapy-associated nausea and vomiting (5.3% vs. 0%, p = 0.0004). The overall frequency of superinfections was similar with both regimens, but Clostridium difficile colitis occurred significantly more often in patients receiving imipenem plus vancomycin (5 vs. 0, p = 0.02). In this study cefoperazone-sulbactam plus vancomycin was an effective alternative to imipenem plus vancomycin for initial therapy of fever in neutropenic patients.", "A prospective, open label, randomized, multicentre study was conducted, comparing the efficacy and safety of cefepime with that of imipenem-cilastatin for the management of febrile neutropenia in patients with haematological malignancies. Furthermore, the safety of early discontinuation of antibiotic therapy in patients with fever of undetermined origin (FUO) was assessed. A total of 180 patients with 207 febrile episodes were randomized at start of fever (105 episodes for cefepime and 102 episodes for imipenem). The 2 groups were comparable in terms of age, gender, underlying malignancy, prior transplantation, and presence of central venous catheters. All patients were neutropenic at inclusion with median absolute neutrophil count (ANC) 0.1 x 10(9)/l(range 0-1 x 10(9)/l), and ANC < or = 0.1 x 10(9)/l in 77% of included patients. The mean duration of neutropenia, with ANC < 0.5 x 10(9)/l was 6.2 d. Febrile episodes were classified as microbiologically documented infection (47%), FUO (43%), or clinically documented infection (10%). At final evaluation 1-2 weeks after completion of antibiotic therapy, monotherapy success rates were 40% and 51% in the cefepime and imipenem-cilastatin groups respectively (p = 0.33). The 4-week overall mortality rate was 5%. Three (2%) of the cefepime treated patients and 4 (3%) of the imipenem-cilastatin treated patients died as a result of infection. Adverse events directly related to antibiotic treatment were uncommon and did not differ between groups. Early discontinuation of antibiotic therapy in 31 patients with FUO 48 h after defervescence was not associated with an increased rate of fever relapse or mortality compared with a subgroup of 29 patients where therapy was continued.", "The empirical treatment of febrile, neutropenic patients with cancer requires antibacterial regimens active against both gram-positive and gram-negative pathogens. This study was performed to demonstrate the noninferiority of monotherapy with piperacillin-tazobactam, compared with cefepime.\n We conducted a randomized-controlled, open-label, multicenter clinical trial among high-risk patients from 34 university-affiliated tertiary care medical centers in the United States, Canada, and Australia who were undergoing treatment for leukemia or hematopoietic stem cell transplantation and were hospitalized for empirical treatment of febrile neutropenic episodes. Patients received piperacillin-tazobactam (4.5 g every 6 h) or cefepime (2 g every 8 h) intravenously. The primary outcome was success (defined by defervescence without treatment modification) at 72 h of treatment, end of treatment, and test of cure in the modified intent-to-treat analysis. Secondary outcomes included time to defervescence, microbiological efficacy, the additional use of glycopeptide antibiotics, emergence of resistant bacteria, and safety.\n For 528 subjects (265 received piperacillin-tazobactam and 263 received cefepime), success rates were 57.7% and 48.3%, respectively (P = .04) at the 72-h time point, 39.6% and 31.6% (P = .06) at end of treatment, and 26.8% and 20.5% (P = .11) at the test-of-cure visit. The analyses demonstrated noninferiority for piperacillin-tazobactam at all time points (P< or = .0001). Treatment with piperacillin-tazobactam was independently associated with treatment success in multivariate analysis (odds ratio, 1.65; 95% confidence interval, 1.04-2.64; P = .035). Both regimens were well tolerated.\n This study demonstrates the noninferiority and safety of piperacillin-tazobactam monotherapy, compared with cefepime, for the empirical treatment of high-risk febrile neutropenic patients with cancer.", "We report on 232 patients undergoing autologous haematopoietic stem cell transplantation (ASCT) entered into a multicentre, randomised trial comparing the efficacy and tolerability of meropenem (MPM) with that of piperacillin/tazobactam (P/T) as empirical antimicrobial first-line therapy for febrile neutropenia. In 27.6% of patients in the MPM group and 22.4% in the P/T group, therapy was initially supplemented with a glycopeptide for venous catheter infection or bacteraemia because of coagulase-negative staphylococci. Complete response rate after 72 h was 63.8% in the MPM group and 49.6% in the P/T group (P = 0.034). Overall complete response rate after treatment modification was 94.0% in the MPM group and 93.1% in the P/T group. Median time to defervescence was 2 d in the MPM group and 3 d in the P/T group. The most frequently isolated pathogens were Gram-positive cocci. Treatment was well tolerated in both groups. One patient (0.4%) died from infection. Empirical first-line therapy with MPM as well as with P/T is safe and effective in febrile episodes emerging after ASCT. Higher response rates to primary treatment can be achieved with MPM.", "To compare the efficacy and safety of panipenem/betamipron with cefepime as empirical monotherapy for adult cancer patients with febrile neutropenia, a randomized, open-label, comparative trial was performed.\n All enrolled patients were randomly assigned to receive either panipenem or cefepime. All febrile episodes were classified as microbiologically defined infection (MDI), clinically defined infection (CDI) or unexplained fever (UF). Clinical responses to antibiotic therapy were defined as success, initial response but regimen modified or failure.\n A total of 116 patients were enrolled: 55 patients in the panipenem group and 61 patients in the cefepime group. Demographic and clinical characteristics were similar in the two groups (P > 0.05). In the final evaluation, the success rate for the panipenem group (89.1%) was similar to that of the cefepime group (91.8%) (non-inferiority, P = 0.002, 95% confidence interval: -13.48%, 10.35%). Of the 18 bacterial isolates, nine (50%) were gram-positive and nine (50%) were gram-negative. The prevalence of adverse events in the panipenem group (23.6%) were similar to those in the cefepime group (23.0%) (P = 0.93). All of the adverse events were well tolerated and transient.\n Although larger studies are necessary, panipenem appeared to be as effective and safe as cefepime for empirical monotherapy in the treatment of adult cancer patients with febrile neutropenia.", "This open, comparative, randomized, multicentre equivalence study compared cefepime 2 g bd and imipenem-cilastatin 1 g tds (50 mg/kg/day) as empirical monotherapy for febrile episodes in a homogeneous cohort of cancer patients with short duration neutropenia following chemotherapy for solid tumour, lymphoma or myeloma. The study was conducted in 17 French anti-cancer centres in 1995 and 1996. Response to monotherapy was assessed 7 days after treatment and was based on resolution of fever and signs and symptoms, eradication of pathogens, absence of new infection, relapse, and death of infectious origin, without addition of other antibiotics. Patients were treated for a minimum of 4 days. Of the 400 episodes randomized, 344 (86%) were evaluable for efficacy. Patient characteristics were comparable between treatment groups. Success of monotherapy was observed in 79% of episodes with cefepime and 72% with imipenem-cilastatin (equivalence, P <0.0001). The response rate for microbiologically documented infections was 66% with cefepime and 61% with imipenem-cilastatin (bacteraemic episodes: 63% for cefepime; 44% for imipenem-cilastatin). A second antibiotic (usually a glycopeptide) was added in 20% and 21% of the cases, respectively. Overall, the response to therapy, with or without an additional antibiotic, was 95% (cefepime) and 90% (imipenem-cilastatin). Survival was similar in both groups (95% and 98%, respectively). Cefepime treatment was better tolerated, with 9% of the patients experiencing related intercurrent events compared with 19% in the imipenem-cilastatin group (P = 0.003). Nausea/vomiting was significantly more frequent in the imipenem-cilastatin group (15%) than in the cefepime group (5%; P = 0.001). Cefepime monotherapy was as effective as, and better tolerated than, imipenem-cilastatin in the empirical treatment of fever during short duration neutropenia.", "Piperacillin/tazobactam was compared with ceftazidime for the empirical treatment of febrile neutropenia in patients with acute leukemia or following autologous peripheral blood stem cell transplantation. Owing to inclusion criteria, it was possible for the same patient to be randomized several times. A total of 219 individual patients were admitted to a prospective randomized clinical study: 24 patients were included twice. Patients (23.5%) remained afebrile. Patients who developed febrile neutropenia were randomized to receive intravenous ceftazidime (n = 74 patients, group I) or piperacillin/tazobactam (n = 87 patients, group II). Response to first-line antibiotic treatment was seen in 55% (group I) and 53% (group II). After the addition of vancomycin, a further 19% (group I) and 24% (group II) of the patients became afebrile. Causes of fever were: microbiologically documented infection in 36 and 34 patients of group I and II; Clostridium difficile in eight and 12 patients of group I and II, and fever of unknown origin in 30 and 41 patients of group I and II. One patient died in each group. Single-agent therapy with piperacillin/tazobactam is as effective as ceftazidime in the treatment of neutropenic fever and is well tolerated. Direct and indirect costs of both treatment regimes are equivalent.", "Monotherapy with cefepime or ceftazidime is an effective alternative to combination therapy for the treatment of febrile neutropenic adult cancer patients. We compared the efficacy and safety of cefepime and ceftazidime as empiric monotherapy of febrile neutropenia in children with cancer.\n A prospective, open label, randomized, comparative study in pediatric cancer patients was conducted at Chang Gung Children's Hospital from January 1, 2000, to April 15, 2001. Patients with fever and neutropenia (absolute neutrophil count of < or = 500/mm3) were randomized to receive either intravenous cefepime or ceftazidime (50 mg/kg/dose as two or three doses daily). Febrile episodes were classified as microbiologically documented infection, clinically documented infection or unexplained fever. Clinical response to therapy was classified as success and failure.\n Ninety-five pediatric cancer patients with 120 febrile neutropenic episodes were randomized to receive empiric treatment with cefepime or ceftazidime. After 72 h of treatment, 82.8% (48 of 58) of the eligible patients in the cefepime group continued with unmodified therapy, compared with 87.9% (51 of 58) in the ceftazidime group. The neutrophil count was <100/mm3 at randomization for 76% of the patients in the cefepime group and 83% of those in the ceftazidime group; the median durations of neutropenia (<500/mm3) were 8.5 and 6.5 days, respectively. Of the 96 evaluable episodes the overall success rate with unmodified empiric therapy until the end of the treatment course in the cefepime group was comparable with that in the ceftazidime group (69% vs. 71%, P = 0.95). The response rate after glycopeptides were added to the regimens was 79.2% for the cefepime group and 77.1% for the ceftazidime group. The bacterial eradication rate was 33% for the cefepime group and 20% for the ceftazidime group (P = 0.85), and the rates of new infections were 10.4% vs. 4.2% (P = 0.67), respectively. Both study drugs were well-tolerated. Three (6.4%) patients in the cefepime group and 2 (4.3%) patients in the ceftazidime group died.\n Cefepime appeared to be as effective and safe as ceftazidime for empiric treatment of febrile episodes in neutropenic pediatric cancer patients.", "To compare meropenem, a carbapenem antibiotic, with ceftazidime for the empirical treatment of patients with febrile neutropenia.\n A prospective, double-blind, randomized clinical trial was conducted at medical centers in North America and the Netherlands. A total of 411 cancer patients (196 treated with meropenem and 215 treated with ceftazidime), who had 471 episodes of fever, participated in the trial. For each neutropenic episode, patients were allocated at random to receive intravenous administration of meropenem (1 g every 8 hours) or ceftazidime (2 g every 8 hours). Treatment could be modified at any time. Key end points were clinical and bacteriologic outcomes, eradication of infecting organism, and adverse events.\n The rate of successful clinical response at the end of therapy was significantly higher for patients treated with meropenem than for those on ceftazidime for all episodes (54% v 44%, respectively) and for episodes of fever of unknown origin (62% v 46%, respectively), but differences between groups were not statistically significant for clinically defined or microbiologically defined infections. Meropenem was significantly more effective than ceftazidime in severely neutropenic (</= 100 cells/microliter) patients (55% v 43%, respectively), bone marrow transplant patients (73% v 27%, respectively), and patients given antibiotic prophylaxis before study entry (71% v 52%, respectively). Common adverse effects of meropenem and ceftazidime therapy were rash, diarrhea, and nausea and vomiting.\n Monotherapy with meropenem represents a suitable choice for initial empirical antibiotic therapy for febrile episodes in neutropenic cancer patients.", "Empirical beta-lactam monotherapy has become the standard therapy in febrile neutropenia. The aim of this study was to compare the efficacy and safety of piperacillin-tazobactam versus carbapenem therapy with or without amikacin in adult patients with febrile neutropenia.\n In this prospective, open, single-center study, 127 episodes were randomized to receive either piperacillin-tazobactam (4 x 4.5 g IV/day) or carbapenem [meropenem (3 x 1 g IV/day) or imipenem (4 x 500 mg IV/day)] with or without amikacin (1 g IV/day). Doses were adjusted according to renal function. Clinical response was determined during and at completion of therapy.\n One hundred and twenty episodes were assessable for efficacy (59 piperacillin-tazobactam, 61 carbapenem). Mean duration of treatment was 14.8 +/- 9.6 days in the piperacillin-tazobactam group and 14.7 +/- 8.8 days in the carbapenem group (P > 0.05). Mean days of fever resolution were 5.97 and 4.48 days for piperacillin-tazobactam and carbapenem groups, respectively (P > 0.05). Similar rates of success without modification were found in the piperacillin-tazobactam (87.9%) and in the carbapenem groups (75.4%; P > 0.05). Fungal infection occurrence rates were 30.5 and 18% in piperacillin-tazobactam and carbapenem groups, respectively (P = 0.05). Antibiotic modification rates were 30.5 and 13.1% (P = 0.02) and the addition of glycopeptides to empirical antibiotic regimens rates were 15.3 and 44.3% for piperacillin-tazobactam and carbapenem groups, respectively (P = 0.001). The rude mortality rates were 14% (6/43) and 29.3% (12/41) in piperacillin-tazobactam and carbapenem groups, respectively (P = 0.08).\n The effect of empirical regimen of piperacillin-tazobactam regimen is equivalent to carbapenem in adult febrile neutropenic patients.", "This is a prospective, randomized, and open-label clinical trial that examines the efficiency and safety of PIP/TAZO monotherapy in comparison to cefepime (CEF), for the empirical treatment of pediatric cancer patients with neutropenia and fever.\n One hundred thirty-one consecutive febrile episodes in 70 neutropenic pediatric cancer patients received randomized treatment either with piperacillin/tazobactam (PIP/TAZO) 80 mg/kg piperacillin/10 mg/kg tazobactam every 6 hr or CEF 50 mg/kg every 8 hr. Clinical response was determined at completion of therapy. Duration of fever, neutropenia, hospitalization, the need for modification of the therapy, and mortality rates were compared between the two groups.\n One hundred twenty-seven episodes in 69 patients (35 females, 34 males) with a median age of 4.2 years were assessed for efficiency (65 PIP/TAZO, 62 CEF). The frequency of success without modification of treatment was nearly identical for both PIP/TAZO (60.0%) and CEF (61.3%) (P > 0.05). The overall response rate, with or without modification of assigned treatment, was 96.9% for PIP/TAZO and 98.4% for CEP (P > 0.05). Infection-related mortality at the end of the febrile episode was 2.4%. Duration of fever and hospitalization were not different between the treatment groups. No major side effects were observed in neither of the groups.\n PIP/TAZO treatment was as effective and safe as CEF monotherapy as an initial empirical regimen in pediatric cancer patients with fever and neutropenia.", "The efficacies of meropenem, a novel carbapenem, and ceftazidime, as empirical therapy of febrile neutropenic patients, were compared in a prospective, randomized clinical trial. One hundred and twelve adult patients were given meropenem 1 g tds iv for 153 episodes of fever, while 109 patients received ceftazidime 2 g tds iv for 151 episodes. All patients survived the first 3 days of therapy and, by the end of the treatment courses, 67 (44%) episodes had responded to meropenem, compared with 62 (41%) to ceftazidime. Eighty (53%) episodes initially treated with ceftazidime and 63 (41%) episodes treated with meropenem were considered to have failed treatment because it was thought necessary to administer additional antibacterial agents; however, modifications were made twice as often because of fever that persisted beyond 2-3 days than because of obvious causes of failure such as persistent infection. Three patients in the ceftazidime group and five in the meropenem group died. Meropenem was well tolerated, with no reports of nausea or toxicity to the central nervous system. Although ceftazidime was shown in the present study to be as effective as meropenem, the broader spectrum of activity of meropenem against Gram-positive cocci suggests that it might be more appropriate as empirical therapy of febrile neutropenic patients who are at high risk of acquiring infections caused by these bacteria.", "With the availability of new, broad-spectrum antibiotics, initial therapy with a single agent has become an alternative to classic combinations in the management of febrile, neutropenic cancer patients. The aims of this study were to compare the efficacy of ceftazidime and imipenem as empirical monotherapy of febrile episodes in neutropenic patients, and to examine the frequency with which second-line antibiotics (amikacin, vancomycin, or both) were required. A prospective clinical trial was carried out in a single centre. Eligible patients with solid tumours or lymphoma were randomised to receive monotherapy with ceftazidime or imipenem. In the event of no response, amikacin and/or vancomycin were added in 48-72 h intervals (sequentially, or according to clinical or microbiological data). Efficacy was evaluable for 111 assessable episodes. Median neutrophil count at entry was 100 cells/microliters and median duration of neutropenia was 4 days. Febrile episodes were classified as microbiologically (34%) or clinically documented (42%), and fever of unknown origin (24%). Gram-negative infections (57%) predominated over gram-positive isolates (30%). The overall success rate with monotherapy (69% versus 70%), or with modification (20% versus 23%) were equivalent for ceftazidime and imipenem (P = 0.75). The mortality in this series was 5%. Single-agent therapy with either ceftazidime or imipenem is effective for the empirical treatment of febrile episodes in neutropenic patients with solid tumours. Early addition of amikacin and/or vancomycin resolves most failures of the first step.", "We aimed at comparing the effectiveness and safety of piperacillin/tazobactam(PIP-TAZ) versus imipenem/cilastin (IMI) administered as empiric monotherapy in patients with febrile neutropenia.\n Patients with hematological diseases who were randomly assigned either PIP-TAZor IMI were enrolled in the study. A sequential strategy of antibiotic therapy addition was applied as long as fever persisted or microorganisms were isolated at 72 h. Moreover, if bacteriologically unconfirmed fever persisted after 5-7 days, an antifungal therapy was started. The treatment was considered successful if fever and clinical signs resolved and/or pathogens were cleared without adding further antibiotics at 72 h. Differences between percentages were analyzed using the *2test.\n 137 patients were evaluated. The successful response rate of PIP-TAZ after 72 h was similar to IMI (32.2 and 35.2%). The defervescence time was shorter (3.6 and 4.2 days) and the bacterial response more favourable with PIP-TAZ than with IMI, but statistically significant differences were not reached. The overall response in both groups was 91%.18.2% of episodes were bacteriologically confirmed. The most frequent isolated microorganism was Staphylococcus coagulase-negative(48.8%). There was one only case of septic shock, within the IMI group, and the overall mortality of the group was 8.7%. The occurrence of vomiting in the IMI group was significantly higher than in the PIP-TAZ group (39.9 and 5.6%; p < 0.0001).\n PIP-TAZ is as effective as IMI and it constitutes a good choice as an initial empiric monotherapy of febrile neutropenia.", "To compare the efficacy of ceftazidime and imipenem monotherapy for fever and neutropenia, and to determine whether fewer antimicrobial modifications (additions or changes) are required by the broader-spectrum agent, imipenem.\n Adult and pediatric patients undergoing chemotherapy for solid tumors, leukemias, or lymphomas were randomized to receive open-label ceftazidime or imipenem on presentation with fever and neutropenia. Success with or without modifications of the initial antibiotic was defined as survival through neutropenia; failure was death due to infection. Comparisons were based on numbers of modifications made to each monotherapy during the course of neutropenia, in patients stratified as having unexplained fever or a documented infection.\n Among 204 ceftazidime and 195 imipenem recipients, the overall success rate with or without modification was more than 98%, regardless of initial antibiotic regimen. Modifications occurred in half of all episodes, primarily in patients with documented infections on either monotherapy. Antianaerobic agents were more frequently added to ceftazidime (P < .001), but addition of other antibiotics, including vancomycin and aminoglycosides, was similar between the two monotherapy groups. Imipenem therapy was associated with significantly greater toxicity, manifested by Clostridium difficile-associated diarrhea and by nausea and vomiting, which required discontinuation of imipenem in 10% of recipients.\n Ceftazidime and imipenem are both effective in the management of fever and chemotherapy-related neutropenia, provided that modifications are made in response to clinical and microbiologic data that emerge during the course of neutropenia. Imipenem, despite its broader antimicrobial spectrum, does not significantly decrease the overall need for antibiotic modifications and is more often complicated by gastrointestinal toxicity.", "In this Swedish multicentre study we compared the efficacy of meropenem with ceftazidime for treatment of febrile neutropenia. 192 patients were randomized and the number of evaluable patients was 92 in the meropenem group and 95 in the ceftazidime group. 40 (43%) patients in the meropenem arm and 49 (52%) in the ceftazidime arm had acute leukaemia. 56 (61%) and 52 (55%) patients respectively had a neutrophil count of < 0.1 x 10(9)/l at randomization and the median duration of neutropenia was 6.5 and 8 d, respectively. Thirty-one (34%) and 28 (29%) patients had a microbiologically defined infection, 14 (15%) and 17 (18%) a clinically defined infection and the remaining 47 (51%) and 50 (53%) had unexplained fever. After 72 h of treatment, 46 (50%) patients in the meropenem arm and 53 (56%) patients in the ceftazidime arm were alive on unmodified monotherapy. 42 (46%) and 47 (49%) of these completed the study on monotherapy alone. Only 2 patients (2%) in each arm had to stop treatment owing to allergic reactions. None of the observed differences were statistically significant and we therefore conclude that meropenem was an effective and safe alternative to ceftazidime for empiric treatment of fever during neutropenia.", "The objective of the presented prospective, randomized study was to compare the efficacy of empirical antimicrobial monotherapy with piperacillin/tazobactam (PIP/TAZ) to cefepime (CEFP) for treatment of infections in neutropenic patients. From a total of 102 febrile episodes 100 were evaluable. The most frequent microorganisms were gram-negative, documented in 22% vs. 24% of the febrile episodes (gram-positives 18% vs. 16%, fungi 2% vs. 4%). The response rate was similar with 22/51 (43%) of episodes treated with PIP/TAZ vs. 19/49 (39%) with CEFP. Of the different infection types classified at the end of the febrile episodes, patients with fever of unknown origin (FUO) and primary bacteremias showed the best initial responses with 25/44 (57%) and 11/22 (50%). Lower initial response rates were found in pneumonias with totally 3/13 (23%) and other clinically documented infections with 2/21 (10%), without any difference between both groups. Gram positive infections showed a higher response with PIP/TAZ than with CEFP (4/9 vs. 0/8), gram negative responded less frequently (3/11 vs. 7/13). The median time until persistent defervescence was equal in both groups (2.5 vs. 2 days), likewise the response rates after the different steps of therapy modifications (change to imipenem or ceftazidim, or addition of gentamycin, vancomycin or amphotericin B). Totally, 96% of febrile episodes responded in both therapy arms. Overall, we found no significant differences in efficacy between the two therapeutic regimens. In conclusion, PIP/TAZ as well as CEFP might be a sufficient initial therapy for febrile neutropenia, but further randomized trials with larger patient numbers are necessary.", "One hundred febrile episodes in 89 neutropenic patients after cytotoxic chemotherapy were randomized to be treated with either ceftazidime or imipenem as initial monotherapy. The clinical characteristics of the two groups of patients were comparable. The response of the fever in patients who received imipenem was significantly better than that in those who received ceftazidime (77 versus 56%, respectively; P = 0.04), especially in those with microbiologically documented infection (81 versus 33%, respectively; P = 0.02). The in vitro susceptibilities and the clinical responses suggested that, with the possible exception of Pseudomonas spp., imipenem was more effective than ceftazidime in treating neutropenic infections caused by both gram-positive and -negative organisms. An additional 23 and 21% of the patients in the ceftazidime and imipenem groups, respectively, responded to the addition of cloxacillin and amikacin following failure of monotherapy. The majority of the treatment failures, relapses, and superinfections were related to resistant infective organisms such as methicillin-resistant Staphylococcus spp. and Pseudomonas spp. or disseminated fungal infections.", "To compare the efficacies of cefepime and ceftazidime as empiric therapy during the management of fever in cancer patients with chemotherapy-induced neutropenia.\n A prospective, double-blind, randomized study of cefepime 2 g every eight hours and ceftazidime 2 g every eight hours was performed in 276 adult neutropenic (absolute neutrophil count < 500/mm3) cancer patients with fever.\n Median duration of neutropenia was five days. Sixty-one percent (n = 188) of the patients were evaluable. Treatment was successful in 57% (58/101) of cefepime-treated patients and 60% (52/87) of ceftazidime-treated patients (95% CI -18 to 12; p = 0.77). Bacteremic clearance occurred in 71% (12/17) of cefepime-treated patients and 40% (6/15) of ceftazidime-treated patients (p = 0.3). Both drugs were well tolerated.\n Cefepime appears to be as effective as ceftazidime in the initial treatment of febrile episodes in adult cancer patients with chemotherapy-associated neutropenia of modest duration.", "The purpose of this study was to compare the efficacy, safety, and cost of piperacillin/tazobactam with cefepime monotherapy in children with febrile neutropenia. A prospective randomized study in children and adolescent with cancer was conducted. Patients were randomly assigned to receive either 80 mg/kg piperacillin/10 mg/kg tazobactam every 6 h (maximum 4.5 g/dose) or cefepime 50 mg/kg every 8 h (maximum 2 g/dose). Treatment modification was defined as all the changes in the empirical antimicrobials after the first 96 h. Overall treatment success was defined as cure of febrile episode with or without modification. Cost of hospitalization, antimicrobial drugs, and supportive therapy were calculated. Fifty febrile neutropenic episodes (25 in the piperacillin/tazobactam group, 25 in the cefepime group) in 27 pediatric cancer patients were evaluated. The groups were comparable in terms of age, gender, body weight, primary diagnosis, disease status, initial neutrophil count, and duration of neutropenia. Microbiologically and clinically documented infection rate was 46%. There was no infection-related mortality in the study period. The treatment success of initial empirical therapy without modification was not different in the 2 groups (56% in piperacillin/tazobactam group and 48% in cefepime group). Anti-anaerobic drugs were added more frequently in the cefepime group. Duration of fever, neutropenia, treatment, and cost of therapy were not different in the treatment groups. Piperacillin/tazobactam monotherapy is as effective as cefepime monotherapy in febrile neutropenia of pediatric cancer patients." ]

[ "3885736" ]

[ "Can preterm deliveries be prevented?" ]

[ "Our hospital serves poor, inner-city women who have a 17% preterm delivery rate. Middle-class women in San Francisco at high risk for preterm delivery have benefited from an antepartum program which emphasized patient education and close follow-up. Using a controlled, randomized design, we are investigating the impact of similar interventions. Patients determined to be at high risk before 18 weeks' gestation on the basis of the Creasy system are randomly assigned to the Preterm Labor Prevention Clinic or serve as high-risk controls. Sixty-four women assigned to the Preterm Labor Prevention Clinic and 68 high-risk control women have been delivered of their infants. No significant differences were noted for the percentages of preterm infants, mean gestational age, or birth weight. Preterm rupture of the membranes accounted for 40% of preterm deliveries in all high-risk patients. Thirty percent of preterm births were indicated for maternal or fetal reasons. The remaining 30% represented failure of tocolytic therapy." ]

[ "11265827", "12016180", "12090970", "17118950", "11330851", "11008086", "17077230", "9083598", "16774462", "15117710", "15249566", "15276393", "12392217", "9158975", "17463382", "16439928", "16182145", "16894074", "16682420", "12718812", "12287798", "2323402", "3792524", "10510075", "11177066", "15661598", "15632336", "2289544", "15279915", "9179578", "15581523", "12065268" ]

[ "Schoolwide effects of a multicomponent HIV, STD, and pregnancy prevention program for high school students.", "Improving teenagers' knowledge of emergency contraception: cluster randomised controlled trial of a teacher led intervention.", "Long-term reductions in sexual initiation and sexual activity among urban middle schoolers in the reach for health service learning program.", "Impact of a theoretically based sex education programme (SHARE) delivered by teachers on NHS registered conceptions and terminations: final results of cluster randomised trial.", "Effects of a parent-child communications intervention on young adolescents' risk for early onset of sexual intercourse.", "Postponing sexual intercourse among urban junior high school students-a randomized controlled evaluation.", "Impact of increased access to emergency contraceptive pills: a randomized controlled trial.", "An impact evaluation of project SNAPP: an AIDS and pregnancy prevention middle school program.", "All4You! A randomized trial of an HIV, other STDs, and pregnancy prevention intervention for alternative school students.", "Draw the line/respect the line: a randomized trial of a middle school intervention to reduce sexual risk behaviors.", "Efficacy of an HIV prevention intervention for African American adolescent girls: a randomized controlled trial.", "Pupil-led sex education in England (RIPPLE study): cluster-randomised intervention trial.", "Preventing pregnancy and improving health care access among teenagers: an evaluation of the children's aid society-carrera program.", "Evaluation of an educational program to prevent adolescent pregnancy.", "REAL men: a group-randomized trial of an HIV prevention intervention for adolescent boys.", "Keepin' it R.E.A.L.!: results of a mother-adolescent HIV prevention program.", "Adult identity mentoring: reducing sexual risk for African-American seventh grade students.", "A randomized controlled trial testing an HIV prevention intervention for Latino youth.", "HIV prevention in Mexican schools: prospective randomised evaluation of intervention.", "Impact of an intervention to improve treatment-seeking behavior and prevent sexually transmitted diseases among Nigerian youths.", "Teen Incentives Program: evaluation of a health promotion model for adolescent pregnancy prevention.", "Helping teenagers postpone sexual involvement.", "Supporting teenagers' use of contraceptives: a comparison of clinic services.", "A school-based AIDS education programme for secondary school students in Nigeria: a review of effectiveness.", "Randomized controlled trial of a safer sex intervention for high-risk adolescent girls.", "Adolescent pregnancy prevention: An abstinence-centered randomized controlled intervention in a Chilean public high school.", "Direct access to emergency contraception through pharmacies and effect on unintended pregnancy and STIs: a randomized controlled trial.", "Evaluating the impact of a theory-based sexuality and contraceptive education program.", "Interactive video behavioral intervention to reduce adolescent females' STD risk: a randomized controlled trial.", "The impact of the Postponing Sexual Involvement curriculum among youths in California.", "The \"Safer Choices\" intervention: its impact on the sexual behaviors of different subgroups of high school students.", "Limits of teacher delivered sex education: interim behavioural outcomes from randomised trial." ]

[ "Few studies have tested schoolwide interventions to reduce sexual risk behavior, and none have demonstrated significant schoolwide effects. This study evaluates the schoolwide effects of Safer Choices, a multicomponent, behavioral theory-based HIV, STD, and pregnancy prevention program, on risk behavior, school climate, and psychosocial variables. Twenty urban high schools were randomized, and cross-sectional samples of classes were surveyed at baseline, the end of intervention (19 months after baseline), and 31 months afterbaseline. At 19 months, the program had a positive effect on the frequency of sex without a condom. At 31 months, students in Safer Choices schools reported having sexual intercourse without a condom with fewer partners. The program positively affected psychosocial variables and school climate for HIV/STD and pregnancy prevention. The program did not influence the prevalence of recent sexual intercourse. Schoolwide changes in condomuse demonstrated that aschool-based program can reduce the sexual risk behavior of adolescents.", "To assess the effectiveness of a teacher led intervention to improve teenagers' knowledge about emergency contraception.\n Cluster randomised controlled trial.\n 24 mixed sex, state secondary schools in Avon, south west England.\n 1974 boys and 1820 girls in year 10 (14-15 year olds).\n Teachers gave a single lesson on emergency contraception to year 10 pupils. The teachers had previously received in-service training on giving the lesson. The pupils were actively involved during the lesson.\n Questionnaires distributed to pupils at baseline and six months after the intervention assessed their knowledge of the correct time limits for hormonal emergency contraception and for use of the intrauterine device as emergency contraception, the proportion of pupils who were not virgins, the proportion who had used emergency contraception, and the pupils' intention to use emergency contraception in the future.\n The proportion of pupils knowing the correct time limits for both types of emergency contraception was significantly higher in the intervention group than in the control group at six months' follow up (hormonal contraception: proportion of boys 15.9% higher (95% confidence interval 6.5% to 25.3%), girls 20.4% (10.4% to 30.4%); intrauterine device used as emergency contraception: boys 4.2% (0.7% to 7.7%), girls 10.7% (0.4% to 21.0%). The number of pupils needed to be taught for one more pupil to know the correct time limits was six for boys and five for girls. The intervention and control groups did not differ in the proportion of pupils who were not virgins, in the proportion who had used emergency contraception, and in the proportion intending to use emergency contraception in the future.\n The intervention significantly improved the proportion of boys and girls knowing the correct time limits for both types of emergency contraception. The intervention did not change the pupils' sexual activity or use of emergency contraception.", "To evaluate the sustained effectiveness of a middle school service learning intervention on reducing sexual initiation and recent sex among urban African-American and Latino adolescents from 7th grade through the 10th grade.\n During the fall of seventh grade and again in eighth grade, students were randomly assigned by classroom to participate either in community youth service (CYS) or not (controls). Service learning is an educational strategy that couples meaningful service in the community with classroom instruction. Students in both intervention and control conditions received classroom health lessons. Surveys were conducted at seventh grade baseline and at the end of 10th grade, approximately 2 years after intervention. Self-reported sexual behaviors of youths who had participated in CYS were compared with those of controls receiving classroom curriculum alone (n = 195).\n CYS participants were significantly less likely than controls to report sexual initiation (2 years CYS, odds ratio [OR] = 0.32; 1 year, OR = 0.49) as well as recent sex (2 years CYS, OR = 0.39; 1 year CYS, OR = 0.48). Among those who were virgins at seventh grade, 80% of males in the curriculum-only condition had initiated sex, compared with 61.5% who received 1 year of CYS, and 50% who received 2 years. Among females, the figures were 65.2%, 48.3%, and 39.6%, respectively.\n A service learning intervention that combines community involvement with health instruction can have a long-term benefit by reducing sexual risk taking among urban adolescents.", "To assess the impact of a theoretically based sex education programme (SHARE) delivered by teachers compared with conventional education in terms of conceptions and terminations registered by the NHS.\n Follow-up of cluster randomised trial 4.5 years after intervention.\n NHS records of women who had attended 25 secondary schools in east Scotland.\n 4196 women (99.5% of those eligible).\n SHARE programme (intervention group) v existing sex education (control group).\n NHS recorded conceptions and terminations for the achieved sample linked at age 20.\n In an \"intention to treat\" analysis there were no significant differences between the groups in registered conceptions per 1000 pupils (300 SHARE v 274 control; difference 26, 95% confidence interval -33 to 86) and terminations per 1000 pupils (127 v 112; difference 15, -13 to 42) between ages 16 and 20.\n This specially designed sex education programme did not reduce conceptions or terminations by age 20 compared with conventional provision. The lack of effect was not due to quality of delivery. Enhancing teacher led school sex education beyond conventional provision in eastern Scotland is unlikely to reduce terminations in teenagers.\n ISRCTN48719575 [controlled-trials.com].", "The quality of parent-child communications about sex and sexuality appears to be a strong determinant of adolescents' sexual behavior. Evaluations of interventions aimed at improving such communications can help identify strategies for preventing early onset of sexual behavior.\n A school-based abstinence-only curriculum was implemented among 351 middle school students, who were randomly assigned to receive either the classroom instruction alone or the classroom instruction enhanced by five homework assignments designed to be completed by the students and their parents. An experimental design involving pretest and posttest surveys was used to assess the relative efficacy of the curriculum delivered with and without the parent-child homework assignments.\n In analyses of covariance controlling for baseline scores, immediately after the intervention, adolescents who received the enhanced curriculum reported greater self-efficacy for refusing high-risk behaviors than did those who received the classroom instruction only (mean scores, 16.8 vs. 15.8). They also reported less intention to have sex before finishing high school (0.4 vs. 0.5), and more frequent parent-child communications about prevention (1.6 vs. 1.0) and sexual consequences (1.6 vs. 1.1). In all significant comparisons, the direction of the findings favored adolescents who received the enhanced curriculum. Dose-response relationships supported the findings.\n Parent-child homework assignments designed to reinforce and support school-based prevention curricula can have an immediate impact on several key determinants of sexual behavior among middle school adolescents.", "To describe a randomized, controlled evaluation of a school-based intervention to delay sexual intercourse among urban junior high school students.\n Six Washington, D.C., junior high schools were randomly assigned to the intervention or nonintervention control condition for an educational program. During the first school year, seventh graders (n = 582) from the six schools obtained written parental consent to participate. Three health professionals (one per intervention school) implemented the program, which consisted of reproductive health classes, the Postponing Sexual Involvement Curriculum, health risk screening, and \"booster\" educational activities during the following (eighth grade) school year. Cross-sectional surveys were administered at baseline, the end of the seventh grade, and the beginning and end of the eighth grade. Intervention and control group differences in virginity, attitudes toward delayed sex and childbearing, and sexual knowledge and behavior were assessed at all four time points.\n At baseline, 44% of the seventh grade males and 81% of the seventh grade females reported being virgins. At the end of the seventh grade (first follow-up), after controlling for baseline study group differences, intervention-group females were more likely to report virginity, self-efficacy to refuse sex with a boyfriend, and the intention to avoid sexual involvement during the following 6 months. At the end of the eighth grade, significantly more intervention- than control-group females reported virginity, birth control use at last intercourse (for nonvirgins), and knowledge of adolescent reproductive health and confidentiality rights. No changes in virginity, self-efficacy to refuse sex, or sexual intent for the next 6 months were observed among male participants at any time during the study. However, on all three follow-up surveys, intervention-group males scored significantly higher than their control-group counterparts in knowledge of birth control method efficacy. No change in attitudes toward abstinence was observed for either gender at any follow-up point.\n Gender differences in baseline sexual activity rates and in various study outcomes suggest a possible need for separate, gender-specific intervention activities that can adequately address the social and cognitive needs of both sexes.", "To assess how a strategy to maximize access to emergency contraceptive pills would affect rates of pregnancy and sexually transmitted infections.\n Sexually active women, 14-24 years old, were randomly assigned to two methods of access to emergency contraceptive pills: increased access (two packages of pills dispensed in advance with unlimited resupply at no charge) or standard access (pills dispensed when needed at usual charges). Participants were followed for 1 year to assess incidence of pregnancy, gonorrhea, chlamydia, and trichomonas.\n The numbers of women enrolled in the increased and standard access groups were 746 and 744, respectively. More than 93% of participants completed a full year of follow-up. The incidence of pregnancy was similar in both groups (increased access group: 9.9/100 woman years, 95% confidence interval [CI] 7.7-12.6; standard access group: 10.5/100 woman years, 95% CI 8.2-13.2). Aggregate rates of gonorrhea, chlamydia, and trichomonas were also similar in the two groups (increased access group: 6.9/100 woman years, 95% CI 5.1-9.1; standard access group: 7.6/100 woman years, 95% CI 5.7-9.9). The increased access group used emergency contraceptive pills substantially more often and sooner after coitus than the standard access group. No other differences were noted between groups in self-reported measures of sexual behavior and contraceptive use.\n This intensive strategy to enhance access to emergency contraceptive pills substantially increased use of the method and had no adverse impact on risk of sexually transmitted infections. However, it did not show benefit in decreasing pregnancy rates.\n II-1.", "A theory-based curriculum designed to delay the onset of intercourse and increase use of condoms was implemented in the classrooms of six Los Angeles middle schools.\n The curriculum activities were very interactive, emphasized skill building, and were implemented by well trained peer educators, including young HIV-positive males and teen mothers. To evaluate the impact of the curriculum, 102 classrooms of students were randomly assigned to receive either the existing curriculum or the existing curriculum plus the intervention curriculum. Students completed confidential questionnaires before program implementation, five months later, and 17 months later. A total of 1,657 students completed both the baseline and 17-month follow-up questionnaires.\n Analyses of these data revealed that the curriculum significantly increased knowledge, significantly improved only two out of 21 attitudes or beliefs, and did not significantly change sexual or contraceptive behaviors.\n Well implemented programs that are based on upon theory, use interactive activities, and utilize well-trained peer educators do not always change important sexual attitudes and behaviors among middle school youth.", "This study evaluated All4You!, a theoretically based curriculum designed to reduce sexual risk behaviors associated with HIV, other STDs, and unintended pregnancy among students in alternative schools. The study featured a randomized controlled trial involving 24 community day schools in northern California. A cohort of 988 students was assessed four times during an 18-month period using a self report questionnaire. At the 6-month follow-up, the intervention reduced the frequency of intercourse without a condom during the previous 3 months, the frequency of intercourse without a condom with steady partners, and the number of times students reported having intercourse in the previous 3 months. It also increased condom use at last intercourse. These behavioral effects were no longer statistically significant at the 12- and 18-month follow-ups. The All4You! intervention was effective in reducing selected sexual risk behaviors among students in alternative school settings; however, the effects were modest and short term.", "This study evaluated the long-term effectiveness of Draw the Line/Respect the Line, a theoretically based curriculum designed to reduce sexual risk behaviors among middle school adolescents.\n The randomized controlled trial involved 19 schools in northern California. A cohort of 2829 sixth graders was tracked for 36 months.\n The intervention delayed sexual initiation among boys, but not girls. Boys in the intervention condition also exhibited significantly greater knowledge than control students, perceived fewer peer norms supporting sexual intercourse, had more positive attitudes toward not having sex, had stronger sexual limits, and were less likely to be in situations that could lead to sexual behaviors. Psychosocial effects for girls were limited.\n The program was effective for boys, but not for girls.", "African American adolescent girls are at high risk for human immunodeficiency virus (HIV) infection, but interventions specifically designed for this population have not reduced HIV risk behaviors.\n To evaluate the efficacy of an intervention to reduce sexual risk behaviors, sexually transmitted diseases (STDs), and pregnancy and enhance mediators of HIV-preventive behaviors.\n Randomized controlled trial of 522 sexually experienced African American girls aged 14 to 18 years screened from December 1996 through April 1999 at 4 community health agencies. Participants completed a self-administered questionnaire and an interview, demonstrated condom application skills, and provided specimens for STD testing. Outcome assessments were made at 6- and 12-month follow-up.\n All participants received four 4-hour group sessions. The intervention emphasized ethnic and gender pride, HIV knowledge, communication, condom use skills, and healthy relationships. The comparison condition emphasized exercise and nutrition.\n The primary outcome measure was consistent condom use, defined as condom use during every episode of vaginal intercourse; other outcome measures were sexual behaviors, observed condom application skills, incident STD infection, self-reported pregnancy, and mediators of HIV-preventive behaviors.\n Relative to the comparison condition, participants in the intervention reported using condoms more consistently in the 30 days preceding the 6-month assessment (unadjusted analysis, intervention, 75.3% vs comparison, 58.2%) and the 12-month assessment (unadjusted analysis, intervention, 73.3% vs comparison, 56.5%) and over the entire 12-month period (adjusted odds ratio, 2.01; 95% confidence interval [CI], 1.28-3.17; P =.003). Participants in the intervention reported using condoms more consistently in the 6 months preceding the 6-month assessment (unadjusted analysis, intervention, 61.3% vs comparison, 42.6%), at the 12-month assessment (unadjusted analysis, intervention, 58.1% vs comparison, 45.3%), and over the entire 12-month period (adjusted odds ratio, 2.30; 95% CI, 1.51-3.50; P<.001). Using generalized estimating equation analyses over the 12-month follow-up, adolescents in the intervention were more likely to use a condom at last intercourse, less likely to have a new vaginal sex partner in the past 30 days, and more likely to apply condoms to sex partners and had better condom application skills, a higher percentage of condom-protected sex acts, fewer unprotected vaginal sex acts, and higher scores on measures of mediators. Promising effects were also observed for chlamydia infections and self-reported pregnancy.\n Interventions for African American adolescent girls that are gender-tailored and culturally congruent can enhance HIV-preventive behaviors, skills, and mediators and may reduce pregnancy and chlamydia infection.", "Improvement of sex education in schools is a key part of the UK government's strategy to reduce teenage pregnancy in England. We examined the effectiveness of one form of peer-led sex education in a school-based randomised trial of over 8000 pupils.\n 29 schools were randomised to either peer-led sex education (intervention) or to continue their usual teacher-led sex education (control). In intervention schools, peer educators aged 16-17 years delivered three sessions of sex education to 13-14 year-old pupils from the same schools. Primary outcome was unprotected (without condom) first heterosexual intercourse by age 16 years. Analysis was by intention to treat.\n By age 16 years, significantly fewer girls reported intercourse in the peer-led arm than in the control arm, but proportions were similar for boys. The proportions of pupils reporting unprotected first sex did not differ for girls (8.4% intervention vs 8.3% control) or for boys (6.2% vs 4.7%). Stratified estimates of the difference between arms were -0.4% (95% CI -3.7% to 2.8%, p=0.79) for girls and -1.4% (-4.4% to 1.6%, p=0.36) for boys. At follow-up (mean age 16.0 years [SD 0.32]), girls in the intervention arm reported fewer unintended pregnancies, although the difference was borderline (2.3% vs 3.3%, p=0.07). Girls and boys were more satisfied with peer-led than teacher-led sex education, but 57% of girls and 32% of boys wanted sex education in single-sex groups.\n Peer-led sex education was effective in some ways, but broader strategies are needed to improve young people's sexual health. The role of single-sex sessions should be investigated further.", "Despite the recent declines in rates of teenage pregnancy, relatively little is known about the few programs that have been successful in reducing adolescent pregnancy.\n Six agencies in New York City each randomly assigned 100 disadvantaged 13-15-year-olds to their usual youth program or to the intervention being tested--the Children's Aid Society-Carrera program, a year-round afterschool program with a comprehensive youth development orientation. Both program and control youth were followed for three years. Multivariate regression analyses assessed the effects of program participation on the odds of current sexual activity, use of a condom along with a hormonal contraceptive, pregnancy and access to good health care.\n Seventy-nine percent of participants remained in the program for three full years. Female program participants had significantly lower odds than controls of being sexually active (odds ratio, 0.5) and of having experienced a pregnancy (0.3). They had significantly elevated odds of having used a condom and a hormonal method at last coitus (2.4). However, participation in the program created no significant impact on males' sexual and reproductive behavior outcomes. Nonetheless, program participants of both genders had elevated odds of having received good primary health care (2.0-2.1).\n This program is one of only four whose evaluation has successfully documented declines in teenage pregnancy using a random-assignment design. Better outcomes among males may be achieved if programs reach them even earlier than their teenage years.", "The authors evaluated the effectiveness of a school-based sex education program in decreasing rates of sexual intercourse, improving birth control use, and decreasing the incidence of pregnancies among teenagers 16 years of age and younger. Twenty-one schools received either the McMaster Teen Program or the conventional didactic sex education program. Preprogram, the mean age of the students was 12.6 years. There were no statistically significant differences between groups in time to first sexual activity for males, chi 2(1) = 2.93, p = 0.09; time to first sexual activity for females, chi 2(1) = 0.50, p = 0.48; and time to first pregnancy, chi 2(1) = 1.90, p = 0.17. Significantly more experimental group males reported always using birth control at year 1 (difference 8.9%; 95% confidence interval [CI] = 0.4, 17.4). Limitations of the program that may have influenced the results were the exclusion of contraception information and its short duration.", "We tested the efficacy of an intervention among 11- to 14-year-old adolescent boys to promote delay of sexual intercourse, condom use among those who were sexually active, and communication on sexuality between fathers (or father figures) and sons.\n Sites were randomly assigned to the intervention and control groups. Assessments were conducted prior to the intervention and at 3-, 6-, and 12-month follow-up interviews.\n A total of 277 fathers and their sons completed baseline assessments. Most participants were African American, and most fathers lived with their sons. Significantly higher rates of sexual abstinence and condom use and of intent to delay initiation of sexual intercourse were observed among adolescent boys whose fathers participated in the intervention. Fathers in the intervention group reported significantly more discussions about sexuality and greater intentions to discuss sexuality than did control-group fathers.\n The study demonstrates that fathers can serve as an important educator on HIV prevention and sexuality for their sons.", "The concern that adolescents may be placing themselves at risk for contracting HIV has led to widespread public and parental support for HIV prevention programs. Several programs on increasing communication between parents and teenagers have been tested, but the study of the impact of these programs on resulting sexual behavior is lacking.\n To test the efficacy of two interventions for mothers and their adolescents in delaying initiation of sexual intercourse for youth who are not sexually active and encouraging the use of condoms among sexually active youth.\n Employed were a control group and two treatment groups: one based on social cognitive theory (SCT) and the other a life skills program (LSK) based on problem behavior theory. Assessments were conducted before the intervention (baseline) and at 4, 12, and 24 months after the baseline assessment.\n Adolescents and their mothers (total N = 582) enrolled in the trial. At baseline, the adolescents ranged in age 11-14 years and were mostly male and African American. The mean age of the mothers was 37.9 years, and most were African American and single. The primary analyses showed no difference among groups in abstinence rates for adolescents. However, adolescents in the LSK group demonstrated an increase in the condom use rate, and those in the SCT and control groups scored higher on human immunodeficiency virus (HIV) knowledge than those in the LSK group. Mothers showed substantial increases over time in comfort talking about sex and self-efficacy. For HIV knowledge, mothers in the SCT group scored significantly higher than those in the LSK and control groups.\n The results of this study are comparable to previous studies that have included mothers in the HIV education of their adolescents. Although the program did not demonstrate a substantial effect on abstinence rates, increases were observed in condom use among adolescents and in mother's sex-based discussions and comfort in talking about sexual issues.", "This study was undertaken to determine whether the Adult Identity Mentoring (AIM) project successfully promotes abstinence, delays initiation of sex, and decreases intention to engage in sex.\n Twenty middle school classes of African-American seventh graders were randomly assigned to receive either the AIM intervention or a standard health education control curriculum. The AIM is a 10-session curriculum based on the theory of possible selves. Class exercises encourage students to articulate a possible future self-identity and to develop self-promotion skills. Surveys about sexual activity were conducted before the intervention, 19 weeks after baseline, and again at 1 year after the intervention.\n Hierarchical logistic regression analyses showed significant effects for the intervention on sexual intentions, abstinence, and a trend toward fewer virgins initiating intercourse for the first time, 19 weeks after baseline. Specifically, students who received the intervention showed decreased intention to engage in sex and increased abstinence compared with students not receiving the intervention. Effects for 1-year follow-up, with smaller sample size, showed only that AIM male participants maintained the significant abstinence effect.\n A new intervention, AIM was evaluated among African-American seventh graders. This program, by focusing students on positive future selves, effectively modified sexual risk without directly providing instruction on sexually explicit topics.", "To test the efficacy of a prevention intervention to reduce sexual risk behavior among Latino adolescents.\n Randomized controlled trial from April 2000 through March 2003, with data collection before and after intervention and at 3, 6, and 12 months.\n Northeast Philadelphia schools.\n Latinos aged 13 through 18 years (249 males and 304 females); 81.6% retained at 12-month follow-up.\n The HIV and health-promotion control interventions consisted of six 50-minute modules delivered by adult facilitators to small, mixed-gender groups in English or Spanish. Main Outcome Measure Self-reported sexual behavior.\n Analyses using generalized estimation equations over the follow-up period revealed that adolescents in the HIV intervention were less likely to report sexual intercourse (odds ratio, 0.66; 95% confidence interval [CI], 0.46-0.96), multiple partners (odds ratio, 0.53; 95% CI, 0.31-0.90), and days of unprotected intercourse (relative risk, 0.47; 95% CI, 0.26-0.84) and more likely to report using condoms consistently (odds ratio, 1.91; 95% CI, 1.24-2.93). Baseline sexual experience and language use moderated intervention efficacy. Adolescents assigned to the HIV intervention who were sexually inexperienced at baseline reported fewer days of unprotected sex (relative risk, 0.22; 95% CI, 0.08-0.63); Spanish speakers were more likely to have used a condom at last intercourse (odds ratio, 4.73; 95% CI, 1.72-12.97) and had a greater proportion of protected sex (mean difference, 0.35; P<.01) compared with similar adolescents in the health-promotion intervention.\n Results provide evidence for the efficacy of HIV intervention in decreasing sexual activity and increasing condom use among Latino adolescents.", "To assess effects on condom use and other sexual behaviour of an HIV prevention programme at school that promotes the use of condoms with and without emergency contraception.\n Cluster randomised controlled trial.\n 40 public high schools in the state of Morelos, Mexico.\n 10 954 first year high school students.\n Schools were randomised to one of three arms: an HIV prevention course that promoted condom use, the same course with emergency contraception as back-up, or the existing sex education course. Self administered anonymous questionnaires were completed at baseline, four months, and 16 months. Students at intervention schools received a 30 hour course (over 15 weeks) on HIV prevention and life skills, designed in accordance with guidelines of the joint United Nations programme on HIV/AIDS. Two extra hours of education on emergency contraception were given to students in the condom promotion with contraception arm.\n Primary outcome measure was reported condom use. Other outcomes were reported sexual activity; knowledge and attitudes about HIV and emergency contraception; and attitudes and confidence about condom use.\n Intervention did not affect reported condom use. Knowledge of HIV improved in both intervention arms and knowledge of emergency contraception improved in the condom promotion with contraception arm. Reported sexual behaviour was similar in the intervention arms and the control group.\n A rigorously designed, implemented, and evaluated HIV education course based in public high schools did not reduce risk behaviour, so such courses need to be redesigned and evaluated. Addition of emergency contraception did not decrease reported condom use or increase risky sexual behaviour but did increase reported use of emergency contraception.", "Interventions to treat STDs have been reported to reduce HIV incidence. Interventions to improve treatment-seeking for STDs may impact on the duration and prevalence of STDs. Nigeria has high rates of STDs and an increasing incidence of HIV.\n To evaluate the impact of an intervention on STD treatment-seeking behavior and STD prevalence among Nigerian youth.\n A randomized controlled trial in 12 schools in Edo State was conducted to evaluate an intervention to improve STD treatment-seeking and STD treatment provision. The intervention, based on formative research, consisted of community participation, peer education, public lectures, health clubs in the schools, and training of STD treatment providers, including those with no formal training. A questionnaire measured outcomes before and 10 months into the intervention. The effect of the intervention among four randomly selected intervention schools compared to eight randomly selected control schools was assessed using logistic regression with Huber's formula to account for school clusters.\n One thousand eight hundred and ninety-six and 1858 youths 14-20 years of age were enrolled in the pre- and post-intervention surveys. Youths in the intervention schools, compared to control schools, reported statistically significant improvements in knowledge of STDs, condom use, partner awareness that the youth had an STD, and STD treatment-seeking behavior. Treatment by private physicians increased (OR=2.1, 95% CI=1.1-4.0), and treatment by patent medicine dealers or pharmacists decreased (OR=0.44, 95% CI=0.22-0.88). The reported prevalence of STD symptoms in the past 6 months was significantly reduced in the intervention compared to control schools (OR=0.68, 95% CI=0.48-0.95).\n Significant improvements in treatment-seeking for STD symptoms can be effected among Nigerian youths. The prevalence of reported STD symptoms can be decreased by improving treatment-seeking for and awareness of STDs.", "nan", "In 1983, the Henry W. Grady Memorial Hospital in Atlanta began a family planning-based outreach program for eighth graders in a local school system. The program is led by older teenagers and focuses on helping students resist peer and social pressures to initiate sexual activity. Evaluation of the program, based on telephone interviews with 536 students from the hospital's low-income population, revealed that among students who had not had sexual intercourse, those who participated in the program were significantly more likely to continue to postpone sexual activity through the end of the ninth grade than were similar students who did not participate in the program. Because of their lower rate of sexual activity, program students also experienced comparatively fewer pregnancies than no-program students.", "A program to provide teenage family planning clinic patients with special services designed to improve their ability to practice contraception effectively and avoid conception produced neither of these expected effects. Two types of special services were tested in nine clinics: one, to promote greater involvement of the teenager's family through special counseling sessions (family support); and the other, to provide more frequent contact between the teenager and clinic staff through telephone calls (periodic support). The services were provided in the six weeks following the first clinic visit. Only 36 percent of the girls who agreed to be in the family support group attended any counseling sessions, and only five percent of them came with a parent. Participation was greater in the periodic support group--84 percent of teenagers in the group received the follow-up phone calls. During the 15 months following the initial clinic visit, there were no significant differences in regularity of contraceptive use and pregnancy rates between the teenagers who received the special support services and those who received only the regular clinic services. About 40 percent of the special-service groups reported always using a contraceptive method during the study period, compared with 48 percent of controls; and about 40 percent of the former said they had rarely or never used a method, compared with 27 percent of the latter. The cumulative 15-month pregnancy rate was about 13 percent in both the special-service and the control groups.", "Nigerian secondary school students are becoming sexually active at an increasing earlier age. Sexually active students are at risk of contacting STDs, including HIV infection. As a result, health education initiatives to increase level of knowledge, influence attitudes and encourage safe sexual practices are being implemented in schools, but the effectiveness of these programmes have not been evaluated. In this study, the knowledge, attitude and sexual risk behaviors of 223 students who received a comprehensive health education intervention were compared with 217 controls. At post-test, intervention students exhibited greater knowledge about HIV/AIDS transmission and prevention (P < 0.05). Intervention students were less likely to feel AIDS is a white man's disease and were more likely to be tolerant of people living with the disease (P < 0.05). After the intervention, the mean number of reported sexual partners among the experimental students significantly decreased from 1.51 to 1.06, while it increased from 1.3 to 1.39 among the controls. Among the intervention students there was also an increase in consistent use of the condom and the use of the condom at last sexual intercourse. We conclude that students can benefit from specific education programmes that transmit important information necessary to prevent risky behavior, and improve knowledge and attitudes on HIV/AIDS.", "To determine the effect of an individualized safer sex intervention on condom use and recurrent sexually transmitted disease (STD) among female adolescents diagnosed as having an STD.\n Randomized controlled trial.\n Urban children's hospital adolescent clinic and inpatient service.\n One hundred twenty-three adolescents with cervicitis or pelvic inflammatory disease.\n Participants completed a questionnaire and then were randomized to receive standard STD education or to watch a videotape and have an individualized intervention session. Follow-up questionnaires were completed at 1, 3, 6, and 12 months. Intervention participants met with an educator at 1, 3, and 6 months to discuss interim sexual history and review the intervention.\n Change in self-reported condom use and recurrence of STD. Other self-reported behaviors, sexual risk knowledge, attitudes toward condoms, and condom use negotiation skills were also assessed.\n At 1 month, compared with control participants, intervention participants had increased sexual risk knowledge and more positive attitudes toward condoms and tended to use condoms more with a nonmain partner. At 6 months, fewer intervention participants than controls had sex with a nonmain sexual partner in the previous 6 months. At 12 months, intervention participants were less likely to have a current main partner and had a lower rate of recurrent STD than controls, but these differences were not significant.\n This individualized safer sex intervention may improve condom use and decrease the number of partners among adolescent girls who have had an STD. Studies with larger samples are needed to determine definitive intervention effects on recurrent STD in this high-risk population.", "To evaluate the efficacy of an abstinence-centered sex education program in adolescent pregnancy prevention, the TeenSTAR Program was applied in a high school in Santiago, Chile.\n A total of 1259 girls from a Santiago high school were divided into three cohorts depending on the year they started high school: the 1996 cohort of 425 students, which received no intervention; the 1997 cohort, in which 210 students received an intervention and 213 (control group) did not; and the 1998 cohort, in which 328 students received an intervention and 83 (control group) did not. Students were randomly assigned to control and intervention groups in these cohorts, before starting with the program. We conducted a prospective, randomized study using the application of the TeenSTAR sex education program during the first year of high school to the intervention groups in the 1997 and 1998 cohorts. All cohorts were followed up for 4 years; pregnancy rates were recorded and subsequently contrasted in the intervention and control groups. Pregnancy rates were measured and Risk Ratio with 95% confidence interval were calculated for intervention and control groups in each cohort.\n Pregnancy rates for the intervention and control groups in the 1997 cohort were 3.3% and 18.9%, respectively (RR: 0.176, CI: 0.076-0.408). Pregnancy rates for the intervention and control groups in the 1998 cohort were 4.4% and 22.6%, respectively (RR 0.195, CI: 0.099-0.384).\n The abstinence-centered TeenSTAR sex education intervention was effective in the prevention of unintended adolescent pregnancy.", "It is estimated that half of unintended pregnancies could be averted if emergency contraception (EC) were easily accessible and used.\n To evaluate the effect of direct access to EC through pharmacies and advance provision on reproductive health outcomes.\n A randomized, single-blind, controlled trial (July 2001-June 2003) of 2117 women, ages 15 to 24 years, attending 4 California clinics providing family planning services, who were not desiring pregnancy, using long-term hormonal contraception or requesting EC.\n Participants were assigned to 1 of the following groups: (1) pharmacy access to EC; (2) advance provision of 3 packs of levonorgestrel EC; or (3) clinic access (control).\n Primary outcomes were use of EC, pregnancies, and sexually transmitted infections (STIs) assessed at 6 months; secondary outcomes were changes in contraceptive and condom use and sexual behavior.\n Women in the pharmacy access group were no more likely to use EC (24.2%) than controls (21.0%) (P = .25). Women in the advance provision group (37.4%) were almost twice as likely to use EC than controls (21.0%) (P<.001) even though the frequency of unprotected intercourse was similar (39.8% vs 41.0%, respectively, P = .46). Only half (46.7%) of study participants who had unprotected intercourse used EC over the study period. Eight percent of participants became pregnant and 12% acquired an STI; compared with controls, women in the pharmacy access and advance provision groups did not experience a significant reduction in pregnancy rate (pharmacy access group: adjusted odds ratio [OR], 0.98; 95% confidence interval [CI], 0.58-1.64; P = .93; advance provision group: OR, 1.10; 95% CI, 0.66-1.84, P = .71) or increase in STIs (pharmacy access group: adjusted OR, 1.08, 95% CI, 0.71-1.63, P = .73; advance provision group: OR, 0.94, 95% CI, 0.62-1.44, P = .79). There were no differences in patterns of contraceptive or condom use or sexual behaviors by study group.\n While removing the requirement to go through pharmacists or clinics to obtain EC increases use, the public health impact may be negligible because of high rates of unprotected intercourse and relative underutilization of the method. Given that there is clear evidence that neither pharmacy access nor advance provision compromises contraceptive or sexual behavior, it seems unreasonable to restrict access to EC to clinics.", "A controlled field study involving 1,444 adolescent males and females 13-19 years of age was performed to compare a sexuality education program based on the health belief model and social learning theory with several publicly funded community-based and school-based interventions. Among males who had never had intercourse prior to participating in the study, those in the experimental program were more likely than those in the comparison programs to maintain abstinence over the next year; there was no program effect, however, among females. Among female adolescents who initiated intercourse after the start of the study, attendees of the comparison programs were more likely to have used an effective contraceptive at most recent intercourse and to have used an effective method more consistently than were those who attended the experimental program; no such association was seen among comparable young men. Both experimental and comparison programs significantly increased the consistent use of effective methods among teenagers who had been coitally active before attending the programs. Among males, however, when preintervention contraceptive efficiency was held constant, the experimental program led to significantly greater contraceptive efficiency during the follow-up year than did the comparison programs; among females, the two approaches produced an equivalent degree of improvement. Finally, prior exposure to sexuality education was associated with greater contraceptive efficiency at the one-year follow-up among almost all sexual-experience and gender groups, regardless of the type of intervention program attended.", "A longitudinal randomized design was used to evaluate the impact of a theoretically based, stand-alone interactive video intervention on 300 urban adolescent girls' (a) knowledge about sexually transmitted diseases (STDs), (b) self-reported sexual risk behavior, and (c) STD acquisition. It was compared to two controls, representing high-quality informational interventions. One used the same content in book form; the other used commercially available brochures. Following randomization, the interventions were administered at baseline, with booster sessions at 1, 3, and 6 months. Self-reports revealed that those assigned to the interactive video were significantly more likely to be abstinent in the first 3 months following initial exposure to the intervention, and experienced fewer condom failures in the following 3 months, compared to controls. Six months after enrollment, participants in the video condition were significantly less likely to report having been diagnosed with an STD. A non-significant trend in data from a clinical PCR assay of Chlamydia trachomatis was consistent with that finding.", "Postponing Sexual Involvement (PSI) is a widely implemented middle school curriculum designed to delay the onset of sexual intercourse. In an evaluation of its effectiveness among seventh and eighth graders in California, 10,600 youths from schools and community-based organizations statewide were recruited and participated in randomly assigned intervention or control groups; the curriculum was implemented by either adult or youth leaders. Survey data were collected before the program was implemented, and at three months and 17 months afterward. At three months, small but statistically significant changes were found in fewer than half of the measured attitudes, behaviors and intentions related to sexual activity; at 17 months, none of these significant positive effects of the PSI program had been sustained. At neither follow-up were there significant positive changes in sexual behavior; Youths in treatment and control groups were equally likely to have become sexually active, and youths in treatment groups were not less likely than youths in control groups to report a pregnancy or a sexually transmitted infection. The evaluation suggests that PSI may be too modest in length and scope to have an impact on youths' sexual behavior.", "To measure the relative impact of a school-based human immunodeficiency virus (HIV)-, sexually transmitted disease (STD)-, and pregnancy-prevention intervention on sexual risk-taking behaviors of different subgroups of students.\n Twenty schools were randomly assigned to receive Safer Choices or a standard knowledge-based HIV-education program. Safer Choices was designed to reduce unprotected sex by delaying initiation of sex, reducing its frequency, or increasing condom use. Its five components included: school organization, an intensive curriculum with staff development, peer resources and school environment, parent education, and school-community linkages. A total of 3869 9th-grade students were tracked for 31 months. Results are presented for initiation of sex, frequency of unprotected sex, number of unprotected sexual partners, condom use, and contraceptive use. These results are presented separately by gender, race/ethnicity, prior sexual experience, and prior sexual risk-taking. Statistical analyses included multilevel, repeated measures logistic and Poisson regression models.\n Safer Choices had one or more positive behavioral effects on all subgroups. On four outcomes that could be affected by condom use, it had a greater impact on males than on females. It had greater effects on Hispanics, including a delay in sexual activity, than on other racial/ethnic groups. Its greatest overall effect was an increase in condom use among students who had engaged in unprotected sex before the intervention.\n Safer Choices reduced one or more measures of sexual risk taking over 31 months among all groups of youth, and was especially effective with males, Hispanics, and youth who engaged in unprotected sex and thus were at higher risk for HIV, other STD infections and pregnancy.", "To determine whether a theoretically based sex education programme for adolescents (SHARE) delivered by teachers reduced unsafe sexual intercourse compared with current practice.\n Cluster randomised trial with follow up two years after baseline (six months after intervention). A process evaluation investigated the delivery of sex education and broader features of each school.\n Twenty five secondary schools in east Scotland.\n 8430 pupils aged 13-15 years; 7616 completed the baseline questionnaire and 5854 completed the two year follow up questionnaire.\n SHARE programme (intervention group) versus existing sex education (control programme).\n Self reported exposure to sexually transmitted disease, use of condoms and contraceptives at first and most recent sexual intercourse, and unwanted pregnancies.\n When the intervention group was compared with the conventional sex education group in an intention to treat analysis there were no differences in sexual activity or sexual risk taking by the age of 16 years. However, those in the intervention group reported less regret of first sexual intercourse with most recent partner (young men 9.9% difference, 95% confidence interval -18.7 to -1.0; young women 7.7% difference, -16.6 to 1.2). Pupils evaluated the intervention programme more positively, and their knowledge of sexual health improved. Lack of behavioural effect could not be linked to differential quality of delivery of intervention.\n Compared with conventional sex education this specially designed intervention did not reduce sexual risk taking in adolescents." ]

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[ "Pharmacist telemonitoring of antidepressant use: effects on pharmacist-patient collaboration.", "Evaluation of a clinical pharmacist in caring for hypertensive and diabetic patients.", "The physician and pharmacist team. An effective approach to cholesterol reduction.", "Evaluation of a pharmaceutical care model on diabetes management.", "Improving medication use in newly admitted home healthcare patients: a randomized controlled trial.", "Repeat prescribing: a role for community pharmacists in controlling and monitoring repeat prescriptions.", "Pharmacoeconomic evaluation of a pharmacist-managed hypertension clinic.", "Can a self-management programme delivered by a community pharmacist improve asthma control? A randomised trial.", "Effect of clinical pharmacists on drug prescribing in a primary-care clinic.", "Experience-based group education in Type 2 diabetes: a randomised controlled trial.", "Effect of a pharmaceutical care program on vascular risk factors in type 2 diabetes: the Fremantle Diabetes Study.", "Effectiveness of pharmacist care for patients with reactive airways disease: a randomized controlled trial.", "Proactive case management of high-risk patients with type 2 diabetes mellitus by a clinical pharmacist: a randomized controlled trial.", "Pharmacist involvement in primary care improves hypertensive patient clinical outcomes.", "Does encouraging good compliance improve patients' clinical condition in heart failure?", "Reduction in heart failure events by the addition of a clinical pharmacist to the heart failure management team: results of the Pharmacist in Heart Failure Assessment Recommendation and Monitoring (PHARM) Study.", "Can clinical pharmacists affect SF-36 scores in veterans at high risk for medication-related problems?", "Effects of \"group detailing\" on the prescribing of lipid-lowering drugs: a randomized controlled trial in Swedish primary care.", "Developing and implementing a pharmaceutical care model in an ambulatory care setting for patients with diabetes.", "Modification of general practitioner prescribing of antibiotics by use of a therapeutics adviser (academic detailer).", "Improving primary care in rural Alabama with a pharmacy initiative.", "Caring for poorly controlled diabetes mellitus: a randomized pharmacist intervention.", "Comprehensive pharmaceutical care in the chain setting.", "Role effectiveness of a pharmacist in the maintenance of patients with hypertension and congestive heart failure.", "Effects of coaching by community pharmacists on psychological symptoms of antidepressant users; a randomised controlled trial.", "A randomized trial of the effect of community pharmacist intervention on cholesterol risk management: the Study of Cardiovascular Risk Intervention by Pharmacists (SCRIP).", "Community pharmacist outreach program directed at physicians treating congestive heart failure.", "Pharmaceutical care of patients with heart failure.", "A randomized, controlled trial of a clinical pharmacist intervention to improve inappropriate prescribing in elderly outpatients with polypharmacy.", "Physician-pharmacist comanagement of hypertension: a randomized, comparative trial.", "The impact of a pharmacotherapy consultation on the cost and outcome of medical therapy.", "Randomized trial of pharmacist interventions to improve depression care and outcomes in primary care.", "Effect of pharmacist intervention and initiation of home blood pressure monitoring in patients with uncontrolled hypertension.", "Evaluation of the impact of a pharmaceutical care program in children with asthma.", "Impact of pharmacist-conducted home visits on the outcomes of lipid-lowering drug therapy.", "Impact of a collaborative care model on depression in a primary care setting: a randomized controlled trial.", "Clinical and economic outcomes in the hypertension and COPD arms of a multicenter outcomes study.", "A randomised controlled trial of the effect of educational outreach by community pharmacists on prescribing in UK general practice.", "The Kaiser Permanente/USC Patient Consultation Study: change in quality of life. University of Southern California.", "Guidelines and educational outreach visits from community pharmacists to improve prescribing in general practice: a randomised controlled trial.", "Improving the outcomes of anticoagulation: an evaluation of home follow-up of warfarin initiation.", "Impact of a pharmaceutical care program in a community pharmacy on patients with dyslipidemia.", "Is untargeted outreach visiting in primary care effective? A pragmatic randomized controlled trial." ]

[ "To explore the impact of telephone-based education and monitoring by community pharmacists on multiple outcomes of pharmacist-patient collaboration.\n A randomized, controlled, unblinded, mixed experimental design.\n Eight Wisconsin community pharmacies within a large managed care organization.\n A total of 63 patients presenting new antidepressant prescriptions to their community pharmacies.\n Patients were randomized to receive either three monthly telephone calls from pharmacists providing pharmacist-guided education and monitoring (PGEM) or usual pharmacist's care. Usual care is defined as that education and monitoring which pharmacists may typically provide patients at the study pharmacies.\n Patient's frequency of feedback with the pharmacist, antidepressant knowledge, antidepressant beliefs, antidepressant adherence at 3 and 6 months, improvement in depression symptoms, and orientation toward treatment progress.\n Of the 60 patients who completed the study, 28 received PGEM and 32 received usual pharmacist's care. Results showed that PGEM had a significant and positive effect on patient feedback, knowledge, medication beliefs, and perceptions of progress. There were no significant group differences in patient adherence or symptoms at 3 months; however, PGEM patients who completed the protocol missed fewer doses than did the usual care group at 6 months (P < or = .05).\n Antidepressant telemonitoring by community pharmacists can significantly and positively affect patient feedback and collaboration with pharmacists. Longer-term studies with larger samples are needed to assess the generalizability of findings. Future research also needs to explore additional ways to improve clinical outcomes.", "nan", "To assess the effect of a program that encourages teamwork between physicians and pharmacists on attempts to lower total cholesterol levels and to meet recommended goals proposed by the National Cholesterol Education Program (NCEP).\n A single-blind, randomized, controlled trial lasting 6 months.\n An ambulatory primary care center.\n A sample of 94 patients with total cholesterol levels of 240 mg/dL (6.2 mmol/L) or higher.\n Equal numbers of patients were randomly assigned to a control arm in which standard medical care was received and an intervention arm which implemented close interaction between physicians and pharmacists.\n Absolute change in total cholesterol levels from baseline values and the percentage of patients who achieved an NCEP goal after 6 months of intervention were determined. The rate of success in achieving NCEP goals in the intervention arm was double the rate in the control arm (43% vs 21%, P < .05). Total cholesterol levels in the intervention arm declined 44 +/- 47 mg/dL (1.1 +/- 1.2 mmol/L) versus 13 +/- 51 mg/dL (0.3 +/- 1.3 mmol/L) in the control arm (p < .01). The effect of intervention on reducing total cholesterol levels was similar for men and women and did not appeared to be altered by age. The effect of intervention was greatest in patients with coronary heart disease (p < .01) followed by those without disease but with two or more coronary heart disease risk factors (p < .05). An effect of intervention was absent in patients without coronary heart disease and with fewer than two risk factors.\n Attempts to lower total cholesterol levels and achieve NCEP goals are likely to be more successful when combined with programs that include teamwork between physicians and pharmacists. Some programs, however, may be more successful for high-risk patients, for whom it is often easier to provide more aggressive therapies. Although altering adverse lipid profiles in lower-risk patients may be difficult, achieving optimal cholesterol levels could have an important impact on preventing movement to higher risk strata.", "To assess the effectiveness of a pharmaceutical care model on the management of non-insulin-dependent diabetes mellitus (NIDDM) in urban African-American patients.\n Eligible patients were randomized to either a pharmacist intervention or control group and followed over a 4-month period. Patients in the intervention group received diabetes education, medication counseling, instructions on dietary regulation, exercise, and home blood glucose monitoring, and evaluation and adjustment of their hypoglycemic regimen. Patients in the control group continued to receive standard medical care provided by their physicians.\n A university-affiliated internal medicine outpatient clinic.\n The study population consisted of urban African American patients with NIDDM currently attending the clinic.\n Primary outcome measures included fasting plasma glucose and glycated hemoglobin concentrations. Secondary outcome endpoints included blood pressure, serum creatinine, creatinine clearance, microalbumin to creatinine ratio, total cholesterol, triglycerides, high-density lipoprotein, and low density lipoprotein concentrations. Quality-of-life assessments were performed in both groups at baseline and at the end of the study.\n Thirty-nine patients (17 intervention, 22 control) completed the study. The intervention group consisted of 12 women and 5 men with a mean +/- SD age of 59 +/- 12 years, total body weight (TBW) of 93 +/- 22 kg, body mass index (BMI) of 34 +/- 7 kg/m2, and duration of NIDDM 6.8 +/- 6.5 years. The control group consisted of 15 women and 7 men with a mean age of 65 +/- 12 years, TBW of 88 +/- 19 kg, BMI of 33 + 7 kg/m2, and a duration of NIDDM of 6.2 +/- 4.8 y. Significant improvement in glycated hemoglobin (p = 0.003) and fasting plasma glucose (p =0.015) was achieved in the intervention group. No change in glycemia was observed in the control subjects. Statistically significant differences in the final glycated hemoglobin (p = 0.003) and fasting plasma glucose (p = 0.022) concentrations were noted between groups. No significant changes in blood pressure control, lipid profile, renal function parameters, weight, or quality-of-life measures were noted within or between groups.\n Our data demonstrate the effectiveness of pharmaceutical care in the reduction of hyperglycemia associated with NIDDM in a group of urban African-American patients.", "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.", "Traditional systems of managing repeat prescribing have been criticised for their lack of clinical and administrative controls.\n To compare a community pharmacist-managed repeat prescribing system with established methods of managing repeat prescribing.\n A randomised controlled intervention study (19 general medical practices, 3074 patients, 62 community pharmacists). Patients on repeat medication were given sufficient three-monthly scripts, endorsed for monthly dispensing, to last until their next clinical review consultation with their general practitioner (GP). The scripts were stored by a pharmacist of the patient's choice. Each monthly dispensing was authorised by the pharmacist, using a standard protocol. The cost of the drugs prescribed and dispensed was calculated. Data on patient outcomes were obtained from pharmacist-generated patient records and GP notes.\n A total of 12.4% of patients had compliance problems, side-effects, adverse drug reactions, or drug interactions identified by the pharmacist. There were significantly more problems identified in total in the intervention group. The total number of consultations, deaths, and non-elective hospital admissions was the same in both groups. Sixty-six per cent of the study patients did not require their full quota of prescribed drugs, representing 18% of the total prescribed costs (estimated annual drug cost avoidance of 43 Pounds per patient).\n This system of managing repeat prescribing has been demonstrated to be logistically feasible, to identify clinical problems, and to make savings in the drugs bill.", "To measure clinical, economic, and humanistic outcomes associated with a pharmacist-managed hypertension clinic compared with physician-managed clinics.\n Prospective, randomized, comparative study.\n Managed care organization.\n A total of 330 patients with mild-to-moderate essential hypertension.\n Hypertension care provided by either the pharmacist-managed hypertension clinic or physician-managed general medical clinics.\n Baseline and 6-month evaluations consisted of systolic and diastolic blood pressure measurements, a short-form health survey, and collection of health care utilization information. After treatment, blood pressure measurements were significantly lower (p<0.001) in the pharmacist-managed hypertension clinic group than in the physician-managed clinic group. Patient satisfaction was significantly higher in the hypertension clinic group. Total costs for the hypertension clinic group were not different from those of the physician-managed clinic group ($242.46 vs $233.20, p=0.71), but cost:effectiveness ratios were lower in the hypertension clinic group ($27 vs $193/mm Hg for systolic blood pressure readings, and $48 vs $151/mm Hg for diastolic blood pressure readings).\n In a hypertension clinic, pharmacists can be a cost-effective alternative to physicians in management of patients, and they can improve clinical outcomes and patient satisfaction.", "No randomised studies have addressed whether self-management for asthma can be successfully delivered by community pharmacists. Most randomised trials of asthma self-management have recruited participants from secondary care; there is uncertainty regarding its effectiveness in primary care. A randomised controlled study was undertaken to determine whether a community pharmacist could improve asthma control using self-management advice for individuals recruited during attendance at a community pharmacy.\n Twenty four adults attending a community pharmacy in Tower Hamlets, east London for routine asthma medication were randomised into two groups: the intervention group received self-management advice from the pharmacist with weekly telephone follow up for 3 months and the control group received no input from the pharmacist. Participants self-completed the North of England asthma symptom scale at baseline and 3 months later.\n The groups were well matched at baseline for demographic characteristics and mean (SD) symptom scores (26.3 (4.8) and 27.8 (3.7) in the intervention and control groups, respectively). Symptom scores improved in the intervention group and marginally worsened in the control group to 20.3 (4.2) and 28.1 (3.5), respectively (p<0.001; difference adjusted for baseline scores=7.0 (95% CI 4.4 to 9.5).\n A self-management programme delivered by a community pharmacist can improve asthma control in individuals recruited at a community pharmacy. Further studies should attempt to confirm these findings using larger samples and a wider range of outcome measures.", "The effect of clinical pharmacy services on prescribing patterns and drug costs for nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates in a primary-care clinic operated by a health-maintenance organization (HMO) was studied. Two pharmacists provided clinical services to a randomly selected cluster of family practice physicians in the HMO for six months. A second family practice cluster served as a control group. The pharmacists alerted prescribers to the availability of low-cost alternatives (such as ibuprofen and salicylates) and reviewed the medication profiles of patients receiving high-cost NSAIDs. Data were collected for both physician clusters for nine months before and six months after the pharmacists' intervention. Changes in the mean numbers of prescriptions for ibuprofen and piroxicam per 1000 enrollees per physician in the baseline and evaluation periods were not significantly different between the two groups. Significantly more prescriptions for salicylates were written by physicians in the intervention group than in the control group during the evaluation period. Annualized mean drug ingredient costs per enrollee and per prescription for NSAIDS and salicylates decreased during the evaluation period in both groups, but these differences were not significant. In relatively unstructured interactions with physicians and nurses, clinical pharmacists were not able to reduce the costs associated with NSAIDs but did have a modest effect on altering salicylate prescribing patterns. This clinical pharmacy program was not economically self-sustaining during the first six months of operation, since operating costs exceeded anticipated savings.", "Few studies have demonstrated an effect of educational interventions on glycaemic control in persons with Type 2 diabetes longer than 3-6 months after baseline. We aimed to investigate the effectiveness of an experience-based group educational programme 24 months after baseline and to pinpoint mediators that might play a role in achieving desired metabolic outcomes. We conducted a randomised controlled trial inviting self-referred persons with Type 2 diabetes (N=77 randomised). The pharmacist-led, year-long intervention was based on participants' experiences of glucose regulation during the monthly group discussions. We measured HbA1c at 0, 6, 12, and 24 months and a questionnaire was administered at baseline and final follow-up. Our findings indicated that participating in the intervention programme significantly decreased HbA1c by 0.4% at 24 months after baseline. Initial HbA1c, satisfaction with own diabetes-related knowledge, and treatment were found directly related to glycaemic outcomes. The intervention group exercised more in order to lower blood-glucose levels and was also more able to predict current blood-glucose levels before measuring it. Experience-based group education was effective in decreasing participants' HbA1c 1-year after completed intervention. Early effect of the intervention was followed by relapse after 12 months and a new, significant decrease at 24 months; this dual course implies that follow-up of educational interventions should involve several consecutive measurements to capture possible late effects. Both biomedical and subjective factors played a role in accounting for the variance of HbA1c at 2-year follow-up after baseline.", "To examine the effect of a 12-month pharmaceutical care (PC) program on vascular risk in type 2 diabetes.\n We recruited 198 community-based patients randomized to PC or usual care. PC patients had face-to-face goal-directed medication and lifestyle counseling at baseline and at 6 and 12 months plus 6-weekly telephone assessments and provision of other educational material. Clinical, biochemical, and medication-related data were sent regularly to each patient's physician(s). The main outcome measure was change in HbA(1c). A diabetes-specific risk engine was used to estimate changes in 10-year coronary heart disease (CHD) and stroke risk in patients without a history of cardiovascular disease.\n At total of 180 patients (91%) completed the study. Mean (95% CI) reductions were greater in PC case subjects (n = 92) than control subjects (n = 88) for HbA(1c) (-0.5% [95% CI -0.7 to -0.3] vs. 0 [-0.2 to 0.2]) and systolic (-14 mmHg [-19 to -9] vs. -7 [-11 to -2]) and diastolic (-5 mmHg [-8 to -3] vs. -2 [-4 to 1]) blood pressure (P < or = 0.043). The improvement in HbA(1c) persisted after adjustment for baseline value and demographic and treatment-specific variables. The median (interquartile range) 10-year estimated risk of a first CHD event decreased in the PC case subjects (25.1% [15.6-36.2] to 20.3 [14.6-30.2]; n = 42, P = 0.002) but not in the control subjects (26.1% [17.2-39.4] vs. 26.4 [16.7-38.0]; n = 52, P = 0.17).\n A 12-month PC program in type 2 diabetes reduced glycemia and blood pressure. Pharmacist involvement contributed to improvement in HbA(1c) independently of pharmacotherapeutic changes. PC could prove a valuable component of community-based multidisciplinary diabetes care.", "It is not known whether patient outcomes are enhanced by effective pharmacist-patient interactions.\n To assess the effectiveness of a pharmaceutical care program for patients with asthma or chronic obstructive pulmonary disease (COPD).\n Randomized controlled trial conducted at 36 community drugstores in Indianapolis, Ind. We enrolled 1113 participants with active COPD or asthma from July 1998 to December 1999. Outcomes were assessed in 947 (85.1%) participants at 6 months and 898 (80.7%) at 12 months.\n The pharmaceutical care program (n = 447) provided pharmacists with recent patient-specific clinical data (peak expiratory flow rates [PEFRs], emergency department [ED] visits, hospitalizations, and medication compliance), training, customized patient educational materials, and resources to facilitate program implementation. The PEFR monitoring control group (n = 363) received a peak flow meter, instructions about its use, and monthly calls to elicit PEFRs. However, PEFR data were not provided to the pharmacist. Patients in the usual care group (n = 303) received neither peak flow meters nor instructions in their use; during monthly telephone interviews, PEFR rates were not elicited. Pharmacists in both control groups had a training session but received no components of the pharmaceutical care intervention.\n Peak expiratory flow rates, breathing-related ED or hospital visits, health-related quality of life (HRQOL), medication compliance, and patient satisfaction.\n At 12 months, patients receiving pharmaceutical care had significantly higher peak flow rates than the usual care group (P =.02) but not than PEFR monitoring controls (P =.28). There were no significant between-group differences in medication compliance or HRQOL. Asthma patients receiving pharmaceutical care had significantly more breathing-related ED or hospital visits than the usual care group (odds ratio, 2.16; 95% confidence interval, 1.76-2.63; P<.001). Patients receiving pharmaceutical care were more satisfied with their pharmacist than the usual care group (P =.03) and the PEFR monitoring group (P =.001) and were more satisfied with their health care than the usual care group at 6 months only (P =.01). Despite ample opportunities to implement the program, pharmacists accessed patient-specific data only about half of the time and documented actions about half of the time that records were accessed.\n This pharmaceutical care program increased patients' PEFRs compared with usual care but provided little benefit compared with peak flow monitoring alone. Pharmaceutical care increased patient satisfaction but also increased the amount of breathing-related medical care sought.", "To evaluate the effect of case management by a clinical pharmacist on glycemic control and preventive measures in patients with type 2 diabetes mellitus.\n Randomized controlled trial in a university-affiliated primary care internal medicine clinic.\n We recruited 80 patients with poorly controlled type 2 diabetes mellitus. A clinical pharmacist provided evaluation and modification of pharmacotherapy, self-management diabetes education, and reinforcement of diabetes complications screening processes through clinic visits and telephone follow-up. The main clinical outcome was hemoglobin A1C (HbA1C) level; process measures included HbA1C and low-density lipoprotein measurement, retinal examination, urine microalbumin testing (or use of angiotensin-converting enzyme inhibitors), and monofilament screening for diabetic neuropathy.\n Patients in the intervention and control groups were similar in age, sex, mean HbA1C levels (10.1% and 10.2%, respectively; P = .65), and current treatment regimens at baseline. Patients who received case management by the clinical pharmacist achieved greater reduction in HbA1C levels than those in the control group (2.1% vs 0.9%, P = .03). Three of the 5 process measures were conducted more frequently in the intervention group than the control group, including low-density lipoprotein measurement (100.0% vs 85.7%, P = .02), retinal examination (97.3% vs 74.3%), and monofilament foot screening (92.3% vs 62.9%).\n Proactive diabetes case management by a pharmacist substantially improved glycemic control and diabetes process-of-care measures. This approach, integrated with and based in the primary care setting, was an effective and efficient approach to improving care, especially for those with poor glycemic control at baseline.", "The practice of pharmaceutical care in primary care settings in Thailand is currently not generally accepted.\n To evaluate the effect of pharmacist involvement in treatment with hypertensive patients in primary care settings.\n The treatment objective was to stabilize the blood pressure (BP) of hypertensive patients in accordance with the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure guidelines. Patients were randomly assigned to a pharmacist-involved group (treatment) or a group with no pharmacist involvement (control). Pre- and post-test BPs, tablet counts, lifestyle modifications, and pharmacists' recommendations were recorded. The 6-month study was carried out in Mahasarakham University pharmacy and 2 primary care units. Patients were monitored monthly by reviewing their medications and supported by providing pharmaceutical care and counseling.\n From a total of 235 patients, the treatment group (n = 118) had a significant reduction in both systolic (S) and diastolic (D) BP compared with the 117 patients of the control group (p = 0.037, 0.027, respectively). The 158 patients (76 treatment, 82 control) with BPs >or=140/90 mm Hg at the beginning of the study showed significant BP reductions (p = 0.002 SBP, 0.008 DBP). The proportion of 158 patients whose BP became stabilized was higher in the treatment group (p = 0.017). The treatment group showed significantly better adherence (p = 0.014) and exercise control (p = 0.012) at the end of the study. Physicians accepted 42.72% of medication modifications and 5.34% of the suggestions for additional investigations.\n Hypertensive patients who received pharmacist input achieved a significantly greater benefit in BP reduction, BP control, and improvement in adherence rate and lifestyle modification.", "The aim of this study was to determine whether improved compliance by intensive medication counselling, given by a pharmacist, to elderly patients with chronic stable heart failure can influence both objective and subjective measures of heart failure. Elderly patients were randomly allocated to receive a 3-month counselling programme, or no counselling. Measures recorded at the beginning and end of the study included; submaximal 6-minute exercise tests, visual analogue scores of breathlessness, the Nottingham Health Profile, and clinical signs of heart failure. Compliance was measured by a tablet count and medication knowledge assessed by means of a questionnaire. There was no significant difference between the groups in their initial level of compliance, medication knowledge or other assessments. Compliance improved for the counselled group by 32% (P < 0.001) but remained unchanged for controls. Medication knowledge improved for the counselled group only. The 6-minute exercise test improved by 20 metres from a baseline of 137 m for the counselled group (P < 0.005) but worsened by 22 m for the control group (P < 0.01). Distance to breathlessness improved for the counselled patients and worsened for controls. In contrast bodyweight, jugular venous pressure and Nottingham Health Profile scores did not change significantly for either group. Peripheral and pulmonary oedema scores improved for the counselled group (P < 0.01) but remained unchanged for controls. A small improvement was seen in the visual analogue scores (P < 0.05) for the counselled group only. Improved compliance due to intensive medication counselling had a small but measurable beneficial effect on objective measures of heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)", "The multidisciplinary approach to managing heart failure has been shown to improve outcomes. The role of a clinical pharmacist in treating heart failure has not been evaluated.\n One hundred eighty-one patients with heart failure and left ventricular dysfunction (ejection fraction <45) undergoing evaluation in clinic were randomized to an intervention or a control group. Patients in the intervention group received clinical pharmacist evaluation, which included medication evaluation, therapeutic recommendations to the attending physician, patient education, and follow-up telemonitoring. The control group received usual care. The primary end point was combined all-cause mortality and heart failure clinical events. All clinical events were adjudicated by a blinded end point committee.\n Baseline characteristics were similar except for slightly higher age in the intervention group. Median follow-up was 6 months. All-cause mortality and heart failure events were significantly lower in the intervention group compared with the control group (4 vs 16; P= .005). In addition, patients in the intervention group received higher angiotensin-converting enzyme inhibitor doses as reflected by the median fraction of target reached (25th and 75th percentiles), 1.0 (0.5 and 1) and 0.5 (0.1875 and 1) in the intervention and control groups, respectively (P<.001). The use of other vasodilators in angiotensin-converting enzyme inhibitor-intolerant patients was higher in the intervention group (75% vs 26%; P= .02).\n Outcomes in heart failure can be improved with a clinical pharmacist as a member of the multidisciplinary heart failure team. This observation may be due to higher doses of angiotensin-converting enzyme inhibitors and/or closer follow-up.", "An objective of pharmaceutical care is for pharmacists to improve patients' health-related quality of life (HRQOL) by optimizing medication therapy.\n The objective of this study was to determine whether ambulatory care clinical pharmacists could affect HRQOL in veterans who were likely to experience a drug-related problem.\n This was a 9-site, randomized, controlled trial involving Veterans Affairs Medical Centers (VAMCs). Patients were eligible if they met > or = 3 criteria for being at high risk for drug-related problems. Enrolled patients were randomized to either usual medical care or usual medical care plus clinical pharmacist interventions. HRQOL was measured with the SF-36 questionnaire administered at baseline and at 6 and 12 months.\n In total, 1,054 patients were enrolled; 523 were randomized to intervention, and 531 to control. After patient age, site, and chronic disease score were controlled for, the only domain that was significantly different between groups over time was the bodily pain scale, which converged to similar values at the end of the study. Patients' rating of the change in health status in the past 12 months was statistically different between groups, intervention patients declining less (-2.4 units) than control subjects (-6.3 units) (P < 0.004). This difference was not considered clinically meaningful. However, a dose-response relationship was observed for general health perceptions (P = 0.004), vitality (P = 0.006), and change in health over the past year (P = 0.007).\n These results suggest that clinical pharmacists had no significant impact on HRQOL as measured by the SF-36 for veterans at high risk for medication-related problems.", "The objective was to study the effect of \"academic group detailing\" on the prescribing of lipid-lowering drugs in Swedish primary care. A randomized controlled trial was conducted, randomization being by group. Groups of doctors at 134 community health centres were randomly allocated to an intervention and a control group. The 67 intervention health centres were offered four sessions, conducted by a pharmacist, with group information on guidelines for the management of hyperlipidaemia. The number of prescriptions of lipid-lowering drugs per month increased in the intervention health centres and the increase was statistically different from the corresponding change in the control health centres among women in the age group 30-65 years (p = 0.03). The prescription of first-line lipid-lowering drugs increased by 20% in the intervention health centres (p = 0.03). \"Academic group detailing\" by pharmacists to primary care doctors can be an effective method for influencing prescribing practices.", "This study evaluated pharmaceutical care as an adjunct to an existing, coordinated-care program at a Regional Diabetes Center. The progress of a control group receiving the standard pharmacist instruction was compared with two treatment groups receiving additional small group or individual supplementary education for a 2-month period. Outcome evaluation included assessment of individual diabetes management through blood glucose monitoring and responses on a pretest and posttest questionnaire. Patients in the treatment groups demonstrated significantly lower average weekly blood glucose levels and a decreased incidence of hyperglycemic episodes compared with the control group. Questionnaire data for both treatment groups demonstrated a significant increase in patient understanding of diabetes medications and medications for associated illnesses, an increase in knowledge about blood glucose monitoring, and a positive difference in perceptions/attitudes toward diabetes and communication with the pharmacist. This approach is consistent with the concept of pharmaceutical care in which the pharmacist helps patients avoid long-term complications and thus improve their quality of life.", "This was a pilot study of the use of a clinical pharmacist as a therapeutics adviser (academic detailer) to modify antibiotic prescribing by general practitioners.\n Following a visit by the adviser (March-May), 112 general practitioners were recruited and randomised to control or active groups. A panel of experts prepared a best practice chart of recommended drugs for upper and lower respiratory tract infections, otitis media and urinary tract infections. The adviser made a 10-15 min visit to each prescriber in the active group (June-July), gave them the chart and discussed its recommendations briefly. Doctors in the control group were not visited nor given the chart. Prescription numbers for all prescribers were obtained from the Commonwealth Health Insurance Commission for the pre(March-May) and postdetailing (August-September) periods using a three month lag time for data collection. Data for total numbers of prescriptions and for selected individual antibiotics used in these two periods were analysed using nonparametric statistics.\n Prescribing patterns were similar for the control and active groups in the predetailing period. For both groups, there were significant (P<0.03) increases (45% for control and 40% for active) in total number of antibiotic prescriptions in the post compared with the predetailing period. This trend was anticipated on the basis of the winter seasonal increase in respiratory infections. In line with the chart recommendations for first-line treatment, doctors in the active group prescribed significantly more amoxycillin (P<0.02) and doxycycline (P<0.001) in the post vs predetailing periods. By contrast, doctors in the control group prescribed significantly more cefaclor (P<0.03) and roxithromycin (P<0.03), drugs that were not recommended. The total cost of antibiotics prescribed by doctors in the control group increased by 48% ($37 150) from the preto postdetailing periods. In the same time period, the costs for the active group increased by only 35% ($21 020).\n We conclude that the academic detailing process was successful in modifying prescribing patterns and that it also decreased prescription numbers and costs. Application of the scheme on a nationwide basis could not only improve prescriber choice of the most appropriate antibiotic but also result in a significant saving of health care dollars.", "The effect of pharmaceutical care on the prevention, detection, and resolution of medication-related problems in high-risk patients in a rural community was studied. Adult patients who received care at clinics in a medically underserved area of Alabama and who were identified as being at high risk of medication-related adverse events were randomly assigned to a control group or an intervention group. The control group received standard medical care, and the intervention group received pharmaceutical care, including a medical record review, a medication history review, pharmacotherapeutic evaluation, and patient medication education and monitoring over a one-year period. A total of 69 patients completed the study (33 in the intervention group and 36 in the control group). The percentage of patients responding to hypertension, diabetes, dyslipidemia, and anticoagulation therapy increased significantly in the intervention group and declined in the control group. Ratings for inappropriate prescribing improved in all 10 domains evaluated in the intervention group but worsened in 5 domains in the control group. There were no significant differences between the groups at 12 months in health-related quality of life or medication misadventures. Medication compliance scores improved in the intervention group but not in the control group. Medication knowledge increased in the intervention group and decreased in the control group. Pharmaceutical care in a rural, community-based setting appeared to reduce inappropriate prescribing, enhance disease management, and improve medication compliance and knowledge without adversely affecting health-related quality of life.", "There is limited information from randomized controlled studies about the influence of pharmacist interventions on diabetes control.\n To evaluate the effect of a pharmacist intervention on improving diabetes control; secondary endpoints were medication appropriateness and self-reported adherence.\n A randomized, controlled, multi-clinic trial was conducted in the University of Washington Medicine Neighborhood Clinics. Seventy-seven subjects, > or =18 years old with a hemoglobin (Hb) A(1c) > or =9% at baseline and taking at least one oral diabetes medication, were randomized to receive a pharmacist intervention (n = 43) or usual care (n = 34) for 6 months followed by a 6-month usual-care observation period for both groups. Subjects met with a clinical pharmacist to establish and initiate a diabetes care plan followed by weekly visits or telephone calls to facilitate diabetes management and adherence. HbA(1c), medication appropriateness, and self-reported adherence were assessed at baseline, 6 months, and 12 months.\n The mean HbA(1c) did not differ between groups over the 12-month period (p = 0.61). A reduction in HbA(1c) was noted for both groups over time compared with baseline (p = 0.001); however, control subjects relied more heavily on provider visits. Medication appropriateness was not improved for diabetes medications (p = 0.65). Self-reported adherence was not significantly improved by the intervention.\n This pharmacist intervention did not significantly improve diabetes control, but did allow for similar HbA(1c) control with fewer physician visits. Medication appropriateness and self-reported adherence compared with usual care in individuals with poorly controlled diabetes were not changed.", "A controlled, randomized study was conducted in two chain pharmacies to determine the clinical value of comprehensive pharmacy services for hypertensive patients in a chain pharmacy setting. Twenty-seven patients were enrolled as intervention participants with 26 control subjects. Monthly services for the intervention group included blood pressure and heart rate assessments and counseling on lifestyle modifications and drug therapy. Control patients received initial and final blood pressure measurements and minimal counseling. Both study and control groups completed quality-of-life questionnaires upon entering and completing the study. Results showed that blood pressure control was significantly improved in the study group. Compliance rates as well as energy/fatigue scores (a quality-of-life scale) improved in the study group compared with the control population. Community pharmacists in chain stores could have a beneficial effect on the health care of large numbers of patients if pharmaceutical care programs were developed.", "This study was designed to measure the role effectiveness of pharmacists in the management of patients with hypertension and congestive heart failure. Based on therapy protocols established by physicians and pharmacists prior to the study, the pharmacist was measured against the standard for providing primary care--i.e., the physician. The study showed that the pharmacist competently elected drug therapy and identified adverse drug reactions. As a group, the 20 study patients, whose therapy was determined by the pharmacist, were better managed than the 20 control patients (p less than 0.05). It is suggested that the pharmacist is effective in the role of managing patients with hypertension and congestive heart failure.", "Community pharmacists strive to deliver pharmaceutical care to patients. At the moment, coaching of depressive primary care patients on taking their antidepressants (ADs) is not yet part of their standard care package.\n To investigate the effects of coaching by community pharmacists on psychological symptoms.\n A randomised controlled trial with a 6-month follow-up. Outcomes: psychological symptoms with the Hopkins Symptom Checklist (SCL). Intention-to-treat (ITT) was performed with (1) last observation carried forward and (2) with group mean imputation (GMI).\n Analyses with LOCF and GMI resulted in different findings. The LOCF method revealed that at the 6-month follow-up, the intervention patients were less depressed and less anxious than the controls. The intervention was particularly effective in patients with lower levels of education who received pharmacist's coaching. However, ITT with the GMI method showed no differences in psychological symptoms. Differences between LOCF and GMI were explained by the selective attrition in the intervention arm (attrition intervention patients had lower initial SCL-item scores on depression and anxiety than the completers) and by the higher attrition rate in controls.\n Our study indicates that the interpretation of the effects of an intervention on psychological symptoms can differ substantially by the way missing values are imputed. If both LOCF and GMI produce significant differences, efficacy can be concluded. If not, the effects based on ITT analyses with LOCF are based on artefacts. We recommend that positive intervention effects should only be reported when findings with LOCF and GMI are in accordance.", "Despite clear evidence for the efficacy of lowering cholesterol levels, there is a deficiency in its real-world application. There is a need to explore alternative strategies to address this important public health problem. This study aimed to determine the effect of a program of community pharmacist intervention on the process of cholesterol risk management in patients at high risk for cardiovascular events.\n A randomized controlled trial conducted in 54 community pharmacies (1998-2000) included patients at high risk for cardiovascular events (with atherosclerotic disease or diabetes mellitus with another risk factor). Patients randomized to pharmacist intervention received education and a brochure on risk factors, point-of-care cholesterol measurement, referral to their physician, and regular follow-up for 16 weeks. Pharmacists faxed a simple form to the primary care physician identifying risk factors and any suggestions. Usual care patients received the same brochure and general advice only, with minimal follow-up. The primary end point was a composite of performance of a fasting cholesterol panel by the physician or addition or increase in dose of cholesterol-lowering medication.\n The external monitoring committee recommended early study termination owing to benefit. Of the 675 patients enrolled, approximately 40% were women, and the average age was 64 years. The primary end point was reached in 57% of intervention patients vs 31% in usual care (odds ratio, 3.0; 95% confidence interval, 2.2-4.1; P<.001).\n A community-based intervention program improved the process of cholesterol management in high-risk patients. This program demonstrates the value of community pharmacists working in collaboration with patients and physicians.", "The predictive value of digoxin and furosemide treatment for identifying patients receiving treatment for congestive heart failure (CHF), the use of angiotensin-converting-enzyme (ACE) inhibitors in this population, and the ability of a pharmacist outreach program to address underutilization of ACE inhibitors were studied. All physicians and owner-managers of community pharmacies on Newfoundland's Avalon Peninsula were asked to participate in the study. Pharmacists who agreed to participate were asked to list patients of the participating physicians with prescriptions for (1) furosemide and digoxin with and without an ACE inhibitor or angiotensin II-receptor inhibitor and (2) an ACE inhibitor. Physicians were visited by a pharmacist and asked whether each of their patients receiving digoxin and furosemide was being treated for CHF and to identify further cases of CHF among their patients receiving an ACE inhibitor. Intervention-group physicians received academic detailing on the use and dosage of ACE inhibitors and angiotensin II-receptor inhibitors for CHF. Both groups were reinterviewed after three months to establish what if any changes in therapy had occurred for each patient discussed during the first visit. The positive predictive value of digoxin and furosemide treatment for identifying patients receiving treatment for CHF was 94%. Seventy-six percent of patients identified by physicians as CHF patients who were taking digoxin and furosemide were treated with an ACE inhibitor. Thirty-six percent of patients treated with an ACE inhibitor for CHF received the targeted dosage. Four physicians stated that the outreach visit influenced their prescribing, but there was no significant difference in ACE inhibitor prescribing between the intervention and control groups. A pharmacist outreach program involving the use of prescription records and academic detailing did not affect prescribing or dosages of ACE inhibitors but demonstrated value as a quality assurance tool.", "The aim of this study was to investigate the impact of a pharmacist-led pharmaceutical care programme, involving optimization of drug treatment and intensive education and self-monitoring of patients with heart failure (HF) within the United Arab Emirates (UAE), on a range of clinical and humanistic outcome measures.\n The study was a randomized, controlled, longitudinal, prospective clinical trial at Al-Ain Hospital, Al-Ain, UAE. Patients were recruited from the general medical wards and from cardiology and medical outpatient clinics. HF patients who fulfilled the entrance criteria, and had no exclusion criteria present, were identified for inclusion in the study. After recruitment, patients were randomly assigned to one of two groups: intervention group or control group. Intervention patients received a structured pharmaceutical care service while control patients received traditional services. Patient follow-up took place when patients attended scheduled outpatient clinics (every 3 months). A total of 104 patients in each group completed the trial (12 months). The patients were generally suffering from mild to moderate HF (NYHA Class 1, 29.5%; Class 2, 50.5%; Class 3, 16%; and Class 4, 4%).\n Over the study period, intervention patients showed significant (P < 0.05) improvements in a range of summary outcome measures [AUC (95% confidence limits)] including exercise tolerance [2-min walk test: 1607.2 (1474.9, 1739.5) m.month in intervention patients vs. 1403.3 (1256.5, 1549.8) in control patients], forced vital capacity [31.6 (30.8, 32.4) l.month in the intervention patients vs. 27.8 (26.8, 28.9) in control patients], health-related quality of life, as measured by the Minnesota living with heart failure questionnaire [463.5 (433.2, 493.9) unit.month in intervention patients vs. 637.5 (597.2, 677.7) in control patients; a lower score in this measure indicates better health-related quality of life]. The number of individual patients who reported adherence to prescribed medications was higher (P < 0.05) in the intervention group (85 vs. 35), as was adherence to lifestyle advice (75 vs. 29) at the final assessment (12 months). There was a tendency to have a higher incidence of casualty department visits by intervention patients, but a lower rate of hospitalization.\n The research provides clear evidence that the delivery of pharmaceutical care to patients with HF can lead to significant clinical and humanistic benefits.", "To evaluate the effect of sustained clinical pharmacist interventions involving elderly outpatients with polypharmacy and their primary physicians.\n Randomized, controlled trial of 208 patients aged 65 years or older with polypharmacy (> or = 5 chronic medications) from a general medicine clinic of a Veterans Affairs Medical Center. A clinical pharmacist met with intervention group patients during all scheduled visits to evaluate their drug regimens and make recommendations to them and their physicians. Outcome measures were prescribing appropriateness, health-related quality of life, adverse drug events, medication compliance and knowledge, number of medications, patient satisfaction, and physician receptivity.\n Inappropriate prescribing scores declined significantly more in the intervention group than in the control group by 3 months (decrease 24% versus 6%, respectively; P = 0.0006) and was sustained at 12 months (decrease 28% versus 5%, respectively; P = 0.0002). There was no difference between groups at closeout in health-related quality of life (P = 0.99). Fewer intervention than control patients (30.2%) versus 40.0%; P = 0.19) experienced adverse drug events. Measures for most other outcomes remained unchanged in both groups. Physicians were receptive to the intervention and enacted changes recommended by the clinical pharmacist more frequently than they enacted changes independently for control patients (55.1% versus 19.8%; P <0.001).\n This study demonstrates that a clinical pharmacist providing pharmaceutical care for elderly primary care patients can reduce inappropriate prescribing and possibly adverse drug effects without adversely affecting health-related quality of life.", "To compare the effectiveness of an evidence-based, systematic approach to hypertension care involving comanagement of patients by primary care physicians and clinical pharmacists versus usual care in reducing blood pressure in patients with uncontrolled hypertension.\n Patients in a staff model medical group with uncontrolled hypertension were randomized to either a usual care (UC) or a physician-pharmacist comanagement (PPCM) group. All physicians in the study received both group and individual education and participated in the development of an evidence-based hypertension treatment algorithm. Physicians were then given the names of their patients whose medical records documented elevated blood pressures (defined as systolic > or = 140 mm Hg and/or diastolic > or = 90 mm Hg for patients aged < 65 yrs, and systolic > or = 160 mm Hg and/or diastolic > or = 90 mm Hg for those aged > or = 65 yrs). Patients randomized to the UC group were managed by primary care physicians alone. Those randomized to the PPCM group were comanaged by their primary care physician and a clinical pharmacist, who provided patient education, made treatment recommendations, and provided follow-up. Blood pressure measurements, antihypertensive drugs, and visit costs/patient were obtained from medical records.\n One hundred ninety-seven patients with uncontrolled hypertension participated in the study. Both PPCM and UC groups experienced significant reductions in blood pressure (systolic -22 and -11 mm Hg, respectively, p < 0.01; diastolic -7 and -8 mm Hg, respectively, p < 0.01). The reduction in systolic blood pressure was greater in the PPCM group after adjusting for differences in baseline blood pressure between the groups (p < 0.01). More patients achieved blood pressure control in the PPCM than in the UC group (60% vs 43%, p = 0.02). Average provider visit costs/patient were higher in the UC than the PPCM group ($195 vs $160, p = 0.02).\n An evidence-based, systematic approach using physician-pharmacist comanagement for patients with uncontrolled hypertension resulted in improved blood pressure control and reduced average visit costs/patient.", "One important task for physicians is to optimize their patients' medication regimen. Involvement of clinical pharmacists who have specific training in drug regimen design has been associated with improved patient outcomes for specific medical conditions, eg, hypertension and anticoagulation. This prospective, randomized trial investigated whether a single consultation by a clinical pharmacist with high-risk patients and their primary physicians would result in improved prescribing outcomes.\n Patients at risk for medication-related problems were identified and randomized to receive a pharmacotherapy consultation (consult group) or usual medical care (control group). Outcomes, including the number of drugs, number of doses per day, cost of medications, and patient reports of adverse effects, were recorded at baseline and at 6 months following the intervention.\n Fifty-six subjects were evaluable: 29 in the control group, and 27 in the consult group. Six months after the consultation, the number of drugs, the number of doses, and the 6-month drug costs all decreased in the consult group and increased in the control group; the net difference was 1.1 drugs (P = .004), 2.15 doses per day (P = .007), $586 per year (P = .008). The side effects score improved by 1.8 points more in the consult group compared with the control group (P = NS). Similarly, the prescribing convenience score in the consult group improved by 1.4 points more than that of the control group (P = NS).\n This study demonstrates several important benefits of integration of a clinical pharmacist into a primary care setting, including improvement in cost and simplification of the medication regimen with no reduction in quality of care.", "The impact of pharmacist interventions on the care and outcomes of patients with depression in a primary care setting was evaluated.\n Patients diagnosed with a new episode of depression and started on anti-depressant medications were randomized to enhanced care (EC) or usual care (UC) for one year. EC consisted of a pharmacist collaborating with primary care providers to facilitate patient education, the initiation and adjustment of antidepressant dosages, the monitoring of patient adherence to the regimen, the management of adverse reactions, and the prevention of relapse. The patients in the UC group served as controls. Outcomes were measured by the Hopkins Symptom Checklist, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for major depression, health-related quality of life, medication adherence, patient satisfaction, and use of depression-related health care services. An intent-to-treat analysis was used.\n Seventy-four patients were randomized to EC or UC. At baseline, the EC group included more patients diagnosed with major depression than did the UC group (p = 0.04). All analyses were adjusted for this difference. In both groups, mean scores significantly improved from baseline for symptoms of depression and quality of life at three months and were maintained for one year. There were no statistically significant differences between treatment groups in depression symptoms, quality of life, medication adherence, provider visits, or patient satisfaction.\n Frequent telephone contacts and interventions by pharmacists and UC in a primary care setting resulted in similar rates of adherence to antidepressant regimens and improvements in the outcomes of depression at one year.", "This prospective, randomized, controlled study evaluated the impact of pharmacist-initiated home blood pressure monitoring and intervention on blood pressure control, therapy compliance, and quality of life (QOL). Subjects were 36 patients with uncontrolled stage 1 or 2 hypertension. Eighteen subjects received home blood pressure monitors, a diary, and instructions to measure blood pressure twice every morning. Home measurements were evaluated by a clinical pharmacist by telephone, and the patient's family physician was contacted with recommendations if mean monthly values were 140/90 mm Hg or higher. Eighteen control patients did not receive home monitors or pharmacist intervention. Office blood pressure measurements and QOL surveys (SF-36) were obtained at baseline and after 6 months. Mean absolute reductions in systolic and diastolic pressures were significantly reduced from baseline in intervention subjects (17.0 and 10.5 mm Hg, both p < 0.0001) but not in controls (7.0 and 3.8 mm Hg, p = 0.12 and p = 0.09). More intervention subjects (8) had blood pressure values below 140/90 at 6 months compared with controls (4). During the study 83.3% (15) of intervention subjects had drug therapy changes versus 33% (6) of controls (p < 0.01). Compliance and QOL were not significantly affected. Our data suggest that the combination of pharmacist intervention with home monitoring can improve blood pressure control in patients with uncontrolled hypertension. This may be related to increased modifications of drug regimens.", "The objective of this study was to evaluate the impact of a pharmaceutical care program on children with asthma. A comprehensive asthma education and monitoring program that includes basic asthma knowledge, symptoms and exacerbation evaluation, pharmacotherapy assessment including inhaler technique, and quality of life measurements was developed and applied in an outpatient paediatric clinic of the Catholic University of Chile. All patients with moderate asthma scheduled for outpatient visits with their internist over a 1-year period were referred for pharmacist intervention. Patients (aged 7-17) with moderate asthma attending the clinic were allocated to the intervention (group A) or control group (group B). Intervention patients were educated on their disease, pharmacotherapy, self-management, and inhalation techniques. The group B were children with their regular treatment for asthma but without pharmaceutical intervention. A paediatric asthma quality of life questionnaire (PAQLQ) was applied to both groups at 0, 2, and 9 weeks to assess the quality of life. Spirometry was done at the beginning and at the completion of the 9-week study. Beta-agonists used by each patient were also recorded. Eleven children (10.0+/-0.7 years) were included in the pharmaceutical care program, and ten children (9.9+/-0.6 years) in group B. For the individual domains of activities (A), emotions (E), and symptoms (S) there was a significant improvement in the children who received pharmaceutical care in comparison with those who did not receive it. The scores of group B did not change during the 9 weeks of follow-up. There were no significant changes in spirometric values in either group.", "To evaluate a pharmacist-conducted educational and monitoring programme, designed to promote dietary and lifestyle modification and compliance with lipid-lowering drug therapy, for patients with dyslipidaemia.\n This was a prospective, randomized, controlled study. The participants were 94 adults, with 81 completing the study (intervention group: 39; control group: 42), with a cardiovascular-related diagnosis and discharged from hospital, between April and October 2001, on lipid-lowering drug therapy. Patients in the intervention group were visited at home monthly by a pharmacist, who educated the patients on the goals of lipid-lowering treatment and the importance of lifestyle issues in dyslipidaemia and compliance with therapy, assessed patients for drug-related problems, and measured total blood cholesterol levels using point-of-care testing. Patients in the control group received standard medical care. The main outcome measure was total blood cholesterol levels after 6 months, and an evaluation of patient and general practitioner satisfaction with the programme.\n There was no significant difference in baseline total blood cholesterol levels between the two groups. The reduction over the course of the study in cholesterol levels within the intervention group was statistically significant (4.9 +/- 0.7 to 4.4 +/- 0.6, P<0.005), whereas there was no change within the control group (P=0.26). At follow-up, 44% of the intervention group patients and 24% of the control group patients had cholesterol levels below 4.0 mmol/L (P=0.06). The reduction in total cholesterol in the intervention group should translate to an expected 21% reduction in cardiovascular mortality risk and a 16% reduction in total mortality risk--more than twice the risk reduction achieved in the control group. In addition, the programme was very well received by the patients and their general practitioners, by satisfaction questionnaire.\n A pharmacist-conducted educational and monitoring intervention improved the outcomes of lipid-lowering drug therapy.", "To measure the effects of a collaborative care model that emphasized the role of clinical pharmacists in providing drug therapy management and treatment follow-up to patients with depression, we conducted a randomized controlled trial at a staff model health maintenance organization. We compared the outcomes of subjects treated in this collaborative care model (75 patients, intervention group) with subjects receiving usual care (50 patients, control group). After 6 months, the intervention group demonstrated a significantly higher drug adherence rate than that of the control group (67% vs 48%, odds ratio 2.17, 95% confidence interval 1.04-4.51, p=0.038). Patient satisfaction was significantly greater among members randomly assigned to pharmacists' services than among controls, and provider satisfaction surveys revealed high approval rates as well. Changes in resource utilization were favorable for the intervention group, but differences from the control group did not achieve statistical significance. Clinical improvement was noted in both groups, but the difference was not significant. Clinical pharmacists had a favorable effect on multiple aspects of patient care. Future studies of this model in other health care settings appear warranted.", "To evaluate the impact of pharmaceutical care on selected clinical and economic outcomes in patients with hypertension or chronic obstructive pulmonary disease (COPD) in ambulatory care settings.\n Clinic patients with hypertension or COPD were randomly assigned to a treatment group (pharmaceutical care) or a control group (traditional pharmacy care) over a six-month period. Clinical pharmacists and pharmacy residents conducted the protocols. There were 133 evaluable patients (63 treatment and 70 control) in the hypertension study arm and 98 evaluable patients (43 treatment and 55 control) in the COPD study arm.\n 10 Departments of Veterans Affairs medical centers and 1 academic medical center.\n Patient-centered pharmaceutical care model (employing standardized care) implemented by clinical pharmacy residents.\n Patient knowledge, medication compliance, and health resource use.\n The hypertension treatment group had a significantly greater reduction in systolic blood pressure from visit 1 to visit 5 than did the control group. In the COPD study arm, trends were positive in the treatment group for patients ratings of symptom interference with activities and dyspnea measures. There was a significant difference between the hypertension treatment and control group for compliance. There were no significant changes in compliance scores in the COPD study arm. Mean number of hospitalizations and other health care provider visits was higher for the hypertension control group. For patients with COPD, hospitalizations increased in the control group, and the number of other health care provider visits was higher in the control group.\n Pharmacists' participation in a pharmaceutical care program resulted in disease state improvement in ambulatory patients with hypertension and COPD.", "Educational outreach visits are commonly used to promote changes in prescribing in family practice. However, the effectiveness of outreach visits has not been evaluated across a range of settings.\n To estimate the effectiveness of educational outreach visits on United Kingdom (UK) general practice prescribing and to examine the extent to which practice characteristics influenced outcome.\n Randomised controlled trial.\n General practices in 12 health authorities in England.\n Educational outreach visits were made to practices that received two of four guidelines. Each practice provided data on treatment of patients for all four guidelines for both pre and post-intervention periods. The primary outcome is average effect across all four guidelines. Secondary analyses examined the predictive effect of practice and guideline characteristics.\n Seventy per cent of practices approached agreed to take part in the intervention. Overall, educational outreach was associated with a significant improvement in prescribing practice (odds ratio [OR] = 1.24 [95% CI = 1.07 to 1.42]), a 5.2% (95% CI = 1.7% to 8.7%) increase in the number of patients treated within the guideline recommendations. Smaller practices (two or fewer full-time equivalent practitioners) responded much more favourably to educational outreach than larger practices. Smaller practices improved their performance in line with the guidelines by 13.5% (95% CI = 6% to 20.9%) attributable to outreach, while larger practices improved by only 1.4% (95% CI = -2.4% to 5.3%, P-value for interaction <0.001).\n In large practices, educational outreach alone is unlikely to achieve worthwhile change. There is good evidence to support the use of educational outreach visits in small practices.", "The impacts of two models of pharmacist consultation on patient function and health-related quality of life (HRQOL) relative to a control model were studied. Patients in the random-assignment study and the areawide study of the Kaiser Permanente/USC Patient Consultation Study were surveyed three times over a two-year period. The patients were receiving pharmaceutical services under the Kaiser Permanente model of consultation (KP model), a state model of consultation, or a control model and were stratified according to prescription drug use. A global visual-analogue scale and Short Form-36 were used to assess HRQOL. In the areawide study, only 2 of 42 comparisons of the effects of the KP or state model on HRQOL were significant; both were associated with the state model and involved only small increases. In the random-assignment study, 3 of 21 estimated effects of the KP model on HRQOL were positive and significant; 2 of these were significantly different between the KP model and the state model. Although the KP and state models of consultation were associated with some changes in HRQOL, the overall influence was not consistent and not clinically important.", "To evaluate the effectiveness of guidelines with or without one-to-one educational outreach visits by community pharmacists in improving general practice prescribing for non-steroidal anti-inflammatory drugs (NSAIDs).\n Cluster randomised trial of 20 general practices within Avon, England. Practices were randomised to three groups: control; mailed guidelines; mailed guidelines plus educational outreach visits. General practitioners (GPs) in the latter group received two one-to-one outreach visits from community pharmacists. Changes in prescribing were measured using outcomes derived from prescribing analysis and cost (PACT) data. The primary outcome measure was change in the volume of prescribing for ibuprofen, diclofenac and naproxen as a percentage of total NSAID prescribing. Six secondary outcomes included other measures of prescribing quality and volume. A cost-benefit analysis was performed.\n No significant differences were observed for the primary outcome measure: practices receiving outreach visits prescribed only 2.1% [95% confidence interval (CI): -0.8 to 5.0] more of the three recommended NSAIDs than the control practices did and 1.6% (95% CI: -1.4 to 4.7) more than practices that received guidelines only. Following adjustment for multiple comparisons, only one secondary outcome showed a statistically significant difference between the groups: the proportion of prescribing of the five most frequently used drugs was 2.2% (95% CI: 0.9 to 3.6) higher in the educational outreach group compared with the control group. A net increase in costs was shown with both interventions.\n Although good prescribing at baseline in the participating practices limited the capacity for improvement, this trial provides no evidence that guidelines with or without educational outreach visits from community pharmacists lead to substantial improvements in prescribing behaviour.", "A number of studies have reported that the risk of bleeding associated with warfarin is highest early in the course of therapy. This study examined the effect of a programme focused on the transition of newly anticoagulated patients from hospital to the community.\n Open-label randomized controlled trial.\n Home-based follow-up of patients discharged from acute care hospital in southern Tasmania, Australia.\n A total of 128 patients initiated on warfarin in hospital and subsequently discharged to general practitioner (GP) care were enrolled in the study. Sixty were randomized to home monitoring (HM) and 68 received usual care (UC).\n HM patients received a home-visit by the project pharmacist and point-of-care international normalized ratio (INR) testing on alternate days on 4 occasions, with the initial visit two days after discharge. The UC group was solely managed by the GP and only received a visit 8 days after discharge to determine anticoagulant control.\n At discharge, 42% of the HM group and 45% of the UC group had a therapeutic INR. At day 8, 67% of the HM patients had a therapeutic INR, compared with 42% of UC patients (P < 0.002). In addition, 26% of UC patients had a high INR, compared with only 4% of HM patients. Bleeding events were assessed 3 months after discharge and occurred in 15% of HM patients, compared with 36% of the UC group (P < 0.01).\n This programme improved the initiation of warfarin therapy and resulted in a significant decrease in haemorrhagic complications in the first 3 months of therapy.", "Inappropriate use of medications is a significant problem in health care today. A possible solution to this problem may be achieved through better control of patients' drug therapy.\n To design a pharmaceutical care program for dyslipidemic patients within a community pharmacy setting that provides education in the areas of medication compliance and lifestyle modifications, while emphasizing the importance of achieving cholesterol goals to ensure improvement in quality of life.\n Patients at an outpatient pharmacy volunteered to be surveyed for 16 weeks. Although both the intervention and control groups were surveyed, the randomly selected intervention group was interviewed more frequently and more comprehensively. Cholesterol, triglycerides, glucose, weight, risk factors, drug-related problems (DRPs), and quality of life were measured via a survey at the onset of the study and continually measured until the study's conclusion.\n In the intervention group, 26 DRPs were detected, of which 24 were resolved; in the control group, 26 DRPs were detected, of which 5 were resolved. When comparing initial and final blood cholesterol levels in the intervention group, the mean decrease was 27.0 +/- 41.1 mg/dL (p = 0.0266); in the control group, the average blood cholesterol level decreased by a mean of 1.4 +/- 37.2 mg/dL (p = 0.6624). In the intervention group, the triglyceride level decreased an average of 50.5 +/- 80.3 mg/dL (p = 0.0169), while the control group experienced a mean triglyceride level increase of 29.6 +/- 118.5 mg/dL (p = 0.1435). As a result of the intervention, the quality of life in the intervention group was improved.\n Short-term pharmaceutical care plans developed in a retail pharmacy within the proper setting may contribute to improved blood lipid values, cardiovascular disease risk factors, and patients' quality of life.", "There is increasing evidence that clinical guidelines can lead to improvements in clinical care. However, they are not self-implementing. Outreach visits may improve prescribing behaviour.\n Within a before-and-after pragmatic randomized controlled trial, involving all general practices in one health district, routine methods were used to distribute guidelines for management of Helicobacter pylori eradication. Intervention practices were offered a visit and the conduct of an audit by a pharmacist trained in the techniques of outreach visiting. The intervention was evaluated using level three Prescribing Analysis and Cost (PACT) data for metronidazole and omeprazole for the two 12 month periods around the introduction of the guidelines.\n Of the 38 intervention practices 19 accepted an outreach visit and three accepted the offer of an audit. There was a significant increase in omeprazole use during the study of 0.24 [95 per cent confidence interval (CI) +0.19 to +0.29] dose units per year but no effect from the offer [-0.02 (95 per cent CI -0.12 to +0.08) dose units] or acceptance of a visit [-0.03 (95 per cent CI -0.15 to +0.08) dose units]. The results for metronidazole were similar, with an increase in use of 0.028 (95 per cent CI +0.018 to +0.038) dose units per year. The effect of the intervention was a non-significant change in prescribing of -0.005 (95 per cent CI -0.025 to +0.015) dose units. Accepting a visit had little effect on prescribing: a change of 0.003 (95 per cent CI -0.021 to +0.027) dose units.\n The routine use of untargeted outreach visiting is probably not a worthwhile strategy." ]

[ "12825763", "8950666", "3914085" ]

[ "Effects of cervical traction and exercise therapy in cervical spondylosis.", "Design and assessment of an adaptive intermittent cervical traction modality with EMG biofeedback.", "Cervical spine disorders. A comparison of three types of traction." ]

[ "A randomised clinical trial was conducted in the Department of Physical Medicine, Chittagong Medical College Hospital from July, 2001 to June, 2002. The objectives of the study were to find out the effects of cervical traction (CT) and exercise on the patients with chronic cervical spondylosis. A total of 199 patients with cervical spondylosis were included in the clinical trial. One hundred patients were treated with cervical traction plus exercise and 99 patients were treated with non-steroidal anti-inflammatory drug (NSAID). Posture correction advice was given to all patients. The patients were treated for 6 weeks. There was a marked improvement in both the groups after treatment (P<0.001). But there was nearly significant difference regarding improvement in treatment with CT plus exercise than with NSAID (P = 0.06). The results indicate that the improvement of the patients with chronic cervical spondylosis was more in CT plus exercise than analgesics. So, CT & neck muscle strengthening exercise may have some more beneficial effects than NSAIDs on chronic cervical spondylosis.", "An intermittent cervical traction modality with closed-loop traction force control based on EMG biofeedback was developed and used for clinical study. This system consists of a EMG scanner, on-line self-adjusted traction force controller, audio/video alarm system, real time therapeutic status display, computer interface hardware, and control software. Twenty-four subjects with diagnosed cervical radiculopathy and muscle spasm symptom who were randomly divided into two groups served as subjects in this study. The control and experimental groups were treated with conventional open loop and new EMG biofeedback closed loop traction control protocols respectively. The results of this study indicate that the average reductions in paraspinal EMG signal during traction after 7 weeks treatment for experimental and control groups were 71 and 50 percent, respectively (p < 0.001). These results not only support the clinical use of intermittent, sitting traction to produce cervical paraspinal muscle relaxation, but also revealed that the average myoelectric activity of cervical paraspinal muscle during traction was reduced as traction force increased over the 7-week duration of traction treatment. Through EMG biofeedback traction force control, muscle injury, neck soreness, or pain after traction may be avoided.", "A randomized clinical trial was conducted to evaluate the efficacy of three commonly employed forms of traction in the treatment of cervical spine disorders. One hundred consenting men and women with disorders of the cervical spine were randomly assigned to one of four treatment groups, static traction, intermittent traction, manual traction, or no traction. All patients, regardless of group assignment, were seen twice weekly. The four groups were shown to be similar with regard to age, sex, diagnosis, chronicity, and prescores on the seven outcome measures. Although the entire cohort of neck patients, regardless of group assignment, improved significantly on all the outcome variables over the 6-week period, patients receiving intermittent traction performed significantly better than those assigned to the no traction group in terms of pain (P = 0.03), forward flexion (P = 0.01), right rotation (P = 0.004) and left rotation (P = 0.05)." ]

[ "3409924", "2231212", "1996894", "12897285", "10228288" ]

[ "Effects of prolonged versus acute indomethacin therapy in very low birth-weight infants with patent ductus arteriosus.", "Prolonged indomethacin therapy for the prevention of recurrences of patent ductus arteriosus.", "Prolonged low dose indomethacin for persistent ductus arteriosus of prematurity.", "Randomized trial of prolonged low-dose versus conventional-dose indomethacin for treating patent ductus arteriosus in very low birth weight infants.", "Short versus prolonged indomethacin therapy for patent ductus arteriosus in preterm infants." ]

[ "Indomethacin has proven effective in closing the patent ductus arteriosus (PDA) in most low birth weight (LBW) neonates with this disorder. Early reopening of the ductus is a problem and often leads to the need for surgery. Prolonged use of indomethacin for several days has been suggested as a means to alleviate this problem. The present study was designed to determine if prolonged therapy over 5 days is more effective than a two-dose regimen in preventing reopening of the PDA. Seventy neonates were randomized for either prolonged therapy over 1 week or to receive two doses of indomethacin. All infants were given two doses of indomethacin 0.15 mg per kg, 12h apart. The maintenance group received an additional 0.1 mg per kg daily for 5 days. Ten days after the infants' initial dose of indomethacin, 6 of 22 in the nonmaintenance group as compared to 0 of 22 in the maintenance group had reopening of their ductus arteriosus. Ten infants in the maintenance group eventually had the ductus reopen at a median of 29, range 11-66 days compared to a median of 3, range 2-44 days in the nonmaintenance group. Significantly fewer babies in the maintenance group had a grade II-IV intraventricular hemorrhage compared to the nonmaintenance group. There was no other significant difference in the two groups in the incidence of necrotizing enterocolitis, retrolental fibroplasia or death. Indomethacin given over 5 days is effective for closure of the ductus arteriosus and will prevent reopening until after the acute clinical course in babies under 1500 g; however, the overall incidence of reopening was not different.", "We tested the hypothesis that prolonged maintenance indomethacin therapy would allow more effective closure of patent ductus arteriosus (PDA) and thereby decrease the recurrence rate. Thirty-nine low birthweight neonates (less than 1500 gm) with confirmed PDA were randomly assigned in a double-blind fashion to receive standard indomethacin therapy (three doses), followed either by maintenance indomethacin therapy (0.2 mg/kg/day) for 5 days or by an equivalent volume of placebo for 5 days. Of the 20 infants who received maintenance indomethacin therapy, two (10%) required additional therapy and one of these required surgical ligation. Of the 19 infants who received only the first three indomethacin doses, nine (47%) required additional therapy for PDA (p less than 0.05) and seven of these had a ligation (p less than 0.05). We conclude that maintenance indomethacin therapy, in comparison with short-term indomethacin therapy, decreases the incidence of surgical PDA ligations, eliminates most PDA recurrences, and does not increase toxic effects of indomethacin in the low birth weight infant with PDA.", "A total of 121 infants who required indomethacin for persistent ductus arteriosus in Liverpool and Cambridge over a four year period were randomised to receive either 0.1 mg/kg daily for six days or 0.2 mg/kg every 12 hours for three doses. The groups were of similar birth weight and gestational and postnatal age, though those treated with a low dose were by chance receiving a higher percentage of oxygen at the start of treatment and there were more deaths from bronchopulmonary dysplasia in this group. Of 59 infants treated with the prolonged course 53 (90%) responded initially to indomethacin compared with 48 of 62 (77%) treated conventionally--a difference of 13% (95% confidence interval for the difference 0 to 26%). Of the 53 responders 11 (21%) relapsed after low dose indomethacin, whereas after the shorter course 19 of 48 (40%) relapsed. This difference was significant (95% confidence intervals 3 to 37%). Side effects, mainly gastrointestinal haemorrhage, were similar in both groups. Significantly fewer infants experienced a rise in serum creatinine or urea concentration after treatment with low dose indomethacin. A prolonged low dose course of indomethacin offers advantages over conventional treatment.", "Indomethacin is used for closing the patent ductus arteriosus in premature infants. Prolonged low-dose indomethacin given over 6 days could potentially improve closure rates because ductal constriction is maintained long enough for more effective anatomic closure. We compared the efficacy of this regimen to conventional dosing in a cohort of very low birth weight infants.\n In a 2-arm clinical trial, 140 infants were randomized to either conventional dose (0.2 mg/kg/dose every 12 hours for 3 doses) or prolonged low-dose indomethacin (0.1 mg/kg/dose daily for 6 doses). The primary outcome measure was ductal closure rate, and the secondary outcomes were the need for a second course of treatment, surgical ligation rates, and side effects.\n Ductal closure after 1 course of indomethacin was similar between the 2 groups: 68% for the conventional dose group and 72% for the prolonged low dose (mean difference -4%; 95% confidence interval: -19% to 11%). The incidence of transient oliguria was higher in the conventional dose group, 31% versus 9%. There was a trend toward more necrotizing enterocolitis in the prolonged low-dose group, 7.0% versus 1.4%.\n There was no difference in efficacy between the 2 dosing regimens. In view of this and with its higher incidence of necrotizing enterocolitis, we do not recommend using prolonged low-dose indomethacin for closing the patent ductus arteriosus in very low birth weight infants.", "To evaluate whether a prolonged low-dose course of indomethacin would produce an improved closure rate and have fewer side effects compared with a short standard dosage schedule in the management of patent ductus arteriosus (PDA) in preterm infants.\n Sixty-one infants of gestational ages 24 to 32 weeks with a PDA confirmed with echocardiography were randomized to receive 0.2 to 0.1 to 0.1 mg/kg indomethacin in 24 hours (short course, n = 31) or 0.1 mg/kg every 24 hours 7 times (long course, n = 30). Echocardiography was done 3, 9, and 14 days after the treatment was started, and side effects were monitored.\n Primary PDA closure occurred more often in the short course group (94% vs 67%, P =.011), but the sustained closure rates were not different (74% vs 60%). Surgical PDA ligations were less frequent in the short course group than in the long course group. The short course group had a shorter duration of oxygen supplementation, less frequent symptoms of necrotizing enterocolitis, and a lower rate of urea retention. Mortality and other neonatal morbidity rates were similar.\n A prolonged low-dosage indomethacin regimen offers no advantage compared with a standard-dosage short course in the management of a hemodynamically significant PDA in preterm infants." ]

[ "9177597", "2347498", "12215960", "2768768", "11736621", "2295775", "2038520", "9619472", "2803624" ]

[ "Mood, physical working capacity and cognitive performance in the elderly as related to physical activity.", "Psychological and cognitive effects of an exercise program for community-residing older adults.", "Improvement of cognitive function by mental and/or individualized aerobic training in healthy elderly subjects.", "Cardiovascular and behavioral effects of aerobic exercise training in healthy older men and women.", "Effect of aerobic exercise on tracking performance in elderly people: a pilot study.", "Effect of aerobic and resistance training on fractionated reaction time and speed of movement.", "Reaction time unchanged in older women following aerobic training.", "Psychological and cognitive outcomes of a randomized trial of exercise among patients with chronic obstructive pulmonary disease.", "Improving aerobic capacity in healthy older adults does not necessarily lead to improved cognitive performance." ]

[ "The age-related decline in physical working capacity, cognitive performance, and psychological well-being can presumably be modified by regular physical exercise. The present study comprises 20 men and 20 women with a mean age of 66 years. Half of the participants were randomly assigned to an exercise group, the remaining half to a control group. The members of the exercise group exercised individually through regular walking (three times a week) during a period of three months. The control group performed instead a series of mental tasks with the same regularity. Results showed significant differences in favor of the exercise group on complex tasks at the post-test, whereas only minor differences were found on simple tasks. Mood improvements were uniform, regardless of exercise involvement. The latter can be taken to indicate that exercise is not the most important factor, instead social context and regular contacts with other people may be equally important for elderly individuals.", "This study examined the effects of a 12-week aerobic exercise program on psychological well-being and cognitive functioning in a group of ethnically diverse older adults living in an urban community. Forty-eight older men and women (mean age = 72 +/- 6) were randomly assigned to one of three groups: an aerobic exercise training group, a social activity control group, or a waiting list group. Results indicated little change in psychological well-being and provided limited support for the association of physiological improvement with enhanced mastery and cognitive functioning.", "The aim of this study was to compare the effects of aerobic and mental training on cognitive function and to determine if the association of the two techniques shows better results. Thirty-two healthy elderly subjects (60 - 76 years) were assigned to one of four groups: aerobic training, mental training, combined aerobic and mental training and a control group. All subjects took two cognitive tests and an incremental exercise test before and after the training period. The intensity of exercise was individualized at the heart rate corresponding to the ventilatory threshold of each subject. After two months, the control group showed no alteration in physiological and cognitive variables. After the training period, the results showed a significant improvement in VO(2)max (F = 4.45, DF = 1, p < 0.05) of 12 % and 11 % in aerobic training and combined aerobic and mental training groups, respectively. Logical memory (F = 4.31, DF = 1, p < 0.05), as well as paired associates learning scores (F = 5.47, DF = 1, p < 0.05) and memory quotient (F = 6.52, DF = 1, p < 0.01) were significantly improved in the three trained groups. The mean difference in memory quotient between pre and post training was significantly higher in the combined aerobic and mental training group compared to aerobic training or mental training groups (F = 11.60, DF = 3, p < 0.001). We conclude that the specific aerobic training and mental training used in this study could induce the same degree of improvement in cognitive function and that combined training seemed to lead to greater effects than either technique alone.", "The cardiovascular and behavioral adaptations associated with a 4-month program of aerobic exercise training were examined in 101 older men and women (mean age = 67 years). Subjects were randomly assigned to an Aerobic Exercise group, a Yoga and Flexibility control group, or a Waiting List control group. Prior to and following the 4-month program, subjects underwent comprehensive physiological and psychological evaluations. Physiological measures included measurement of blood pressure, lipids, bone density, and cardiorespiratory fitness including direct measurements of peak oxygen consumption (VO2) and anaerobic threshold. Psychological measures included measures of mood, psychiatric symptoms, and neuropsychological functioning. This study demonstrated that 4 months of aerobic exercise training produced an overall 11.6% improvement in peak VO2 and a 13% increase in anaerobic threshold. In contrast, the Yoga and Waiting List control groups experienced no change in cardiorespiratory fitness. Other favorable physiological changes observed among aerobic exercise participants included lower cholesterol levels, diastolic blood pressure levels, and for subjects at risk for bone fracture, a trend toward an increase in bone mineral content. Although few significant psychological changes could be attributed to aerobic exercise training, participants in the two active treatment groups perceived themselves as improving on a number of psychological and behavioral dimensions.", "Although much is known about the benefits of aerobic exercise on cardiovascular health, little research has been done on the effect of aerobic exercise on motor performance. This study examined whether aerobic exercise has an effect on visuospatial information processing during finger-movement tracking in elderly subjects.\n Fifteen elderly subjects (mean age=83.2 years, SD=5.7, range=72-91) from a senior housing complex were randomly assigned to a control group or an experimental (exercise) group. Twelve subjects completed the study, and data obtained for 10 subjects were used for data analysis (2 control subjects were eliminated to allow for matched-pairs analysis between the experimental and control groups). The control group (n=5) had a mean age of 80.2 years (SD=7.8). Subjects in the experimental group (n=5) had a mean age of 84.8 years (SD=2.5).\n The intervention consisted of group exercise 3 times a week for 8 consecutive weeks, and included calisthenics (eg, marching in place, side stepping, mock boxing), stationary bicycling, and walking. A finger-movement tracking test and submaximal graded exercise tolerance step tests were performed before and after training to determine changes in finger-movement tracking and any aerobic training effects.\n Matched-pairs t tests showed a difference in tracking from pretest to posttest in the experimental group compared with the control group. Step test performance did not differ between the 2 groups.\n The results of this small-scale study with a limited number of subjects indicate that, for elderly people, finger-movement tracking performance can improve with aerobic exercise, despite the absence of an aerobic training effect. Possible mechanisms for the treatment effect on information processing are discussed.", "To evaluate the effect of aerobic and variable resistance exercise training on fractionated reaction time (RT) and speed of movement (SM) in elderly individuals, premotor time (PMT), motor time (MT), total RT, and SM were measured in 49 healthy, untrained men and women, 70 to 79 years of age, before and after 6 months of training. Subjects were randomized into either a walk/jog (n = 17), a strength training (n = 20), or a control group (n = 12). Improvements in aerobic capacity were only weakly related to reduced total RT (r = 0.30, p less than .05). Analysis of covariance revealed that there were no differences (p greater than .05) among the three groups after training with respect to PMT, MT, total RT, and SM. These findings indicate that 6 months of aerobic and strength training did not induce significant changes in RT or SM in this group.", "The effect of aerobic exercise on reaction time in older women was investigated. 14 women (M age = 65 yr.) were carefully screened for health status and lifestyle, then assigned to a random order of the exercise and control groups (ns = 7). Pre- and posttraining tests of aerobic capacity, simple reaction time, and choice reaction time were administered. The exercise group rode a stationary bicycle ergometer for 8 consecutive weeks for 3 35- to 40-min. sessions per week. There were no significant pretraining differences between groups on simple reaction time, choice reaction time, or estimated VO2max. No posttraining differences for simple and choice reaction time were found even though the exercise group had a significantly higher VO2max than the controls. Contrary to some other findings, the data indicate that reaction time may be independent of aerobic training in healthy older women.", "Exercise rehabilitation is recommended increasingly for patients with chronic obstructive pulmonary disease (COPD). This study examined the effect of exercise and education on 79 older adults (M age = 66.6 +/- 6.5 years; 53% female) with COPD, randomly assigned to 10 weeks of (a) exercise, education, and stress management (EXESM; n = 29); (b) education and stress management (ESM; n = 25); or (c) waiting list (WL; n = 25). EXESM included 37 sessions of exercise, 16 educational lectures, and 10 weekly stress management classes. ESM included only the 16 lectures and 10 stress management classes. Before and after the intervention, assessments were conducted of physiological functioning (pulmonary function, exercise endurance), psychological well-being (depression, anxiety, quality of life), and cognitive functioning (attention, motor speed, mental efficiency, verbal processing). Repeated measures multivariate analysis of variance indicated that EXESM participants experienced changes not observed among ESM and WL participants, including improved endurance, reduced anxiety, and improved cognitive performance (verbal fluency).", "The effects of aerobic exercise training in a sample of 85 older adults were investigated. Ss were assigned randomly to either an aerobic exercise group, a nonaerobic exercise (yoga) group, or a waiting-list control group. Following 16 weeks of the group-specific protocol, all of the older Ss received 16 weeks of aerobic exercise training. The older adults demonstrated a significant increase in aerobic capacity (cardiorespiratory fitness). Performance on reaction-time tests of attention and memory retrieval was slower for the older adults than for a comparison group of 24 young adults, and there was no improvement in the older adults' performance on these tests as a function of aerobic exercise training. Results suggest that exercise-related changes in older adults' cognitive performance are due either to extended periods of training or to cohort differences between physically active and sedentary individuals." ]

[ "3982903", "2181103", "2052460" ]

[ "Aminophylline versus doxapram in idiopathic apnea of prematurity: a double-blind controlled study.", "A blinded, randomized, placebo-controlled trial to compare theophylline and doxapram for the treatment of apnea of prematurity.", "[A comparison of the efficacy of aminophylline and doxapram in preventing idiopathic apnea in preterm newborn infants]." ]

[ "A double-blind controlled study, in two parts, was undertaken to compare the effectiveness of aminophylline and doxapram therapy in idiopathic apnea of prematurity. In the first part of this study, eight of 15 infants responded to doxapram therapy with complete cessation of apneic spells and six of 11 infants responded similarly to administration of aminophylline. These differences were statistically insignificant. In the second part of the study, assessment was made of whether the addition of doxapram to aminophylline therapy was effective in treatment of apnea of prematurity that had been unresponsive to aminophylline alone. Of ten infants who continued to have apneic spells during treatment with aminophylline, eight responded to the addition of doxapram with complete cessation of apnea. Nine infants received placebo in addition to aminophylline, and none had a reduction in frequency of apnea.", "A blinded, randomized, placebo-controlled trial was conducted to evaluate the effectiveness of theophylline and doxapram therapy in 31 infants with significant apnea of prematurity. Of 10 infants, two had a short-term response to placebo, 8 of 10 infants to theophylline, and 7 of 11 infants to doxapram (placebo vs treatment with theophylline or doxapram: p = 0.01). The two infants who initially responded to placebo remained responsive for the duration of the study. Of the eight infants in whom treatment with placebo failed, five were randomly assigned to receive theophylline, for a total of 15 infants treated with theophylline, and two of the eight were randomly assigned to receive doxapram, for a total of 13 infants treated with doxapram; the remaining infant required tracheal intubation. Of the 15 infants randomly assigned to receive theophylline, seven responded for the duration of the study; of the eight infants who did not respond to treatment with theophylline, five responded to doxapram, one responded to a combination of theophylline and doxapram, and two remained resistant to treatment. Of the 13 infants randomly assigned to receive doxapram four responded for the duration of the study; of the nine who did not respond to doxapram, seven responded to theophylline, one responded to a combination of theophylline and doxapram, and one remained resistant to treatment. This study demonstrates that although therapy with theophylline or doxapram is associated with a significant short-term reduction in the incidence of apnea compared with that in placebo-treated infants, the long-term response to treatment is frequently incomplete and is not sustained more than 1 week.", "Doxapram is an analeptic of the respiratory system that has been used in the last few years for the treatment of idiopathic apnea spells in infants who show resistance to methylxantine. In this study we have compared the efficacy of aminophylline and doxapram for the prevention of idiopathic apnea spells in two groups of preterm infants comparable for gestational age, birthweight and postnatal age. The two drugs resulted to be effective in preventing the spells of apnea in 66% and 60% of the cases respectively. In the cases in which there was a partial or negative response, the association of the two substances resulted in a noticeable reduction of the apnea spells. The positive effect of the association of aminophylline and doxapram is probably due to the different action mechanism on the stimulation of the respiratory system." ]

[ "16428356", "17162192", "9445490" ]

[ "Early postnatal allopurinol does not improve short term outcome after severe birth asphyxia.", "Effect of allopurinol supplementation on nitric oxide levels in asphyxiated newborns.", "Effect of allopurinol on postasphyxial free radical formation, cerebral hemodynamics, and electrical brain activity." ]

[ "To investigate whether postnatal allopurinol would reduce free radical induced reperfusion/reoxygenation injury of the brain in severely asphyxiated neonates.\n In an interim analysis of a randomised, double blind, placebo controlled study, 32 severely asphyxiated infants were given allopurinol or a vehicle within four hours of birth.\n The analysis showed an unaltered (high) mortality and morbidity in the infants treated with allopurinol.\n Allopurinol treatment started postnatally was too late to reduce the early reperfusion induced free radical surge. Allopurinol administration to the fetus with (imminent) hypoxia via the mother during labour may be more effective in reducing free radical induced post-asphyxial brain damage.", "This study aimed to investigate the effect of allopurinol in the management of cerebral hypoxia-ischemia by monitoring nitric oxide levels of serum and cerebrospinal fluid. Sixty asphyxiated infants were divided randomly into two groups. Group I infants (n = 30) received allopurinol (40 mg/kg/day, 3 days) within 2 hours after birth. Group II infants (n = 30) received a placebo. Twenty healthy neonates served as control subjects. Cerebrospinal fluid and serum nitric oxide levels were measured within 0-24 hours and 72-96 hours after birth. Both serum and cerebrospinal fluid concentrations of nitric oxide were higher in severely asphyxiated infants (40.86 +/- 8.97, 17.3 +/- 3.63 micromol/L, respectively) but lower in mildly asphyxiated infants (25.85 +/- 3.57, 5.70 +/- 2.56 micromol/L, respectively) than in moderately asphyxiated infants (35.86 +/- 5.38, 11.06 +/- 3.37 micromol/L, respectively) within the first 0-24 hours after birth. Serum nitric oxide levels in control subjects were lower than those of moderately and severely asphyxiated infants. Serum nitric oxide levels of Group I infants within 72-96 hours after birth decreased significantly from their corresponding levels within 0-24 hours after birth. The asphyxiated newborns treated with allopurinol had better neurologic and neurodevelopmental outcome at 12 or more months of age.", "Free radical-induced postasphyxial reperfusion injury has been recognized as an important cause of brain tissue damage. We investigated the effect of high-dose allopurinol (ALLO; 40 mg/kg), a xanthine-oxidase inhibitor and free radical scavenger, on free radical status in severely asphyxiated newborns and on postasphyxial cerebral perfusion and electrical brain activity.\n Free radical status was assessed by serial plasma determination of nonprotein-bound iron (microM), antioxidative capacity, and malondialdehyde (MDA; microM). Cerebral perfusion was investigated by monitoring changes in cerebral blood volume (delta CBV; mL/100 g brain tissue) with near infrared spectroscopy; electrocortical brain activity (ECBA) was assessed in microvolts by cerebral function monitor. Eleven infants received 40 mg/kg ALLO intravenously, and 11 infants served as controls (CONT). Plasma nonprotein-bound iron, antioxidative capacity, and MDA were measured before 4 hours, between 16 and 20 hours, and at the second and third days of age. Changes in CBV and ECBA were monitored between 4 and 8, 16 and 20, 58 and 62, and 104 and 110 hours of age.\n Six CONT and two ALLO infants died after neurologic deterioration. No toxic side effects of ALLO were detected. Nonprotein-bound iron (mean +/- SEM) in the CONT group showed an initial rise (18.7 +/- 4.6 microM to 21.3 +/- 3.4 microM) but dropped to 7.4 +/- 3.5 microM at day 3; in the ALLO group it dropped from 15.5 +/- 4.6 microM to 0 microM at day 3. Uric acid was significantly lower in ALLO-treated infants from 16 hours of life on. MDA remained stable in the ALLO group, but increased in the CONT group at 8 to 16 hours versus < 4 hours (mean +/- SEM; 0.83 +/- 0.31 microM vs 0.50 +/- 0.14 microM). During 4 to 8 hours, delta CBV-CONT showed a larger drop than delta CBV-ALLO from baseline. During the subsequent registrations CBV remained stable in both groups. ECBA-CONT decreased, but ECBA-ALLO remained stable during 4 to 8 hours of age. Neonates who died had the largest drops in CBV and ECBA.\n This study suggests a beneficial effect of ALLO treatment on free radical formation, CBV, and electrical brain activity, without toxic side effects." ]

[ "3925335", "1864478", "8601999", "3928820", "6408500", "7823066", "8191881", "4207990" ]

[ "Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures.", "Cognitive impairment in new cases of epilepsy randomly assigned to carbamazepine, phenytoin and sodium valproate.", "Randomised comparative monotherapy trial of phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed childhood epilepsy.", "A prospective study between carbamazepine, phenytoin and sodium valproate as monotherapy in previously untreated and recently diagnosed patients with epilepsy.", "A double-blind study comparing carbamazepine with phenytoin as initial seizure therapy in adults.", "Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomised comparative monotherapy trial.", "Effects of phenytoin and carbamazepine on cognitive functions in newly diagnosed epileptic patients.", "Carbamazepine for epilepsy. A controlled prospective evaluation." ]

[ "We conducted a 10-center, double-blind trial to compare the efficacy and toxicity of four antiepileptic drugs in the treatment of partial and secondarily generalized tonic-clonic seizures in 622 adults. Patients were randomly assigned to treatment with carbamazepine, phenobarbital, phenytoin, or primidone and were followed for two years or until the drug failed to control seizures or caused unacceptable side effects. Overall treatment success was highest with carbamazepine or phenytoin, intermediate with phenobarbital, and lowest with primidone (P less than 0.002). Differences in failure rates of the drugs were explained primarily by the fact that primidone caused more intolerable acute toxic effects, such as nausea, vomiting, dizziness, and sedation. Decreased libido and impotence were more common in patients given primidone. Phenytoin caused more dysmorphic effects and hypersensitivity. Control of tonic-clonic seizures did not differ significantly with the various drugs. Carbamazepine provided complete control of partial seizures more often than primidone or phenobarbital (P less than 0.03). Overall, carbamazepine and phenytoin are recommended drugs of first choice for single-drug therapy of adults with partial or generalized tonic-clonic seizures or with both.", "Sixty-four new cases of childhood epilepsy were randomly assigned to either carbamazepine, phenytoin or sodium valproate, and were assessed with cognitive tests before medication and three subsequent times over a year. Carbamazepine in moderate dosage adversely affected memory, but sodium valproate and phenytoin did not.", "The medical treatment of childhood epilepsy is largely influenced by clinical trials in adult patients. We know of only one randomised comparative trial (of two drugs) in newly diagnosed childhood epilepsy. We have undertaken a long-term, prospective, randomised, unmasked, pragmatic trial of the comparative efficacy and toxicity of four standard antiepileptic drugs used as monotherapy in children with newly diagnosed epilepsy.\n Between 1981 and 1987, 167 children aged 3-16 years, who had had at least two previously untreated tonic-clonic or partial seizures, with or without secondary generalisation, were randomly allocated treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform to standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to achieving 1-year remission.\n The overall outcome with all four drugs was good. 20% of children remained free of seizures and 73% had achieved 1-year remission by 3 years of follow-up. We found no significant differences between the drugs for either measure of efficacy at 1, 2, or 3 years of follow-up. The overall frequency of unacceptable side-effects necessitating withdrawal of the randomised drug was 9%. This total included six of the first ten children assigned phenobarbitone; no further children were allocated this drug. Of the other three drugs, phenytoin (9%) was more likely to be withdrawn than carbamazepine (4%) or sodium valproate (4%). INTERPRETATION Our data will inform choice of drug and outcome with four of the standard drugs available for newly diagnosed tonic-clonic or partial seizures with or without secondary generalisation in children.", "One hundred and eighty one patients with previously untreated epilepsy were randomised to sodium valproate, phenytoin or carbamazepine as monotherapy and followed up for a median period which ranged from 14 to 24 months. All three drugs were highly effective in the control of generalised seizures but less effective for partial seizures. Excellent or good control was achieved with therapeutic levels of sodium valproate and carbamazepine, but with subtherapeutic levels of phenytoin.", "Carbamazepine was compared with phenytoin in a double-blind study. Of 87 patients, data on 70 patients were complete and used for analysis. Thirty-five patients were treated with each drug. The incidence of major side effects, minor side effects, and complete control (85%) was the same in both groups. A mild but significant elevation of WBC count was found before initiation of drug treatment in the patients presenting with generalized convulsive seizures. Sporadically, elevations in SGOT and LDH were seen; WBC counts below 4,000 were reported, but these were not clinically significant.", "Recent studies have shown that most newly diagnosed epileptic patients can be satisfactorily treated with a single antiepileptic drug. We therefore undertook a prospective randomised pragmatic trial of the comparative efficacy and toxicity of four major antiepileptic drugs, utilised as monotherapy in newly diagnosed epileptic patients. Between 1981 and 1987 243 adult patients aged 16 years or over, newly referred to two district general hospitals with a minimum of two previously untreated tonic-clonic or partial with or without secondary generalised seizures were randomly allocated to treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform with standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to enter one year remission. The overall outcome with all of the four drugs was good with 27% remaining seizure free and 75% entering one year of remission by three years of follow up. No significant differences between the four drugs were found for either measure of efficacy at one, two, or three years of follow up. The overall incidence of unacceptable side effects, necessitating withdrawal of the randomised drug, was 10%. For the individual drugs phenobarbitone (22%) was more likely to be withdrawn than phenytoin (3%), carbamazepine (11%), and sodium valproate (5%). In patients with newly diagnosed tonic-clonic or partial with or without secondary generalised seizures, the choice of drug will be more influenced by considerations of toxicity and costs.", "Phenytoin (PT) and carbamazepine (CBZ) are the two most prescribed anticonvulsants in Finland. Their effect on the cognitive functions of 43 newly diagnosed epileptic patients was examined. The medication was randomly assigned. The patients were tested before the medication was started, and after half a year's therapy. In order to estimate the practice effect in repeated testing a control group of 21 volunteers was similarly tested and retested. Both anticonvulsants, PT in particular, decrease the normal practice effect observed in neuropsychological testing. Compared to the CBZ group, patients with PT became somewhat slower, and their visual memory decreased. Within the PT group the motor slowing was more marked in female patients, and in patients having higher PT serum levels. In PT and CBZ groups there was an equal decrease in negative mood i.e. tension, depression, bewilderment and irritability.", "nan" ]

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[ "Salmeterol xinafoate in the treatment of mild to moderate asthma in primary care. UK Study Group.", "Formoterol, 24 microg bid, and serious asthma exacerbations: similar rates compared with formoterol, 12 microg bid, with and without extra doses taken on demand, and placebo.", "A placebo-controlled, crossover comparison of salmeterol and salbutamol in patients with asthma.", "Salmeterol: a four week study of a long-acting beta-adrenoceptor agonist for the treatment of reversible airways disease.", "Salmeterol powder compared with albuterol aerosol as maintenance therapy for asthma in adolescent and adult patients.", "The long-acting beta2-agonist salmeterol xinafoate: effects on airway inflammation in asthma.", "Tachyphylaxis following regular use of formoterol in exercise-induced bronchospasm.", "Inhaled salmeterol and fluticasone: a study comparing monotherapy and combination therapy in asthma.", "Comparison of powder and aerosol formulations of salmeterol in the treatment of asthma.", "A comparison of salmeterol with albuterol in the treatment of mild-to-moderate asthma.", "Long-term effects of a long-acting beta 2-adrenoceptor agonist, salmeterol, on airway hyperresponsiveness in patients with mild asthma.", "Sensitivity of quality of life domains and constructs to longitudinal change in a clinical trial comparing salmeterol with placebo in asthmatics.", "A placebo-controlled clinical trial of regular monotherapy with short-acting and long-acting beta(2)-agonists in allergic 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.", "A twelve-week comparison of salmeterol and salbutamol in the treatment of mild-to-moderate asthma: a Canadian multicenter study.", "Continuous eformoterol and beta 2-receptor responsiveness.", "Asthma control during long-term treatment with regular inhaled salbutamol and salmeterol.", "Long-acting beta2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: a randomized controlled trial.", "Nocturnal asthma: effect of salmeterol on quality of life and clinical outcomes.", "The effects of regular inhaled formoterol, budesonide, and placebo on mucosal inflammation and clinical indices in mild asthma.", "Subsensitivity of bronchodilator and systemic beta 2 adrenoceptor responses after regular twice daily treatment with eformoterol dry powder in asthmatic patients.", "The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol.", "Low-dose formoterol Turbuhaler (Oxis) b.i.d., a 3-month placebo-controlled comparison with terbutaline (q.i.d.).", "A randomized, 12-week, double-blind, placebo-controlled study comparing formoterol dry powder inhaler with albuterol metered-dose inhaler.", "Efficacy, safety, and impact on quality of life of salmeterol in patients with moderate persistent asthma.", "A dose-response study with formoterol Turbuhaler as maintenance therapy in asthmatic patients.", "Tolerance to the protective effects of salmeterol on methacholine-induced bronchoconstriction: influence of inhaled corticosteroids.", "Efficacy and tolerability of formoterol Turbuhaler in children.", "A randomized, double-blind trial of the effect of treatment with formoterol on clinical and inflammatory parameters of asthma in children.", "Changes in methacholine induced bronchoconstriction with the long acting beta 2 agonist salmeterol in mild to moderate asthmatic patients.", "The effect of salmeterol on nocturnal symptoms, airway function, and inflammation in asthma.", "Formoterol delivered via the dry powder Aerolizer inhaler versus albuterol MDI and placebo in mild-to-moderate asthma: a randomized, double-blind, double-dummy trial.", "Inhaled formoterol dry powder in the treatment of patients with reversible obstructive airway disease. A 3-month, placebo-controlled comparison of the efficacy and safety of formoterol and salbutamol, followed by a 12-month trial with formoterol.", "Salmeterol compared with current therapies in chronic asthma.", "Salmeterol and fluticasone propionate combined in a new powder inhalation device for the treatment of asthma: a randomized, double-blind, placebo-controlled trial.", "[Treatment with salmeterol and quality of life in patients with asthma].", "One-year efficacy and safety of inhaled formoterol dry powder in children with persistent asthma.", "Efficacy and safety of formoterol delivered via a new multidose dry powder inhaler (Certihaler) in adolescents and adults with persistent asthma.", "Bronchodilator subsensitivity after chronic dosing with eformoterol in patients with asthma.", "The efficacy and safety of inhaled salmeterol 50 microg bd in older patients with reversible airflow obstruction.", "Lack of subsensitivity to albuterol after treatment with salmeterol in patients with asthma.", "Effect of long-term salmeterol treatment on exercise-induced asthma.", "Efficacy of salmeterol xinafoate powder in children with chronic persistent asthma.", "Efficacy, tolerability, and effect on asthma-related quality of life of formoterol bid via multidose dry powder inhaler and albuterol QID via metered dose inhaler in patients with persistent asthma: a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study.", "Effect of salmeterol on seasonal changes in airway responsiveness and exhaled nitric oxide in pollen-sensitive asthmatic subjects.", "Reduced protection against exercise induced bronchoconstriction after chronic dosing with salmeterol.", "Effect of long-term salmeterol therapy compared with as-needed albuterol use on airway hyperresponsiveness.", "A 3-month comparison of formoterol with terbutaline via turbuhaler. A placebo-controlled study.", "A comparison of beclomethasone, salmeterol, and placebo in children with asthma. Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group.", "A comparison of regular salmeterol vs 'as required' salbutamol therapy in asthmatic children." ]

[ "Clinical studies of inhaled salmeterol xinafoate have been conducted mainly in moderately to severely affected asthmatic subjects in hospital settings. This study was conducted to investigate the effectiveness of this drug in patients with milder asthma in primary care.\n A multicentre, double blind, randomised, parallel group comparison of salmeterol xinafoate in a dose of 50 micrograms twice daily with placebo, both administered from a four-place dry powder inhaler (Diskhaler), was performed over six weeks in United Kingdom general practices.\n A total of 427 asthmatic patients aged 18 years or older were randomised to receive salmeterol or placebo in a 2:1 ratio. Of the total randomised population, 247 patients were previously on short acting bronchodilators alone whilst 180 patients were concurrently receiving up to 400 micrograms inhaled corticosteroid. Mean morning peak expiratory flow rose more in the salmeterol group than in the placebo group (treatment difference 17 l/min, 95% confidence interval 9 to 26 l/min) but there was a smaller, non-significant difference in mean evening peak expiratory flow. Improvements occurred in the salmeterol-treated group compared with placebo for wheeze, shortness of breath, undisturbed nights, and relief medication use, irrespective of concomitant inhaled corticosteroid use. In addition, improvement in activity restriction was seen in the salmeterol group compared with placebo in the subgroup receiving only bronchodilator.\n Salmeterol is effective and well tolerated in the short term in mildly asthmatic adult patients irrespective of concomitant use of inhaled corticosteroid therapy.", "The primary objective was to determine whether high-dose formoterol, 24 mug bid, was associated with more asthma exacerbations compared with lower formoterol doses in patients with stable persistent asthma. Serious asthma exacerbations (life threatening or requiring hospitalization) were the primary end point. Secondary end points included significant exacerbations requiring systemic corticosteroids, all exacerbations, and changes in FEV1.\n In a multicenter, placebo-controlled, parallel-group study, patients were randomized to 16 weeks of treatment with formoterol, 24 microg bid; formoterol, 12 microg bid, with up to two additional 12-microg doses daily on demand for worsening symptoms (12 microg bid plus on demand); formoterol, 12 microg bid; or placebo. The formoterol 12-microg-bid plus on-demand regimen was administered open label, while the other three regimens were double blind.\n Outpatient clinics.\n A total of 2,085 patients aged > or = 12 years with stable, persistent asthma were enrolled and treated; 65% (n = 1,347) received regular concomitant antiinflammatory therapy during the study.\n Nine patients had respiratory-related serious adverse events (SAEs) requiring hospitalization: two patients (0.4%) in the 24-microg-bid group; one patient (0.2%) in the 12-microg-bid plus on-demand group; five patients (0.9%) in the 12-microg-bid group; and one patient (0.2%) in the placebo group. All of these events were asthma related, except for two SAEs in the 12-microg-bid group that were later considered not to be asthma related by independent reviewers who were not associated with the conduct of the study. The proportions of patients with significant asthma exacerbations (requiring systemic corticosteroids) were similar in the 24-microg-bid group (6.3%, 33 of 527 patients), 12-microg-bid group (5.9%, 31 of 527 patients) and placebo group (8.8%, 45 of 514 patients) and lower in the 12-microg-bid plus on-demand group (4.4%, 23 of 517 patients; p = 0.0057 vs placebo). All treatments were well tolerated. All formoterol treatment regimens had a significant effect on FEV1 measured 2 h after dose during the study (p < 0.0001 vs placebo); and on predose trough FEV1 measured at all visits after baseline (p < 0.002 vs placebo).\n Treatment with formoterol, 24 microg bid, was not associated with an increase in serious asthma exacerbations compared with the lower formoterol doses or placebo.", "We compared the effects of salmeterol (Sm) (50 micrograms twice daily) with that of salbutamol (Sb) (200 micrograms four times daily) and placebo (P) in patients with mild-to-moderate asthma with asthma symptoms and related the effectiveness of these therapies between patients who used concurrent inhaled corticosteroids (ICS) and those who did not. The study was a 12-wk, multicenter, double-blind, placebo-controlled crossover trial with 367 adult asthmatics randomized to each trial medication for 4 wk. Inhaled Sb was provided as rescue medication to all patients throughout the trial. Only 80% of patients, albeit the majority, were receiving maintenance treatment with ICS throughout this trial; this reflects practice current in early 1990. Each study day, patients recorded their morning and evening peak expiratory flows (PEF), assessment of asthma symptoms, and use of rescue medication. Both morning and evening PEF were greater during treatment with Sm than with Sb (mean differences between the treatments of 29.8 and 14.3 L/min, respectively) or P (27.7 and 20.3 L/min, respectively) (p < 0.0001). Sm was also more effective than Sb or P in lowering diurnal variation in PEF and increasing the percentage of symptom-free days and rescue-free days and nights with no sleep disturbance (p < or = 0.0004). Sb was more effective than P in increasing evening PEF and the percentage of symptom-free days (p < 0.05) and rescue-free days (p < 0.0001). The same clinical superiority of Sm compared with Sb and P was observed in those patients using ICS (p < 0.001 for all treatment comparisons), and to a greater extent than in those patients not using ICS (i.e., Sm was more effective than Sb and P in just six of the 20 treatment comparisons; p < 0.05). In conclusion, Sm 50 micrograms twice daily is effective in the management of mild-to-moderate asthma and it further improves asthma control in patients already using ICS.", "A total of 1,068 patients, aged 18-70 yrs, with mild to moderate reversible airways disease, were recruited into a multicentre, double-blind, parallel group study in 76 European centres. Following a 2 week run-in period, the 692 patients fulfilling the entry criteria were randomized to 4 weeks treatment with either salmeterol 12.5, 50 or 100 micrograms or placebo b.d. all given by pressurized inhaler, with assessments of symptoms and ventilatory lung function prior to dosing. All three doses of salmeterol had significant efficacy, manifested by increased morning and evening peak expiratory flow rate (PEFR) (by 35-59 l.min-1 and 11-38 l.min-1, respectively), by reduced diurnal variation in PEFR, and by reduced requirement for additional bronchodilator for symptomatic relief. These effects were dose-related. Daytime asthma symptoms and nocturnal awakenings were significantly reduced by salmeterol treatment, although these reductions were not dose-related. The incidence of adverse events was low. Pharmacologically predictable events (e.g. tremor) were more frequent after treatment with 100 micrograms b.d. than with placebo. On the basis of the efficacy and side-effect information, 50 micrograms b.d. is considered to be the optimum dose for the treatment of this group of asthmatics.", "Two multicenter, randomized, double-masked, placebo-controlled studies involving 451 adolescent and adult patients with mild-to-moderate asthma compared the efficacy and safety of salmeterol powder 50 micrograms twice daily with albuterol 180 micrograms four times daily or placebo (with albuterol as needed) for 12 weeks. Patients had forced expiratory volume in 1 second (FEV1) of 50% to 80%. Throughout the 12-week treatment period, the mean change from baseline in percentage of predicted FEV1 was significantly greater with salmeterol than with placebo; mean area under the curve for FEV1 was significantly greater with salmeterol than with albuterol or placebo. Significant improvements in morning and evening peak expiratory flow, percentage of nights without awakening, and asthma symptoms were observed with salmeterol. Salmeterol was well tolerated, and no clinically significant changes in electrocardiographic activity were observed.", "Salmeterol xinafoate is an inhaled long-acting beta2-adrenoceptor agonist recently introduced for the treatment of asthma. Both in vitro and animal studies suggest that it may have anti-inflammatory activities of benefit in this disease. To assess this directly, the effects of 6 weeks' treatment with salmeterol on indices of clinical activity, airway dysfunction and inflammation in subjects with stable atopic asthma were investigated. In a double blind study, asthmatic patients were randomized to 6 weeks' treatment with either salmeterol 50 microg twice daily (n=14) or placebo (n=12). They underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy immediately before starting treatment and again after 6 weeks. Treatment with salmeterol improved clinical indices of asthma activity, but there were no changes in BAL differential cell counts or mediator levels, and no change in T-cell numbers or activation status. In the biopsy specimens there were no changes in numbers of inflammatory cells, sub-basement membrane collagen deposition or mast cell degranulation. Regular treatment with salmeterol improves clinical indices of asthma but has no effect on the underlying inflammatory process. These findings strengthen guideline recommendations that long-acting beta2-agonists should not be prescribed as sole antiasthma medication.", "Formoterol is a highly effective therapeutic agent in the prevention of exercise-induced bronchospasm (EIB). Regular use of beta-adrenergic drugs may result in a reduction in the protective effect afforded by these bronchodilators against bronchoconstrictor stimuli. It is unknown whether this effect extends to formoterol and exercise.\n We performed a randomized, double-blind, parallel clinical trial in 19 patients with EIB. Each patient received inhaled formoterol or placebo twice daily during 4 weeks. Patients performed two exercise tests in a cycle ergometer on the 1st, 14th, and 28th study days separated 3 hours from each other. A dose of formoterol was given 30 min prior to the 2nd test.\n There were significant differences in bronchoprotection between days 1 and 14 (p = .012) and between days 1 and 28 (p = .012) in the formoterol group. No differences were found in the placebo group. The evolution of the bronchoprotection index was also significantly different between the formoterol and the placebo group (p = .002) from day 1 to 28.\n Tachyphylaxis developed to the protective effect of formoterol against EIB after 4 weeks of regular dosing. Tolerance was already found on day 14, though not progressive. Formoterol should be recommended only as needed in EIB.", "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.", "The efficacy and safety of the aerosol metered-dose inhaler (MDI) formulation of salmeterol for asthma symptoms have been established. Recently, salmeterol has been introduced as a micronized powder formulation administered via a breath-activated multidose powder inhaler (Diskus).\n A multicenter, randomized, double-blind, double-dummy, parallel-group, placebo-controlled study involving 498 adolescents and adults with mild-to-moderate asthma was conducted to compare the efficacy and safety of salmeterol powder 50 microg twice daily via Diskus, salmeterol aerosol 42 microg twice daily via MDI, and placebo.\n Patients were randomized to one of the three treatment groups for 12 weeks. Efficacy was assessed by serial measurements of forced expiratory volume in one second (FEV1) over 12 hours, daily peak expiratory flow (PEF), self-rated asthma symptom scores, nighttime awakenings, and supplemental albuterol use. Safety of each treatment was evaluated by monitoring vital signs, electrocardiograms, Holter monitoring, and occurrence of adverse events.\n As compared with placebo, both salmeterol powder and aerosol produced significant improvement in FEV1 and PEF and decreased nighttime awakenings and supplemental albuterol use. There were no significant differences in the efficacy of the two salmeterol formulations. The magnitude of improvement in pulmonary function was undiminished over the 12-week study. Both formulations of salmeterol were well tolerated, with safety profiles not significantly different from placebo.\n Results of this study indicate that salmeterol, administered either as a powder 50 microg twice daily via Diskus or as an aerosol 42 microg twice daily via MDI, produces clinically significant and comparable improvement in pulmonary function and is well tolerated in patients with mild-to-moderate persistent asthma.", "An effective, long-acting bronchodilator could benefit patients with asthma who have symptoms not controlled by antiinflammatory drugs. We compared a new long-acting, inhaled beta 2-adrenoceptor agonist, salmeterol, with a short-acting beta 2-agonist, albuterol, in the treatment of mild-to-moderate asthma.\n We randomly assigned 234 patients (150 male and 84 female patients 12 to 73 years old) to one of three treatment groups: one group received 42 micrograms of salmeterol twice daily, one received 180 micrograms of albuterol four times daily, and one received placebo. Treatment was assigned in a double-blind fashion, and all patients could use supplemental inhaled albuterol as needed during the 12-week treatment period.\n Measurements of the forced expiratory volume in one second, performed hourly for 12 consecutive hours, showed that a single dose of salmeterol produced a greater mean area under the curve than two doses of albuterol taken 6 hours apart (6.3 vs. 4.9 liter.hr, P < 0.05). The difference was significant on day 1 and at week 4 of the study, but not at week 8 or 12. Salmeterol was also more effective than albuterol or placebo (with albuterol taken as needed) in increasing the morning peak expiratory flow rate: salmeterol induced a mean increase of 24 liters per minute over the pretreatment values, as compared with a decrease of 6 liters per minute with albuterol (P < 0.001) and an increase of 1 liter per minute with placebo (P = 0.002). The mean overall symptom score was improved most by salmeterol treatment (P < 0.05), with the number of days with symptoms and of nights with awakenings decreasing by 22 percent and 52 percent, respectively; there were no differences in results between albuterol treatment and placebo administration. We found no evidence of tolerance to the bronchodilating effects of salmeterol, and adverse reactions to all the treatments were infrequent and mild.\n For the management of mild-to-moderate asthma, salmeterol given twice daily is superior to albuterol given either four times daily or as needed.", "Asthma is characterized by hyperresponsiveness of the airways to bronchoconstrictive stimuli. Long-acting beta 2-adrenoceptor agonists have been introduced as a new therapeutic approach, but there is growing concern about whether control of asthma may deteriorate with the regular use of these agents. We investigated the long-term effects of the beta 2 agonist salmeterol on bronchodilation and on airway hyperresponsiveness to the bronchoconstrictive agent methacholine in mild asthma.\n In a parallel, double-blind study, 24 patients with mild asthma were randomly assigned to treatment with either inhaled salmeterol (50 micrograms, twice daily) (n = 12) or placebo (n = 12) during an eight-week trial. Methacholine challenge was performed before, during, and after the treatment period. Methacholine responsiveness was measured as the provocative concentration (PC20) that caused a 20 percent decrease in the forced expiratory volume in one second (FEV1).\n There was a significant increase in FEV1 one hour after the inhalation of salmeterol (P = 0.006), which did not differ significantly on days 0, 28, and 56 of the treatment period (increase, 9.8, 9.4, and 8.8 percent of predicted FEV1, respectively; P = 0.91). On the first treatment day, salmeterol afforded significant protection against methacholine-induced bronchoconstriction, as shown by a 10-fold increase in the PC20 as compared with the value at entry (P less than 0.001). After four and eight weeks of treatment, however, the salmeterol-induced change in the PC20 was significantly attenuated (P less than 0.001) to only a twofold increase. Two and four days after treatment ended, the PC20 was not significantly different from the value before treatment (P = 0.15).\n Regular treatment of patients with mild asthma with salmeterol leads to tolerance to its protective effects against a bronchoconstrictor stimulus, in this case inhaled methacholine, despite well-maintained bronchodilation. This finding raises concern about the effectiveness of prolonged therapy with long-acting beta 2-adrenoceptor agonists in asthma.", "The quality of life (QOL) benefits of salmeterol versus placebo were compared in a double-blind, multicentre study using the Living with Asthma Questionnaire (LWAQ) which was scored in three different ways. First, the overall LWAQ score showed that salmeterol enhanced QOL compared to placebo. Second, when the LWAQ was analysed in terms of its two construct subscales we found, as predicted previously, that the Problem construct was more sensitive to longitudinal change compared with the Evaluation construct. Third, when the LWAQ was analysed in terms of its 11 domain subscales we found a significant improvement for salmeterol compared with placebo on three domains, Sport, Sleep, and Work and other activities. Analysing clinical trial results in terms of construct subscales and domain subscales provides different kinds of information each of which is useful. Analysis in terms of overall QOL scores is less informative.", "Some recent studies suggest that regular beta(2)-agonist use may result in inadequate control of asthma. It has been hypothesized that this occurs particularly in allergic asthmatic patients exposed to relevant allergens. Moreover, it is still unclear whether this occurs during the use of both short-acting and long-acting beta(2)-agonists.\n Asthmatic patients (n = 145) allergic to house dust mite (HDM) were randomly allocated to monotherapy with a short-acting beta(2)-agonist (SA; n = 48), a long-acting beta(2)-agonist (LA; n = 50), or placebo (n = 47), double blind, double dummy. The study covered three periods: (1) a 4-week run-in period, in which no changes took place; followed by (2) cessation of treatment with asthma medication including inhaled corticosteroids, introduction of allergen avoidance measures (active/placebo treatment) to lower HDM exposure in the active group, and an 8-week washout period to adjust patients to these changes; followed by (3) a 12-week study medication period. At the start of the 12-week medication period, and every 4 weeks thereafter, spirometric measurements (FEV(1) and provocative concentration of histamine causing a 20% fall in FEV(1) [PC(20)]) were performed. Peak flow and asthma symptoms were recorded daily. Additionally, at the start and every 6 weeks thereafter, dust samples were collected from mattresses and living room and bedroom floors to assess HDM (der p 1) concentrations. Effects on FEV(1), PC(20), peak flow, and asthma symptoms were analyzed with repeated-measurement analysis and corrected for the exposure to HDM allergens.\n There were no significant differences among the three medication groups after 12 weeks for FEV(1). However, a significant decrease in mean FEV(1) percent predicted (95% confidence interval [CI]) was observed within the SA group: - 6.6 (- 10.4 to - 2.8) (p = 0.0002). A decrease in geometric mean PC(20) (95% CI) of - 1.2 (- 1.96 to - 0.44) doubling concentration was observed within the SA group (p = 0.05). No significant changes in FEV(1) and PC(20) were observed > 12 weeks within the LA group or the placebo group. There were neither changes in peak flow and asthma symptom scores among the three medication groups nor within the groups. Moreover, none of the parameters showed interactive effects with allergen exposure.\n There were no significant differences among the three medication groups for FEV(1) and PC(20). The within-treatment group comparison showed a significant small decline in FEV(1) for the SA group (but not for the LA group), which could indicate that monotherapy with SAs might have negative effects on FEV(1). This was not seen during regular use of LAS: No clear pathophysiologic mechanism can explain these findings at the moment. Relatively high or low exposure to allergens did not alter these findings.", "nan", "A long-acting inhaled bronchodilator that is both well tolerated and effective could allow for improved control of both daytime and nighttime symptoms in patients with asthma who use frequent as-needed short-acting bronchodilators despite antiinflammatory treatment.\n We compared the efficacy and safety of inhaled salmeterol, 50 micrograms twice daily, with inhaled salbutamol, 200 micrograms four times daily, delivered through a metered-dose inhaler for 3 months in a multicenter, randomized, double-blind, parallel-group study of 228 patients (aged 12 to 76 years) with mild-to-moderate asthma.\n A single morning dose of salmeterol produced improvement in FEV1 that was significantly greater (p < or = 0.012) than that produced by two doses of salbutamol (taken 6 hours apart) when patients were assessed 3 to 6 hours and 10 to 12 hours after the dose. This greater bronchodilation was present on day 1 of the study and after 4, 8, and 12 weeks of regular treatment. Over the 12 weeks, compared with salbutamol, salmeterol treatment was associated with a greater mean improvement in morning peak expiratory flow (35 L/min vs -3 L/min, p < 0.001), a higher percentage of days with no symptoms (29% vs 15%; p = 0.012), and a higher percentage of nights with no awakenings (14% vs -1%; p < 0.001). Adverse events were similar for both treatments.\n In this study salmeterol, 50 micrograms twice daily, was well tolerated and more effective than salbutamol, 200 micrograms four times daily, in improving symptoms and lung function in patients with mild-to-moderate asthma.", "nan", "The adverse effects of long term treatment of asthma with the short acting beta agonist fenoterol have been established in both epidemiological and clinical studies. A study was undertaken to investigate the efficacy and safety of long term treatment with salbutamol and salmeterol in patients with mild to moderate bronchial asthma.\n In a two centre double dummy crossover study 165 patients were randomly assigned to receive salbutamol 400 micrograms q.i.d., salmeterol 50 micrograms b.i.d., or placebo via a Diskhaler. All patients used salbutamol as required for symptom relief. The study comprised a four week run in and three treatment periods of 24 weeks, each of which was followed by a four week washout. Asthma control was assessed by measuring mean morning and evening peak expiratory flow rate (PEFR), a composite daily asthma score, and minor and major exacerbation rates. Washout assessments included methacholine challenge and bronchodilator dose response tests. Analysis was by intention to treat.\n Data from 157 patients were analysed. Relative to placebo, the mean morning PEFR increased by 30 l/min (95% CI 26 to 35) for salmeterol but did not change for salbutamol. Evening PEFR increased by 25 l/min (95% CI 21 to 30) and 21 l/min (95% CI 17 to 26), respectively (p < 0.001). Salmeterol improved the asthma score compared to placebo (p < 0.001), but there was no overall difference with salbutamol. Only daytime symptoms were improved with salbutamol. The minor exacerbation rates were 0.29, 0.88, and 0.97 exacerbations/patient/year for salmeterol, salbutamol and placebo, respectively (p < 0.0001 for salmeterol). The corresponding major exacerbation rates were 0.22, 0.51 and 0.40, respectively (p < 0.03 for salmeterol). For salbutamol the asthma score deteriorated over time (p < 0.01), and the time spent in major exacerbation was significantly longer compared with placebo (12.3 days (95% CI 4.2 to 20.4) versus 8.4 days (95% CI 5.2 to 11.6), p = 0.02). There was no evidence of rebound deterioration in asthma control, lung function, or bronchial hyper-responsiveness following cessation of either active treatment, and no evidence of tolerance to salbutamol or salmeterol.\n Regular treatment with salmeterol is effective in controlling asthma symptoms and reduces minor more than major exacerbation rates. Salbutamol was associated with improved daytime symptoms but subtle deterioration in asthma control occurred over time. Salbutamol should therefore be used only as required.", "Long-acting beta(2)-agonists are prescribed for patients with persistent asthma and are sometimes used without inhaled corticosteroids (ICSs). No evidence exists, however, to support their use as monotherapy in adults with persistent asthma.\n To examine the effectiveness of salmeterol xinafoate, a long-acting beta(2)-agonist, as replacement therapy in patients whose asthma is well controlled by low-dose triamcinolone acetonide, an ICS.\n A 28-week, randomized, blinded, placebo-controlled, parallel group trial conducted at 6 National Institutes of Health-sponsored, university-based ambulatory care centers from February 1997 to January 1999.\n One hundred sixty-four patients aged 12 through 65 years with persistent asthma that was well controlled during a 6-week run-in period of treatment with inhaled triamcinolone (400 microg twice per day).\n Patients were randomly assigned to continue triamcinolone therapy (400 microg twice per day; n = 54) or switch to salmeterol (42 microg twice per day; n = 54) or to placebo (n = 56) for 16 weeks, after which all patients received placebo for an additional 6-week run-out period.\n Change in morning and evening peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV(1)), self-assessed asthma symptom scores, rescue albuterol use, asthma-specific quality-of-life scores, treatment failure, asthma exacerbation, bronchial reactivity, and markers of airway inflammation, compared among the 3 treatment groups.\n During the 16-week randomized treatment period, no significant differences between the salmeterol and triamcinolone groups were observed for conventional outcomes of clinical studies of asthma therapy-morning PEF, evening PEF, asthma symptom scores, rescue albuterol sulfate use, or quality of life. Both active treatments were superior to placebo. However, the salmeterol group had more treatment failures than the triamcinolone group (13/54 [24%] vs 3/54 [6%]; P =.004), as well as more asthma exacerbations (11/54 [20%] vs 4/54 [7%]; P =.04), greater increases in median (interquartile range) sputum eosinophils (2.4% [0.0% to 10.6%] vs -0.1% [-0.7% to 0.3%]; P<.001), eosinophil cationic protein (71 [-2 to 430] U/L vs -4 [-31 to 56] U/L; P =.005), and tryptase (3.1 [2.1 to 7.6] ng/mL vs 0.0 [0.0 to 0.7] ng/mL; P<.001). The duration of benefit when patients were switched from active treatment to placebo after 22 weeks of randomized treatment was not significantly longer in the triamcinolone group than in the salmeterol group.\n Patients with persistent asthma well controlled by low doses of triamcinolone cannot be switched to salmeterol monotherapy without risk of clinically significant loss of asthma control.", "To evaluate the effect of salmeterol on asthma-specific quality of life in patients experiencing significant nocturnal symptoms.\n Randomized, double-blind, placebo-controlled, multicenter clinical trial.\n Allergy/respiratory care clinics.\n Nonsmokers > or = 12 years of age with nocturnal asthma symptoms on at least 6 of 14 days during screening and > or = 15% decrease in peak expiratory flow (PEF) from baseline on nocturnal awakening at least once during screening.\n Salmeterol, 42 microg, or placebo twice daily. Patients were allowed to continue theophylline, inhaled corticosteroids, and \"as-needed\" albuterol.\n Outcome measures included Asthma Quality of Life Questionnaire (AQLQ) global and individual domain scores, FEV1, PEF, nighttime awakenings, asthma symptoms, and supplemental albuterol use. Mean change from baseline for the global and domain AQLQ scores was significantly greater (p < or = 0.005) with salmeterol compared with placebo. At week 12, salmeterol significantly (p < 0.001 compared with placebo) increased mean change from baseline in FEV1, morning and evening PEF, percentage of symptom-free days, percentage of nights with no awakenings due to asthma, and the percentage of days and nights with no supplemental albuterol use. Significant improvements in PEF were observed after treatment with salmeterol regardless of concomitant treatment with theophylline (p < 0.05).\n These results provide evidence that validates the role of salmeterol in improving quality of life in patients with moderate persistent asthma who exhibited nocturnal asthma symptoms and supports the efficacy of salmeterol compared with that of placebo (ie, \"as-needed\" albuterol).", "The present study was designed to observe the effects of 8 wk of treatment with formoterol (Foradil) 24 microgram, budesonide 400 microgram, and matched placebo inhaled twice a day on inflammatory indices in the bronchial mucosa of 64 patients with mild atopic asthma. Biopsies were obtained at the start and 1 wk before stopping a 9-wk period of treatment, and inflammatory cell numbers were assessed in the submucosa and epithelium by immunohistochemistry. Regular formoterol significantly reduced the number of submucosal mast cells, with a similar trend for eosinophils but not activated T cells. A subgroup analysis conducted in biopsies with >= 10 eosinophils per mm2 revealed a significant reduction in eosinophil numbers when compared with both pretreatment baseline (p < 0.01) and changes after placebo (p < 0.01). Parallel, but less pronounced, effects were observed on mast cell but not on CD25(+) T cell numbers. There was no effect of any of the three treatments on BAL levels of mast cell or eosinophil mediators. We conclude that regular treatment with inhaled formoterol reduces rather than increases inflammatory cells in the mucosa of asthmatic patients. It is possible that these cellular effects of formoterol may contribute to the therapeutic efficacy of this drug when used regularly in the treatment", "There is controversy as to the role of long acting beta 2 agonists such as eformoterol and, in particular, whether bronchodilator tolerance occurs during continuous therapy. The purpose of this study was to extend previous observations of bronchodilator subsensitivity with metered dose eformoterol aerosol in order to assess whether tolerance also occurs with a dry powder formulation of the same drug.\n Sixteen asthmatic patients of mean age 33 (range 18-53) years and FEV1 (% predicted) of 64 (3)%, of whom 13 were receiving inhaled corticosteroids, received regular treatment with eformoterol 24 micrograms twice daily or placebo twice daily (without beta 2 agonists) given concurrently for four weeks in a randomised double blind cross-over design. An initial two week run-in was used when beta 2 agonists were withdrawn and substituted with ipratropium bromide. Dose-response curves to eformoterol (cumulative dose 6-102 micrograms) for airways and systemic beta 2 responses were constructed at the end of each treatment period.\n Baseline values for airways and systemic responses were similar. The peak delta FEV1 response from the dose-response curve (as change from baseline) and the delta response for FEV1 and FEF25-75 at six hours after the last dose were attenuated after eformoterol compared with placebo: peak delta FEV1 response 1.001 with placebo v 0.841 with eformoterol (95% CI 0.04 to 0.28); at six hours 0.931 with placebo v 0.581 with eformoterol (95% CI 0.20 to 0.50); and for delta FEF25-75 at six hours 1.29 1/s with placebo v 0.87 1/s with eformoterol (95% CI 0.15 to 0.69). Morning peak expiratory flow rate was significantly improved during treatment with eformoterol (451 1/min) compared with placebo (399 1/min) (95% CI 21 to 82). Systemic beta 2 responses were blunted after eformoterol, together with a reduction in lymphocyte beta 2 receptor binding density.\n Regular twice daily eformoterol dry powder may produce bronchodilator subsensitivity in terms of both peak and duration of response to cumulative repeated doses of eformoterol. Systemic beta 2-mediated adverse effects also showed tolerance, which was mirrored by downregulation of lymphocyte beta 2 adrenoceptors.", "To compare the safety of salmeterol xinafoate or placebo added to usual asthma care.\n A 28-week, randomized, double-blind, placebo-controlled, observational study.\n Study subjects were seen once in the study physician's office for screening and were provided all blinded study medication for the entire study period. Follow-up by telephone was scheduled every 4 weeks.\n Subjects (> 12 years old) with asthma as judged by the study physician were eligible. Individuals with a history of long-acting beta2-agonist use were excluded.\n Salmeterol, 42 mug bid via metered-dose inhaler (MDI), and placebo bid via MDI.\n Following an interim analysis in 26,355 subjects, the study was terminated due to findings in African Americans and difficulties in enrollment. The occurrence of the primary outcome, respiratory-related deaths, or life-threatening experiences was low and not significantly different for salmeterol vs placebo (50 vs 36; relative risk [RR] = 1.40; 95% confidence interval [CI], 0.91 to 2.14). There was a small, significant increase in respiratory-related deaths (24 vs 11; RR, 2.16; 95% CI, 1.06 to 4.41) and asthma-related deaths (13 vs 3; RR, 4.37; 95% CI, 1.25 to 15.34), and in combined asthma-related deaths or life-threatening experiences (37 vs 22; RR, 1.71; 95% CI, 1.01 to 2.89) in subjects receiving salmeterol vs placebo. The imbalance occurred largely in the African-American subpopulation: respiratory-related deaths or life-threatening experiences (20 vs 5; RR, 4.10; 95% CI, 1.54 to 10.90) and combined asthma-related deaths or life-threatening experiences (19 vs 4; RR, 4.92; 95% CI, 1.68 to 14.45) in subjects receiving salmeterol vs placebo.\n For the primary end point in the total population, there were no significant differences between treatments. There were small, but statistically significant increases in respiratory-related and asthma-related deaths and combined asthma-related deaths or life-threatening experiences in the total population receiving salmeterol. Subgroup analyses suggest the risk may be greater in African Americans compared with Caucasian subjects. Whether this risk is due to factors including but not limited to a physiologic treatment effect, genetic factors, or patient behaviors leading to poor outcomes remains unknown.", "This study compared the efficacy of a low dose of formoterol Turbuhaler 6 micrograms b.i.d. (F) with that of terbutaline 0.5 mg q.i.d. (T), and placebo (P) from Turbuhaler. After a 2-week run-in, 397 adults with mild to moderate asthma were randomly allocated to one of the treatments for 12 weeks. During run-in, the mean morning peak expiratory flow (PEF) was 360 (F), 368 (T) and 367 1 min-1 (P). F was better than T (P = 0.014) and P (P = 0.0001) in improving morning PEF [mean changes from run-in: 20 (F), 9 (T), and 21 min-1 (P)]. F was statistically significantly more effective than either T or P in reducing asthma symptoms. F gave also statistically significantly higher evening PEF and less use of rescue medication than P. Bronchodilator response to study drugs and additional 1.25 mg terbutaline was similar before and after the 12-week treatment period. There were no adverse effects of clinical relevance. In conclusion, formoterol Turbuhaler, 6 micrograms b.i.d. was more effective in improving PEF and offered better asthma control than either terbutaline Turbuhaler, 0.5 mg q.i.d. or placebo. Regular use of formoterol did not reduce the bronchodilator response to additional terbutaline. There were no clinically relevant adverse effects.", "Formoterol is a beta2-adrenergic agent which, when inhaled, produces rapid and long-lasting bronchodilatation.\n The aim of this study was to compare the efficacy, safety, and tolerability of formoterol powder for inhalation delivered via the Aerolizer device with placebo and with albuterol delivered via metered-dose inhaler in patients with mild to moderate persistent asthma.\n In a multicenter, double-blind, parallel-group study, 541 patients were randomized at 26 trial sites to receive either formoterol, 12 microg twice daily; formoterol, 24 microg twice daily; albuterol, 180 microg four times daily; or a placebo for 12 weeks. The effects of each treatment on lung function, asthma symptoms, and frequency of rescue albuterol use were evaluated. Adverse effects and clinical laboratory parameters were also evaluated.\n The bronchodilatory effects of formoterol were rapid in onset and persisted for 12 hours. Both formoterol doses were more effective than placebo and albuterol for objective measures of lung function. Morning and evening peak expiratory flow rates were more improved with formoterol, and formoterol provided significantly greater improvements in asthma symptom scores compared with both albuterol and placebo. Overall, patients taking formoterol used significantly less rescue medication than did those taking albuterol or placebo. Nocturnal awakenings occurred less often with formoterol than with placebo or albuterol. The therapeutic effects of formoterol were maintained over the entire 12 weeks of treatment. Adverse events were similar for all treatment groups, and clinical laboratory data were unremarkable.\n Rapid-onset, long-acting formoterol, administered via the Aerolizer inhaler, is an effective and safe treatment for patients with mild to moderate persistent asthma.", "To evaluate the efficacy, safety, and impact on asthma-specific quality of life of salmeterol, a highly selective, long-acting beta 2-agonist, compared with that of placebo (i.e., \"as-needed\" albuterol).\n Randomized, double-blind, placebo-controlled, parallel-group, multicenter study.\n Five hundred thirty-eight nonsmoking symptomatic patients 12 years of age and older meeting American Thoracic Society asthma criteria were enrolled at 55 outpatient clinics; 443 patients completed the study. Patients were randomly assigned to treatment with either salmeterol aerosol 42 micrograms twice daily or placebo (as-needed albuterol) for 12 weeks. We assessed changes in quality of life using the Asthma Quality of Life Questionnaire (AQLQ). Efficacy measurements included daily peak expiratory flow (PEF) rate, daytime and nighttime asthma symptoms, results of pulmonary function tests, and supplemental albuterol use. Patients recorded their PEF rate, supplemental albuterol use, and asthma-related symptoms daily. Pulmonary function tests and AQLQ assessments were performed at baseline and after 4, 8, and 12 weeks of treatment. Safety measurements included vital signs, physical examination, and reports of clinical adverse events at baseline and after 4, 8, and 12 weeks of treatment.\n Mean changes from baseline in AQLQ global and domain scores were significantly greater in the salmeterol group compared with the placebo group (P < 0.001). Patients treated with salmeterol also had significant improvements in mean PEF rates, supplemental albuterol use, asthma symptom scores, and forced expiratory volume in 1 second compared with those given placebo. Both salmeterol and placebo were well tolerated and were not associated with any clinically significant changes in vital signs or physical examination findings.\n Salmeterol 42 micrograms twice daily resulted in significantly greater improvements in asthma-specific quality of life, pulmonary function, and asthma symptoms compared with placebo (as-needed albuterol) in patients with moderate persistent asthma.", "The aim of this randomized, double-blind, parallel group study was to determine the lowest effective dose of 6, 12 and 24 microg formoterol fumarate dihydrate Turbuhaler b.i.d. compared with placebo. The 4 week treatment was preceded by a 1 week run-in period. Morning peak expiratory flow (PEF) before intake of the study drug was the primary variable. Patients recorded PEF, prior to and 15 min after intake of the study drug (immediate response), asthma symptoms, and use of rescue medication morning and evening. Of 221 patients (71 females and 150 males), 194 were included in the efficacy per protocol (PP) analysis; mean age 47 yrs, mean forced expiratory volume in one second (FEV1) 2.01 L (58% of predicted), mean FEV1 reversibility 27% at entry. Ninety percent used inhaled steroids. Compared with placebo, 6 microg formoterol b.i.d was found to be the lowest effective dose in the morning (p=0.008) and evening p=0.0041) PEF. The mean increases in PEF were 22 and 23 L x min-1 respectively, compared with placebo. After 6 microg formoterol, the mean immediate increase in morning PEF was 42 L x min-1 compared to an increase of only 9 L x min-1 after placebo (<0.0001). All doses produced a statistically significant decrease in asthma symptoms, day and night, and the need for rescue medication at night. All doses were well-tolerated. In conclusion, the lowest effective dose in this study was formoterol Turbuhaler 6 microg b.i.d.", "Long-acting beta2-adrenoceptor agonists such as salmeterol reduce airway responsiveness for at least 12 h, but this effect seems to decrease with regular use. We evaluated the time-course of the protective effects of salmeterol on methacholine-induced bronchoconstriction, its modulation by inhaled corticosteroids (ICS) and its influence on asthma control. Thirty two subjects (13 males and 19 females) with mild to moderate stable asthma were divided into two groups according to their medication needs: bronchodilators (BD) alone (n=16) or with ICS (n=16). After a 2 week run-in period, a double-blind crossover study was conducted. Subjects from both groups received salmeterol 50 microg b.i.d. or a placebo for 4 weeks each in random order, separated by a 2 week washout period. The provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) was measured before and after each treatment period, 1 h prior to inhalation of salmeterol or placebo and 1 and 12 h after. Baseline forced expiratory volume in one second (FEV1) increased significantly after salmeterol, both after the first dose and at 4 weeks (BD group: 19 and 17%; ICS: 22 and 13%). On the first day of administration, salmeterol provided significant protection in both groups up to 12 h with a PC20 before and 1 and 12 h postdose of 2.2, 21.7 and 12.4, mg x mL(-1), respectively, in the BD group and 2.1, 11.6 and 55 mg x mL(-1), respectively, in the ICS group. After 4 weeks, this effect was significantly attenuated in both groups with a PC20 before, 1 and 12 h postdose of 3.3, 10.9 and 7.1 mg x mL(-1), respectively, in the BD group and 2.1, 5.0 and 2.3 mg x mL(-1), respectively, in the ICS group. This loss of protective effect was of similar magnitude in both groups. Respiratory symptoms, rescue beta2-agonist use and baseline FEV1 did not change significantly throughout the study in both groups. In conclusion, the bronchoprotective effect of salmeterol decreased with regular use both 1 and 12 h postdose; inhaled corticosteroids did not prevent this reduction. However, the development of tolerance was not associated with loss of asthma control.", "A randomised, double-blind trial was undertaken to investigate the efficacy and tolerability of formoterol Turbuhaler in children with mild to moderate asthma. After a two-week run-in, 248 children aged 6-17 years were randomised to receive formoterol 4.5 and 9 pmicro b.i.d. or placebo for 12 weeks. Morning PEF (primary variable), was significantly improved versus placebo only in the formoterol 9 pmicro b.i.d. group (13 l/min, 95% CCI 1.9, 24.2%; p = 0 .02). Both formoterol 4.5 and 9 pmicro significantly increased the pre-bronchodilator FEV1 by 5.2-6.7% (p < 0 .05) and reduced use of daytime relief medication versus placebo (p < 0 .05). Formoterol 9 pmicro significantly reduced night-time reliever use and awakenings due to asthma versus placebo (p < 0.05). Both doses of formoterol were as well tolerated as placebo. In conclusion, formoterol 4.5 and 9 micro b.i.d. is effective and well tolerated as maintenance therapy in children with mild to moderate asthma.", "In addition to their bronchodilating effect, long-acting inhaled beta-agonists have recently been shown to have some anti-inflammatory properties.\n The purpose of this study was to evaluate the effect of formoterol on inflammatory mediators in children.\n In this double-blind, randomized, placebo-controlled trial, 34 children, aged 6 to 18 years, with moderate atopic asthma, were randomly allocated to receive formoterol or matching placebo for 4 weeks. The primary endpoint of this study was to determine changes in serum levels of inflammatory markers after treatment with formoterol; secondary endpoints included clinical efficacy and bronchial hyperreactivity. The following parameters were measured: symptom score, forced expiratory volume in 1 second (FEV1), provocative concentration of histamine causing a 20% fall in FEV1 (PC20) for histamine and peripheral blood eosinophil count, serum levels of eosinophil cationic protein (ECP), soluble receptor of interleukin-2 (sIL-2R), level of interleukin-4 (IL-4), level of soluble intercellular adhesion molecule-1 (ICAM-1), and immunoglobulin E (IgE) level before and after treatment.\n Compared with placebo, treatment with formoterol significantly improved lung function. The mean value of FEV1 changed from 74% of predicted value before treatment to 80% of predicted value after treatment (P < 0.001). The mean concentration of eosinophil blood count before and after treatment was 379 and 310 cells/mm3 (P = 0.035); ECP was 93 and 83 mcg/L; and serum IL-4 was 0.13 and 0.11 pg/mL (P = 0.001). There was no significant difference between formoterol and placebo recipients in PC20H, and serum concentration of sIL-2R, sICAM-1, or IgE after treatment. The group that received formoterol showed improvement in pulmonary function as measured by FEV1 (P < 0.001), and PC20H (P = 0.04) after 4 weeks of treatment. These patients also showed improvement of clinical symptoms (P < 0.001). Serum marker measurements in the formoterol group showed decreased concentrations of eosinophil blood count, ECP, and IL-4, but there was no difference in before and after measurements of sIL-2R, sICAM-1, and IgE.\n These results indicate that formoterol has measurable anti-inflammatory properties and can diminish asthma symptoms and bronchial hyperreactivity.", "Beta-2 agonists protect against non-specific bronchoconstricting agents such as methacholine, but it has been suggested that the protection afforded by long acting beta 2 agonists wanes rapidly with regular treatment.\n The changes in airway responsiveness were investigated during and after eight weeks of regular treatment with salmeterol 50 micrograms twice daily in 26 adult asthmatic patients, 19 of whom were receiving maintenance inhaled corticosteroids. The study was of a randomised, placebo controlled, double blind design. Airway responsiveness to methacholine was measured as PD20 by a standardised dosimeter technique 12 hours after the first dose, at four weeks and eight weeks during treatment (12 hours after the last dose of test medication), and at 60 hours, one week and two weeks after stopping treatment.\n There were no significant differences between the baseline characteristics of the two groups. A significant improvement in PD20 was seen at all points during treatment with salmeterol compared with the placebo group, with no significant fall off with time. PD20 measurements returned to baseline values after cessation of treatment with no significant difference from the placebo group.\n Salmeterol gave significant protection against methacholine induced bronchoconstriction 12 hours after administration. This protection was of small magnitude, but there was no significant attenuation with eight weeks of regular use and no rebound increase in airway responsiveness on stopping treatment in a group of moderate asthmatic patients, the majority of whom were receiving inhaled corticosteroids.", "To determine the efficacy of salmeterol alone in a group of patients with moderate asthma with nocturnal worsening of symptoms.\n Double-blind, randomized, placebo-controlled crossover study.\n Tertiary care hospital specializing in respiratory diseases.\n Ten patients with nocturnal asthma.\n Subjects were randomized to salmeterol, 100 micrograms twice daily, or placebo for 6 weeks with a 1-week washout between treatment periods. Symptoms, nocturnal awakenings, and beta 2-agonist use were recorded daily. Spirometry was performed at weeks 1 and 6 of each period at bedtime and at 4 AM, and methacholine challenge was performed at 4 AM followed by bronchoscopy with BAL. BAL fluid analysis included cell count and differential count, eosinophil cationic protein, Charcot-Leyden crystal protein, leukotriene B4, and thromboxane B2.\n The percentage of nights with awakenings decreased significantly with salmeterol (69.8 +/- 8.7% vs 30.6 +/- 10.8% for placebo and salmeterol, respectively; p = 0.02). The percentage of 24-h days with supplemental inhaled beta 2-agonist use significantly decreased with salmeterol (85.9 +/- 9.4% vs 70.4 +/- 10.1% for placebo and salmeterol, respectively; p = 0.04). There were no significant differences in bronchial reactivity, 4 AM FEV1, overnight percentage change in FEV1, or indexes of airway inflammation.\n Salmeterol alone improves the number of nocturnal awakenings and supplemental 24-h beta 2-agonist use in nocturnal asthma without significantly altering lung function and airway inflammation.", "The objectives of this study were to compare the efficacy and tolerability of twice-daily formoterol dry powder 12 microg and 24 microg (Foradil) delivered via Aerolizer inhaler with four times daily albuterol (salbutamol) 180 microg delivered via metered dose inhaler (MDI) and placebo. A total of 554 adolescents and adults (ages 12-75 years) with mild-to-moderate asthma were randomized to this 12-week, multicenter, double-blind, double-dummy, placebo-controlled, parallel-group study. Twelve-hour spirometry measurements were taken at weeks 0, 4, 8, and 12. A total of 484 patients completed the study (122, 116, 127, and 119 given formoterol 12 microg, formoterol 24 microg, albuterol, and placebo, respectively). For the primary efficacy variable, the forced expiratory volume in 1 second (FEV1), both formoterol 12 microg and 24 microg were statistically superior to placebo at all time points on all test days (p < or = 0.017) and to albuterol at most time points on all test days (p < or = 0.001). The onset of improvement in FEV1 was rapid, with 15% increase within 5 min in 57%, 71%, and 65% of formoterol 12 microg, formoterol 24 microg, and albuterol patients, respectively. Formoterol was also superior to placebo and albuterol in terms of secondary efficacy variables: FEV1 area under the curve, percentage of predicted FEV1, forced vital capacity and forced expiratory flow, asthma symptom scores, and peak expiratory flows. In conclusion, both formoterol doses were superior to placebo in all lung function measurements. Overall, compared with albuterol, both formoterol doses produced superior bronchodilation. Formoterol and albuterol were safe and well-tolerated.", "Inhaled formoterol is a potent selective beta 2-agonist with rapid onset and at least 12-h duration of bronchodilation. The aim of the study was to compare the bronchodilating effect of inhaled formoterol dry powder (dp) 12 micrograms b.i.d. with salbutamol dp 400 micrograms q.i.d. and placebo in patients with reversible obstructive airway disease (ROAD). The study design consisted of a closed 12-week double-blind, placebo-controlled, multicenter trial followed by an open noncomparative, multicenter, 12-month follow-up trial, in which the tolerability of formoterol dp was assessed. A total of 304 patients (146 men, 158 women) aged 18-79 years, ill during 0.1-64 years, were randomized. No demographic or baseline differences were found among the different treatment groups. The bronchodilating effect of formoterol, assessed by morning premedication PEFR, was significantly superior to placebo (P < 0.0001) and salbutamol (P < 0.0001). Efficacy was maintained during the open follow-up study with 12 micrograms b.i.d. in most of the patients. A few patients, however, needed 24 micrograms b.i.d. to control their ROAD. Formoterol 12 micrograms b.i.d. significantly reduced morning and evening asthma symptoms and sleep disturbances, and reduced significantly the need for rescue medication. The tolerability of the three treatment groups was comparable. In conclusion, formoterol 12 micrograms dp b.i.d. was significantly superior to both salbutamol 400 micrograms dp q.i.d. and placebo, and reduced asthma symptoms significantly. Overall, formoterol showed a tolerability profile comparable to that of salbutamol, and no tachyphylaxis was observed during 1 year of treatment.", "Therapy with salmeterol, a long-acting, selective, inhaled beta 2-adrenergic agonist, is effective and safe for patients with persistent asthma; however, few long-term studies comparing salmeterol with current combination treatment regimens have been reported.\n A multicenter, randomized, placebo-controlled, double-blind study was conducted in 386 patients over 41 to 46 weeks in 27 medical centers (two thirds of the investigators were primary care physicians). Patients were randomized to receive either salmeterol or placebo, and further randomized to weaning or nonweaning from current asthma therapies (except inhaled corticosteroids). Treatment groups were: salmeterol/weaning (S + W), placebo/weaning (P + W), salmeterol/no weaning (S + NW), and placebo/no weaning (P + NW). Attempts at active weaning were carried out at the discretion of the investigator for 2 to 6 weeks. Pulmonary function, albuterol use, and asthma symptoms were measured.\n The clinical benefits of salmeterol occurred despite weaning off existing nonsteroidal asthma medications. The mean morning peak expiratory flow rate was significantly increased in the S + W group (32.3 L/min) compared with both the P + W (4.9 L/min) and P + NW (6.8 L/min) groups (P < .001). Compared with the P + W and P + NW groups, the S + W group experienced significant (P < .05) improvements in overall mean asthma symptom scores, mean number of puffs of supplemental albuterol, the percentage of days with no supplemental albuterol use, and the mean number of awakenings caused by asthma (except for the P + NW comparison, P = .090). No significant differences were noted between treatment groups in any safety evaluation, including 12-lead electrocardiograms.\n The addition of salmeterol in the treatment of persistent asthma resulted in sustained improvement in pulmonary function and symptoms. The long-term use of salmeterol is safe and improves the clinical course and stability of asthma following reductions in nonsteroidal asthma therapy.", "Many patients with persistent asthma need both long-acting bronchodilators and inhaled corticosteroids for optimal asthma control.\n Our purpose was to compare the efficacy and safety of salmeterol 50 microg combined with fluticasone 100 microg (in a combination dry powder product) with that of placebo, fluticasone, or salmeterol alone.\n A 12-week randomized, double-blind, multicenter study was conducted in 356 patients aged 12 years or older with asthma. After a 14-day screening period, patients were randomized to treatment with salmeterol 50 microg combined with fluticasone 100 microg (combination product), salmeterol 50 microg, fluticasone 100 microg, or placebo administered in the Diskus dry powder inhaler (GlaxoWellcome, UK) twice daily.\n Mean change in FEV(1) at end point was significantly (P < or =.003) greater with the combination product (0.51 L) compared with placebo (0.01 L), salmeterol (0.11 L), and fluticasone (0.28 L). The combination product significantly increased (P < or =.013) area under the curve compared with placebo and fluticasone on day 1 and compared with placebo, salmeterol, and fluticasone at week 1 and week 12. Patients in the combination product group were less likely to withdraw from the study because of worsening asthma compared with those in the other groups (P < or =.020). The combination product significantly increased (P < or =.012) morning PEF (combination, 52.5 L/min; placebo, -23.7 L/min; salmeterol, -1.7 L/min; fluticasone, 17.3 L/min) and evening PEF at end point compared with the other groups. The combination product significantly (P < or =.025) reduced symptom scores and albuterol use compared with the other treatments and increased the percentage of nights with no awakenings and the percentage of days with no symptoms compared with placebo and salmeterol. All treatments were equally well tolerated.\n Salmeterol 50 microg and fluticasone 100 microg combined in the Diskus powder delivery device offers significant clinical advantages over salmeterol or fluticasone alone at the same doses.", "The aim of this study was to assess an influence of 4-week treatment with salmeterol on quality of life in asthmatic patients. It was a double blind, placebo controlled study. On the first visit spirometer parameters and PC20H were measured. Within one week of observation all patients recorded scores of asthma symptoms and after that time 22 patients were randomised to the treatment with salmeterol or placebo. On the fourth visit 4-week salmeterol or placebo therapy was finished and all parameters were carried out as on the first visit. Symptoms severity recorded in diary cards was reduced after 4-week of salmeterol therapy. Four week treatment with salmeterol did not change PC20H. Treatment with salmeterol reduced severity of asthma symptoms and use of short-acting beta 2-agonists. The reduction of asthma severity and the use of bronchodilators was more pronounced in the group of patients treated with salmeterol than in the placebo group, but the differences were not significant.", "The long-term efficacy and safety of formoterol dry powder capsules for inhalation in pediatric asthma have not previously been evaluated.\n We examined the effectiveness of inhaled formoterol over a period of 12 months in asthmatic children who were still symptomatic despite anti-inflammatory treatment.\n After a run-in period, 518 patients (5 to 12 years old) were randomized in a double-blind manner to receive 12 or 24 microg formoterol dry powder (Foradil, Novartis Pharma AG, Basel, Switzerland) or placebo twice daily for 12 months. The drug was administered by inhaler (Aerolizer, Novartis Pharma AG) and was given in addition to their anti-inflammatory treatment. The primary variable was the area under the curve for forced expiratory volume in 1 second measured over 12 hours after the morning dose of study medication.\n The area under the curve for forced expiratory volume in 1 second after the first dose of treatment and after 3 and 12 months of treatment was significantly greater for patients receiving formoterol 12 microg and 24 microg than for patients receiving placebo (all P < or = 0.0062). Compared with placebo, both doses of formoterol significantly improved morning and evening premedication peak expiratory flow rate (all P < 0.001). In the group treated with formoterol 24 microg, median symptom score and median dose of rescue medication at night were lower than during the run-in period, whereas the opposite occurred in the placebo group. The incidence of hospitalizations for asthma was higher in the formoterol groups than in the placebo group.\n Our results indicate that, in asthmatic children who are still symptomatic despite anti-inflammatory therapy, the addition of formoterol consistently improves airflow obstruction and nocturnal symptoms and reduces the use of rescue medication. However, this treatment requires close disease monitoring to detect early signs of acute exacerbation.", "Our objective was to compare the efficacy and safety of formoterol (Foradil) delivered via a novel multidose dry powder inhaler (Certihaler) with placebo and albuterol [pressurized metered-dose inhaler (pMDI)], in patients with persistent asthma. After a 2-week run-in phase, 265 patients (13-81 years) previously treated with regular/PRN bronchodilators for persistent asthma were randomized to 12 weeks' double-blind treatment with formoterol 10 microg BID via Certihaler (n = 86), albuterol 180 microg QID via pMDI (n = 88) or placebo (n = 91). The primary efficacy variable was 12-hour AUC of FEV1 after 12 weeks' treatment. Secondary efficacy variables included peak expiratory flow (PEF), rescue bronchodilator medication use, asthma-related quality of life (Juniper Mini Asthma Quality of Life Questionnaire), and asthma symptom scores. Formoterol via the Certihaler had an onset of action within 5 minutes and was associated with a clinically relevant and statistically significant increase in 12-hour AUC of FEV1 after 12 weeks' treatment compared with placebo and albuterol (p < 0.001 and p < 0.05, respectively). Average PEF was significantly superior for formoterol compared with placebo and albuterol (p < 0.001 and p < 0.05, respectively). Compared with placebo, rescue albuterol use during the study was significantly lower for formoterol (p < 0.01) and was accompanied by a trend toward an improvement in asthma-related quality of life (QoL). Asthma symptom scores improved to a similar extent for all treatment groups. Treatment with formoterol via Certihaler was well tolerated. Formoterol 10 microg BID, delivered via the novel Certihaler device, is well tolerated and provides rapid, long-lasting, and clinically superior bronchodilation to placebo and albuterol via pMDI in patients with persistent asthma.", "The aim of the present study was to evaluate in vivo and in vitro beta 2-adrenoceptor responsiveness after chronic inhaled therapy with the long-acting beta 2-agonist eformoterol or placebo, given twice daily, in patients with mild to moderate asthma.\n Seven asthmatic patients, age 34 +/- 5 years were evaluated. Mean forced expiratory volume in 1 second (FEV1) (% predicted) at entry was 58 +/- 5%. After at least 2 weeks run-in without beta 2-agonist therapy, patients were randomized to receive regular treatment with eformoterol 24 micrograms twice daily or placebo twice daily given by metered-dose inhaler for 4 weeks, in a double-blind, crossover design. Dose-response curves (DRC) to eformoterol (cumulative dose 6 micrograms to 126 micrograms) for airways and systemic beta 2-responses were constructed at the end of each treatment period. Responses were measured at baseline, 30 minutes after each dose, and for 6 hours after the last dose. In addition, in vitro parameters of lymphocyte beta 2-receptor function were evaluated prior to the DRC after each treatment period.\n There was a nonsignificant trend towards higher baseline values after eformoterol compared with placebo for FEV1: 0.16 L (95% CI -0.04 to 0.36) and forced expiratory flow (FEF25-75): 0.27 L/sec (95% CI -0.08 to 0.62). The peak bronchodilator response from the DRC and response 6 hours after the last dose were both significantly (P < 0.05) attenuated after chronic therapy with eformoterol compared with placebo. The mean differences between eformoterol and placebo for delta FEV1 were as follows: peak: 0.26 L (95% CI 0.09 to 0.43), and at 6 hours: 0.39 L (95% CI 0.20 to 0.58). Corresponding values for delta FEF25-75 were as follows: peak: 0.41 L/sec (95% CI 0.10 to 0.71), 6 hours 0.52 L/sec (95% CI 0.22 to 0.82). Systemic responses were likewise significantly blunted after eformoterol treatment compared with placebo. There was also subsensitivity of lymphocyte beta 2-adrenoceptor function after treatment with eformoterol compared with placebo.\n Our results suggest that chronic therapy with eformoterol produces (1) tachyphylaxis to its bronchodilator response, which was greatest at 6 hours after the last dose, (2) tachyphylaxis of extrapulmonary beta 2-mediated responses, and (3) subsensitivity of in vitro beta 2-adrenoceptor function.", "Twenty-eight patients aged 64-88 years with reversible airflow obstruction, showing a diurnal variation in peak expiratory flow rate (PEFR) of over 15% or symptoms of airflow obstruction on 4 days of the last week of the run-in period, were entered into a randomized, double-blind, placebo-controlled, cross-over study to evaluate the efficacy of salmeterol 50 microg twice daily by metered-dose inhaler. Salmeterol or matching placebo were each given for 28 days. Mean morning PEFR was 258.71/min on slameterol and 242. 41/min on placebo (adjusted mean difference = 16.31/min; 95% CI = 7. 4, 25.21/min;p = 0.0011). Diurnal variation in PEFR was 7.31/min on salmeterol and 17.51/min on placebo (adjusted mean difference = 10. 31/min; 95% CI -2.0, 0.5 actuations/day; p = 0.0015). After 28 days of treatment the patients' assessment of efficacy was statistically significantly in favour of salmeterol (p = 0.05). Salmeterol was well tolerated as assessed by pulse, blood pressure, haematological and biochemical variables and number of adverse events. Salmeterol 50 microg bd is an effective and well-tolerated therapy for elderly patients with reversible airflow obstruction.", "The development of tolerance to the bronchodilator effects of beta2-agonists used in asthma therapy has been the subject of debate. We conducted two placebo-controlled crossover studies to assess the bronchodilator response to a short-acting beta2-agonist before and after chronic therapy with salmeterol. Patients in one study were corticosteroid-naive; patients in the other study were using inhaled corticosteroids. Changes in FEV1 after cumulative doubling doses of inhaled albuterol were assessed after a 2-wk beta-agonist washout period, before administering study medication on Day 1, and again after 28 d of therapy. Ipratropium bromide was provided as rapid-relief treatment for asthma, and use of any beta2-agonist except the study treatment was prohibited. On both assessment days for salmeterol, and during placebo administration periods, significant increases from predose FEV1 values were observed beginning with the lowest dose of albuterol and continuing throughout the dose-response assessment (p </= 0.001). These increases in FEV1 were maintained for 6 h after the last dose of albuterol (p < 0.05). There were no statistically significant differences in the albuterol dose response following salmeterol or placebo. These studies indicate that irrespective of concurrent corticosteroid treatment, chronic therapy with salmeterol does not result in tolerance to the bronchodilator effects of albuterol.", "With long-term administration of salmeterol, the extent of protection afforded by the drug against experimental precipitants of asthma such as methacholine and adenosine may decrease. Whether this effect extends to a clinically relevant stimulus such as exercise is unknown.\n We performed a random-order, double-blind, crossover trial in 20 patients with exercise-induced asthma. Each patient received inhaled salmeterol or placebo twice daily for a month, with a one-week washout period between treatments. The patients performed cycle ergometry while breathing frigid air 30 minutes after the morning dose and 9 hours later on the 1st, 14th, and 29th study days. The primary end point was the extent of the decrease in forced expiratory volume in 1 second (FEV1) 10 minutes after exertion.\n With placebo, significant airway narrowing developed at all times (mean [+/-SE] decrease from base line in FEV1, 19+/-2 percent in the morning and 18+/-2 percent in the evening). The morning dose of salmeterol attenuated the degree of bronchoconstriction at all times (decrease in FEV1 on day 1, 5+/-2 percent; on day 14, 10+/-3 percent; and on day 29, 9+/-3 percent; P=0.10). Its ability to act throughout the day, however, decreased with long-term administration (decrease in FEV1 from morning to evening on day 1, 6+/-2 percent; on day 14, 15+/-3 percent; and on day 29, 14+/-3 percent; P=0.003).\n Protection against exercise-induced asthma is maintained with long-term administration of salmeterol, but the length of time that the drug remains active after a single dose decreases.", "The efficacy and safety of salmeterol powder have not previously been evaluated in children with asthma in the United States.\n The efficacy and safety of salmeterol powder versus placebo were compared in children between the ages of 4 and 11 years with chronic persistent asthma.\n A randomized, double-blind, placebo-controlled, parallel group trial was performed at 11 clinical centers. Two hundred seven patients were randomly assigned to receive 50 microg salmeterol powder or placebo (and albuterol as needed) twice daily via a breath-actuated device for 12 weeks. Twelve-hour serial pulmonary function assessments were conducted on day 1 and at week 12. Daily recordings of morning and evening peak expiratory flow (PEF), supplemental albuterol use, asthma symptoms, and nocturnal awakenings were assessed.\n On day 1 and at week 12, weighted mean percent of predicted PEF (P < .001, day 1 and P=.008, week 12) and weighted mean forced expiratory volume in one second (P < .001, day 1 and week 12) were significantly higher at all timepoints evaluated over the 12-hour postdosing period in patients treated with salmeterol powder compared with placebo. Overall reductions in supplemental albuterol use and mean asthma symptom scores were also significantly greater in children administered salmeterol compared with placebo (P=.004 and P=.006, respectively). The frequency of adverse events was similar in the two treatment groups.\n Salmeterol powder (50 microg twice daily) is effective and safe in producing bronchodilation and relieving symptoms in children with chronic persistent asthma during 12 weeks of treatment.", "Inhaled beta(2)-agonists are widely used in asthma treatment. The design limitations of pressurized metered dose inhalers (pMDIs) have prompted the development of dry powder inhalers (DPIs) for the delivery of asthma medications.\n The goal of this study was to evaluate the efficacy, tolerability, and effect on asthma-related quality of life (QOL) of a long-acting beta(2)-adrenoreceptor agonist, formoterol, delivered via multidose DPI, compared with albuterol delivered via pMDI or placebo in adolescents and adults with persistent asthma.\n This multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study was conducted in outpatient clinics at 18 US centers. Adolescents and adults with persistent asthma received formoterol 10 pg BID via multidose DPI, albuterol 180 microg QID via pMDI, or placebo for 12 weeks. The primary efficacy variable was the 12-hour AUC of forced expiratory volume in 1 second (FEV(1)) after 12 weeks treatment. Secondary efficacy variables included asthma-related QOL, asthma symptom scores, rescue medication use, and other pulmonary function measures.\n A total of 239 patients (147 females, 92 males; age range, 13-85 years) with persistent asthma were enrolled (formoterol, n = 80; albuterol, n = 79; placebo, n = 80). Formoterol delivered via the multidose DPI resulted in clinically relevant and statistically significant increases in 12-hour AUC of FEV(1) after 12 weeks of treatment compared with albuterol pMDI and placebo (P < 0.019 and P < 0.001, respectively). Asthma-related QOL (total score) was significantly improved with formoterol treatment compared with placebo (P < 0.015). Nocturnal asthma symptom scores significantly improved with formoterol compared with albuterol and placebo (P < 0.001 and P < 0.003, respectively) and rescue medication use was significantly less with formoterol compared with albuterol and placebo (P < 0.004 and P < 0.002, respectively). Treatment with formoterol was well tolerated.\n In this study of adolescents and adults with persistent asthma, 12 weeks of treatment with formoterol 10 microg BID delivered via a multidose DPI provided significantly greater 24-hour bronchodilation compared with albuterol and placebo and resulted in significant improvements in asthma-related QOL compared with placebo. Formoterol was well tolerated in these patients.", "Using a model of natural allergen exposure, we examined the effect of regular treatment with salmeterol on allergen-induced changes in airway responsiveness and exhaled nitric oxide (ENO).\n Double-blind, randomized, parallel-group study.\n Specialist allergy unit in a university hospital.\n Asthmatic patients sensitized to pollen allergens were randomly allocated to monotherapy with salmeterol (n = 14) or placebo (n = 13).\n Salmeterol, 25 micro g, and placebo inhalers, two puffs bid, for 6 weeks.\n Spirometry, the level of a provocative concentration of a substance (methacholine) causing a 20% fall in FEV(1) (PC(20)), the PC(20) level for adenosine 5'-monophosphate (AMP), and ENO were measured before the pollen season and were repeated at the height of the pollen season after 6 weeks of treatment with salmeterol or placebo.\n The decrease in FEV(1) during the pollen season was significantly larger in the placebo group than in the salmeterol group, the mean difference in the change between the groups being 0.20 L (95% confidence interval, 0.03 to 0.35; p = 0.047). Changes in PC(20) for methacholine, PC(20) for AMP, and ENO levels were not significantly different between treatment groups. However, a mean (+/- SEM) decrease in the PC(20) for methacholine of -1.0 +/- 0.4 doubling concentrations was observed within the placebo group (p = 0.03), whereas no significant changes were observed within the salmeterol group. A significant decrease in PC(20) for AMP (doubling concentrations) was observed within the placebo group (-2.1 +/- 0.6; p = 0.003) and the salmeterol group (-1.5 +/- 0.4; p = 0.003). ENO concentrations increased significantly among the placebo and the salmeterol groups during natural pollen exposure.\n These observations indicate that natural allergen exposure and the regular use of salmeterol are not associated with a greater increase in ENO and airway responsiveness than allergen exposure alone.", "The purpose of the present study was to assess the degree of protection of inhaled salmeterol against exercise-induced bronchoconstriction (EIB) after chronic compared with single dosing in patients with asthma. Twelve patients with exercise-induced asthma took part in a randomized double-blind crossover study to compare the duration of action of inhaled salmeterol 50 micrograms twice daily for 4 weeks with that of placebo. A standardized exercise test was performed at 6 h and 12 h after dosing on the first and last day of each treatment period. Salmeterol produced significant protection against EIB at 6 and 12 h after the first dose in comparison with placebo, whereas there was no significant attenuation of EIB after 4 weeks of chronic treatment with salmeterol. The percentage fall in FEV1 after exercise challenge at 6 h was (first dose): placebo 34.8 +/- 4.9% vs. salmeterol 11.9 +/- 2.8% (P < 0.05); (4 weeks): placebo 32.9 +/- 5.3% vs. salmeterol 24.0 +/- 4.4% (NS). These results suggest that tachyphylaxis may develop to the functional antagonism of salmeterol against EIB.", "To determine the effect of long-term salmeterol aerosol therapy on airway hyperresponsiveness measured by methacholine challenge.\n Randomized, double-blind, placebo-controlled, multicenter study.\n Thirty-one clinical centers in the United States.\n Four hundred eight asthmatic patients > or = 12 years of age with baseline FEV1 of > or = 70% of predicted values. Patients were not using inhaled corticosteroids.\n Twice-daily salmeterol aerosol, 42 microg, or placebo via metered-dose inhaler for 24 weeks. Backup albuterol was available.\n Pulmonary function tests were performed before, during, and after treatment. Subjects recorded asthma-related symptoms, morning and evening peak expiratory flow (PEF) levels, and use of supplemental albuterol daily on diary cards. Methacholine challenges were performed 10 to 14 h postdose at weeks 4, 12, and 24, and 3 and 7 days posttreatment. Over 24 weeks of treatment, salmeterol provided significant (p < 0.001) protection against methacholine-induced bronchoconstriction of approximately one doubling dose of methacholine when compared to placebo with no evidence for a progressive decrease in protection. A rebound increase in airway hyperresponsiveness was not observed 3 and 7 days after cessation of salmeterol therapy. Salmeterol treatment resulted in sustained improvements of 0.21 to 0.26 L in morning premedication FEV1 and an improvement of 26.2 L/min in morning PEF when compared to placebo (p < 0.001). The use of salmeterol significantly reduced combined daytime asthma symptoms by 20% when compared to placebo (p = 0.005). A total of 34 and 48 exacerbations, respectively, were reported in the Salmeterol and placebo groups, and no evidence was present for a difference in the severity of asthma exacerbations between groups. Adverse event profiles were similar for the salmeterol and placebo groups.\n Regular long-term use of salmeterol aerosol resulted in sustained improvements in pulmonary function and asthma symptom control over the 24-week treatment period. There was no increase in bronchial hyperresponsiveness or loss of bronchoprotection at 24 weeks from that seen following 4 weeks of therapy. There was no evidence of rebound airway hyperresponsiveness after cessation of salmeterol treatment. Regular treatment with the long-acting beta-agonist salmeterol does not lead to clinical instability or vulnerability to unpredictable asthma attacks.", "Oxis Turbuhaler is a new dry powder formulation of long-acting beta2-agonist formoterol. This study compared the efficacy and safety of regular use of the long-acting beta2-agonist formoterol and the short-acting terbutaline for 3 months in patients with asthma.\n After 1-week run-in, 343 patients received either formoterol 12 microg bid (F) (delivered dose of 9 microg), terbutaline 500 microg qid (T) or placebo qid, in a parallel-group, double-blind, randomized manner. They had a mean of 61% of predicted forced expiratory volume in 1 second (FEV1) and a mean reversibility of 26%. Eighty-nine percent used inhaled corticosteroids.\n During run-in mean morning peak expiratory flow (PEF L/min) for F was 366 and 348 for T, and 344 for placebo (P). The F group improved morning PEF significantly compared with P (P = .0022) and T (P = .0001). Changes from run-in were + 18, -1.5, and +5 L/min after F, T, and P, respectively. The F group was statistically significantly better than P and T in increasing evening PEF and in reducing night-time asthma. The F and T statistically significantly reduced the use of rescue medication compared with P. The bronchodilating response to the study drug and to an additional 1.25 mg terbutaline was of the same magnitude before and throughout the study. No statistically significant treatment-by-time interaction was observed (P > .20). There were no adverse effects of clinical relevance.\n Formoterol Turbuhaler, 12 microg bid, was more effective than terbutaline Turbuhaler, 0.5 mg qid, and placebo. Regular use of formoterol or terbutaline did not significantly influence the response to additional inhalation of terbutaline.", "An inhaled glucocorticoid is currently the medication of choice for long-term control of persistent asthma in children. The role of long-acting beta2-adrenergic-receptor agonists, such as salmeterol, needs to be defined.\n We conducted a randomized, double-blind, placebo-controlled, parallel-group, one-year study of 241 children (mean [+/-SD] age, 9.3+/-2.4 years) with clinically stable asthma and less than one month of prior glucocorticoid use. We compared inhaled beclomethasone dipropionate (200 microg twice daily) with salmeterol xinafoate (50 microg twice daily) and placebo (lactose). The primary outcome measure, airway responsiveness (as assessed with a methacholine challenge) was evaluated before treatment; after 3, 6, 9, and 12 months of treatment (12 and 36 hours after study medications had been withheld); and 2 weeks after the end of treatment. Spirometry, symptoms, use of rescue medication (200 microg of albuterol inhaled as needed), and adverse effects were also assessed.\n During months 1 through 12 overall, beclomethasone was associated with significantly less airway hyperresponsiveness than salmeterol (P= 0.003) or placebo (P<0.001). This effect was lost two weeks after treatment had been stopped. As compared with placebo, beclomethasone was associated with less variability between morning and evening in the peak expiratory flow (P=0.002), as was salmeterol (P=0.02). Beclomethasone was also associated with a reduced need for albuterol as rescue therapy (P<0.001) and fewer withdrawals because of asthma exacerbations (P=0.03), but salmeterol was not (P=0.09 and 0.55, respectively). During months 1 through 12, linear growth was 3.96 cm in the children receiving beclomethasone, as compared with 5.40 cm in the salmeterol group (P=0.004) and 5.04 cm in the placebo group (P=0.018). Height was not measured after treatment ended.\n Beclomethasone was effective in reducing airway hyperresponsiveness and in controlling symptoms of asthma, but it was associated with decreased linear growth. Salmeterol was not as effective as beclomethasone in reducing airway hyperresponsiveness or in controlling symptoms; however, it was an effective bronchodilator and was not associated with rebound airway hyperresponsiveness, masking of symptoms, or adverse effects.", "In a multicentre, double-blind, randomized, parallel study, 426 asthmatic children aged 5-15 years old received salmeterol 50 micrograms b.i.d. or placebo b.i.d. via the Diskhaler. All patients had access to inhaled salbutamol to be used on an 'as required' (p.r.n.) basis for symptomatic relief. The study design comprised a 2-week baseline, a 12-month treatment period incorporating a 2-week 'off treatment' after 6 months, and a 2-week follow-up period at the end of the trial. At the end of 12 months of treatment with salmeterol, the adjusted change from baseline for morning and evening peak expiratory flow rate (PEF) was 56 and 47 l min-1, respectively, and this was significantly greater than placebo (P < 0.01; P < 0.05). Exacerbation rates did not differ between groups and results were not dependent upon concurrent inhaled steroid use. Neither treatment caused a change of > or = 1 doubling dose in PC20/PD20 either during or on stopping treatment. Treatment with regular salmeterol 50 micrograms b.i.d. over a 12-month treatment period provides a significant, rapid and well-maintained improvement in lung function without increasing bronchial reactivity or asthma exacerbation rates compared to p.r.n. salbutamol." ]

[ "2511939", "8815995", "17650736", "16634339", "11043871", "1604262", "16703253", "7706955", "9460148", "16103847", "16816758", "2312568", "15107368", "3081211", "12016348", "10888946" ]

[ "Early mobilisation and outcome in acute sprains of the neck.", "Multimodal treatment to prevent the late whiplash syndrome.", "Cognitive behavioural components in physiotherapy management of chronic whiplash associated disorders (WAD)--a randomised group study.", "The effectiveness of a supervised physical training model tailored to the individual needs of patients with whiplash-associated disorders--a randomized controlled trial.", "Acute whiplash-associated disorders (WAD): the effects of early mobilization and prognostic factors in long-term symptomatology.", "Low energy high frequency pulsed electromagnetic therapy for acute whiplash injuries. A double blind randomized controlled study.", "Adjuvant laser acupuncture in the treatment of whiplash injuries: a prospective, randomized placebo-controlled trial.", "Phasic exercises for cervical rehabilitation after \"whiplash\" trauma.", "Acute treatment of whiplash neck sprain injuries. A randomized trial of treatment during the first 14 days after a car accident.", "A randomized controlled trial of an educational intervention to prevent the chronic pain of whiplash associated disorders following rear-end motor vehicle collisions.", "A psycho-educational video used in the emergency department provides effective treatment for whiplash injuries.", "Whiplash injuries. A trial of early management.", "Randomised, controlled outcome study of active mobilisation compared with collar therapy for whiplash injury.", "Early mobilization of acute whiplash injuries.", "Evaluation of electromagnetic fields in the treatment of pain in patients with lumbar radiculopathy or the whiplash syndrome.", "Early intervention in whiplash-associated disorders: a comparison of two treatment protocols." ]

[ "To assess the long term effect of early mobilisation exercises in patients with acute sprains of the neck after road accidents.\n Single blind randomised prospective study of patients receiving physiotherapy, advice on mobilisation, or on an initial period of rest followed up after two years by postal questionnaire.\n Accident and emergency department in urban hospital.\n 247 Consecutive patients (mean age at injury 30.6 years) presenting within 48 hours after injury with no pre-existing disease of the neck or serious skeletal injury. Of these, 167 patients responded to the questionnaire; 77 who responded but had not completed their treatment or review course were included in the analysis as a fourth group (non-attenders).\n Presence of symptoms after two years.\n Of the 167 patients (68%) responding, the percentage of patients still with symptoms was not significantly different in those receiving rest or physiotherapy (46%, 12/26 v 44%, 24/54), but that in those receiving advice on early mobilisation was significantly lower (23%, 11/48, p = 0.02). Of the 104 patients without symptoms, 94 (90%) recovered within six months and 62 (60%) within three months. Patients without symptoms who received advice or physiotherapy wore a collar for a significantly shorter time than those with persistent symptoms (mean duration 1.4 (SD 0.7) months v 2.8 (1.6) months, p = 0.005 and 1.6 (1.1) months v 1.8 (1.3) months, p = 0.006 respectively).\n Advice to mobilise in the early phase after neck injury reduces the number of patients with symptoms at two years and is superior to manipulative physiotherapy. Prolonged wearing of a collar is associated with persistence of symptoms.", "In order to assess the long-term efficacy of a multi-modal rehabilitation approach on whiplash injury, 60 patients were recruited within two months after neck injury. They were randomly allocated either to an experimental multimodal treatment (A) consisting of postural training, manual technique and psychological support or to a control treatment (B), using physical agents only, such as electrical and sonic modalities. Pain level, range of movement, self-rating scale of treatment efficacy and return-to-work delay were evaluated before and at the end of treatment, and later, 30 and 180 days after randomisation. The benefit obtained with treatment \"A\" was greater and longer lasting than that experienced using \"B\", despite the fact that the same benefit was obtained in joint mobility in the two groups. Patients undergoing the experimental treatment returned to their usual occupations sooner than the controls. The results seem to confirm the hypothesis of a multifactorial involvement as a possible mechanism for the late whiplash syndrome.", "Different types of integrated management programmes have lately been introduced in the treatment of Whiplash Associated Disorders (WAD). In this study regular primary care physiotherapy and physiotherapy management with integrated components of cognitive-behavioural origin was compared in an experimental group study. The predictive value of self-efficacy was also addressed. In all thirty-three patients with chronic WAD were included in the trial. Results revealed no significant differences between groups in self-ratings of disability or pain intensity. However, among the self-reported benefits of treatment, patients in the experimental group reported significantly less pain than did the comparison group. At three months follow-up the experimental group also reported better performance of daily activities. Between group differences in the coping repertoire were found at pre-, post-and three-month follow-up. Generally, patients with high self-efficacy reported less use of 'maladaptive' and passive coping style than less self-efficient subjects at all times. In conclusion cognitive behavioural components can be useful in physiotherapy treatment for patients with chronic WAD, but their contributions are not yet fully understood. Self-efficacy is related to patients' use of different coping styles. Positive long-term outcomes in WAD-patients could therefore be improved by boosting self-efficacy and by teaching patients to use active, adaptive coping strategies.", "To evaluate the effects of a physical training programme which is supervised and tailored to meet the needs of patients with subacute whiplash-associated disorders.\n A randomized controlled trial with follow-up at three and nine months after randomization.\n An interdisciplinary rehabilitation centre.\n Forty-seven patients with subacute disorders following a whiplash trauma.\n Patients were randomized to a supervised training group or a self-administered home training group.\n Primary outcome measures were the Self-Efficacy Scale, the Tampa Scale for Kinesiophobia and the Pain Disability Index. Secondary outcome measures were neck pain intensity, sensory and affective dimensions of pain, pain location and duration, muscle tenderness, grip strength, cervical mobility, sick leave and analgesic consumption.\n Forty patients (85%) completed the intervention period, and the drop-outs were followed up by intention-to-treat. The results showed that supervised training was significantly more favourable than home training, with a more rapid improvement in self-efficacy (P = 0.03), fear of movement/(re)injury (P = 0.03) and pain disability (P = 0.03) at three months. Further, supervised training significantly reduced the frequency of analgesic consumption (P = 0.03). The improvements were partly maintained at nine months, even though there was no amelioration in pain and physical disorders. Despite the favourable outcome, supervised intervention did not reduce sick leave.\n The findings indicate a treatment approach that is feasible in the rehabilitation of patients with subacute whiplash-associated disorders in the short term, but additional research is needed to extend these findings and elucidate treatment strategies that also are cost effective.", "To compare two different home exercise programmes for patients with acute whiplash-associated disorders (WAD). A further aim was to describe the initial prognostic variables related to self-reported pain at six months follow-up.\n A randomized treatment study with a follow-up period of six months.\n The study was undertaken in an orthopaedic clinic at a university hospital.\n A total of 59 symptomatic (neck pain, stiffness, etc.) patients with acute whiplash injury.\n Patients were randomized to a regular treatment group (RT group) and an additional-exercise treatment group (AT group).\n Pain Disability Index (PDI), Self-Efficacy Scale (SES), Coping Strategies Questionnaire (CSQ), neck range of motion (ROM), head posture, kinaesthetic sensibility, visual analogue scale (VAS).\n Patients given an additional exercise did not improve more than patients with regular treatment. Only one CSQ item, 'Ability to decrease pain', showed a significant difference between the groups in its pattern of change over time: the AT group had a significant increase between three and six months whilst values in the RT group decreased. Nonsymptomatic patients at six months follow-up were characterized by initially better self-efficacy, lower disability and significantly different patterns in the use of 'behavioural coping strategies' when compared with symptomatic patients. The nonsymptomatic patients also reported more frequent training than symptomatic patients, i.e. they complied better with the treatment regime.\n This home exercise programme, including training of neck and shoulder ROM, relaxation and general advice seems to be sufficient treatment for acute WAD patients when used on a daily basis. Additionally, patients reporting low self-efficacy and high disability levels may profit from more attention initially, as these psychological factors are significant predictors of pain at long-term follow-up.", "The standard treatment of acute whiplash injuries (soft collar and analgesia) is frequently unsuccessful. Pulsed electromagnetic therapy PEMT (as pulsed 27 MHz) has been shown to have pro-healing and anti-inflammatory effects. This study examines the effect of PEMT on the acute whiplash syndrome. One half of the 40 patients entering the study received active PEMT collars: the other half facsimile (placebo). All patients were given instructions to wear the collar for eight hours a day at home and advised to mobilise their necks. At 2 and 4 weeks the actively treated group had significantly improved (p less than 0.05) in terms of pain (visual analogue scale). By chance movement scores for the PEMT group were significantly worse at entry to the study than the control group (p less than 0.05). At 12 weeks they had become significantly better (p less than 0.05). PEMT as described is safe for domiciliary use and this study suggests that PEMT has a beneficial effect in the management of the acute whiplash injury.", "Following introduction of the compulsory use of seat belts in cars, whiplash injuries of the cervical spine have become common in everyday practice. Current treatment approaches lead to resolution of the symptoms within a short time in most cases but cannot prevent a small proportion of patients developing persistent health problems. The effects of adjuvant treatment with laser acupuncture on the acute symptoms and the results one year after the injury were studied in this prospective, randomized, placebo-controlled single-blind study. One group of patients (n = 23) were treated with laser acupuncture (5 mW HeNe laser on 22 acupuncture points for 15 s each) plus cervical collar and a combination of paracetamol and chlormezanone; a second group (n = 22) received the same treatments but with the use of a placebo laser. The treatment was given three times per week until the patient was asymptomatic. No statistically significant advantage of the laser acupuncture treatment was found in the acute phase (mobility in all three planes, duration of pain and duration of use of a cervical collar) or the chronic phase (drug use and the incidences of chronic recurrent problems such as myofascial pain, headaches, vertigo and tinnitus).\n Adjuvant laser acupuncture with a 5 mW HeNe laser and an irradiation time of 15 s appears to be ineffective in the management of whiplash injuries.", "To assess whether \"phasic\" exercises, including rapid eye-head-neck-arm movements, can benefit patients with chronic cervical injuries.\n A randomized, controlled, double blind study involving 30 chronic patients, who were allocated to either group 1 or group 2. The study period was for 8 wk.\n The study was conducted in a private practice.\n Thirty chronic motor vehicle accident patients who continued to experience increased pain/soreness/stiffness of the cervical musculature with sports/activities requiring rapid head neck movements were selected for the study.\n Group 1 patients (n = 15) had standard exercises (stretching/isometric/isokinetic) and chiropractic therapy. Group 2 patients (n = 15) had \"phasic\" exercises and chiropractic therapy. Patients in both groups exercised for a minimum of four times weekly, for 8 wk.\n Pre and Post Pain and Disability Index was administered to both groups.\n Group 1, which had standard exercises and chiropractic therapy, improved by 7.4% (p > .05). Group 2, which had \"phasic\" exercises and chiropractic therapy, improved by 48.3% (p > .001). Confounders were identified, which explains the minimal improvement of group 1 and the remarkable results of group 2.\n It would appear that any rehabilitation program for chronic neck-injured patients should involve exercises that address the following: eye-head-neck-arm coordinated movements, coordination of the entire vertebral column,/ and return the \"phasic\" component of the musculature to functional levels. Additional studies will address the effect of these exercises on the strength, range of motion and pain improvement of the cervical spine in normal, acute and chronic patients.", "A single-blinded, randomized treatment study with a follow-up period of 6 months.\n To study the long-term consequences of whiplash neck sprain injuries in patients treated with two different regimes during the first 14 days after the car accident. Patients in the first group were encouraged to act as usual, i.e., continue to engage in their normal, pre-injury activities; that group was compared with another group of patients who were given time off from work and who were immobilized using a soft neck collar. The end point of the comparison was the evaluation of subjective symptoms 6 months after the accident.\n Few randomized treatment studies have been performed to evaluate the clinical outcome for patients with neck sprain.\n Patients who participated in the study were recruited from the Emergency Clinic at the University Hospital in Trondheim, Norway. The study group included 201 patients (47% of the study group) with neck sprain that resulted from a car accident. Neck and shoulder movements and subjective symptoms, which were assessed using several different measurements, were assessed during the follow-up period.\n There was a significant reduction of symptoms from the time of intake to 24 weeks after the treatment period in both groups. There was a significantly better outcome for the act-as-usual group in terms of subjective symptoms, including pain localization, pain during daily activities, neck stiffness, memory, and concentration, and in terms of visual analog scale measurements of neck pain and headache.\n The outcome was better for patients who were encouraged to continue engaging in their normal, pre-injury activities as usual than for patients who took sick leave from work and who were immobilized during the first 14 days after the neck sprain injury.", "Concealed allocation, multicenter, single-blind, randomized controlled clinical trial.\n To assess the efficacy of an educational video in the tertiary prevention of persistent WAD symptoms following rear-end motor vehicle collisions (MVCs).\n Whiplash-associated disorders (WAD) are an important and costly health problem. There is a lack of high quality evidence surrounding efficacy of treatments for WAD. Existing research supports active interventions and early return to regular activities.\n Consecutive patients presenting to four tertiary care emergency departments following rear-end MVCs were eligible. Following informed consent, patients were allocated, using central randomization, to receive an educational video plus usual care or usual care alone. The video provided reassurance, and advice about posture, return to regular activities, exercises, and pain-relief methods. Data were collected by telephone using standardized questionnaires. The primary outcome was presence of Persistent WAD Symptoms at 24 weeks postinjury, based on the frequency and severity of neck, shoulder, or upper back pain. The absolute difference in proportion of patients with persistent WAD symptoms and rate ratios were calculated. Changes in pain scores were compared using the Mann-Whitney U test.\n The intervention (n = 206) and control (n = 199) groups were similar at baseline (mean age 38.4 years; 64% female). Overall, the proportion of subjects with Persistent WAD Symptoms decreased from 89.1% at baseline to 33.6% at 24 weeks after injury. At 24 weeks, the proportion of subjects with persistent WAD symptoms in the intervention group was 7.9% (95% CI, -2.0, 17.8) lower than the control group. The median improvement in pain score at 24 weeks was 3 for the intervention group and 2 for the control group (P = 0.016).\n The presence of persistent WAD symptoms following simple rear-end MVCs was high in this sample. The video group demonstrated a trend toward less severe WAD symptoms. We recommend evaluating other educational interventions that could reduce WAD symptoms.", "Randomized control trial conducted between June 2000 and September 2002.\n To determine whether a short psycho-educational video shown in the Emergency Department shortly after the injury would produce follow-up pain reductions and reduced medical utilization.\n Chronic pain following a whiplash injury is one example of the massive medical/legal problem of chronic muscular pain. Approaches using local pain sources (trigger points) have shown promise as treatment models for this type of pain.\n 1) Setting: Emergency Departments (ED) and urgent care (UC) facilities. 2) Patients: 126 patients entering EDs or UCs. 3) Intervention: Patients assigned to 12-minute video or care as usual. 4) Main Outcome Measures: Short Form Musculoskelatal Function Assessment (SMFA), phone questionnaires assessing: narcotics use, ER use, UC use, surgical consultations, etc.\n Patients viewing the video had dramatically lower pain ratings at a 1-month follow (6.09 [10.6] vs. 21.23 [17.4], P < 0.001) and this pattern held for the 3- and 6-month follow-up period. Similarly, for 17 of 21 items asked at follow-up, the video group showed superior outcomes (chi2 ranged from 5 to 35, P < 0.05, all). For example, 4% of video patients were using narcotics at 6 month post ED visit compared with 36% of controls. The brief psycho-educational video had a profound effect on subsequent pain and medical utilization.", "We have conducted a prospective trial of the management of 135 adult patients who had sustained soft-tissue injuries of the neck in vehicle accidents. Early traction and physiotherapy was compared with rest in a collar and unsupervised mobilisation. No benefit from the active treatment could be identified; moulded collars in slight flexion gave the best pain relief and are recommended.", "Standard therapy in Germany for acute whiplash injury has traditionally included a soft collar (cervical orthosis), an approach that is passive compared with early exercise and mobilisation. The purpose of this study is to examine the recovery in the first six weeks of groups of acute whiplash injury patients subjected to two different treatment approaches, the traditional approach of a collar compared with active, early mobilisation.\n Between August 1997 and February 2000 a randomised clinical trial with a total of 200 patients was performed. A total of 97 were randomly assigned to a collar therapy group, and 103 to the exercise group, treated by a physiotherapist. Study participants recorded average pain and disability twice (baseline and six week follow up) during a one week period by diary, using numeric visual analogue (VAS) rating scales ranging from 0 to 10.\n The initial mean VAS pain intensity and VAS disability reported by the collar therapy group and the exercise group showed no statistical difference. The mean VAS pain rating reported by the collar therapy group after six weeks was 1.60 and mean VAS disability rating was 1.56. The mean VAS pain intensity of the exercise group was 1.04 and mean VAS disability was 0.92. These differences between the groups were both significant, as was the reduction in the prevalence of symptoms in the exercise therapy group compared with the collar group at six weeks.\n Early exercise therapy is superior to the collar therapy in reducing pain intensity and disability for whiplash injury.", "Acute whiplash injuries are a common cause of soft tissue trauma for which the standard treatment is rest and initial immobilisation with a soft cervical collar. Because the efficacy of this treatment is unknown a randomised study in 61 patients was carried out comparing the standard treatment with an alternative regimen of early active mobilisation. Results showed that eight weeks after the accident the degree of improvement seen in the actively treated group compared with the group given standard treatment was significantly greater for both cervical movement (p less than 0.05) and intensity of pain (p less than 0.0125).", "Back pain and the whiplash syndrome are very common diseases involving tremendous costs and extensive medical effort. A quick and effective reduction of symptoms, especially pain, is required. In two prospective randomized studies, patients with either lumbar radiculopathy in the segments L5/S1 or the whiplash syndrome were investigated. Inclusion criteria were as follows: either clinically verified painful lumbar radiculopathy in the segments L5/S1 and a Laségue's sign of 30 degrees (or more), or typical signs of the whiplash syndrome such as painful restriction of rotation and flexion/extension. Exclusion criteria were prolapsed intervertebral discs, systemic neurological diseases, epilepsy, and pregnancy. A total of 100 patients with lumbar radiculopathy and 92 with the whiplash syndrome were selected and entered in the study following a 1:1 ratio. Both groups (magnetic field treatment and controls) received standard medication consisting of diclofenac and tizanidine, while the magnetic field was only applied in group 1, twice a day, for a period of two weeks. In patients suffering from radiculopathy, the average time until pain relief and painless walking was 8.2 +/- 0.5 days in the magnetic field group, and 11.7 +/- 0.5 days in controls p < 0.04). In patients with the whiplash syndrome, pain was measured on a ten-point scale. Pain in the head was on average 4.6 before and 2.1 after treatment in those receiving magnetic field treatment, and 4.2/3.5 in controls. Neck pain was on average 6.3/1.9 as opposed to 5.3/4.6, and pain in the shoulder/arm was 2.4/0.8 as opposed to 2.8/2.2 (p < 0.03 for all regions). Hence, magnetic fields appear to have a considerable and statistically significant potential for reducing pain in cases of lumbar radiculopathy and the whiplash syndrome.", "A prospective randomized trial in 97 patients with a whiplash injury caused by a motor vehicle collision.\n The study evaluates early active mobilization versus a standard treatment protocol and the importance of early versus delayed onset of treatment.\n There is no compelling evidence to date on the management of acute whiplash-associated disorders. The few studies describing treatment, however, provide evidence to support the recommendation that an active treatment in the acute stage is preferable to rest and a soft collar in most patients.\n Patients were randomized to four groups. Active versus standard treatment and early (within 96 hours) versus delayed (after 2 weeks) treatment. Measures of range of motion and pain were registered initially and at 6 months.\n Eighty-eight patients (91%) could be followed up at 6 months. Active treatment reduced pain more than standard treatment (P < 0.001). When type and onset of treatment were analyzed, a combined effect was seen. When active treatment was provided, it was better when administered early, and if standard treatment was provided, it was better when administered late for reduction of pain (P = 0.04) and increasing cervical flexion (P = 0.01).\n In patients with whiplash-associated disorders caused by a motor vehicle collision treatment with frequently repeated active submaximal movements combined with mechanical diagnosis and therapy is more effective in reducing pain than a standard program of initial rest, recommended use of a soft collar, and gradual self-mobilization. This therapy could be performed as home exercises initiated and supported by a physiotherapist." ]

[ "15450766", "417428", "15936036" ]

[ "Effect of mannitol on regional cerebral blood flow in patients with intracerebral hemorrhage.", "Is there a real treatment for stroke? Clinical and statistical comparison of different treatments in 300 patients.", "Mannitol in intracerebral hemorrhage: a randomized controlled study." ]

[ "To evaluate the regional cerebral blood flow (rCBF) changes following IV mannitol bolus in patients with intracerebral hemorrhage (ICH).\n In a hospital based randomized placebo controlled study, 21 CT proven ICH patients with Glasgow coma scale (GCS) score of 5 or more were subjected to clinical evaluation including GCS and Canadian Neurological stroke (CNS) scale. Cranial SPECT study was undertaken before and 60 min after 20% mannitol 100 ml IV in 20 min or sham infusion. The SPECT images were semi-quantitatively analyzed and asymmetry index of basal ganglia, frontal, parietal and occipital regions were calculated.\n There were 12 patients in mannitol and nine in control group who were evenly matched for age, mean arterial blood pressure, GCS score and size of hematoma. Only one patient died in mannitol group. Following mannitol, GCS score improved in six, worsened in two and remained unaltered in four patients. In the control group, GCS improved in seven, worsened in none and was unchanged in two patients. SPECT studies revealed reduction in asymmetry index in basal ganglia in four, frontal region in six, parietal in four and occipital region in five patients in mannitol group. In control group, asymmetry index was reduced in basal ganglia in one, frontal and parietal region in three each and occipital region in five patients. These differences between control and study group were not significant.\n Mannitol does not seem to significantly change the regional cerebral blood flow (rCBF) in ICH patients as evaluated by SPECT study.", "In the absence of universally accepted criteria for the medical treatment of stroke, we made a rigorously randomized comparative study of different treatments in 300 patients. One group of patients received only a general supportive treatment designed to ensure adequate supplies of water, electrolytes and calories, plus whatever was needed to prevent infection and correct extant associated pathology. Three other groups of patients were treated in the same way but were also given, respectively, one of the following medications: Hydergine (Sandoz) (a mixture of three ergot alkaloids), dexamethasone, and mannitol. No statistically significant difference emerged among any of the treatment groups and the reference group in terms of objective therapeutic results. The authors concluded that, at least with the dosage used in this study, none of the treatments proved more useful than conventional supportive therapy in the first 10 days after a stroke.", "To study the usefulness of mannitol in spontaneous intracerebral hemorrhage (ICH) patients.\n 128 CT proven supratentorial ICH patients within 6 days of ictus were randomized into study and control groups. The study group received mannitol 20%, 100 ml every 4 h for 5 days, tapered in the next 2 days. The control group received sham infusion. Primary endpoint was 1-month mortality and secondary endpoint functional disability at 3 months assessed by Barthel index score.\n There were 65 patients in study and 63 in control groups. The study and control groups were evenly matched regarding age, Glasgow coma scale (GCS) score, Canadian Neurological Scale (CNS) score, pupillary asymmetry, pyramidal signs on non-hemiplegic side, and location, midline shift and ventricular extension of hematoma. At 1 month, 16 patients died in each group. The primary and secondary endpoints were not significantly different between the two groups.\n Low dose mannitol does not seem to be beneficial in patients with ICH." ]

[ "14623733" ]

[ "A phase 1 trial of riluzole in spinal muscular atrophy." ]

[ "Severe spinal muscular atrophy (SMA) (Werdnig-Hoffmann disease, acute SMA, and SMA I) is a disease of the motor neuron characterized by onset before 6 months of age, failure ever to achieve sitting without support, and a life expectancy of 2 years or less. There is no known treatment for SMA, and, until recently, no therapeutic trials have been attempted. There is reason to believe that glutamate, an excitatory neurotransmitter, enhances programmed cell death of anterior horn cells. Riluzole, a glutamate inhibitor, has been shown to slow the rate of decline in patients with amyotrophic lateral sclerosis, another form of motor neuron disease.\n To determine whether a glutamate inhibitor might be tolerated by infants with SMA and, furthermore, whether this medication could have a positive effect on life expectancy.\n Subjects with homozygous deletions of the survival motor neuron gene were recruited from pediatric neuromuscular clinics and randomized in a 2:1 ratio, 2 riluzole to 1 placebo. Neurologic examination was performed at the first visit by one of the investigators. Complete blood count, hepatic and renal screens, and urinalysis were performed at baseline, 2 weeks, 1 month, 2 months, 3 months, 6 months, and 9 months after drug or placebo was started. An electrocardiogram was done at baseline, 3 months, 6 months, and 12 months. Treatment was stopped after 9 months, and blood work was repeated at 12 months. Treatment was reinstituted at 1 year if requested by the parents. The enrollment goal was 30 patients; however, support from the pharmaceutical company was withdrawn when Rhone-Poulenc Rorer was taken over by Aventis. The investigational review boards of the participating centers approved the protocol and consent forms.\n Seven patients received riluzole and 3 received placebo medication. All 3 patients in the placebo group died (mean age, 9 months). Three of 7 who received active drug are still living at ages 513 years, 4 years, and 30 months. None of the 10 subjects experienced adverse effects or changes in laboratory test results. None showed any change in motor abilities.\n Riluzole appears to be safe in young children. This was a limited study with insufficient power to show a difference between the 2 groups. Because there is a suggestion of possible benefit in treated subjects, we recommend further study of riluzole in pediatric patients with SMA." ]

[ "15661416" ]

[ "The comparison of artificial urinary sphincter implantation and endourethral macroplastique injection for the treatment of postprostatectomy incontinence." ]

[ "To compare the effectiveness of macroplastique injection with artificial urinary sphincter implantation (AUS) for treatment of postprostatectomy incontinence (PPI).\n A prospective randomized clinical trial including 45 patients with PPI was performed secondary to radical retropubic prostatectomy (RRP), transvesical prostatectomy (TVP), transurethral prostatectomy (TURP), and TURP with TVP, in 12, 16, 16, 1 patients respectively. Patients were divided into two groups as minimal (group I) and total incontinence (group II) according to the severity of incontinence. Respectively, Group I (n = 21) and group II (n = 24) patients were randomized as AUS implantation (n = 11, n = 11) and macroplastique injection (n = 10, n = 13). Follow-up period was 48 (6-84) months in patients with macroplastique injection and 60 (8-120) months in AUS implantation. The success of the treatment was evaluated by calculating the average number of pads used by the patient per day, the weight of the pads and score of quality of life survey scale for each group both in the preoperative and in the postoperative period.\n There were statistically significant differences between preoperative and postoperative average pad weight, average number of pads and quality of life scores, both in patients with minimal and total incontinence. In group I there was no statistically significant difference between the two techniques. However, in group II there was a significant difference favoring AUS implantation.\n Endourethral injection should be the treatment of choice for patients with minimal incontinence, whereas AUS implantation as the first choice for patients with total incontinence." ]

[ "11941174", "7446190" ]

[ "Weekly ECT in Geriatric Depression.", "Unilateral and bilateral ECT in elderly patients. A comparative study." ]

[ "Fifteen elderly depressed psychiatric inpatients were randomly assigned to receive either standard three-times-weekly electroconvulsive therapy (ECT) or once-weekly ECT. Outcome measures included cognitive assessment and antidepressant response. Although both groups improved with treatment, the three-times-weekly group improved substantially more quickly. There was no difference in cognitive effect between the two groups. We conclude that the traditional three-times-weekly schedule of ECT may optimally balance speed of antidepressant response and cognitive impairment.", "Twenty-nine depressed elderly patients receiving ECT were randomly assigned to a unilateral or bilateral group; post-ictal recovery times, memory changes, and clinical improvement during and after each course were measured by blind and independent observers. All patients but one showed full recovery on testing 3 weeks after treatment. There was no significant difference between the unilateral and bilateral groups either in terms of improvement or the number of treatments needed in each course. A good outcome was predicted by the presence of pathological guilt, impairment of work and interest, agitation, subjectively depressed mood, psychic anxiety and greater overall severity. Longer duration of illness predicted a relatively poor outcome. Memory functions showed uniform impairment before treatment, but during treatment all improved, with some changes reaching high statistical significance; on testing 3 weeks after treatment memory functions in all patients had reached normal values. There was no difference between the two groups. Post-ictal recovery times were significantly longer in the bilateral than in the unilateral group after the first treatment and after the fifth treatment more than three times as long. Recovery time showed a significant decrease during courses of unilateral treatment. There was a very low incidence of side-effects, and all were relatively mild. We conclude that unilateral ECT is a safe and highly effective treatment for selected elderly patients suffering from depression, but that there is nothing to be said for the continued use of bilateral ECT." ]

[ "10870068", "7480054", "10987238" ]

[ "A randomized, controlled, parallel-group clinical trial comparing multilayer bandaging followed by hosiery versus hosiery alone in the treatment of patients with lymphedema of the limb.", "The use of compression to treat lymphoedema.", "Treatment of breast-cancer-related lymphedema with or without manual lymphatic drainage--a randomized study." ]

[ "Multilayered, low stretch bandages (MLB) combined with exercises, skin care, and manual lymphatic drainage therapy are recommended as an intensive phase of treatment for lymphedema patients. The relative efficacy of each of the components of this comprehensive treatment program have not been determined. This study aimed to compare the effect of multilayer bandaging as an initial phase of lymphedema treatment followed by elastic hosiery versus hosiery alone.\n A randomized, controlled, parallel-group trial was undertaken in the setting of the Lymphedema Clinic, The Royal Marsden Hospital, London. Ninety women with unilateral lymphedema (of the upper or lower limbs) were enrolled in the study. The interventions consisted of 18 days of multilayer bandaging followed by elastic hosiery or hosiery alone, each for a total period of 24 weeks. The main outcome measure was the percentage reduction in excess limb volume.\n The reduction in limb volume by MLB followed by hosiery was approximately double that from hosiery alone and was sustained over the 24-week period. The mean overall percentage reduction at 24 weeks was 31% (n = 32) for MLB versus 15.8% (n = 46) for hosiery alone, for a mean difference of 15. 2% (95% confidence interval, 6.2-24.2) (P = 0.001).\n Multilayer bandaging as an initial phase of treatment for lymphedema patients, followed by hosiery, achieves greater and more sustained limb volume reduction than hosiery alone.\n Copyright 2000 American Cancer Society.", "Lymphoedema in breast cancer patients can be treated. Patients need to feel that they have control over arm swelling. The treatment needs to be initiated by a physiotherapist working with a nurse specialist.", "A prospective randomized study was carried out to investigate whether the addition of manual lymphatic drainage (MLD) to the standard therapy could improve treatment outcome in women with lymphedema of the ipsilateral arm after breast cancer treatment. Forty-two patients were randomly assigned to receive standard therapy or standard therapy plus MLD 8 times in 2 weeks and training in self-massage. The standard therapy consisted of use of a compression garment, exercises and information about lymphedema and skin care. The efficacy of treatment was evaluated by reduction in lymphedema volume during treatment and by improvement in symptoms potentially related to lymphedema. The patients were followed-up for a total of 12 months. The study showed that both groups obtained a significant reduction in edema and that MLD did not contribute significantly to reduce edema volume." ]

[ "2435738", "6751162" ]

[ "Intra-arterial prostacyclin compared to Praxilene in the management of severe lower limb ischaemia: a double blind trial.", "The usefulness of naftidrofuryl in severe peripheral ischaemia--a symptomatic assessment using linear analogue scales." ]

[ "The effectiveness of a 72 h. intra-arterial prostacyclin infusion has been compared to that of naftidrofuryl oxalate (Praxilene) in a double blind study of 29 patients with ischaemic rest pain in 30 legs. Long-term relief of symptoms was achieved in 14 legs (47%) and major limb amputation avoided in 18 (60%). No significant difference was demonstrated between the results of prostacyclin infusion and those of Praxilene.", "The effect of Naftidrofuryl (Nafronyl) on the symptoms of severe peripheral vascular disease has been studied in 40 hospital inpatients. Assessment of ischaemic symptoms and of symptoms which may occur with any type of chronic pain was made using a linear analogue system. Patients treated with naftidrofuryl showed a significant symptomatic improvement compared to patients treated without vasoactive drug therapy. These results show that this drug has a useful place in the treatment of severe ischaemic symptoms during assessment for vascular reconstruction and in those patients found to be unsuitable for limb-salvage operations." ]

[ "10519348" ]

[ "Early discharge of preterm infants needing limited special care, followed by domiciliary nursing care." ]

[ "The aim of this study was to evaluate the effect of early discharge, followed by domiciliary nursing care, on infant health and utilization of health services in preterm infants still in need of special care (mainly gavage feeding). In total, 88 infants who were physiologically stable, but in need of further special care such as gavage feeding, were allocated to an early discharge group (EDG = 45 infants) and offered home visits by a nurse backed up by a neonatologist, or to a control group offered standard neonatal care (CG = 43 infants). Infants in the EDG spent 30.6 d (mean) in hospital after birth compared with 46.3 d in the CG (p = 0.003). On average, the domiciliary nurse spent 10.4 h with each family in the EDG, including a median number of 5 home visits, scheduled telephone contact and travelling time. The infants had a mean of 1.7 scheduled visits and 0.4 unscheduled visits to the neonatal ward. The domiciliary nurse received a mean of 0.9 telephone calls from the parents. When the period of domiciliary care in the EDG (post-conceptional age 35.9-38.7 wk) was compared with the corresponding time in hospital in the CG (post-conceptional age 35.6-38.6 wk), no statistical differences were observed in infant health, surgical procedures or medication. However, a reduced incidence of respiratory infections was observed in the EDG (6 versus 16 infants; p = 0.02). Nine infants in the EDG were re-hospitalized. The two groups did not differ in the numbers of rehospitalizations and non-elective contacts with the health services during the first year after discharge. In conclusion, early discharge of preterm infants still requiring special care, followed by domiciliary nursing care, was associated neither with an increased utilization of health services after discharge, nor with infant morbidity after discharge. More information on safety is needed before widespread early discharge can be advocated." ]

[ "18648227", "16571960", "17667567", "18385265", "17457124", "18946293", "17312208", "16357116" ]

[ "Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points: an international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial.", "Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study.", "Reversal of rocuronium-induced (1.2 mg/kg) profound neuromuscular block by sugammadex: a multicenter, dose-finding and safety study.", "Reversal of rocuronium-induced neuromuscular block with sugammadex is faster than reversal of cisatracurium-induced block with neostigmine.", "Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study: efficacy, safety, and pharmacokinetics.", "Reversal of profound rocuronium-induced blockade with sugammadex: a randomized comparison with neostigmine.", "A randomized, dose-finding, phase II study of the selective relaxant binding drug, Sugammadex, capable of safely reversing profound rocuronium-induced neuromuscular block.", "Org 25969 (sugammadex), a selective relaxant binding agent for antagonism of prolonged rocuronium-induced neuromuscular block." ]

[ "Sugammadex (Org 25969), a novel, selective relaxant binding agent, was specifically designed to rapidly reverse rocuronium-induced neuromuscular blockade. The efficacy and safety of sugammadex for the reversal of profound, high-dose rocuronium-induced neuromuscular blockade was evaluated.\n A total of 176 adult patients were randomly assigned to receive sugammadex (2, 4, 8, 12, or 16 mg/kg) or placebo at 3 or 15 min after high-dose rocuronium (1.0 or 1.2 mg/kg) during propofol anesthesia. The primary endpoint was time to recovery of the train-of-four ratio to 0.9. Neuromuscular monitoring was performed using acceleromyography.\n Sugammadex administered 3 or 15 min after injection of 1 mg/kg rocuronium decreased the median recovery time of the train-of-four ratio to 0.9 in a dose-dependent manner from 111.1 min and 91.0 min (placebo) to 1.6 min and 0.9 min (16 mg/kg sugammadex), respectively. After 1.2 mg/kg rocuronium, sugammadex decreased time to recovery of train-of-four from 124.3 min (3-min group) and 94.2 min (15-min group) to 1.3 min and 1.9 min with 16 mg/kg sugammadex, respectively. There was no clinical evidence of reoccurrence of neuromuscular blockade or residual neuromuscular blockade. Exploratory analysis revealed that prolongation of the corrected QT interval considered as possibly related to sugammadex occurred in one patient. Another two patients developed markedly abnormal arterial blood pressure after sugammadex that lasted approximately 15 min.\n Sugammadex provides a rapid and dose-dependent reversal of profound neuromuscular blockade induced by high-dose rocuronium (1.0 or 1.2 mg/kg) in adult surgical patients.", "Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block.\n Twenty-seven male surgical patients aged 18-64 yr were randomly assigned to receive placebo or sugammadex (0.5, 1.0, 2.0, 3.0, or 4.0 mg/kg) for reversal of 0.6 mg/kg rocuronium-induced neuromuscular block. Anesthesia was induced and maintained using intravenous fentanyl and propofol. Neuromuscular function was assessed using acceleromyography. Sugammadex or placebo was administered at reappearance of T2 of the train-of-four. The primary efficacy variable was the time required for recovery to a train-of-four ratio of 0.9.\n Sugammadex decreased median recovery time in a dose-dependent manner from 21.0 min in the placebo group to 1.1 min in the group receiving 4.0 mg/kg sugammadex. Doses of sugammadex of 2.0 mg/kg or greater reversed rocuronium-induced neuromuscular block within 3 min. A median of 59-77% of sugammadex was excreted unchanged in the urine within 16 h, mostly in the first 8 h. Sugammadex increased the proportion of the rocuronium dose excreted unchanged in the urine (from a median of 19% in the placebo group to 53% in the 4.0-mg/kg group within 16 h). Sugammadex was safe and well tolerated. No evidence of recurarization was observed in any patient.\n At doses of 2.0 mg/kg or greater, sugammadex safely reversed 0.6 mg/kg rocuronium-induced neuromuscular block in a dose-dependent manner. Sugammadex enhanced renal excretion of rocuronium and was excreted unchanged by the kidneys.", "Reversal of rocuronium-induced neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a modified gamma-cyclodextrin derivative. This study investigated the efficacy and safety of sugammadex in reversing rocuronium-induced profound neuromuscular blockade at 5 min in American Society of Anesthesiologists physical status I and II patients.\n Forty-five American Society of Anesthesiologists physical status I and II patients (aged 18-64 yr) scheduled to undergo surgical procedures (anticipated anesthesia duration >/= 90 min) were randomly assigned to a phase II, multicenter, assessor-blinded, placebo-controlled, parallel, dose-finding study. Anesthesia was induced and maintained with propofol and an opioid. Profound neuromuscular blockade was induced with 1.2 mg/kg rocuronium bromide. Sugammadex (2.0, 4.0, 8.0, 12.0, or 16.0 mg/kg) or placebo (0.9% saline) was then administered 5 min after the administration of rocuronium. Neuromuscular function was monitored by acceleromyography, using train-of-four nerve stimulation. Recovery time was the time from the start of administration of sugammadex or placebo, to recovery of the train-of-four ratio to 0.9. Safety assessments were performed on the day of the operation and during the postoperative and follow-up period.\n A total of 43 patients received either sugammadex or placebo. Increasing doses of sugammadex reduced the mean recovery time from 122 min (spontaneous recovery) to less than 2 min in a dose-dependent manner. Signs of recurrence of blockade were not observed. No serious adverse events related to sugammadex were reported. Two adverse events possibly related to sugammadex were reported in two patients (diarrhea and light anesthesia); however, both patients recovered without sequelae.\n Sugammadex rapidly and effectively reversed profound rocuronium-induced neuromuscular blockade in humans and was well tolerated.", "Reversal of the residual effect of rocuronium or cisatracurium by neostigmine may be slow and associated with side-effects. This randomized, safety-assessor-blinded study compared the efficacy of sugammadex, a selective relaxant binding agent for reversal of rocuronium-induced neuromuscular block, with that of neostigmine for reversal of cisatracurium-induced neuromuscular block. The safety of sugammadex and neostigmine was also evaluated.\n Adult surgical patients (ASA class I-III) were randomized to sugammadex 2.0 mg kg(-1) for reversal of block induced by rocuronium 0.6 mg kg(-1), or neostigmine 50 microg kg(-1) for reversal of block induced by cisatracurium 0.15 mg kg(-1). Anaesthesia was induced and maintained using i.v. propofol and remifentanil, fentanyl, or sufentanil. Neuromuscular function was monitored using acceleromyography (TOF-Watch SX). Sugammadex or neostigmine was administered at reappearance of T(2). The primary efficacy variable was time for recovery of the train-of-four (TOF) ratio to 0.9.\n Eighty-four patients were randomized, 73 of whom received sugammadex (n=34) or neostigmine (n=39). Time from start of administration of reversal agent to recovery of the TOF ratio to 0.9 was 4.7 times faster with sugammadex than with neostigmine (geometric mean=1.9 vs 9.0 min, P<0.0001). Reversal of block was sustained in all patients. There were no serious adverse effects from either reversal agent and no significant changes in any measure of safety, except for similar elevations in urinary N-acetyl glucosaminidase in both groups.\n Sugammadex 2.0 mg kg(-1) administered at reappearance of T(2) was significantly faster in reversing rocuronium-induced blockade than neostigmine was in reversing cisatracurium-induced block.", "Sugammadex reverses the neuromuscular blocking effects of rocuronium by chemical encapsulation. The efficacy, safety, and pharmacokinetics of sugammadex for reversal of profound rocuronium-induced neuromuscular blockade were evaluated.\n Ninety-eight male adult patients were randomly assigned to receive sugammadex (1, 2, 4, 6, or 8 mg/kg) or placebo at 3, 5, or 15 min after 0.6 mg/kg rocuronium. Patients were anesthetized with propofol and fentanyl. The primary endpoint of the study was the time to achieve a recovery of train-of-four ratio to 0.9. Neuromuscular blockade was measured using acceleromyography. Concentrations of rocuronium and sugammadex were determined in venous blood and urine samples. A population pharmacokinetic model using NONMEM (GloboMax LLC, Hanover, MD) was applied.\n The mean time to recovery of the train-of-four ratio to 0.9 after dosing at 3, 5, and 15 min decreased from 52.1, 51.7, and 35.6 min, respectively, after administration of placebo to 1.8, 1.5, and 1.4 min, respectively, after 8 mg/kg sugammadex. Sugammadex was safe and well tolerated. However, 20.4% of patients showed signs of inadequate anesthesia after its administration. The median cumulative excretion of rocuronium in the urine over 24 h was 26% in the placebo group and increased to 58-74% after 4-8 mg/kg sugammadex. The mean plasma clearances of sugammadex and rocuronium were 0.084 and 0.26 l/min, respectively.\n In male subjects, sugammadex safely reversed profound neuromuscular blockade induced by 0.6 mg/kg rocuronium in a dose-dependent manner. Sugammadex enhanced the renal excretion of rocuronium, and its clearance is approximately one third that of rocuronium.", "Traditionally, reversal of nondepolarizing neuromuscular blocking agents was achieved using acetylcholinesterase inhibitors, but these are unable to adequately reverse profound blockade. Sugammadex is a novel reversal agent, reversing the effects of rocuronium by encapsulation. This study assessed the efficacy and safety of sugammadex versus neostigmine for reversal of profound rocuronium-induced neuromuscular blockade.\n This phase III, randomized study enrolled surgical patients, aged 18 yr or older with American Society of Anesthesiologists physical status I-IV. Patients were randomized to receive sugammadex (4.0 mg/kg) or neostigmine (70 microg/kg) plus glycopyrrolate (14 microg/kg). Anesthetized patients received an intubating dose of rocuronium (0.6 mg/kg), with maintenance doses (0.15 mg/kg) as required. Neuromuscular monitoring was performed by acceleromyography. Sugammadex or neostigmine was administered at reappearance of 1-2 posttetanic counts (profound neuromuscular blockade). The primary efficacy parameter was the time from sugammadex or neostigmine-glycopyrrolate administration to return of the train-of-four ratio to 0.9.\n In the intent-to-treat population (n = 37 in each group), geometric mean time to recovery to a train-of-four ratio of 0.9 with sugammadex was 2.9 min versus 50.4 min with neostigmine-glycopyrrolate (P < 0.0001) (median, 2.7 min vs. 49.0 min). Most sugammadex patients (97%) recovered to a train-of-four ratio of 0.9 within 5 min after administration. In contrast, most neostigmine patients (73%) recovered between 30 and 60 min after administration, with 23% requiring more than 60 min to recover to a train-of-four ratio of 0.9.\n Recovery from profound rocuronium-induced neuromuscular blockade was significantly faster with sugammadex versus with neostigmine, suggesting that sugammadex has a unique ability to rapidly reverse profound rocuronium neuromuscular blockade.", "The reversal of a deep neuromuscular blockade remains a significant clinical problem. Sugammadex, a modified gamma-cyclodextrin, encapsulates steroidal neuromuscular blocking drugs, promoting their rapid dissociation from nicotinic receptors. Sugammadex is the first drug that acts as a selective relaxant binding agent.\n We enrolled 50 patients into a Phase II dose-finding study of the efficacy and safety of sugammadex. Subjects, anesthetized with nitrous oxide and propofol, were randomized to one of two doses of rocuronium (0.6 or 1.2 mg/kg) and to one of five doses of sugammadex (0.5, 1.0, 2.0, 4.0, or 8.0 mg/kg). Neuromuscular monitoring was performed using the TOF Watch SX acceleromyograph. Recovery was defined as a train-of-four ratio > or =0.9. Sugammadex was administered during profound block when neuromuscular monitoring demonstrated a posttetanic count of one or two.\n Reversal of neuromuscular block was obtained after administration of sugammadex in all but the lowest dose groups (0.5-1.0 mg/kg) where several subjects could not be adequately reversed. At the 2 mg/kg dose all patients were reversed with sugammadex, but there was significant variability (1.8-15.2 min). Patient variability decreased and speed of recovery increased in a dose-dependent manner. At the highest dose (8 mg/kg), mean recovery time was 1.2 min (range 0.8-2.1 min). No serious adverse events were reported during this trial.\n Sugammadex was well tolerated and effective in rapidly reversing profound rocuronium-induced neuromuscular block. The mean time to recovery decreased with increasing doses. Profound rocuronium-induced neuromuscular block can be reversed successfully with sugammadex at doses >/=2 mg/kg.", "Org 25969 is a cyclodextrin compound designed to reverse a rocuronium-induced neuromuscular block. The aim of this study was to explore the efficacy, dose-response relation and safety of Org 25969 for reversal of a prolonged rocuronium-induced neuromuscular block.\n Thirty anaesthetized adult patients received rocuronium 0.6 mg kg(-1) as an initial dose followed by increments to maintain a deep block at a level of <10 PTCs (post-tetanic counts) recorded every 6 min. Neuromuscular monitoring was carried out using accelerometry, in a train-of-four (TOF) mode using TOF-WatchSX. At recovery of T2, following at least 2 h of neuromuscular block, patients received their randomly assigned dose of 0.5, 1.0, 2.0, 4.0 or 6.0 mg kg(-1) of Org 25969. Anaesthesia and neuromuscular monitoring were continued for a minimum period of 30 min after Org 25969 administration. The main end-point of the study was the time to achieve a sustained recovery of TOF ratio to 0.9. Patients were followed up for 7 days after anaesthesia.\n The results showed a dose-related decrease in the average time taken to attain a TOF ratio of 0.9 from 6:49 (min:s) with the 0.5 mg kg(-1) dose to 1:22 with the 4.0 mg kg(-1) dose. Weighted non-linear regression analysis showed the fastest achievable time to TOF ratio of 0.9 to be 1:35. Org 25969 produced no major adverse effects.\n Org 25969 effectively reversed a deep and prolonged neuromuscular block induced by rocuronium. The effective reversal dose appears to be 2-4 mg kg(-1)." ]

[ "11230031", "12082182", "10079459" ]

[ "Psychological therapies for adults with anorexia nervosa: randomised controlled trial of out-patient treatments.", "Randomized controlled trial of a treatment for anorexia and bulimia nervosa.", "Empirical comparison of two psychological therapies. Self psychology and cognitive orientation in the treatment of anorexia and bulimia." ]

[ "Currently, without systematic evidence, psychotherapy for anorexia nervosa in adults draws on psychodynamic, cognitive and systemic theories.\n To assess effectiveness of specific psychotherapies in out-patient management of adult patients with anorexia nervosa.\n Eighty-four patients were randomised to four treatments: three specific psychotherapies - (a) a year of focal psychoanalytic psychotherapy; (b) 7 months of cognitive-analytic therapy (CAT); (c) family therapy for 1 year - and (d) low contact, 'routine' treatment for 1 year (control).\n At 1 year, there was symptomatic improvement in the whole group of patients. This improvement was modest, several patients being significantly undernourished at follow-up. Psychoanalytic psychotherapy and family therapy were significantly superior to the control treatment; CAT tended to show benefits.\n Psychoanalytic and family therapy are of specific value in the out-patient treatment of adult patients with anorexia.", "Evidence for the effectiveness of existing treatments of patients with eating disorders is weak. Here we describe and evaluate a method of treatment in a randomized controlled trial. Sixteen patients, randomly selected out of a group composed of 19 patients with anorexia nervosa and 13 with bulimia nervosa, were trained to eat and recognize satiety by using computer support. They rested in a warm room after eating, and their physical activity was restricted. The patients in the control group (n = 16) received no treatment. Remission was defined by normal body weight (anorexia), cessation of binge eating and purging (bulimia), a normal psychiatric profile, normal laboratory test values, normal eating behavior, and resumption of social activities. Fourteen patients went into remission after a median of 14.4 months (range 4.9-26.5) of treatment, but only one patient went into remission while waiting for treatment (P = 0.0057). Relapse is considered a major problem in patients who have been treated to remission. We therefore report results on a total of 168 patients who have entered our treatment program. The estimated rate of remission was 75%, and estimated time to remission was 14.7 months (quartile range 9.6 > or = 32). Six patients (7%) of 83 who were treated to remission relapsed, but the others (93%) have remained in remission for 12 months (quartile range 6-36). Because the risk of relapse is maximal in the first year after remission, we suggest that most patients treated with this method recover.", "The authors investigated the applicability of self psychological treatment (SPT) and cognitive orientation treatment (COT) to the treatment of anorexia and bulimia. Thirty-three patients participated in this study. The bulimic patients (n = 25) were randomly assigned either to SPT, COT, or control/nutritional counseling only (C/NC). The anorexic patients (n = 8) were randomly assigned to either SPT or COT. Patients were administered a battery of outcome measures assessing eating disorders symptomatology, attitudes toward food, self structure, and general psychiatric symptoms. After SPT, significant improvement was observed. After COT, slight but nonsignificant improvement was observed. After C/NC, almost no changes could be detected." ]

[ "12419136", "15336770", "21091527", "15642030", "15877748", "21219392", "16969659", "16820037", "15642026" ]

[ "Effects of non-surgical treatment modalities on peri-implantitis.", "Sustained release of doxycycline for the treatment of peri-implantitis: randomised controlled trial.", "Treatment of peri-implantitis using an Er:YAG laser or an air-abrasive device: a randomized clinical trial.", "Clinical evaluation of an Er:YAG laser for nonsurgical treatment of peri-implantitis: a pilot study.", "Treatment of peri-implantitis by the Vector system.", "Impact of the method of surface debridement and decontamination on the clinical outcome following combined surgical therapy of peri-implantitis: a randomized controlled clinical study.", "Nonsurgical treatment of moderate and advanced periimplantitis lesions: a controlled clinical study.", "Healing of intrabony peri-implantitis defects following application of a nanocrystalline hydroxyapatite (Ostim) or a bovine-derived xenograft (Bio-Oss) in combination with a collagen membrane (Bio-Gide). A case series.", "Therapy of peri-implantitis with resective surgery. A 3-year clinical trial on rough screw-shaped oral implants. Part I: clinical outcome." ]

[ "To evaluate the effects of local-delivery of 25% metronidazol gel and mechanical cleaning using ultrasonic carbon fiber tip on dental implants with peri-implantitis.\n 27 implants with peri-implantitis were randomly assigned to receiving either 25% metronidazol gel treatment or carbon fiber tip ultrasonic scaling. All parameters including plaque index (PLI), probing depth (PD) of pocket, sulcular bleeding index (SBI), and BANA enzyme analysis were measured at baseline, 1, 2, 6 and 12 weeks after treatment.\n Statistically significant decrease (P < 0.05) in SBI, BANA test and PLI occurred in both treatment groups at all time intervals compared to baseline. PD had a decreasing tendency in both groups, but only metronidazole group reached statistically significant level (P < 0.05) at 2 and 6 week intervals compared to baseline. None of the treatment modalities produced any side effects on the implant and peri-implant tissues.\n Both 25% metronidazol gel and mechanical cleaning using ultrasonic carbon fiber tip can be safely and effectively used in the treatment of peri-implant diseases.", "With the increased use of osseointegrated implants and with many implants functioning for a long time, the treatment of peri-implantitis has become important. Animal studies and clinical case reports have shown that the principle of guided bone regeneration can be applied to the surgical treatment of moderate to profound loss of bone around the implant, but we have found no published clinical studies. Patients and methods: Twenty-eight patients whose ages ranged from 25 to 78 years and who had a total of 48 peri-implant defects were examined at baseline (week 0) and after 18 weeks. This included the recording of bleeding on probing, pocket probing depths, and probing attachment levels at six sites for each tooth. For 2-18 weeks before week 0 all patients had been treated for peri-implantitis, including motivation, instruction in oral hygiene, and implant scaling with a hand plastic instrument. They were then randomly allocated to continue with this treatment or to have in addition mechanical debridement and local application of Atridox trade mark which slowly release doxycycline. Results: Patients treated with Atridox trade mark showed a significantly greater gain in mean (S.D.) probing attachment levels than those not treated with Atridox. Only subjects treated with Atridox had a significant gain in mean bleeding on probing (P = 0.001). Application of the biodegradable sustained release device after initial periodontal treatment resulted in a significant gain in mean probing attachment levels in the Atridox trade mark group and a significant reduction in pocket probing depths. There was also a significant difference in mean probing attachment levels (0.6mm).", "Non-surgical peri-implantitis therapies appear to be ineffective. Limited data suggest that ER:YAG laser therapy improves clinical conditions. The present study aimed at comparing the treatment effects between air-abrasive (AM) and Er:YAG laser (LM) mono-therapy in cases with severe peri-implantitis.\n Twenty-one subjects in each group were randomly assigned to one time intervention by an air-abrasive device or an Er:YAG laser. Clinical data were collected before treatment and at 6 months. Data analysis was performed using repeat univariate analysis of variance controlling for subject factors.\n No baseline subject characteristic differences were found. Bleeding on probing and suppuration decreased in both the groups (p<0.001). The mean probing depth (PPD) reductions in the AM and LM groups were 0.9 mm (SD 0.8) and 0.8 mm (SD ± 0.5), with mean bone-level changes (loss) of -0.1 mm (SD ± 0.8) and -0.3 mm (SD ± 0.9), respectively (NS). A positive treatment outcome, PPD reduction ≥0.5 mm and gain or no loss of bone were found in 47% and 44% in the AM and LM groups, respectively.\n The clinical treatment results were limited and similar between the two methods compared with those in cases with severe peri-implantitis.\n © 2010 John Wiley & Sons A/S.", "The aim of this controlled, parallel design clinical study was to compare the effectiveness of an Er:YAG laser (ERL) to that of mechanical debridement using plastic curettes and antiseptic therapy for nonsurgical treatment of peri-implantitis. Twenty patients with moderate to advanced peri-implantitis lesions were randomly treated with either (1) an ERL using a cone-shaped glass fiber tip at an energy setting of 100 mJ/pulse and 10 pps (ERL), or (2) mechanical debridement using plastic curettes and antiseptic therapy with chlorhexidine digluconate (0.2%) (C). The following clinical parameters were measured at baseline, 3 and 6 months after treatment by one blinded and calibrated examiner: Plaque index (PI), bleeding on probing (BOP), probing depth (PD), gingival recession (GR) and clinical attachment level (CAL). At the baseline examination, there were no statistically significant differences in any of the investigated parameters. Mean value of BOP decreased in the ERL group from 83% at baseline to 31% after 6 months (P < 0.001) and in the C group from 80% at baseline to 58% after 6 months (P < 0.001). The difference between the two groups was statistically significant (P < 0.001, respectively). The sites treated with ERL demonstrated a mean CAL change from 5.8 +/- 1 mm at baseline to 5.1 +/- 1.1 mm (P < 0.01) after 6 months. The C sites demonstrated a mean CAL change from 6.2 +/- 1.5 mm at baseline to 5.6 +/- 1.6 mm (P < 0.001) after 6 months. After 6 months, the difference between the two groups was statistically not significant (P > 0.05). Within the limits of the present study, it was concluded that (i) at 6 months following treatment both therapies led to significant improvements of the investigated clinical parameters, and (ii) ERL resulted in a statistically significant higher reduction of BOP than C.", "To compare the effectiveness of treatment of peri-implantitis with a novel ultrasonic device, the Vector system, with that of subgingival debridement with carbon fiber curettes.\n The study, comprising 11 patients with at least two screw type implants with bleeding on probing (BOP), probing pocket depth (PPD) > or =5 mm, and at least 1.5 mm radiographic bone loss and exposed implant threads, was carried out as a single blind randomized clinical trial. At baseline one randomly chosen implant in each patient was treated by the Vector system (test) while the other implant (control) was treated by submucosal debridement with a carbon fiber curette. After 3 months, the same treatments were repeated. Plaque, BOP, and PPD were recorded on all implant surfaces at baseline, and after 3 and 6 months. Bone levels were recorded on radiographs taken prior to the start of the study, and after 6 months.\n Oral hygiene around both test and control implants was improved at 3 and 6 months compared with baseline. At 6 months, four of the Vector-treated sites, and only one site treated with curettes, had stopped to bleed. In neither the test nor the control group, were there any differences between baseline and 6 months regarding PPD and bone levels.\n Although there was a greater reduction in the number of sites with BOP following treatment with the Vector system than following instrumentation with carbon fiber curettes, there was no significant difference between the two methods.", "The study aimed at investigating the impact of two surface debridement/decontamination (DD) methods on the clinical outcomes of combined surgical treatment of peri-implantitis.\n Thirty-two patients suffering from advanced peri-implantitis (n=38 combined supra- and intra-bony defects) were treated with flap surgery, granulation tissue removal, and implantoplasty at buccally and supracrestally exposed implant parts. The intra-bony aspects were randomly allocated to surface DD using either (i) an Er:YAG laser (ERL) device, or (ii) plastic curets+cotton pellets+sterile saline (CPS). In both groups, the intra-bony component was augmented with a natural bone mineral and covered with a collagen membrane. Clinical and radiographic parameters were recorded at baseline and after 6 months of non-submerged healing.\n Two patients were lost during follow-up. At 6 months, ERL-treated sites failed to reveal higher reductions in mean bleeding on probing (ERL: 47.8 ± 35.5 versus CPS: 55.0 ± 31.1%) and CAL values (ERL: 1.5 ± 1.4 versus CPS: 2.2 ± 1.4 mm) when compared with the CPS group. Both groups exhibited a comparable radiographic bone fill at the intra-bony defect component.\n The study failed to demonstrate a significant impact of the method of surface DD on the clinical outcome following combined surgical therapy of advanced peri-implantitis lesions.\n © 2011 John Wiley & Sons A/S.", "The aim of this controlled, parallel design clinical study was to evaluate the effectiveness of an Er:YAG (erbium-doped:yttrium, aluminum, and garnet) laser for nonsurgical treatment of periimplantitis lesions. Twenty patients, each of whom displayed at least one implant with (a) moderate and (b) advanced periimplantitis (n=40 implants; IMZ, ITI, Spline Twist, ZL-Duraplant, Camlog), were randomly instrumented nonsurgically using either (1) an Er:YAG laser (100 mJ/pulse, 10 Hz) device (LAS) or (2) mechanical debridement using plastic curettes and antiseptic therapy with chlorhexidine digluconate (0.2%) (C). The following clinical parameters were measured at baseline, 3, 6, and 12 months after treatment: plaque index, bleeding on probing (BOP), probing depth, gingival recession, and clinical attachment level (CAL). Mean BOP improved significantly in both groups at 3, 6, and 12 months (a- lesions: P<0.001 and b- lesions: P<0.01, respectively). After 3 and 6 months, the mean reduction of BOP was significantly higher in the LAS group when compared to the C group (a- and b- lesions: P<0.01 and P<0.05, respectively). At 3 and 6 months, both groups revealed significant CAL gains at a- and b- lesions (P<0.01, respectively). In both groups, however, the mean CAL at a- and b- lesions was not significantly different from the respective baseline values at 12 months (P>0.05, respectively). Although treatment of periimplantitis lesions with LAS resulted in a significantly higher BOP reduction than C, its effectiveness seemed to be limited to a period of 6 months, particularly at b- lesions.", "The aim of the present case series was to evaluate the healing of intrabony peri-implantitis defects following application of a nanocrystalline hydroxyapatite (NHA) or a bovine-derived xenograft in combination with a collagen membrane (BDX+BG).\n Twenty-two patients having moderate peri-implantitis (n=22 intrabony defects) were randomly treated with (i) access flap surgery (AFS) and the application of NHA, or with AFS and the application of BDX+BG. Clinical parameters were recorded at baseline and after 6 months of non-submerged healing.\n Post-operative wound healing revealed that NHA compromized initial adhesion of the mucoperiosteal flaps in all patients. At 6 months after therapy, NHA showed a reduction in the mean PD from 7.0+/-0.6 to 4.9+/-0.6 mm and a change in the mean clinical attachment loss (CAL) from 7.5+/-0.8 to 5.7+/-1.0 mm. In the BDX+BC group, the mean PD was reduced from 7.1+/-0.8 to 4.5+/-0.7 mm and the mean CAL changed from 7.5+/-1.0 to 5.2+/-0.8 mm.\n Within the limits of the present case series, it can be concluded that at 6 months after surgery both therapies resulted in clinically important PD reductions and CAL gains.", "The purpose of this randomized clinical trial was to compare the clinical outcome of two different surgical approaches for the treatment of peri-implantitis. Seventeen patients with ITI(R) implants were included consecutively over a period of 5 years. The patients were randomized with a lottery assignment. Ten patients were treated with resective surgery and modification of surface topography (test group). The remaining seven patients were treated with resective surgery only (control group). Clinical parameters (suppuration, modified plaque index - mPI, modified bleeding index - mBI, probing pocket depth - PPD, pseudopocket - DIM, mucosal recession - REC, probing attachment level - PAL) were recorded at baseline, as well as 6, 12, 24 and 36 months after treatment. The cumulative survival rate for the implants of the test group was 100% after 3 years. After 24 months, two hollow-screw implants of control group were removed because of mobility. Consequently, the cumulative survival rate was 87.5%. The recession index in the control group was significantly lower than in the test group at 24 months (Student's t-value of -2.14). On the contrary, control group showed higher PPD, PAL and mBI indexes than test group (Student's t-values of +5.5, +2.4 and +9.61, respectively). The PPD and mBI indexes for the implants of the control group were significantly higher at baseline than 24 months later (Student's t-values of +3.18 and +3.33, respectively). Recession and PAL indexes resulted in values significantly lower than baseline (Student's t-values of -4.62 and -2.77, respectively). For the implants of the test group PPD and mBI indexes were significantly higher at baseline than 36 months after (Student's t-values of +11.63 and +16.02, respectively). Recession index resulted in values significantly lower at baseline (Student's t-value of -5.05). No statistically significant differences were found between PAL index measurement at baseline and 36 months later (Student's t-value of +0.89). In conclusion, resective therapy associated with implantoplasty seems to influence positively the survival of oral implants affected by inflammatory processes." ]

[ "17074563", "9924306", "10571341", "16581422", "9111254", "9355184" ]

[ "Laser treatment in patients with bilateral large drusen: the complications of age-related macular degeneration prevention trial.", "Prophylactic laser treatment in early age related maculopathy reduced the incidence of exudative complications.", "Therapeutic benefits of infrared (810-nm) diode laser macular grid photocoagulation in prophylactic treatment of nonexudative age-related macular degeneration: two-year results of a randomized pilot study.", "Prophylactic treatment of age-related macular degeneration report number 1: 810-nanometer laser to eyes with drusen. Unilaterally eligible patients.", "A pilot randomized controlled study on the effect of laser photocoagulation of confluent soft macular drusen.", "Laser photocoagulation for macular soft drusen. Updated results." ]

[ "To evaluate the efficacy and safety of low-intensity laser treatment in the prevention of visual acuity (VA) loss among participants with bilateral large drusen.\n Multicenter randomized clinical trial. One eye of each participant was assigned to treatment, and the contralateral eye was assigned to observation.\n A total of 1052 participants who had > or =10 large (>125 microm) drusen and VA> or =20/40 in each eye enrolled through 22 clinical centers.\n The initial laser treatment protocol specified 60 barely visible burns applied in a grid pattern within an annulus between 1500 and 2500 mum from the foveal center. At 12 months, eyes assigned to treatment that had sufficient drusen remaining were retreated with 30 burns by targeting drusen within an annulus between 1000 and 2000 mum from the foveal center.\n Proportion of eyes at 5 years with loss of > or =3 lines of VA from baseline. Secondary outcome measures included the development of choroidal neovascularization or geographic atrophy (GA), change in contrast threshold, change in critical print size, and incidence of ocular adverse events.\n At 5 years, 188 (20.5%) treated eyes and 188 (20.5%) observed eyes had VA scores > or = 3 lines worse than at the initial visit (P = 1.00). Cumulative 5-year incidence rates for treated and observed eyes were 13.3% and 13.3% (P = 0.95) for choroidal neovascularization and 7.4% and 7.8% (P = 0.64) for GA, respectively. The contrast threshold doubled in 23.9% of treated eyes and in 20.5% of observed eyes (P = 0.40). The critical print size doubled in 29.6% of treated eyes and in 28.4% of observed eyes (P = 0.70). Seven treated eyes and 14 observed eyes had an adverse event of a > or =6-line loss in VA in the absence of late age-related macular degeneration or cataract.\n As applied in the Complications of Age-Related Macular Degeneration Prevention Trial, low-intensity laser treatment did not demonstrate a clinically significant benefit for vision in eyes of people with bilateral large drusen.", "To investigate the effect of prophylactic laser treatment on drusen area and incidence of exudative lesions in patients with soft drusen maculopathy.\n In a prospective study, patients with early age related maculopathy (ARM) and good visual acuity were randomized to laser treatment or to a control group. Each group consisted of two subgroups: a fellow eye group and a bilateral drusen group. At 3 years, 36 of 38 enrolled patients remained in the study. Photocoagulation was performed with an argon green laser, approximately 100 mild laser burns being placed on and between the drusen in a perifoveal temporal horseshoe-shaped area. Both cases and controls were subjected to fundus colour photographs and fluorescein angiograms at regular intervals, and the drusen area was calculated in both photographs and angiograms. At baseline, there were no significant differences (p > 0.3-0.8) in drusen area between the groups.\n In the treatment group, mean drusen area decreased significantly in the fundus photographs as well as in the angiograms (p < 0.001). Visual acuity and colour contrast sensitivity (CCS) did not change significantly. All these results are valid also for the subgroups. In the control group, however, mean drusen area increased significantly (p < 0.001). Mean visual acuity decreased significantly (p < 0.01) as did the colour contrast sensitivity along the tritan axis (p = 0.02). For the fellow eye control group (n = 7), the increase in drusen area in fundus photographs and the decrease in CCS along the tritan axis were not statistically significant (p = 0.57 and p = 0.37, respectively). Furthermore, at 3 years, five patients in the control group showed exudative lesions (1/7 in the fellow eye group and 4/12 in the bilateral drusen group), whereas no such complications occurred in the treatment group. One patient developed a small atrophy, however. Thus, there is now a significant difference (p = 0.047), however with a large 95% confidence interval, 0.06-0.46, regarding exudative complications between the treated group and the control group in our small patient material.\n Perifoveal mild laser treatment causes a reduction in drusen area in patients with soft drusen maculopathy and may lower the incidence of exudative lesions.", "This pilot study collected preliminary information on the effectiveness and safety of infrared (810-nm) diode laser macular grid photocoagulation in patients with nonexudative age-related macular degeneration (AMD). Results from this pilot study were used in designing a larger, multicenter, randomized clinical trial.\n A multicenter, randomized, controlled, clinical trial.\n A total of 229 eyes of 152 patients with AMD were enrolled in the pilot study. Seventy-five patients with 1 eye eligible (75 eyes) were enrolled in the unilateral arm of the study; 77 patients with both eyes eligible (154 eyes) were enrolled in the bilateral arm of the study. In the unilateral study arm, 32 eyes were randomized to the observation group, 27 eyes were treated with visible endpoint burns, and 16 eyes were treated with invisible endpoint (subthreshold) lesions. In the bilateral study arm, 77 eyes were in the observation group, 36 eyes were treated with visible burns, and 41 eyes were treated with subthreshold (invisible) lesions.\n Eyes were treated with infrared (810-nm) diode laser macular grid photocoagulation using either visible burns or subthreshold (invisible) lesions and compared to eyes receiving no treatment.\n Reduction of drusen, change in visual acuity, and rate of choroidal neovascularization (CNV) membrane formation.\n At 12 months after treatment, 62% of eyes treated with visible burns had a clinically significant reduction in drusen, whereas this proportion (65%) was reached in 18 months for eyes treated with subthreshold lesions. At 24 months' follow-up, treated eyes had a significant reduction in drusen compared to observation eyes (P < 0.0001). Visual acuity was significantly improved in treated eyes at 12, 18, and 24 months compared to observation eyes (P < 0.001). Choroidal neovascularization formation was similar in treated and observation eyes through 24 months' follow-up. Complications included CNV associated with six eyes treated with visible burns and a juxtafoveal laser scar in one eye treated with visible burns.\n Infrared (810-nm) diode laser macular grid photocoagulation in patients with nonexudative AMD significantly reduces drusen levels (P < 0.0001) and significantly improves visual acuity (P < 0.001) when either visible endpoint burns or subthreshold endpoint lesions are used. Complications were fewer using subthreshold endpoint lesions. A larger, multicenter, prospective clinical trial with longer follow-up is needed to determine the efficacy of treatment in reducing the rate of CNV formation. Data from this clinical pilot study have been used to design the Prophylactic Treatment of AMD Trial (PTAMD), a multicenter, randomized, prospective clinical trial currently in progress comparing subthreshold (invisible) treatment to observation in eyes with nonexudative AMD.", "To determine the effects of subthreshold 810-nm-diode laser treatment on the rate of development of choroidal neovascularization (primary end point) and the effect on visual acuity (VA) in participants with multiple large drusen in one eye and a preexisting neovascular age-related macular degeneration (AMD) lesion in the other.\n Multicenter, prospective, randomized controlled trial.\n Two hundred forty-four patients > or =50 years of age and with a neovascular or advanced AMD lesion in one eye and, in the fellow \"study\" eye, (1) at least 5 drusen > or = 63 mum in diameter, (2) Early Treatment Diabetic Retinopathy Study best-corrected VA (BCVA) of 20/63 or better, and (3) no evidence of neovascularization at baseline.\n Patients were randomized to treatment or observation of their study eye at each of 22 centers. At each visit, the protocol specified that BCVA, a complete retinal examination, and fluorescein angiography be documented. Treated eyes had a grid of 48 extrafoveal, subthreshold diode (810 nm) laser spots, 125 mum in diameter, placed in an annulus outside of the foveola. Patients were seen at baseline and at 3, 6, 12, 18, 24, 30, and 36 months after randomization. No retreatments were allowed.\n Development of choroidal neovascularization (as confirmed by fluorescein angiography) and change in BCVA.\n Throughout follow-up, the rate of choroidal neovascularization events in treated eyes consistently exceeded that in observed eyes. At 1 year, the difference was 15.8% versus 1.4% (P = 0.05). Most of the intergroup differences in choroidal neovascularization events occurred during the first 2 years of follow-up. Treated eyes showed a higher rate of VA loss (> or =3 lines) at 3- and 6-month follow-ups relative to observed eyes (8.3% vs. 1% and 11.4% vs. 4%, respectively; Ps = 0.02, 0.07). After 6 months, no significant differences were observed in VA loss between groups.\n Prophylactic subthreshold 810-nm-diode laser treatment to an eye with multiple large drusen in a patient whose fellow eye has already suffered a neovascular event places the treated eye at higher risk of developing choroidal neovascularization. We advise against using prophylactic subthreshold diode laser treatment in these eyes.", "The authors determined the effect of photocoagulation of drusen on visual acuity and progression to subretinal neovascular membranes (SRNV).\n One of paired eyes was randomized to photocoagulation with other eye to control in 27 patients having symmetrical maculopathy and visual acuities, aged 46 to 81 years (mean, 69.7 years); follow-up 1 to 6 years (mean, 3.2 years).\n Final visual acuity was improved in treated eye or decreased in control eye in 12 patients, equal in 13 patients, and decreased in treated eye in 2 patients (P < 0.006). Progression to SRNV was less with treatment.\n Laser photocoagulation of confluent soft macular drusen may improve long-term visual prognosis.", "To update the results of a study on the disappearance of macular soft drusen after laser treatment in the natural evolution of age-related macular degeneration.\n A total of 46 patients with confluent soft drusen and pigmentary changes were studied prospectively. Group 1 was composed of 30 patients with bilateral drusen; the authors randomly assigned one eye of each patient for treatment and the fellow eye for the control. In 16 patients a choroidal neovascular membrane was present in one eye, and treatment was applied to the fellow eye (group 2). Argon green laser treatment was applied directly to the soft drusen in the temporal macula.\n All treated drusen disappeared in a mean of 3.5 months after treatment, and untreated drusen disappeared in all but three patients in an average of 8.5 months. After an average period of 3 years, only one control eye and none of the treated eyes in group 1 developed a choroidal neovascular membrane (P = 0.500). In group 2, neovascularization occurred in 18% of the patients. The initial improvement in Snellen acuity after subfoveal drusen disappearance diminished as a consequence of cataract progression.\n Although no definitive conclusions should be made because of the small number of patients studied, results seem to show that this treatment does not reduce the risk of choroidal neovascularization in the treated eye of patients with a history of exudative disease in the fellow eye. It may be effective in patients with high-risk bilateral soft drusen, that is, in less advanced stages of the disease." ]

[ "2567756", "3351819", "11247684", "8497357" ]

[ "The effect of incisional plastic drapes and redisinfection of operation site on wound infection following caesarean section.", "Skin preparation methods before cesarean section. A comparative study.", "Do plastic adhesive drapes prevent post caesarean wound infection?", "Preoperative skin preparation and intraoperative pelvic irrigation: impact on post-cesarean endometritis and wound infection." ]

[ "In a randomized prospective multicentre study of post-caesarean wound infection among 1,340 women in eight hospitals, the effect of redisinfection of the skin around the incision before skin closure and the effect of adhesive skin drapes were investigated. The overall rate of wound infection with pus was 5.0% (range 3.5-8.9%). The study showed a reduction in postoperative wound infection associated with redisinfection (P = 5.5%), while no benefit from adhesive plastic drapes could be demonstrated.", "Preoperative skin preparation before cesarean section using a one-minute alcohol wash followed by application of an iodophor-impregnated adhesive film was evaluated in a prospective, randomized, controlled study of 79 patients. The iodophor film was as effective as the five-minute iodophor scrub followed by an iodophor wash, as determined by a reduction in skin bacterial counts. Clinical infectious morbidity was no different between the treatment and control groups, although the study was too small to draw statistically significant conclusions in this respect. This study demonstrated the antimicrobial effectiveness of a new, more rapid method of pre-operative skin preparation before cesarean section as compared to a longer, traditional method. This new, rapid method offers advantages for many patients undergoing abdominal delivery.", "We conducted a prospective randomized controlled double-blind trial at a regional referral centre for the Eastern Cape area, (Livingstone Hospital) to determine whether the use of plastic adhesive drapes intraoperatively would prevent Post Caesarean Section Wound Infection. A total of 620 patients undergoing Caesarean section (CS) were enrolled for randomization in the trial. Fifteen patients were excluded, while 305 received drapes (test group) and 300 did not (control group). Two patients in the control group were subsequently excluded. The primary outcome measure was the presence of Post Caesarean Wound Infection. A secondary outcome measure was the number of days in hospital post operation. The study and control groups were comparable at entry. Results show that 34 patients in the test group (N= 305) developed wound sepsis (11.1%) compared with 30 in the control group (N= 298) (10.1%) (difference not significant; Fisher's exact test 0.6933). Average days spent in hospital postoperatively were similar for both test (infected cases: mean 10.56 SD 3.84; non-infected cases: mean 5.21 SD 1.3) and control groups (infected cases: mean 10.18 SD 3.81; non-infected cases: mean 5.2 SD 0.93) (NS). We concluded that the use of plastic adhesive skin drapes did not avert PCWS or decrease the length of post operative stay in hospital for septic cases.\n Copyright 2001 The Hospital Infection Society.", "To determine the impact of two skin preparation methods and two techniques of pelvic irrigation on the incidence of post-cesarean endometritis and wound infection in an indigent patient population.\n A randomized study was performed in 100 cesarean patients. Subjects were assigned to one of four groups, involving either standard skin preparation (povidone-iodine [7.5%] scrub followed by povidone-iodine [10%] solution) or special skin preparation (5-minute scrub with parachlorometaxylenol followed by povidone scrub and solution), and either normal saline or antibiotic (cefazolin sodium, 1 g in 500 mL normal saline) irrigation of the pelvis and subcutaneous tissue at uterine and fascial closure. Four groups of patients were formed: standard skin preparation plus normal saline irrigation, standard preparation plus antibiotic irrigation, special preparation plus normal saline irrigation, and special preparation plus antibiotic irrigation.\n Endometritis occurred significantly more often in the combined groups that did not include antibiotic irrigation than in the combined groups involving antibiotic irrigation (P < .001). In contrast, comparison of skin preparation methods between povidone-iodine alone versus preparation including parachlorometaxylenol indicated no significant difference (P = .22).\n Skin preparation with an antibacterial scrub in addition to standard povidone-iodine scrub and solution does not appear to play as significant a role in the reduction of post-cesarean endometritis or wound infection as does intraoperative pelvic irrigation with antibiotic solution." ]