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cochrane_sparse_mean

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[ "7847866", "8826488" ]

[ "Topical lidocaine gel relieves postherpetic neuralgia.", "Lidocaine patch: double-blind controlled study of a new treatment method for post-herpetic neuralgia." ]

[ "Postherpetic neuralgia (PHN) following herpes zoster is a common and disabling neuropathic pain syndrome. In a double-blind, three-session study, 5% lidocaine gel or vehicle was applied simultaneously to both the area of pain and to the contralateral mirror-image unaffected skin. In the local session, lidocaine gel was applied to the painful skin area. In the remote session, lidocaine gel was applied to mirror-image skin. In the placebo session, vehicle was applied bilaterally. For cranial PHN, gel was applied without occlusion for 8 hours. For limb or torso PHN, gel was applied under occlusion for 24 hours. The 16 subjects with cranial PHN reported pain relief significantly favoring local drug application at 30 minutes, 2, 4, and 8 hours. The 23 subjects with torso or limb PHN reported significantly lower pain intensity with local drug application at 8 hours and both pain relief and reduced pain intensity at 24 hours. Remote lidocaine application to mirror-image skin was no different from placebo. No systemic adverse effects were reported and blood levels did not exceed 0.6 microgram/ml. Topical application of 5% lidocaine gel relieves PHN pain by a direct drug action on painful skin.", "Post-herpetic neuralgia (PHN) is a common and often intractable neuropathic pain syndrome predominantly affecting the elderly. Topical local anesthetics have shown promise in both uncontrolled and controlled studies. Thirty-five subjects with established PHN affecting the torso or extremities completed a four-session, random order, double-blind, vehicle-controlled study of the analgesic effects of topically applied 5% lidocaine in the form of a non-woven polyethylene adhesive patch. All subjects had allodynia on examination. Up to 3 patches, covering a maximum of 420 cm2, were applied to cover the area of greatest pain as fully as possible. Lidocaine containing patches were applied in two of the four 12-h-long sessions, in one session vehicle patches were applied, and one session was a no-treatment observation session. Lidocaine containing patches significantly reduced pain intensity at all time points 30 min to 12 h compared to no-treatment observation, and at all time points 4--12 h compared to vehicle patches. Lidocaine patches were superior to both no-treatment observation and vehicle patches in averaged category pain relief scores. The highest blood lidocaine level measured was 0.1 micrograms/ml, indicating minimal systemic absorption of lidocaine. Patch application was without systemic side effect and well tolerated when applied on allodynic skin for 12 h. This study demonstrates that topical 5% lidocaine in patch form is easy to use and relieves post-herpetic neuralgia." ]

[ "19438397", "12032877", "15094269", "18977721" ]

[ "A randomized trial comparing plasma drug concentrations and efficacies between 2 nonnucleoside reverse-transcriptase inhibitor-based regimens in HIV-infected patients receiving rifampicin: the N2R Study.", "SENC (Spanish efavirenz vs. nevirapine comparison) trial: a randomized, open-label study in HIV-infected naive individuals.", "Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study.", "Virologic, immunologic, clinical, safety, and resistance outcomes from a long-term comparison of efavirenz-based versus nevirapine-based antiretroviral regimens as initial therapy in HIV-1-infected persons." ]

[ "To our knowledge, to date, no prospective, randomized, clinical trial has compared standard doses of efavirenz- and nevirapine-based antiretroviral therapy among patients with concurrent human immunodeficiency virus type 1 (HIV-1) infection and tuberculosis (TB) who are receiving rifampicin.\n Rifampicin recipients with concurrent HIV-1 infection and TB were randomized to receive antiretroviral therapy that included either efavirenz (600 mg per day) or nevirapine (400 mg per day). Efavirenz and nevirapine concentrations at 12 h after dosing (C12) were monitored at weeks 6 and 12. CD4+ cell counts and HIV-1 RNA levels were assessed every 12 weeks.\n One hundred forty-two patients were randomized into 2 groups equally. The mean body weight of patients was 53 kg, the mean CD4+ cell count was 65 cells/mm3, and the median HIV-1 RNA level was 5.8 log10 copies/mL. At weeks 6 and 12, the mean C12 of efavirenz (+/- standard deviation) were 4.27+/-4.49 and 3.54+/-3.78 mg/L, respectively, and those for nevirapine were 5.59+/-3.48 and 5.6+/-2.65 mg/L, respectively. Interpatient variability in the efavirenz group was 2.3-fold greater than that in the nevirapine group (coefficient of variation, 107% vs. 47%). At week 12, 3.1% of patients in the efavirenz group and 21.3% in the nevirapine group had C12 values that were less than the recommended minimum concentrations (odds ratio, 8.396; 95% confidence interval, 1.808-38.993; P= .002). Intention-to-treat analysis revealed that 73.2% and 71.8% of patients in the efavirenz and nevirapine groups, respectively, achieved HIV-1 RNA levels <50 copies/mL at week 48, with respective mean CD4+ cell counts of 274 and 252 cells/mm3 (P> .05). Multivariate analysis revealed that patients with low C12 values and those with a body weight <55 kg were 3.6 and 2.4 times more likely, respectively, to develop all-cause treatment failure (P< .05).\n Antiretroviral therapy regimens containing efavirenz (600 mg per day) were less compromised by concomitant use of rifampicin than were those that contained nevirapine (400 mg per day) in patients with concurrent HIV-1 infection and TB. Low drug exposure and low body weight are important predictive factors for treatment failure.", "A randomized, open-label, pilot study was undertaken to explore the antiviral activity and tolerability of two nonnucleoside reverse transcriptase inhibitors (NNRTIs), nevirapine (NVP) and efavirenz (EFV).\n HIV-infected antiretroviral-naive adults with CD4 counts >100 cells/mm(3) and detectable plasma HIV RNA below 100,000 copies/mL were randomized to receive didanosine (ddI) and stavudine (d4T) plus either NVP or EFV. Assessments were made every 12 weeks. Primary endpoints were the proportion of patients reaching plasma HIV RNA <50 copies/mL and/or developing NNRTI-related toxicities leading to drug discontinuation. Baseline characteristics were comparable for participants in the EFV (n = 31) and NVP arms (n = 36).\n At 48 weeks, 23/31 (74%) patients in the EFV group and 23/36 (64%) in the NVP group had <50 HIV RNA copies/mL (intention-to-treat analysis). Adverse events led to NNRTI discontinuation in 4 and 3 patients in the EFV and NVP arms, respectively. There were no statistically significant differences between groups regarding any primary endpoint. NVP and EFV along with two NRTIs may be equally well tolerated and effective at achieving <50 HIV RNA copies/mL in naive patients with CD4 counts >100 cells/mm(3) and HIV RNA <10(5) copies/mL.\n A much larger study is needed to demonstrate any significant differences between NVP and EFV, if they exist at all.", "The 2NN Study was a randomised comparison of the non-nucleoside reverse-transcriptase inhibitors (NNRTI) nevirapine and efavirenz.\n In this multicentre, open-label, randomised trial, 1216 antiretroviral-therapy-naive patients were assigned nevirapine 400 mg once daily, nevirapine 200 mg twice daily, efavirenz 600 mg once daily, or nevirapine (400 mg) and efavirenz (800 mg) once daily, plus stavudine and lamivudine, for 48 weeks. The primary endpoint was the proportion of patients with treatment failure (less than 1 log(10) decline in plasma HIV-1 RNA in the first 12 weeks or two consecutive measurements of more than 50 copies per mL from week 24 onwards, disease progression [new Centers for Disease Control and Prevention grade C event or death], or change of allocated treatment). Analyses were by intention to treat.\n Treatment failure occurred in 96 (43.6%) of 220 patients assigned nevirapine once daily, 169 (43.7%) of 387 assigned nevirapine twice daily, 151 (37.8%) of 400 assigned efavirenz, and 111 (53.1%) of 209 assigned nevirapine plus efavirenz. The difference between nevirapine twice daily and efavirenz was 5.9% (95% CI -0.9 to 12.8). There were no significant differences among the study groups in the proportions with plasma HIV-1 RNA concentrations below 50 copies per mL at week 48 (p=0.193) or the increases in CD4-positive cells (p=0.800). Nevirapine plus efavirenz was associated with the highest frequency of clinical adverse events, and nevirapine once daily with significantly more hepatobiliary laboratory toxicities than efavirenz. Of 25 observed deaths, two were attributed to nevirapine.\n Antiretroviral therapy with nevirapine or efavirenz showed similar efficacy, so triple-drug regimens with either NNRTI are valid for first-line treatment. There are, however, differences in safety profiles. Combination of nevirapine and efavirenz did not improve efficacy but caused more adverse events.", "To compare long-term virologic, immunologic, and clinical outcomes in antiretroviral-naïve persons starting efavirenz (EFV)- versus nevirapine (NVP)-based regimens.\n The FIRST study randomized patients into three strategy arms: PI+NRTI, NNRTI+NRTI, and PI+NNRTI+NRTI. NNRTI was determined by optional randomization (NVP or EFV) or by choice. For this randomized substudy, the primary endpoint was HIV RNA >50 copies/mL after 8 months or death. Genotypic resistance testing was done at virologic failure (VF; HIV RNA >1,000 copies/mL at or after 4 months).\n 228 persons (111 randomized to EFV, 117 to NVP) were followed for median 5 years. Rates per 100 person years for the primary endpoint were 41.2 (EFV) and 42.8 (NVP; p = .59). The percent of persons with HIV RNA <50 copies/mL was similar throughout follow-up (p = .24), as were average increases in CD4+ cells (p = .30). 423 persons declining the substudy chose EFV; 264 chose NVP. There were 915 persons in the combined cohort (randomized and choice). In the combined cohort, the risk of VF and VF with any NNRTI or NRTI resistance or resistance of any class was significantly less for EFV compared to NVP.\n EFV-based regimens as initial therapy resulted in a lower risk of VF and VF with resistance than did NVP-based regimens, although immunologic and clinical outcomes were similar." ]

[ "10348277", "5553582", "11820343", "8083096" ]

[ "Psychoeducational group increases vaginal dilation for younger women and reduces sexual fears for women of all ages with gynecological carcinoma treated with radiotherapy.", "Postirradiation vaginitis. An evaluation of prophylaxis with topical estrogen.", "The effect of a clinical nurse specialist in gynaecological oncology on quality of life and sexuality.", "Analysis of complications in a prospective randomized trial comparing two brachytherapy low dose rates in cervical carcinoma." ]

[ "The association between radiotherapy for gynecological carcinoma and sexual dysfunction is well established. Regular vaginal dilation is widely recommended to these women as a way for them to maintain vaginal health and good sexual functioning. However, the compliance rate with this recommendation is low. The purpose of this study was to test the effectiveness of a group psychoeducational program based on the \"information-motivation-behavioral skills\" model of behavior change in increasing the rate of compliance.\n Thirty-two women with Stage I or II cervical or endometrial carcinoma who were being treated with radiotherapy were randomized and received either the experimental group program or the control intervention that consisted of written information and brief counseling. Outcome measures included global sexual health, knowledge about sexuality and cancer, fears about sexuality after cancer, and vaginal dilation compliance.\n Younger women attending the experimental program (44.4%) were significantly more likely to follow recommendations for vaginal dilation than those who received the control intervention (5.6%). Women, regardless of age, who received the experimental intervention reported less fear about sex after cancer treatment. The older women who received the experimental intervention gained more sexual knowledge. There was no evidence that the experimental intervention improved global sexual health.\n This is the first controlled study to provide evidence of an intervention's effectiveness 1. in increasing women's vaginal dilation following radiotherapy for gynecological carcinoma and 2. in reducing their fears about sex after cancer. Most women, particularly younger women, are unlikely to follow the recommendation to dilate unless they are given assistance in overcoming their fears and taught behavioral skills.", "nan", "Gynaecological malignancy has an immense impact on the well-being of women. For many women, however, treatment such as surgery is curative and healthcare intervention focuses on the physiological status of the women. The psychological, social and sexual consequences of the malignancy and its treatment have received little attention in research or in practice. The present study used a mixed quantitative and qualitative design to analyse a specialist nurse intervention (including psychosexual intervention), and to explain the impact of the illness on women's lives. The qualitative arm of the study collected interview data from 20 women and six partners. The randomized controlled trial sample consisted of 36 women, with data collected using a quality of life measure (the EORTC QLQ-C30) and the Lasry Sexual Functioning scale. This paper focuses on the randomized controlled trial data, which identified that sexual functioning and quality of life were improved in the active group who received specialist psychosexual counselling. However, the validity of the sexual functioning scale is challenged by the qualitative results of the study, which emphasize the social meaning of sexuality.", "The analysis of complications in a prospective randomized trial comparing two preoperative brachytherapy low-dose rates in early stage cervical cancer is presented.\n Between 1985 and 1988, 204 patients with Stage I and limited Stage II cervical cancer were randomized to receive one of two preoperative brachytherapy low-dose rates (0.4 and 0.8 Gy/hr). The objective of this trial was to determine the benefits, if any, of the higher-dose rate within the therapeutic arsenal for this patient population, in terms of survival, local control, and complications. The type and severity of all complications were evaluated according to a common glossary and a strict follow-up schedule was established given that the treatment of cervical cancer is multidisciplinary, involving gynecologists, surgeons, and radiotherapists.\n Overall survival: 85% at 2 years and local control: 93% at 2 years, were similarly distributed between the two groups. Regardless of their nature and severity, 139 and 175 complications were observed among 63% and 75% of patients, in the 0.4 and 0.8 Gy/h dose rate groups respectively. Gynecologic and urinary complications were the most frequent (38% and 28% of all complications), followed by vascular (15%), digestive (10%), nervous (5%) and cutaneous (5%). A total of 14 and 17 severe complications (Grade 3) were observed in 7% and 13% of patients, respectively in the 0.4 and 0.8 Gy/h dose rate groups (p = 0.12). Nonparametric survival methods used to compare the time to the first complication did not show a significant difference between the two groups: 62% and 72% at 2 years (p = 0.27). When the first complication and its evolution were considered (early complications), the prevalence of complications was not significantly different between the two groups: 28% vs. 34% at 2 years (p = 0.31). In this prospective trial, patients were regularly followed-up and complications of varying nature and severity were observed in succession during follow-up. When successive complications and their evolution were taken into account, the prevalence of complications was significantly greater in the higher-dose rate group: 30% vs. 45% at 2 years (p = 0.03).\n The results of this trial showed that long-term effects of treatment, when represented by prevalence of complications over time, were more frequent in the higher dose rate group. This underlines the importance of the regular follow-up of patients and of coding, not only the occurrence of all complications, but also their evolution over time." ]

[ "11379375", "14551014", "16368471", "22030384", "16186467", "11109313", "15510930", "8456888", "22132809", "19479489", "15214586", "12576261", "20979461", "17329509", "8259754", "10960626", "17893293", "15989411", "19034054", "17217318", "19863455" ]

[ "The effects of tibolone on vaginal blood flow, sexual desire and arousability in postmenopausal women.", "Efficacy and tolerability of a novel estradiol vaginal ring for relief of menopausal symptoms.", "Pulsed estrogen therapy improves postmenopausal quality of life: a 2-year placebo-controlled study.", "Effects of tibolone on climacteric symptoms and quality of life in breast cancer patients--data from LIBERATE trial.", "Effects of conjugated equine estrogen on health-related quality of life in postmenopausal women with hysterectomy: results from the Women's Health Initiative Randomized Clinical Trial.", "[Influence of hormone replacement therapy on the quality of life in postmenopausal women with hypertension].", "Effect of continuous administration of conjugated estrogen plus medroxyprogesterone acetate (Premelle) in postmenopausal women in Taiwan.", "Quality of life of postmenopausal women on a regimen of transdermal estradiol therapy: a double-blind placebo-controlled study.", "Safety and efficacy of tibolone and menopausal transition: a randomized, double-blind placebo-controlled trial.", "Micro-dose transdermal estradiol for relief of hot flushes in postmenopausal Asian women: a randomized controlled trial.", "Efficacy and safety of oral tibolone 1.25 or 2.5 mg/day vs. placebo in postmenopausal women.", "Effect of raloxifene on sexual function in older postmenopausal women with osteoporosis.", "Clinical and metabolic effects of drospirenone-estradiol in menopausal women: a prospective study.", "Low dose of transdermal estradiol gel for treatment of symptomatic postmenopausal women: a randomized controlled trial.", "Is sexual life influenced by transdermal estrogen therapy? A double blind placebo controlled study in postmenopausal women.", "Raloxifene and estrogen effects on quality of life in healthy postmenopausal women: a placebo-controlled randomized trial.", "Hormone therapy in menopausal women with cognitive complaints: a randomized, double-blind trial.", "Supplementation with DHEA: effect on muscle size, strength, quality of life, and lipids.", "A randomized study of low-dose conjugated estrogens on sexual function and quality of life in postmenopausal women.", "Monophasic estrogen-progestogen therapy and sexuality in postmenopausal women.", "Effects of bazedoxifene/conjugated estrogens on quality of life in postmenopausal women with symptoms of vulvar/vaginal atrophy." ]

[ "To compare the effects of 3 months' tibolone treatment with the effects of placebo on sexual function (in particular, vaginal blood flow, and sexual desire and arousability) and climacteric symptoms in postmenopausal women.\n A randomized, double-blind, cross-over study was conducted in 38 postmenopausal women who received tibolone 2.5 mg/day and placebo. Vaginal blood flow during erotic stimulation by fantasy and film was measured using a vaginal photoplethysmograph and subjects completed sexual function questionnaires and daily diaries.\n Tibolone significantly increased baseline vaginal pulse amplitude (VPA) levels compared with placebo. There were significant treatment differences in VPA in favor of tibolone during fantasy periods but not during erotic film stimulation. Tibolone was associated with significant increases in sexual desire, and the frequency of arousability and of sexual fantasies compared with those with placebo. Vaginal lubrication was significantly improved on tibolone. Twenty-five of 38 (66%) subjects correctly guessed when they were on active treatment. Tibolone was well tolerated.\n Tibolone was associated with significant improvements in sexual function in postmenopausal women, reflecting both its estrogenic and androgenic properties. There were significantly greater increases in vaginal blood flow with tibolone in response to erotic fantasy but not film, suggesting two possible pathways of female sexual response.", "To assess the efficacy, tolerability, and acceptance of a vaginal ring delivering the equivalent of 50 or 100 microg per day of estradiol (E2), compared with placebo, for relief of moderate to severe vasomotor symptoms and urogenital symptoms in postmenopausal women.\n Women with moderate to severe vasomotor symptoms (seven or more per day or 56 per week average) received 13 weeks of treatment with a vaginal ring delivering 50 microg per day E2 (n = 113) or 100 microg per day E2 (n = 112), or a placebo vaginal ring (n = 108). Severity of vasomotor symptoms was assessed by a daily diary card and the Greene Climacteric Scale. Urogenital signs and symptoms were evaluated via patient and physician assessment and vaginal cytology. Participant satisfaction with the vaginal ring was evaluated via questionnaire.\n Vasomotor symptoms significantly improved in both treatment groups, compared with placebo (P <.05). There was a trend toward greater improvement in patient assessment of urogenital signs with active rings compared with placebo. For women with vaginal atrophy at baseline (n = 60), the maturation index improved significantly in both treatment groups compared with placebo. Total Greene Climacteric Scale scores significantly improved for both E2 vaginal ring groups (P <.05) compared with placebo. The vaginal rings were well tolerated. Most adverse events were mild or moderate and consistent with estrogen therapy.\n A novel vaginal ring delivering the equivalent of 50 or 100 microg per day of E2 significantly reduced the number and severity of vasomotor symptoms and improved urogenital symptoms, compared with placebo. The E2 vaginal ring was well tolerated.", "To investigate the effect of pulsed estrogen therapy S21400 (intranasal 17 beta-estradiol) on different quality of life (QoL) dimensions in early postmenopausal women treated with S21400 150 microg per day, S21400 300 microg per day, or placebo in a double blind, randomized, controlled 2-year study.\n QoL was assessed based on the validated Women's Health Questionnaire designed for peri- and post-menopausal women. Three hundred and thirty-five healthy, early postmenopausal Danish women, 53 years of age in average, who completed one questionnaire at baseline and one under study treatment were included in the analysis set. All analyses were performed on an intention-to-treat basis.\n QoL improved significantly in both S21400 groups compared to placebo in the dimensions 'memory/concentration', 'vasomotor symptoms', 'sleep problems' and 'sexual behavior' (difference in mean change scores being respectively +7.9, +28.3, +9.9 and +10.8%, p < 0.001, between the S21400 300 microg and placebo group). There were no significant differences between actively treated groups and placebo in the dimensions 'anxiety/depressed mood' and 'well-being'.\n Pulsed estradiol therapy had a pronounced effect not only on vasomotor symptoms but also a significant and clinically relevant improvement in several other QoL dimensions.", "Climacteric symptoms such as hot flushes and vaginal dryness are very common in breast cancer patients, resulting either from age or adjuvant therapy. Tibolone, a synthetic steroid, is effective in reducing these symptoms in healthy post-menopausal women, but this has never been studied in a large breast cancer population.\n The primary objective of LIBERATE trial was to study safety of tibolone 2.5mg daily versus placebo as primary, in symptomatic breast cancer survivors. The aim of this present paper was to report effects of tibolone on climacteric symptoms, vaginal dryness and health-related quality of life in the study population. This trial is registered with ClinicalTrials.gov, n. NCT00408863.\n The trial was conducted between June 2002 and July 2007. Concerning quality of life variables, a daily Diary Cards during the first three months and the Climacteric Symptoms Form and at each visit were used to register frequency and intensity of hot flushes. Mean vaginal dryness scores were calculated on the basis of individual ratings at baseline and at week 104. A subset of patients assessed their quality of life filling in the Women's Health Questionnaire (WHQ).\n Of the 3148 women recruited, 3133 received trial medication (1575 in the tibolone group and 1558 in the placebo group). The median duration of treatment was 2.75 years. In total 3098 women (1556 on tibolone, 1542 on placebo) were included in the intention-to-treat (ITT) population for efficacy analysis. Data on vaginal dryness are available for 2144 patients and 883 women (438 on tibolone, 445 on placebo) answered to WHQ. The mean change in number of hot flushes per day was 2.74 (43.1%) in the tibolone group and -1.77 (-27.5%) in the placebo group (p<0.0001) at week 12 and -4.62 (-65.6%) on tibolone as compared to -3.73 (-52.5%) on placebo (p<0.0001) at week 104. For the composite score the mean changes at week 12 were -0.19 (-10.6%) and -0.14 (-7.7%), respectively (p=0.0006). Vaginal dryness score improved at week 104 in the tibolone group as compared to placebo (-0.46 versus -0.29, respectively; p<0.0001). Across the assessments up to two years with WHQ, tibolone was more effective than placebo in improving sexual health, sleep quality and mood domains. Women using tamoxifen showed less improvement in climacteric symptoms with tibolone, than women only receiving tibolone without any adjuvant therapy.\n The results of the LIBERATE trial show that tibolone is effective in symptomatic breast cancer patients and improves their quality of life. However, this finding should be judged within the context of the main outcome of the trial, showing that tibolone increases the risk of recurrence. The use of tibolone in women with breast cancer will remain contraindicated and any off-label use incurs a now proven risk.\n Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.", "The Women's Health Initiative (WHI) clinical trial of conjugated equine estrogens (CEEs), involving 10,739 postmenopausal women with hysterectomy, aged 50 to 79 years, was stopped early owing to lack of overall health benefit and increased risk of stroke. Because CEE is still prescribed for treatment of menopausal symptoms and prevention of osteoporosis, it is important to understand the overall impact of this therapy on health-related quality of life (HRQOL).\n All participants completed 6 specific measures of quality of life at baseline and 1 year, and a subsample (n = 1189) also completed the questions 3 years after randomization. Changes in scores were analyzed for treatment effect.\n Randomization to CEE was associated with a statistically significant but small reduction in sleep disturbance at year 1 compared with baseline (mean benefit, 0.4 points on a 20-point scale) and a statistically significant but small negative effect on social functioning (mean effect, -1.3 points on a 100-point scale). There were no significant improvements due to CEE in the areas of general health, physical functioning, pain, vitality, role functioning, mental health, depressive symptoms, cognitive function, or sexual satisfaction at year 1. A subgroup examined 3 years after baseline had no significant benefits for any HRQOL outcomes. Among women aged 50 to 54 years with moderate to severe vasomotor symptoms at baseline, CEE did not improve any of the HRQOL variables at year 1.\n In this trial of postmenopausal women with prior hysterectomy, oral CEE did not have a clinically meaningful effect on HRQOL.", "The effect of hormone replacement therapy (HRT) on the quality of life in women with hypertension is still not clear. Thus, the aim of the study was to assess the effect of hormone replacement therapy on quality of life in postmenopausal women with essential hypertension by using a battery of standardized questionnaires.\n The study population consisted of 53 women (mean age 50.9 +/- 6.3 years) with mild and moderate essential hypertension (mean duration 6.4 +/- 6.4 years). The postmenopausal status was defined as the absence of menstrual blood loss during > 6 months and blood estradiol concentration < 50 pg/ml, accompanied by follicle-stimulating hormone (FSH) levels > 21 U/I. Twenty seven women were blindly randomised to transdermal hormone replacement therapy (HRT) and received 17-beta-estradiol and noretisterone acetate, TTS. Twenty six women were randomly selected as controls. The subjects were evaluated at baseline (after 2 weeks' wash-out from hypotensive drug period) and after three months of HRT using self-administered standardized quality of life questionnaires: the Psychological General Well-being Index (PGWB) and the Subjective Symptoms Assessment Profile (SSA-P).\n No differences were found in blood pressure values, heart rate, body mass index and distribution of body fat tissue between women receiving HRT and controls at baseline and after 3 months of follow-up. There were no significant differences in the baseline total PGWB score as well as in its subscale between two groups. Similarly, the frequency and intensity of subjective symptoms assessed by SSA-profile were the same in both groups at baseline. After 3 months, a significant improvement in PGWB total score was observed in women receiving HRT. This effect was due to improvement in anxiety, positive well-being and vitality. Moreover, emotional distress, symptoms of flushing, sweating and trembling hands also diminished and sexual capacity improved in women treated with HRT.\n A three-month hormone replacement therapy in hypertensive postmenopausal women slightly improves the general well-being, seems to decrease emotional tension, increase sexual capacity and markedly relieves some vasomotor symptoms.", "To compare the metabolic effects on lipids and acceptability and safety of, and compliance with, a continuous administration of conjugated estrogen plus medroxyprogesterone acetate (Premelle) versus a placebo in non-hysterectomized postmenopausal women.\n Sixty-six generally healthy, female, early post-menopausal women, from 45-60 years of age, were randomized for an administration of conjugated estrogen plus medroxyprogesterone acetate (Premelle, Premarin 0.625 mg plus medroxyprogesterone acetate 2.5 mg/tablet orally) or a placebo for 6 months. The changes in each patient's lipid profiles from baseline, the frequency of hot flushes, bleeding occurrences, and climacteric symptoms, were evaluated. Safety was monitored by means of physical examination, Papanicolau smear, transvaginal ultrasonography, and laboratory check-up. Adverse events were also recorded.\n The difference before and after treatment in serum LDL-C and total cholesterol (TC) was statistically significant in the Premelle group (LDL-C, p = 0.006, TC, p = 0.040). No statistically significant difference in the change from baseline was observed in the levels of LDL-C and TC in the placebo treatment group. There was a statistically significant change from baseline in menopausal symptoms, which were evaluated by the Greene Climacteric Scales in the Premelle group. There was no clinically significant finding in the physical examination, vital signs, laboratory data, or endometrial thickness in either treatment group. The difference in the number of patients who reported an adverse event was not statistically significant between the 2 treatment groups.\n This study demonstrated that Premelle was effective in decreasing LDL-C and total cholesterol levels, and also showed an improvement in some menopausal symptoms, such as vasomotor and sexual dysfunction symptoms. No significant bleeding was observed with Premelle, which was well tolerated in this study. The results of this study could support the use of Premelle tablets as a convenient alternative hormone therapy.", "The effect of transdermal estradiol and placebo therapy on the quality of life of postmenopausal women was compared in a randomized trial over 12 weeks.\n Two hundred forty-two women were randomized, and 223 were analyzed for efficacy (n = 112 for estradiol and n = 111 for placebo). The quality of life was assessed by means of a battery of standard questionnaires.\n Quality of life improved after both therapies, but health-related quality of life (p = 0.0003) and well being (p = 0.003) improved more after transdermal estradiol therapy than after placebo. This was also the case for all specific climacteric aspects, including sexual problems (p < 0.0001) and dysfunction (p = 0.01), at comparison with placebo. Self-rated symptom relief was more pronounced with estrogen therapy than with placebo (p < 0.0001).\n It was concluded that estradiol therapy was superior to placebo in relieving symptoms and improving quality of life.", "To evaluate the efficacy, safety and tolerability of Tibolone use during the menopausal transition (MT).\n Sixty-five healthy women aged 40-55 years (48.5 ± 3.5 years) were recruited for a randomized, double-blind controlled trial. Thirty participants were recruited to receive oral Tibolone 2.5 mg/day - Tibolone Group (TG), and 35 participants were assigned to the Placebo Group (PG), which received one capsule of lactose/day. Both groups were treated for 12 consecutive weeks. The Blatt-Kupperman Menopausal Index (KMI) and the Greene Climacteric Scale (GCS) were used. The glycaemic and lipid profiles, biochemical measures of hepatic function and endometrial thickness were measured for safety. A daily registry of complaints related to the treatment was maintained, and anthropometric measures were obtained to assess tolerability.\n A total of 57 women completed the study. After 12 weeks of Tibolone use, the total score and percentage of the KMI and GCS were significantly decreased compared to baseline, which reflected the efficacy of the treatment of climacteric symptoms. The improvement in blood biochemistry, endometrial atrophy and maintenance of the anthropometrical measures reflected the safety of Tibolone use. The absence of serious side effects demonstrated good tolerability for Tibolone use.\n The results showed good efficacy, tolerability and safety of Tibolone use during the MT.", "To compare the effect of micro-dose transdermal estradiol and placebo on the incidence and severity of menopausal symptoms and well-being in postmenopausal Asian women with vasomotor symptoms.\n Multicenter, double-blind, randomized, placebo-controlled study.\n Of 165 subjects randomized to estradiol 0.014 mg/day or placebo for 12 weeks, 80 per group were included in the analysis. Groups were comparable at baseline, although time since menopause was slightly shorter in the estradiol group. There was a greater reduction in mean weekly hot flushes at week 12 in the estradiol group (55%) than the placebo group (40%; p < 0.01), which was evident by week 4. A similar pattern was seen for moderate and severe hot flushes (-58% vs. -39%, respectively). Reductions were statistically significant at weeks 4, 8, and 12. Vaginal pH fell significantly in the estradiol group by week 4 and then remained stable throughout the treatment period, but there were no significant changes in the placebo group. Vaginal maturation value increased more in the estradiol than the placebo group (p < 0.001). Few subjects had vaginal bleeding or spotting. Quality of life improved similarly in both groups. Urogenital symptoms improved considerably from baseline in both treatment groups, with no significant differences. Eight subjects experienced treatment-related adverse events (seven in the estradiol group).\n In Asian women, micro-dose estradiol was significantly superior to placebo in improving vasomotor symptoms. The bleeding profile was comparable with that of placebo. Micro-dose estradiol was safe and well tolerated in Asian women.", "tibolone at usual doses of 2.5 mg/day in postmenopausal women has been shown to improve climacteric complaints, without affecting endometrial thickness and lipid profile or blood glucose. However, the potentially similar efficacy, but better tolerability, of a low dose of this drug (1.25 mg) has never been established.\n 162 healthy, non-obese, post-menopausal women, aged 40-65 years, with an intact uterus were enrolled in a national, single centre, randomised, double blind, placebo controlled, parallel group trial. After 1 week of runin, patients were treated for 24 weeks with placebo, tibolone 1.25 mg or 2.5 mg/day. During the study laboratory tests, endometrial ultrasound scans and mammography were performed. Occurrence of menopausal signs and symptoms, including vaginal bleeding, and quality of sexual life were also checked.\n in the 120 patients terminating the study without major protocol violations, climacteric symptoms were similarly improved by tibolone 1.25 and 2.5 mg (78% and 90% reduction at week 24 for hot flushes, 36% and 34% for sweating episodes and 44% and 51% for vaginal dryness), but not by placebo. Benefits occurred earlier in the group treated with tibolone 2.5 mg. Quality of sexual life was almost invariably improved by tibolone as compared to placebo, but improvement occurred earlier in the tibolone 1.25 mg group. Severity of vaginal bleeding was not different between placebo and active treatment groups, except at week 12 when was higher. At the end of treatment vaginal bleeding occurred in 15% of patients treated with placebo, 14% treated with tibolone 1.25 mg and 12% treated with tibolone 2.5 mg. Endometrial thickness and breast density were not changed by treatment, as well as FSH, 17-beta-estradiol, total cholesterol, HDL and LDL cholesterol, triglycerides and blood glucose. Adverse events were reported by 14.7%, 26.7% and 24.4% of patients treated with placebo, tibolone 1.25 mg and tibolone 2.5 mg/day, respectively.\n tibolone at doses of 1.25 or 2.5 mg/day given for 24 weeks to postmenopausal women displayed similar efficacy and safety profiles, though were more effective than placebo. Tibolone 1.25 mg induced a more gradual relief from climacteric symptoms and a more prompt improvement of sexual function.", "To assess the effect of raloxifene compared with placebo on sexual function in older postmenopausal women undergoing therapy for the treatment of osteoporosis.\n A subset (12%) of English-speaking women in the United States and Canada participating in the Multiple Outcomes of Raloxifene Evaluation Trial were asked to complete a sexual function questionnaire at baseline and after 36 months of treatment. The Multiple Outcomes of Raloxifene Evaluation Trial is a multicenter, randomized, blinded, placebo-controlled clinical trial, in which 7,705 postmenopausal women with osteoporosis were randomly assigned to one of three groups: raloxifene hydrochloride 60 mg per day or 120 mg per day or placebo. In this substudy, 943 women completed the sexual function questionnaire at both visits. Because preliminary analyses showed no differences by raloxifene dose (n = 302 for 60 mg per day; n = 322 for 120 mg/day), the two groups were combined and compared with the placebo group (n = 319). For the given sample size, we had 80% power (alpha =.05, two-sided, ratio of raloxifene to placebo = 2:1) to detect a 10%-16% difference in the proportion of women experiencing no change in sexual function between placebo and treatment groups.\n Overall, sexual function and changes in sexual function from baseline to study end between the raloxifene and placebo groups did not differ. In particular, there were no differences in sexual desire or frequency of sexual activity between the groups. Among sexually active women, there were no differences in enjoyment, satisfaction, orgasm, or reported sexual problems.\n Sexual function in older postmenopausal women with osteoporosis is not affected by treatment with raloxifene.", "To describe the effects of low-dose hormonal replacement therapy (HRT) on quality of life, metabolic parameters and blood pressure in postmenopausal women.\n Postmenopausal women untreated with HRT or sex steroids in the previous 12 months were randomized to treatment with 17β-estradiol (1 mg/day) plus drospirenone (2 mg/day) (E2+DRSP) or to calcium (controls). Quality of life was evaluated by the Women's Health Questionnaire (WHQ) at baseline and after 6 and 12 weeks of treatment. Anthropometric, metabolic and blood pressure measurements were performed before and after 3 months of treatment.\n WHQ domain scores for vasomotor and somatic symptoms, anxiety/fears, depressed mood, sexual behavior and sleep problems decreased significantly in the E2+DRSP group relative to both baseline and control values (p < 0.05). Body mass index was unchanged, while waist circumference decreased significantly (p < 0.001) after E2+DRSP treatment. Significant decreases were also observed after E2+DRSP treatment for blood insulin values, insulin resistance (estimated by homeostasis model assessment) and systolic blood pressure (p < 0.001, all). In subjects with systolic blood pressure < 130 mmHg at baseline, no changes in systolic values were registered, while women with baseline high-normal systolic blood pressure (130-139 mmHg) showed significant decreases (p < 0.0069). E2+DRSP did not modify diastolic blood pressure values. In the calcium-treatment group, there were no significant changes in WHQ scores or in anthropometric, metabolic or blood pressure measurements.\n In postmenopausal women, E2+DRSP administration improves vasomotor symptoms and general aspects of quality of life and may positively influence cardiovascular risk factors.", "To investigate safety and efficacy and identify the lowest effective dose of a new transdermal estradiol (E2) gel for relief of menopausal symptoms in a population of postmenopausal women.\n This study was a randomized, double-blind, placebo-controlled, multicenter, parallel-group study. Postmenopausal women with at least 60 hot flushes per week applied 0.87 g/d (n=136), 1.7 g/d (n=142), or 2.6 g/d (n=69) E2 gel or placebo gel (n=137) topically for 12 weeks. The changes from baseline in hot flush frequency and severity at 4 and 12 weeks and changes from baseline in vaginal atrophy symptoms at 12 weeks were examined.\n With increasing E2 doses, mean trough serum E2 increased from 17 to 29 pg/mL. By weeks 3-5, E2 gel reduced moderate-to-severe hot flush rate by at least seven hot flushes per day (P<.001) and reduced the severity score (P<.01). The numbers needed to treat for benefit for an 80% and 100% decrease in hot flush number were 3.2 and 6.3 for the 0.87-g/d group and 1.3 and 2.3 for the 2.6-g/d group. At week 12, vaginal pH was more acidic and vaginal maturation index more mature compared with placebo (P<.001). The lowest dose improved most bothersome vulvovaginal atrophy symptoms (P<.05). Estradiol gel was well tolerated at the site of application and produced no unexpected adverse effects. The 0.87 g/d dose produced fewest adverse events.\n The 0.87 g/d dose of this new transdermal E2 gel, which delivers an estimated 0.0125 mg E2 daily, delivered the lowest effective dose for treatment of vasomotor symptoms and vulvovaginal atrophy in a population of postmenopausal women.\n ClinicalTrials.gov, www.clinicaltrials.gov, NCT00391417.\n I.", "Two hundred and forty-two postmenopausal women between 45 and 65 years of age requiring hormone replacement therapy for climacteric symptoms were blindly and randomly allocated to treatment either with transdermal estradiol therapy (Estraderm 50 micrograms/24h) (E) or placebo (P). The patches were changed twice a week and treatment continued for 12 weeks. No progestogen supplement therapy was given during the study. No previous hormone replacement therapy had been given for the last six months and the women had had their last menstruation more than six months ago. As a part of a larger study assessing women's quality of life, a Swedish version of 'McCoy's Sex Scale Questionnaire' was administered at the start of treatment and after 12 weeks. This questionnaire contains nine items regarding different aspects of sexual life. The difference between the scorings at the start of treatment and after 12 weeks were calculated for each item and the values of the E and the P groups were compared. Items regarding 'satisfaction with frequency of sexual activity, sexual fantasies, degree of enjoyment, vaginal lubrication and pain during intercourse' were positively influenced in the E group compared to the P group. Items not affected were 'frequency of orgasm and sexual arousal'. A correlation between improved sexual life and quality of life was also found when the results from the McCoy scale were compared with a battery of quality of life questionnaires.", "To assess the effects of raloxifene, estrogen, and placebo on quality of life in healthy, asymptomatic, postmenopausal women.\n In a multicenter, double-blind, 12-month study, 398 women were assigned randomly to one of four groups: raloxifene HCl, 60 (n = 97) or 150 mg/day (n = 100); conjugated equine estrogens, 0. 625 mg/day (n = 96); or placebo (n = 105). The Women's Health Questionnaire, a validated quality-of-life instrument for perimenopausal and postmenopausal women, was administered at baseline and 3-month intervals.\n Overall, quality of life from baseline to end point was preserved equally in all treatment groups. Six domains (depressed mood, somatic symptoms, memory/concentration, sexual behavior, sleep problems, and perceived attractiveness) were unchanged in all groups. Three domains (menstrual symptoms, vasomotor symptoms, and anxiety/fears) were statistically significantly different among groups. Mean scores for menstrual symptoms significantly worsened and vasomotor symptoms significantly improved from baseline to end point in the estrogen group. Mean scores for vasomotor symptoms did not worsen at any point in the raloxifene 60 mg/day group. Mean anxiety/fears scores improved significantly during raloxifene 60 mg/day administration throughout treatment (P <.05), irrespective of previous hormone replacement therapy, baseline estradiol (E2) levels, or years postmenopause.\n Most quality-of-life domains were not affected by treatment with estrogen or raloxifene. Estrogen provided relief from vasomotor symptoms but caused menstrual symptoms. Raloxifene 60 mg/day improved anxiety levels in postmenopausal women.", "To evaluate the effects of hormone therapy (HT) on cognition and subjective quality of life (QoL) in recently postmenopausal women with cognitive complaints.\n Cognitive Complaints in Early Menopause Trial (COGENT) was a randomized, double-blind, placebo-controlled, multicenter, pilot study of 180 healthy postmenopausal women aged 45 to 55 years, randomly assigned to receive either placebo or conjugated equine estrogen 0.625 mg/medroxyprogesterone acetate 2.5 mg for 4 months. Outcome measures included memory, subjective cognition, QoL, sexuality, and sleep, which were assessed at baseline and month 4.\n The study was terminated before the expected final sample size of 275 due to a decrease in enrollment coinciding with the publication of findings from the Women's Health Initiative. There were no differences between groups on any cognitive or QoL measures, except for an increase in sexual interest and thoughts with HT. Modest negative effects on short- and long-term verbal memory approached significance (p < 0.10). Women with baseline vasomotor symptoms (VMS) showed a decrease in VMS and an improvement in general QoL, but no cognitive benefit vs placebo.\n With the power to detect an effect size of >or=0.45, this study suggests potential modest negative effects on verbal memory that are consistent with previous hormone therapy trials in older women.", "To evaluate the effects of combination estrogen/androgen therapy on muscle mass, strength and endurance, serum hormone and lipid profiles, and quality of life measures in postmenopausal women.\n Prospective, randomized, placebo-controlled pilot study at a tertiary care medical center. Fifty postmenopausal women were randomized to a 12-week course of (1) dehydroepiandrostenedione (DHEA) 50 mg daily, (2) conjugated equine estrogen (CEE) 0.625 mg daily, (3) DHEA 50 mg+CEE 0.625 mg daily, or (4) placebo. Main outcome measures of lower extremity muscle (calf) mass, functional muscle parameters, serum hormone and lipid levels, and quality of life (QOL) were obtained at baseline and after treatment. Statistical analysis compared percent change from baseline values and treatment differences among outcomes.\n Significant increases in mean DHEA, DHEA sulfate (DHEA-S), testosterone, and androstenedione levels were noted with DHEA alone or combined DHEA/CEE treatments when compared with placebo. Compared with no hormone therapy, none of the supplemental hormone groups caused significant changes in muscle mass, muscle strength, muscle endurance, feelings of well-being, sleep, or sexual function.\n Androgen replacement therapy, with DHEA, to menopausal women increases serum androgen levels without any appreciable effect on muscle cross-sectional area, muscle strength, muscle function, or improvement in health-related QOL.", "To evaluate the effects of combined vaginal and oral low-dose estrogen plus progestogen therapy (EPT) on the frequency and severity of dyspareunia, sexual function, and quality of life in recently postmenopausal women.\n This outpatient, double-blind, randomized, placebo-controlled trial enrolled 285 healthy, sexually active postmenopausal women aged 45 to 65 years. Women received either one daily oral low-dose conjugated estrogens (0.45 mg)/medroxyprogesterone (1.5 mg) tablet for six 28-day cycles along with 1 g conjugated estrogens vaginal cream (0.625 mg), intravaginally for the first 6 weeks of the trial or a placebo cream and placebo tablet. Efficacy was evaluated using the McCoy Female Sexuality Questionnaire, self-reported daily diary cards, the Brief Index of Sexual Functioning-Women (BISF-W), and the Women's Health Questionnaire.\n The EPT group had a significant decrease in the frequency of dyspareunia compared with baseline and placebo in an analysis of responses to the McCoy Female Sexuality Questionnaire. Also, EPT was associated with a significant improvement in a woman's level of sexual interest, frequency of orgasm, and pleasure of orgasm. There was no effect of EPT use on coital frequency. The EPT group had significant improvement in receptivity/initiation and relationship satisfaction, although not in other BISF-W domains, versus placebo (BISF-W analysis) and significant improvement versus placebo on most Women's Health Questionnaire responses.\n EPT provided a statistically significant improvement compared with placebo in dyspareunia, sexual experience, and quality of life as measured in this study. In general, EPT also improved self-reported sexual perception and enjoyment significantly compared with placebo.", "This study aimed to evaluate the effects of monophasic estrogen-progestogen therapy on the sexuality and climacteric symptoms of postmenopausal women.\n A prospective, randomised, double-blind, crossover, placebo-controlled, single-centre study was carried out over a total of 12 consecutive months in 40 postmenopausal women with an intact uterus who had no contraindications to hormone therapy. Patients received 17beta-estradiol 2mg in combination with norethisterone acetate 1mg (Cliane) daily for 6 months or one placebo tablet daily for 6 months. The tablets were identical in appearance. After 6 months, the groups were crossed over and the patients were followed up for another 6 months. The groups were homogenous with respect to age, height, bodyweight, body mass index and race. For the statistical analysis, the group receiving hormone therapy was referred to as group A and the placebo group was designated group B, irrespective of the placebo/hormone therapy sequence.\n In group A there were fewer hot flashes (F=22.85, p<0.01) and an improvement in sexual interest (F=5.55, p<0.05). The sequence in which the medication was received resulted in a statistically significant difference with respect to dyspareunia (F=9.65, p<0.01) and satisfaction with the duration of penetration (F=6.58, p<0.05). In the intrapatient analysis of variation with respect to orgasmic capability and the presence of dialogue with partner regarding the couple's sexual life, whether the placebo was taken prior to or following hormone therapy was significant (F=17.12, p<0.001 and F=7.10, p<0.05, respectively).\n Monophasic estrogen-progestogen therapy has a beneficial effect on sexuality and on hot flashes in postmenopausal women.", "To evaluate the effects of the tissue selective estrogen complex (TSEC) pairing bazedoxifene (BZA) with conjugated estrogens (CE) on sexual function and quality of life in postmenopausal women.\n In this 12-week, double-blind, placebo-controlled study, postmenopausal, non-hysterectomized women (n = 652) with symptoms of moderate to severe vulvar/vaginal atrophy were randomized to once-daily treatment with BZA 20 mg/CE 0.45 or 0.625 mg, BZA 20 mg, or placebo. The Arizona Sexual Experiences (ASEX) Scale, Menopause-Specific Quality of Life (MENQOL) questionnaire, and Menopause Symptoms Treatment Satisfaction Questionnaire (MS-TSQ) were secondary measures used to assess the effects of BZA/CE on sexual function, menopausal symptoms, and satisfaction with treatment, respectively.\n At week 12, both BZA/CE doses were associated with significant improvement in ease of lubrication score from baseline compared with placebo (p < 0.05) on the ASEX scale, although there was no difference in the change in total score. The MENQOL questionnaire results at week 12 showed significant improvements in vasomotor function, sexual function and total scores with both BZA/CE doses vs. placebo or BZA 20 mg (p < 0.001). The MS-TSQ results showed that BZA/CE-treated subjects reported significantly greater overall satisfaction with treatment, as well as satisfaction with control of hot flushes during the day and night, effect on quality of sleep, and effect on mood or emotions, compared with subjects treated with placebo or BZA 20 mg (all p < 0.05).\n Treatment with BZA/CE for 12 weeks was shown to significantly improve sexual function and quality-of-life measures in symptomatic postmenopausal women." ]

[ "9847275", "9449728", "10793162", "10470755", "16557151", "9449727" ]

[ "Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume reduction in ARDS.", "Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. Pressure- and Volume-Limited Ventilation Strategy Group.", "Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network.", "Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients.", "A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial.", "Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome." ]

[ "Because animal studies have demonstrated that mechanical ventilation at high volume and pressure can be deleterious to the lungs, limitation of airway pressure, allowing hypercapnia if necessary, is already used for ventilation of acute respiratory distress syndrome (ARDS). Whether a systematic and more drastic reduction is necessary is debatable. A multicenter randomized study was undertaken to compare a strategy aimed at limiting the end-inspiratory plateau pressure to 25 cm H2O, using tidal volume (VT) below 10 ml/kg of body weight, versus a more conventional ventilatory approach (with regard to current practice) using VT at 10 ml/kg or above and close to normal PaCO2. Both arms used a similar level of positive end-expiratory pressure. A total of 116 patients with ARDS and no organ failure other than the lung were enrolled over 32 mo in 25 centers. The two groups were similar at inclusion. Patients in the two arms were ventilated with different VT (7.1 +/- 1.3 versus 10.3 +/- 1.7 ml/kg at Day 1, p < 0.001) and plateau pressures (25.7 +/- 5. 0 versus 31.7 +/- 6.6 cm H2O at Day 1, p < 0.001), resulting in different PaCO2 (59.5 +/- 15.0 versus 41.3 +/- 7.6 mm Hg, p < 0.001) and pH (7.28 +/- 0.09 versus 7.4 +/- 0.09, p < 0.001), but a similar level of oxygenation. The new approach did not reduce mortality at Day 60 (46.6% versus 37.9% in control subjects, p = 0.38), the duration of mechanical ventilation (23.1 +/- 20.2 versus 21.4 +/- 16. 3 d, p = 0.85), the incidence of pneumothorax (14% versus 12%, p = 0. 78), or the secondary occurrence of multiple organ failure (41% versus 41%, p = 1). We conclude that no benefit could be observed with reduced VT titrated to reach plateau pressures around 25 cm H2O compared with a more conventional approach in which normocapnia was achieved with plateau pressures already below 35 cm H2O.", "A strategy of mechanical ventilation that limits airway pressure and tidal volume while permitting hypercapnia has been recommended for patients with the acute respiratory distress syndrome. The goal is to reduce lung injury due to overdistention. However, the efficacy of this approach has not been established.\n Within 24 hours of intubation, patients at high risk for the acute respiratory distress syndrome were randomly assigned to either pressure- and volume-limited ventilation (limited-ventilation group), with the peak inspiratory pressure maintained at 30 cm of water or less and the tidal volume at 8 ml per kilogram of body weight or less, or to conventional ventilation (control group), with the peak inspiratory pressure allowed to rise as high as 50 cm of water and the tidal volume at 10 to 15 ml per kilogram. All other ventilatory variables were similar in the two groups.\n A total of 120 patients with similar clinical features underwent randomization (60 in each group). The patients in the limited-ventilation and control groups were exposed to different mean (+/-SD) tidal volumes (7.2+/-0.8 vs. 10.8+/-1.0 ml per kilogram, respectively; P<0.001) and peak inspiratory pressures (23.6+/-5.8 vs. 34.0+/-11.0 cm of water, P<0.001). Mortality was 50 percent in the limited-ventilation group and 47 percent in the control group (relative risk, 1.07; 95 percent confidence interval, 0.72 to 1.57; P=0.72). In the limited-ventilation group, permissive hypercapnia (arterial carbon dioxide tension, >50 mm Hg) was more common (52 percent vs. 28 percent, P=0.009), more marked (54.4+/-18.8 vs. 45.7+/-9.8 mm Hg, P=0.002), and more prolonged (146+/-265 vs. 25+/-22 hours, P=0.017) than in the control group. The incidence of barotrauma, the highest multiple-organ-dysfunction score, and the number of episodes of organ failure were similar in the two groups; however, the numbers of patients who required paralytic agents (23 vs. 13, P=0.05) and dialysis for renal failure (13 vs. 5, P= 0.04) were greater in the limited-ventilation group than in the control group.\n In patients at high risk for the acute respiratory distress syndrome, a strategy of mechanical ventilation that limits peak inspiratory pressure and tidal volume does not appear to reduce mortality and may increase morbidity.", "Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients.\n Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter, randomized trial. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration (plateau pressure) of 50 cm of water or less, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less. The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28.\n The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0 percent vs. 39.8 percent, P=0.007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean [+/-SD], 12+/-11 vs. 10+/-11; P=0.007). The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight (P<0.001), respectively, and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water (P<0.001), respectively.\n In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use.", "To assess the safety and potential efficacy of a mechanical ventilation strategy designed to reduce stretch-induced lung injury in acute respiratory distress syndrome.\n Prospective, randomized, controlled clinical trial.\n Eight intensive care units in four teaching hospitals.\n Fifty-two patients with acute respiratory distress syndrome.\n Traditional tidal volume patients: tidal volume 10-12 mL/kg ideal body weight, reduced if inspiratory plateau pressure was > 55 cm H2O (7.3 kPa). Small tidal volume patients: tidal volume 5-8 mL/kg ideal body weight, to keep plateau pressure < 30 cm H2O (4.0 kPa).\n Mean tidal volumes during the first 5 days in traditional and small tidal volume patients were 10.2 and 7.3 mL/kg, respectively (p < .001), with mean plateau pressure = 30.6 and 24.9 cm H2O (3.3 kPa), respectively (p < .001). There were no significant differences in requirements for positive end-expiratory pressure or FIO2, fluid intakes/outputs, requirements for vasopressors, sedatives, or neuromuscular blocking agents, percentage of patients that achieved unassisted breathing, ventilator days, or mortality.\n The reduced tidal volume strategy used in this study was safe. Failure to observe beneficial effects of small tidal volume ventilation treatment in important clinical outcome variables may have occurred because a) the sample size was too small to discern small treatment effects; b) the differences in tidal volumes and plateau pressures were modest; or c) reduced tidal volume ventilation is not beneficial.", "It has been shown in a two-center study that high positive end-expiratory pressure (PEEP) and low tidal volume (LTV) improved outcome in ARDS. However, that study involved patients with underlying diseases unique to the study area, was conducted at only two centers, and enrolled a small number of patients. We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system (Pflex) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome (ARDS).\n Randomized, controlled clinical trial.\n Network of eight Spanish multidisciplinary intensive care units (ICUs) under the acronym of ARIES (Acute Respiratory Insufficiency: España Study).\n All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study. If 24 hrs after meeting ARDS criteria, the Pao2/Fio2 remained < or =200 mm Hg on standard ventilator settings, patients were randomized into two groups: control and Pflex/LTV.\n In the control group, tidal volume was 9-11 mL/kg of predicted body weight (PBW) and PEEP > or =5 cm H2O. In the Pflex/LTV group, tidal volume was 5-8 mL/kg PBW and PEEP was set on day 1 at Pflex + 2 cm H2O. In both groups, Fio2 was set to maintain arterial oxygen saturation >90% and Pao2 70-100 mm Hg, and respiratory rate was adjusted to maintain Paco2 between 35 and 50 mm Hg.\n The study was stopped early based on an efficacy stopping rule as described in the methods. Of 103 patients who were enrolled (50 control and 53 Pflex), eight patients (five in control, three in Pflex) were excluded from the final evaluation because the random group assignment was not performed in one center according to protocol. Main outcome measures were ICU and hospital mortality, ventilator-free days, and nonpulmonary organ dysfunction. ICU mortality (24 of 45 [53.3%] vs. 16 of 50 [32%], p = .040), hospital mortality (25 of 45 [55.5%] vs. 17 of 50 [34%], p = .041), and ventilator-free days at day 28 (6.02 +/- 7.95 in control and 10.90 +/- 9.45 in Pflex/LTV, p = .008) all favored Pflex/LTV. The mean difference in the number of additional organ failures postrandomization was higher in the control group (p < .001).\n A mechanical ventilation strategy with a PEEP level set on day 1 above Pflex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS.", "In patients with the acute respiratory distress syndrome, massive alveolar collapse and cyclic lung reopening and overdistention during mechanical ventilation may perpetuate alveolar injury. We determined whether a ventilatory strategy designed to minimize such lung injuries could reduce not only pulmonary complications but also mortality at 28 days in patients with the acute respiratory distress syndrome.\n We randomly assigned 53 patients with early acute respiratory distress syndrome (including 28 described previously), all of whom were receiving identical hemodynamic and general support, to conventional or protective mechanical ventilation. Conventional ventilation was based on the strategy of maintaining the lowest positive end-expiratory pressure (PEEP) for acceptable oxygenation, with a tidal volume of 12 ml per kilogram of body weight and normal arterial carbon dioxide levels (35 to 38 mm Hg). Protective ventilation involved end-expiratory pressures above the lower inflection point on the static pressure-volume curve, a tidal volume of less than 6 ml per kilogram, driving pressures of less than 20 cm of water above the PEEP value, permissive hypercapnia, and preferential use of pressure-limited ventilatory modes.\n After 28 days, 11 of 29 patients (38 percent) in the protective-ventilation group had died, as compared with 17 of 24 (71 percent) in the conventional-ventilation group (P<0.001). The rates of weaning from mechanical ventilation were 66 percent in the protective-ventilation group and 29 percent in the conventional-ventilation group (P=0.005): the rates of clinical barotrauma were 7 percent and 42 percent, respectively (P=0.02), despite the use of higher PEEP and mean airway pressures in the protective-ventilation group. The difference in survival to hospital discharge was not significant; 13 of 29 patients (45 percent) in the protective-ventilation group died in the hospital, as compared with 17 of 24 in the conventional-ventilation group (71 percent, P=0.37).\n As compared with conventional ventilation, the protective strategy was associated with improved survival at 28 days, a higher rate of weaning from mechanical ventilation, and a lower rate of barotrauma in patients with the acute respiratory distress syndrome. Protective ventilation was not associated with a higher rate of survival to hospital discharge." ]

[ "5000714", "10458549" ]

[ "Pyrosis and pregnancy.", "Antacids vs. antacids plus non-prescription ranitidine for heartburn during pregnancy." ]

[ "nan", "nan" ]

[ "16123223", "15494430", "15284112", "15668467", "16873669" ]

[ "Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group.", "CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma.", "The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group.", "Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG).", "Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial." ]

[ "Phase 2 studies suggest that the monoclonal antibody rituximab may improve the prognosis of patients with follicular lymphoma (FL) when it is added to chemotherapy. In the current study, 428 patients with untreated, advanced-stage FL were randomly assigned for therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone (n = 205) or CHOP combined with rituximab (R-CHOP) (n = 223). R-CHOP reduced the relative risk for treatment failure by 60% and significantly prolonged the time to treatment failure (P < .001). In addition, a significantly higher overall response rate (96% vs 90%; P = .011) and a prolonged duration of remission (P = .001) were achieved. In spite of a relatively short observation time, these beneficial effects even translated to superior overall survival (P = .016), with 6 deaths in the R-CHOP group compared with 17 deaths in the CHOP group within the first 3 years. The predominant treatment-related adverse effect was myelosuppression. Severe granulocytopenia was more frequently observed after R-CHOP (63% vs 53%; P = .01). However, severe infections were rare and of similar frequency after R-CHOP and CHOP (5% and 7%). Hence, adding rituximab to CHOP significantly improves the outcome for patients with previously untreated advanced-stage FL and does not induce major adverse effects.", "The combination of cyclophosphamide, vincristine, and prednisone (CVP) is one of several standard treatment options for advanced follicular lymphoma. This, like similar chemotherapeutic regimens, induces response rates of 60% to 80%, with a median response duration of under 2 years. Rituximab, a chimeric monoclonal antibody against CD20, is active in follicular lymphoma, both as monotherapy and in combination with chemotherapy. Previously untreated patients with stages III to IV follicular lymphoma were randomly assigned to receive either 8 cycles of CVP plus rituximab (R-CVP; n = 162) or CVP (n = 159). Overall and complete response rates were 81% and 41% in the R-CVP arm versus 57% and 10% in the CVP arm, respectively (P < .0001). At a median follow-up of 30 months, patients treated with R-CVP had a very significantly prolonged time to progression (median 32 months versus 15 months for CVP; P < .0001). Median time to treatment failure was 27 months in patients receiving R-CVP and 7 months in the CVP arm (P < .0001). Rituximab did not add significantly to the toxicity of CVP. The addition of rituximab to the CVP regimen significantly improves the clinical outcome in patients with previously untreated advanced follicular lymphoma, without increased toxicity.", "In follicular lymphoma (FL) and mantle cell lymphoma (MCL) the monoclonal antibody rituximab may improve the prognosis when combined with chemotherapy. This was investigated in a prospective randomized study in patients with relapsed disease. A total of 147 patients were randomized to receive 4 courses of chemotherapy with 25 mg/m(2) fludarabine on days 1 to 3, 200 mg/m(2) cyclophosphamide on days 1 to 3, and 8 mg/m(2) mitoxantrone on day 1 (FCM), alone or combined with rituximab (375 mg/m(2); R-FCM). Of 128 evaluable patients, 62 were randomized for FCM and 66 for R-FCM. R-FCM revealed an overall response rate of 79% (33% complete remission [CR], 45% partial remission [PR]) as compared with 58% for FCM alone (13% CR, 45% PR; P = .01), with similar results in a subgroup analysis of FL (94% vs 70%) and MCL (58% vs 46%). In the total group, the R-FCM arm was significantly superior concerning progression-free survival (PFS; P = .0381) and overall survival (OS; P = .0030). In FL PFS was significantly longer in the R-FCM arm (P = .0139) whereas in MCL a significantly longer OS was observed (P = .0042). There were no differences in clinically relevant side effects in both study arms. Hence, the addition of rituximab to FCM chemotherapy significantly improves the outcome of relapsed or refractory FL and MCL.", "Mantle cell lymphoma (MCL) is characterized by a poor prognosis with a low to moderate sensitivity to chemotherapy and a median survival of only 3 to 4 years. In an attempt to improve outcome, the German Low Grade Lymphoma Study Group (GLSG) initiated a randomized trial comparing the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and rituximab (R-CHOP) with CHOP alone as first-line therapy for advanced-stage MCL.\n One hundred twenty-two previously untreated patients with advanced-stage MCL were randomly assigned to six cycles of CHOP (n = 60) or R-CHOP (n = 62). Patients up to 65 years of age achieving a partial or complete remission underwent a second randomization to either myeloablative radiochemotherapy followed by autologous stem-cell transplantation or interferon alfa maintenance (IFNalpha). All patients older than 65 years received IFNalpha maintenance.\n R-CHOP was significantly superior to CHOP in terms of overall response rate (94% v 75%; P = .0054), complete remission rate (34% v 7%; P = .00024), and time to treatment failure (TTF; median, 21 v 14 months; P = .0131). No differences were observed for progression-free survival. Toxicity was acceptable, with no major differences between the two therapeutic groups.\n The combined immunochemotherapy with R-CHOP resulted in a significantly higher response rate and a prolongation of the TTF as compared with chemotherapy alone. Hence, R-CHOP may serve as a new baseline regimen for advanced stage MCL, but needs to be further improved by novel strategies in remission.", "We evaluated the role of rituximab (R) both in remission induction and maintenance treatment of relapsed/resistant follicular lymphoma (FL). A total of 465 patients were randomized to induction with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (every 3 weeks) or R-CHOP (R: 375 mg/m(2) intravenously, day 1). Those in complete remission (CR) or partial remission (PR) were randomized to maintenance with R (375 mg/m(2) intravenously once every 3 months for a maximum of 2 years) or observation. R-CHOP induction yielded an increased overall response rate (CHOP, 72.3%; R-CHOP, 85.1%; P < .001) and CR rate (CHOP, 15.6%; R-CHOP, 29.5%; P < .001). Median progression-free survival (PFS) from first randomization was 20.2 months after CHOP versus 33.1 months after R-CHOP (hazard ratio [HR], 0.65; P < .001). Rituximab maintenance yielded a median PFS from second randomization of 51.5 months versus 14.9 months with observation (HR, 0.40; P < .001). Improved PFS was found both after induction with CHOP (HR, 0.30; P < .001) and R-CHOP (HR, 0.54; P = .004). R maintenance also improved overall survival from second randomization: 85% at 3 years versus 77% with observation (HR, 0.52; P = .011). This is the first trial showing that in relapsed/resistant FL rituximab maintenance considerably improves PFS not only after CHOP but also after R-CHOP induction." ]

[ "12435255", "7474675", "15766995", "11849464", "9635947", "10860192" ]

[ "Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial.", "\"Strict\" blood pressure control and progression of renal disease in hypertensive nephrosclerosis.", "Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicentre, randomised controlled trial.", "Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes.", "Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group.", "Effect of blood pressure control on diabetic microvascular complications in patients with hypertension and type 2 diabetes." ]

[ "Hypertension is a leading cause of end-stage renal disease (ESRD) in the United States, with no known treatment to prevent progressive declines leading to ESRD.\n To compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classes on glomerular filtration rate (GFR) decline in hypertension.\n Randomized 3 x 2 factorial trial with enrollment from February 1995 to September 1998.\n A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years.\n Participants were randomly assigned to 1 of 2 mean arterial pressure goals, 102 to 107 mm Hg (usual; n = 554) or 92 mm Hg or less (lower; n = 540), and to initial treatment with either a beta-blocker (metoprolol 50-200 mg/d; n = 441), an angiotensin-converting enzyme inhibitor (ramipril 2.5-10 mg/d; n = 436) or a dihydropyridine calcium channel blocker, (amlodipine 5-10 mg/d; n = 217). Open-label agents were added to achieve the assigned BP goals.\n Rate of change in GFR (GFR slope); clinical composite outcome of reduction in GFR by 50% or more (or > or =25 mL/min per 1.73 m2) from baseline, ESRD, or death. Three primary treatment comparisons were specified: lower vs usual BP goal; ramipril vs metoprolol; and amlodipine vs metoprolol.\n Achieved BP averaged (SD) 128/78 (12/8) mm Hg in the lower BP group and 141/85 (12/7) mm Hg in the usual BP group. The mean (SE) GFR slope from baseline through 4 years did not differ significantly between the lower BP group (-2.21 [0.17] mL/min per 1.73 m2 per year) and the usual BP group (-1.95 [0.17] mL/min per 1.73 m2 per year; P =.24), and the lower BP goal did not significantly reduce the rate of the clinical composite outcome (risk reduction for lower BP group = 2%; 95% confidence interval [CI], -22% to 21%; P =.85). None of the drug group comparisons showed consistent significant differences in the GFR slope. However, compared with the metoprolol and amlodipine groups, the ramipril group manifested risk reductions in the clinical composite outcome of 22% (95% CI, 1%-38%; P =.04) and 38% (95% CI, 14%-56%; P =.004), respectively. There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups.\n No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal. Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline.", "Hypertensive nephrosclerosis is a progressive renal disease and the leading cause of end-stage renal disease (ESRD) in blacks in the United States. It is generally believed that hypertensive renal injury is responsible for progressive renal failure; however, it is not known whether pharmacologic lowering of blood pressure to any level prevents progression of renal disease. Accordingly, we performed a long-term prospective randomized trial to determine whether \"strict\" [diastolic blood pressure (DBP) 65 to 80 mm Hg] versus \"conventional\" (DBP 85 to 95 mm Hg) blood pressure control is associated with a slower rate of decline in glomerular filtration rate. Eighty-seven non-diabetic patients (age 25 to 73; 68 black, 58 male) with long-standing hypertension (DBP > or = 95 mm Hg), chronic renal insufficiency (GFR < or = 70 m/min/1.73 m2) and a normal urine sediment were studied. DBP was pharmacologically lowered to < or = 80 mm Hg (3 of 4 consecutive measurements at 1 to 4 weeks intervals) after which patients were randomized. DBP and GFR (renal clearance of 125I-iothalamate) were measured at baseline, at three months and every six months post-randomization. The rate of decline in GFR (GFR slope, in ml/min/1.73 m2/year), estimated by the method of maximum likelihood in a mixed effects model, was the primary outcome variable. In a secondary analysis, 50% reduction in GFR (or a doubling of serum creatinine) from baseline, ESRD and death were combined.(ABSTRACT TRUNCATED AT 250 WORDS)", "In chronic nephropathies, inhibition of angiotensin-converting enzyme (ACE) is renoprotective, but can further renoprotection be achieved by reduction of blood pressure to lower than usual targets? We aimed to assess the effect of intensified versus conventional blood-pressure control on progression to end-stage renal disease.\n We undertook a multicentre, randomised controlled trial of patients with non-diabetic proteinuric nephropathies receiving background treatment with the ACE inhibitor ramipril (2.5-5 mg/day). We randomly assigned participants either conventional (diastolic <90 mm Hg; n=169) or intensified (systolic/diastolic <130/80 mm Hg; n=169) blood-pressure control. To achieve the intensified blood-pressure level, patients received add-on therapy with the dihydropyridine calcium-channel blocker felodipine (5-10 mg/day). The primary outcome measure was time to end-stage renal disease over 36 months' follow-up, and analysis was by intention to treat.\n Of 338 patients who were randomised, three (two assigned intensified and one allocated conventional blood-pressure control) never took study drugs and they were excluded. Over a median follow-up of 19 months (IQR 12-35), 38/167 (23%) patients assigned to intensified blood-pressure control and 34/168 (20%) allocated conventional control progressed to end-stage renal disease (hazard ratio 1.00 [95% CI 0.61-1.64]; p=0.99).\n In patients with non-diabetic proteinuric nephropathies receiving background ACE-inhibitor therapy, no additional benefit from further blood-pressure reduction by felodipine could be shown.", "Although several important studies have been performed in hypertensive type 2 diabetic patients, it is not known whether lowering blood pressure in normotensive (BP <140/90 mm Hg) patients offers any beneficial results on vascular complications. The current study evaluated the effect of intensive versus moderate diastolic blood pressure (DBP) control on diabetic vascular complications in 480 normotensive type 2 diabetic patients.\n The current study was a prospective, randomized controlled trial in normotensive type 2 diabetic subjects. The subjects were randomized to intensive (10 mm Hg below the baseline DBP) versus moderate (80 to 89 mm Hg) DBP control. Patients in the moderate therapy group were given placebo, while the patients randomized to intensive therapy received either nisoldipine or enalapril in a blinded manner as the initial antihypertensive medication. The primary end point evaluated was the change in creatinine clearance with the secondary endpoints consisting of change in urinary albumin excretion, progression of retinopathy and neuropathy and the incidence of cardiovascular disease.\n The mean follow-up was 5.3 years. Mean BP in the intensive group was 128 +/- 0.8/75 +/- 0.3 mm Hg versus 137 +/- 0.7/81 +/- 0.3 mm Hg in the moderate group, P < 0.0001. Although no difference was demonstrated in creatinine clearance (P = 0.43), a lower percentage of patients in the intensive group progressed from normoalbuminuria to microalbuminuria (P = 0.012) and microalbuminuria to overt albuminuria (P = 0.028). The intensive BP control group also demonstrated less progression of diabetic retinopathy (P = 0.019) and a lower incidence of strokes (P = 0.03). The results were the same whether enalapril or nisoldipine was used as the initial antihypertensive agent.\n Over a five-year follow-up period, intensive (approximately 128/75 mm Hg) BP control in normotensive type 2 diabetic patients: (1) slowed the progression to incipient and overt diabetic nephropathy; (2) decreased the progression of diabetic retinopathy; and (3) diminished the incidence of stroke.", "Despite treatment, there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals. Inadequate reduction of their blood pressure is a likely cause, but the optimum target blood pressure is not known. The impact of acetylsalicylic acid (aspirin) has never been investigated in patients with hypertension. We aimed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension.\n 18790 patients, from 26 countries, aged 50-80 years (mean 61.5 years) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg (mean 105 mm Hg) were randomly assigned a target diastolic blood pressure. 6264 patients were allocated to the target pressure < or =90 mm Hg, 6264 to < or =85 mm Hg, and 6262 to < or =80 mm Hg. Felodipine was given as baseline therapy with the addition of other agents, according to a five-step regimen. In addition, 9399 patients were randomly assigned 75 mg/day acetylsalicylic acid (Bamycor, Astra) and 9391 patients were assigned placebo.\n Diastolic blood pressure was reduced by 20.3 mm Hg, 22.3 mm Hg, and 24.3 mm Hg, in the < or =90 mm Hg, < or =85 mm Hg, and < or =80 mm Hg target groups, respectively. The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg. Further reduction below these blood pressures was safe. In patients with diabetes mellitus there was a 51% reduction in major cardiovascular events in target group < or =80 mm Hg compared with target group < or =90 mm Hg (p for trend=0.005). Acetylsalicylic acid reduced major cardiovascular events by 15% (p=0.03) and all myocardial infarction by 36% (p=0.002), with no effect on stroke. There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group, and 129 versus 70 non-fatal major bleeds in the two groups, respectively (p<0.001).\n Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events. The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg. Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infarction. There was no effect on the incidence of stroke or fatal bleeds, but non-fatal major bleeds were twice as common.", "The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial is a prospective randomized blinded clinical trial that compares the effects of intensive versus moderate blood pressure control on the incidence and progression of type 2 diabetic complications. The current article discusses the results of 5.3 years of follow-up of 470 patients with hypertension and evaluates the effects of intensive and moderate blood pressure therapy using nisoldipine versus enalapril as the initial antihypertensive medication for nephropathy, retinopathy, and neuropathy.\n The 470 hypertensive subjects, defined as having a baseline diastolic blood pressure of > or = 90 mmHg, were randomized to intensive blood pressure control (diastolic blood pressure goal of 75 mmHg) versus moderate blood pressure control (diastolic blood pressure goal of 80-89 mmHg).\n The mean blood pressure achieved was 132/78 mmHg in the intensive group and 138/86 mmHg in the moderate control group. During the 5-year follow-up period, no difference was observed between intensive versus moderate blood pressure control and those randomized to nisoldipine versus enalapril with regard to the change in creatinine clearance. After the first year of antihypertensive treatment, creatinine clearance stabilized in both the intensive and moderate blood pressure control groups in those patients with baseline normo- or microalbuminuria. In contrast, patients starting with overt albuminuria demonstrated a steady decline in creatinine clearance of 5-6 ml.min-1.1.73 m-2 per year throughout the follow-up period whether they were on intensive or moderate therapy. There was also no difference between the interventions with regard to individuals progressing from normoalbuminuria to microalbuminuria (25% intensive therapy vs. 18% moderate therapy, P = 0.20) or microalbuminuria to overt albuminuria (16% intensive therapy vs. 23% moderate therapy, P = 0.28). Intensive therapy demonstrated a lower overall incidence of deaths, 5.5 vs. 10.7%, P = 0.037. Over a 5-year follow-up period, there was no difference between the intensive and moderate groups with regard to the progression of diabetic retinopathy and neuropathy. In addition, the use of nisoldipine versus enalapril had no differential effect on diabetic retinopathy and neuropathy.\n Blood pressure control of 138/86 or 132/78 mmHg with either nisoldipine or enalapril as the initial antihypertensive medication appeared to stabilize renal function in hypertensive type 2 diabetic patients without overt albuminuria over a 5-year period. The more intensive blood pressure control decreased all-cause mortality." ]

[ "3560265", "7935634", "3533203", "12045644", "1650023" ]

[ "Influence of hematocrit on cardiopulmonary function after acute hemorrhage.", "Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries.", "Effect of early blood transfusion on gastrointestinal haemorrhage.", "Hypotensive resuscitation during active hemorrhage: impact on in-hospital mortality.", "The rapid infusion system: a superior method for the resuscitation of hypovolemic trauma patients." ]

[ "The 'optimal' hematocrit to which patients should be resuscitated after shock and trauma is controversial. To test the hypothesis that sufficient oxygen delivery can be provided at a lower hematocrit without impairing oxygen consumption or hemodynamic function, 25 patients were prospectively studied immediately following injury and/or acute hemorrhage. Patients were randomized to have their hematocrits (HCT) maintained near 30% (29.7 +/- 0.4% (M +/- SEM); n = 12) or 40% (38.4 +/- 0.6%, n = 13). Cardiopulmonary parameters were measured twice a day for 3 days. Statistical analysis used a repeated measures analysis of variance with patient age, and ventilator parameters (FIO2, PEEP, and ventilator mode) as covariates. Arterial and venous O2 saturations were not significantly different at different hematocrits, although arterial and venous O2 contents were lower at 30% HCT (a = 14.1 +/- 0.2 m10(2)/dl, v = 10.1 +/- 0.3 m10(2)/dl; vs. a = 17.4 +/- 0.4 m10(2)/dl, v = 13.6 +/- 0.6 m10(2)/dl; p less than 0.05). This resulted in a lower oxygen delivery at the lower HCT. Between the two groups, there also was no significant difference in cardiac index (overall mean, 3.64 +/- 0.16 ml/min/m2), heart rate (99 +/- 4 bpm), systemic vascular resistance (1,058 +/- 55 dyne-sec/cm5), or left ventricular stroke work index (4.3 +/- 0.3 X 10(6) dyne-cm/m2). Intrapulmonary shunt was higher with higher hematocrit (22.6 +/- 2.4% at 40% HCT vs. 14.6 +/- 1.6% at 30% HCT; p less than 0.05) with no difference in end-expiratory pressure.(ABSTRACT TRUNCATED AT 250 WORDS)", "Fluid resuscitation may be detrimental when given before bleeding is controlled in patients with trauma. The purpose of this study was to determine the effects of delaying fluid resuscitation until the time of operative intervention in hypotensive patients with penetrating injuries to the torso.\n We conducted a prospective trial comparing immediate and delayed fluid resuscitation in 598 adults with penetrating torso injuries who presented with a pre-hospital systolic blood pressure of < or = 90 mm Hg. The study setting was a city with a single centralized system of pre-hospital emergency care and a single receiving facility for patients with major trauma. Patients assigned to the immediate-resuscitation group received standard fluid resuscitation before they reached the hospital and in the trauma center, and those assigned to the delayed-resuscitation group received intravenous cannulation but no fluid resuscitation until they reached the operating room.\n Among the 289 patients who received delayed fluid resuscitation, 203 (70 percent) survived and were discharged from the hospital, as compared with 193 of the 309 patients (62 percent) who received immediate fluid resuscitation (P = 0.04). The mean estimated intraoperative blood loss was similar in the two groups. Among the 238 patients in the delayed-resuscitation group who survived to the postoperative period, 55 (23 percent) had one or more complications (adult respiratory distress syndrome, sepsis syndrome, acute renal failure, coagulopathy, wound infection, and pneumonia), as compared with 69 of the 227 patients (30 percent) in the immediate-resuscitation group (P = 0.08). The duration of hospitalization was shorter in the delayed-resuscitation group.\n For hypotensive patients with penetrating torso injuries, delay of aggressive fluid resuscitation until operative intervention improves the outcome.", "The effect of citrated stored blood on coagulation was studied initially in a pilot study where 25 patients with acute severe gastrointestinal haemorrhage had their whole blood coagulation measured using the Biobridge Impedance Clotting Time (ICT). This demonstrated that there is a hypercoagulable response to haemorrhage which was partially reversed by blood transfusion. Similar changes were noted in Kaolin Cephalin Clotting Times (KCCT). A further 50 patients were then randomized to receive, during the 24 h after admission, either at least 2 units of blood or no blood transfusion unless the haemoglobin fell below 8 g/dl or they were shocked. In the transfused group nine patients re-bled compared with only one in the non-transfused group (P less than 0.01, chi 2 with Yates' correction). Early blood transfusion appears to reverse the hypercoagulable response to haemorrhage thereby encouraging re-bleeding and hence the need for an operation.", "Traditional fluid resuscitation strategy in the actively hemorrhaging trauma patient emphasizes maintenance of a normal systolic blood pressure (SBP). One human trial has demonstrated improved survival when fluid resuscitation is restricted, whereas numerous laboratory studies have reported improved survival when resuscitation is directed to a lower than normal pressure. We hypothesized that fluid resuscitation titrated to a lower than normal SBP during the period of active hemorrhage would improve survival in trauma patients presenting to the hospital in hemorrhagic shock.\n Patients presenting in hemorrhagic shock were randomized to one of two fluid resuscitation protocols: target SBP > 100 mm Hg (conventional) or target SBP of 70 mm Hg (low). Fluid therapy was titrated to this endpoint until definitive hemostasis was achieved. In-hospital mortality, injury severity, and probability of survival were determined for each patient.\n One hundred ten patients were enrolled over 20 months, 55 in each group. The study cohort had a mean age of 31 years, and consisted of 79% male patients and 51% penetrating trauma victims. There was a significant difference in SBP observed during the study period (114 mm Hg vs. 100 mm Hg, p < 0.001). Injury Severity Score (19.65 +/- 11.8 vs. 23.64 +/- 13.8, p = 0.11) and the duration of active hemorrhage (2.97 +/- 1.75 hours vs. 2.57 +/- 1.46 hours, p = 0.20) were not different between groups. Overall survival was 92.7%, with four deaths in each group.\n Titration of initial fluid therapy to a lower than normal SBP during active hemorrhage did not affect mortality in this study. Reasons for the decreased overall mortality and the lack of differentiation between groups likely include improvements in diagnostic and therapeutic technology, the heterogeneous nature of human traumatic injuries, and the imprecision of SBP as a marker for tissue oxygen delivery.", "The rapid infusion system (RIS), which can deliver fluids/blood products rapidly at precise rates and normothermic conditions, was compared with conventional fluid administration (CFA) in a randomized study of 36 hypovolemic trauma patients. Admission stratification criteria of the groups were similar relative to age, Glasgow Coma Score (GCS), Injury Severity Score (ISS) and plasma lactate. Despite the lack of difference in blood loss between the 24-h survivors of the two groups, the CFA group required greater total fluids (23.6/20.21), red blood cells (5.5/4.61), fresh frozen plasma (FFP) (2.8/1.91), platelets (523/204 ml), and crystalloids (12.9/10.61). Lactate levels were lower in the RIS group at virtually all times from hours 1 to 24 (4.3/5.3 mM/l, t-value = 3.3, DF = 279, P = 0.001). Post-admission hypothermia was greater in the CFA group at all times during the first 24 h (35.2/36.4 degrees C, t-value = 5.6, DF = 250, P = 0.001). The mean partial thromboplastin time was significantly higher in the CFA group (47.3/35.1 s, t-value = 3.1, DF = 279, P = 0.002). The PTT and PT were related to the degree of lactic acidosis (P = 0.0001) and hypothermia (P = 0.001) but not to the amount of FFP given (P = 0.14). The hospital costs, days in the ICU, and days on the ventilator were greater for the CFA group, as was the incidence of pneumonia (0/11 vs. 6/17; P = 0.03). Hypovolemic trauma patients resuscitated with the RIS needed fewer fluid/blood products and had less coagulopathy; more rapid resolution of hypoperfusion acidosis; better temperature preservation; and fewer hospital complications than those resuscitated with conventional methods of fluid/blood product administration." ]

[ "10363537", "16714913", "19110245", "15715034", "19713801", "17459389", "22069407" ]

[ "The effect of relaxation therapy on preterm labor outcomes.", "Does relaxation education in anxious primigravid Iranian women influence adverse pregnancy outcomes?: a randomized controlled trial.", "Effect of integrated yoga on stress and heart rate variability in pregnant women.", "Massage therapy effects on depressed pregnant women.", "Music therapy to relieve anxiety in pregnant women on bedrest: a randomized, controlled trial.", "Psychological factors in preterm labor and psychotherapeutic intervention.", "The effect of participating in the labor preparation classes on maternal vitality and positive affect during the pregnancy and after the labor." ]

[ "To examine the effect of relaxation on preterm labor outcome.\n Quasi-experimental, with women who experienced preterm labor randomly assigned to a control or experimental group. The experimental group was to do a daily relaxation exercise. A third group was added to the study: women who were originally assigned to the relaxation group but were unable to adhere to the daily practice. Final data were analyzed for three groups: control (n = 40), experimental (n = 44), and nonadherent (n = 23) participants.\n Women were referred to the study from physician offices and a hospital-based obstetric triage clinic in the Northwest.\n Total sample was comprised of 107 women with singleton gestations, documented contractions with cervical change, and intact membranes.\n The experimental group was instructed in a progressive relaxation exercise. The participants were given tapes of the exercise and instructed to do it daily.\n Study outcomes included gestational age at birth, rate of pregnancy prolongation, and birth weight.\n The outcome variables were analyzed using analysis of covariance, with the preterm labor risk score entered as a covariate to compensate statistically for group differences. A positive response to the relaxation intervention was found: The experimental group had significantly longer gestations and larger newborns when compared to the control and nonadherent groups.\n Relaxation therapy made a difference in preterm labor outcome. Women who practiced relaxation had larger newborns, longer gestations, and higher rates of pregnancy prolongation. Given the low cost of the intervention, it should be offered to all women at risk for preterm labor.", "Maternal anxiety and stress are found to be predictors of adverse pregnancy outcomes, including low birth weight and prematurity.\n The aim of the study was to determine whether relaxation education in anxious pregnant Iranian women in their first pregnancy affects selected pregnancy outcomes, including birth weight, preterm birth, and surgical delivery rate.\n A total of 110 obstetrically and medically low-risk primigravid women in Iran with a high anxiety level demonstrated by Spielberger's State-Trait Anxiety Inventory were randomly assigned into experimental and control groups.\n In this randomized controlled trial, the experimental group received routine prenatal care along with 7-week applied relaxation training sessions, while the control group received only routine prenatal care. Anxiety and perceived stress were measured by pre-educational and post-educational intervention. Data related to pregnancy outcomes include birth weight, gestational age at birth, and type of delivery.\n Significant reductions in low birth weight, cesarean section, and/or instrumental extraction were found in the experimental group compared with the control group. No significant differences were found in the rate of preterm birth.\n The findings suggest beneficial effects of nurse-led relaxation education sessions during the prenatal period. This intervention could serve as a resource for improving pregnancy outcomes in women with high anxiety.", "To study the effect of integrated yoga practice and guided yogic relaxation on both perceived stress and measured autonomic response in healthy pregnant women.\n The 122 healthy women recruited between the 18th and 20th week of pregnancy at prenatal clinics in Bangalore, India, were randomized to practicing yoga and deep relaxation or standard prenatal exercises 1-hour daily. The results for the 45 participants per group who completed the study were evaluated by repeated measures analysis of variance.\n Perceived stress decreased by 31.57% in the yoga group and increased by 6.60% in the control group (P=0.001). During a guided relaxation period in the yoga group, compared with values obtained before a practice session, the high-frequency band of the heart rate variability spectrum (parasympathetic) increased by 64% in the 20th week and by 150% in the 36th week, and both the low-frequency band (sympathetic), and the low-frequency to high-frequency ratio were concomitantly reduced (P<0.001 between the 2 groups). Moreover, the low-frequency band remained decreased after deep relaxation in the 36th week in the yoga group.\n Yoga reduces perceived stress and improves adaptive autonomic response to stress in healthy pregnant women.", "Eighty-four depressed pregnant women were recruited during the second trimester of pregnancy and randomly assigned to a massage therapy group, a progressive muscle relaxation group or a control group that received standard prenatal care alone. These groups were compared to each other and to a non-depressed group at the end of pregnancy. The massage therapy group participants received two 20 min therapy sessions by their significant others each week for 16 weeks of pregnancy, starting during the second trimester. The relaxation group provided themselves with progressive muscle relaxation sessions on the same time schedule. Immediately after the massage therapy sessions on the first and last days of the 16-week period the women reported lower levels of anxiety and depressed mood and less leg and back pain. By the end of the study the massage group had higher dopamine and serotonin levels and lower levels of cortisol and norepinephrine. These changes may have contributed to the reduced fetal activity and the better neonatal outcome for the massage group (i.e. lesser incidence of prematurity and low birthweight), as well as their better performance on the Brazelton Neonatal Behavior Assessment. The data suggest that depressed pregnant women and their offspring can benefit from massage therapy.", "To explore the effect of music therapy on anxiety alleviation for antepartal women on bedrest in China.\n One hundred and twenty patients recruited from one tertiary hospital in Changsha city, China were enrolled in a randomized controlled trial. Women in the experimental group received music therapy for 30 minutes on 3 consecutive days. Usual care participants had a 30-minute rest on 3 consecutive days. Variables included anxiety (State-Trait Anxiety Inventory), and physiological responses (vital signs, fetal heart rate). Descriptive statistics, t tests, chi tests, Wilcoxon rank sum tests, and Pearson correlation analyses were used to analyze the data.\n Anxiety levels decreased and physiological responses improved significantly in the intervention group, which was provided with music therapy while on bedrest.\n Carefully selected music that incorporates a patient's own preferences may offer an inexpensive and effective method to reduce anxiety for antepartal women with high risk pregnancies who are on bedrest.", "nan", "Pregnant women predispose to physical and emotional diseases. Vitality and positive affect are against the depression and low energetic mood Exercise and physical activities in pregnancy have short and long term consequences for mothers and their growing fetus and affected in mood regulation. Respiratory and relaxation skills could decrease stress, pain and use of analgesics during labor.\n In this study, 117 primigravida and multigravida women (59 women in case and 58 in control groups) were enrolled. Women in case group participated in delivery preparation classes since 20 weeks of pregnancy for 8 sessions. The control group was just received routine pregnancy care. The education was about pregnancy and delivery, physical exercises and relaxation skills. Questionnaires of vitality and positive affect toward the labor were completed three times: before intervention, after the 8(th) session and after delivery to 2 weeks later by an interview. Data analyzed using SPSS16 software and repeated measurement.\n There was a significant difference in vitality and positive affect regarding type of delivery before and after intervention and after delivery in case group(p < 0.0001).There was no significant difference in vitality and positive affect scores after delivery and after intervention (p < 0.083, p < 0.545). There was significant difference in vitality and positive affect scores regarding between case and control groups after the intervention and after the delivery (p < 0.001, p < 0.0001).\n Considering the results of this study, it could be recommended that all pregnant women should contribute in delivery preparation classes to improve their mood, confidence, vitality toward labor." ]

[ "1801561", "7524263", "2527976", "10200128", "3321085", "2459575", "7754764", "2213395", "2437278" ]

[ "Intravenous gamma-globulin treatment in Kawasaki disease.", "A multicenter, randomized, controlled trial of intravenous gamma globulin therapy in children with acute Kawasaki disease.", "Effect of intravenous immune globulin on the coagulopathy of Kawasaki syndrome.", "Selective high dose gamma-globulin treatment in Kawasaki disease: assessment of clinical aspects and cost effectiveness.", "Clinical evaluation of gammaglobulin preparations for the treatment of Kawasaki disease.", "Intravenous gammaglobulin and reduction of coronary artery abnormalities in children with Kawasaki Disease.", "Optimal dosage and differences in therapeutic efficacy of IGIV in Kawasaki disease.", "Treatment of Kawasaki syndrome: a comparison of two dosage regimens of intravenously administered immune globulin.", "High-dose gammaglobulin therapy for Kawasaki disease." ]

[ "A multicenter randomized controlled study was carried out to assess the effectiveness of different, doses and kinds of gamma-globulin in Kawasaki disease. Gamma globulin lowered the incidence of coronary artery abnormalities. The effect of gamma-globulin was dose dependent. The intact type was more effective than the pepsin treated type. To establish the indications for gamma-globulin, a study was made of patients who received neither gamma-globulin nor indomethacin and who, within nine days of onset of illness, satisfied at least four of the following criteria: (1) WBC: more than 12,000/mm; (2) platelet count: less than 35 X 10(4)/mm; (3) CRP: more than 3+; (4) Hct: less than 35%; (5) albumin: less than 3.5 g/dl (6) age: 12 months or less; (7) male sex. This prospective study is continuing. Of 143 children, 73.4% received gamma-globulin, and only two demonstrated small dilatations of the coronary arteries in children who did not receive gamma-globulin. These guidelines seem satisfactory to establish the indications for gamma-globulin in Kawasaki disease.", "We studied the effect of intravenous, polyethyleneglycol-treated, human immunoglobulin, administered at 200 mg/kg per day (group A: n = 147; male 86, female 61; age < 1 year, 50) or 400 mg/kg per day (group B: n = 152; male 87, female 65; age < 1 year, 52) for five consecutive days and compared it with freeze-dried, sulfonated human immunoglobulin [group C: n = 152; male 87, female 65; age < 1 year, 51), administered at 200 mg/kg per day for five consecutive days, on the prevention of coronary artery abnormalities in Kawasaki disease. Echocardiograms were interpreted blindly and independently. Proportions of 87.1%, 95.4%, and 82.3% in groups A, B, and C, respectively, had no coronary artery abnormalities. The confidence limits of difference between the proportions of groups A and C, groups B and C, and groups B and A were -4.4% and 10.4%, 7.8% and 15.9%, and 4.0% and 10.8%, respectively. Duration of fever and serum immunoglobulin G (IgG) levels were correlated with the prevalence of coronary artery abnormalities. We concluded that intravenous, polyethyleneglycol-treated, human immunoglobulin and freeze-dried, sulfonated human immunoglobulin had clinically equivalent effects on coronary artery abnormalities, and that five daily doses of 400 mg/kg of intravenous, polyethyleneglycol-treated, human immunoglobulin is more effective than that of 200 mg/kg gamma globulin.", "We studied the effects of immune globulin and aspirin versus aspirin alone on platelet count, platelet activation, and factor-mediated coagulation in patients with Kawasaki syndrome. Coagulation tests were performed on the day of admission to the study and 4 to 6 days later. Twenty-three patients were enrolled; 12 received immune globulin intravenously plus aspirin, and 11 received aspirin alone. At initiation of the study the groups were comparable with regard to age, sex, race, and time from onset of illness to study entry. Coagulation values were similar at entry with the exception that the aspirin group had a geometric mean platelet count that was higher than the platelet count in the aspirin-immune globulin group (p = 0.02). Four days after entry there were no significant differences between the two groups in any coagulation studies. Although the immune globulin preparation used has been effective in reducing the prevalence of coronary artery aneurysms, it appears to have no early effect on reduction of platelet activation or other measures of coagulopathy. The mechanism of action of immune globulin in patients with Kawasaki syndrome remains to be elucidated.", "High-dose intravenous gamma-globulin (IVGG) plus aspirin (ASA) treatment is effective in preventing coronary artery complications in acute Kawasaki disease (KD). However, gamma-globulin is very expensive, especially in Japan. Furthermore the indication for IVGG treatment and the optimal dose of gamma-globulin remain controversial.\n To examine these two issues, we used Harada's scoring system to investigate whether a single 2 g/kg dose therapy has any advantage over the 5 day 400 mg/kg per day therapy.\n We studied 203 patients with KD who had no coronary artery complications on admission. Of these, 145 patients scored 4 or more on Harada score within the first 9 days of illness and were treated with IVGG treatment. Using a random number table, 72 patients were selected to receive a single 2 g/kg dose (2 g group), while the remaining 73 patients were treated with 400 mg/kg per day for 5 consecutive days (400 mg group). Those who had a Harada score of three or less received no IVGG (non-IVGG group) treatment (58 patients).\n The incidence rate of coronary artery complications in the 2 g group was significantly lower than in the 400 mg group. The duration of high fever, positive duration of C-reactive protein and the number of hospital days in the 2 g group were each significantly shorter than in the 400 mg group. The total medical expense in the 2 g group was significantly lower than in the 400 mg group. There were no coronary artery complications in the non-IVGG group.\n It was found to be clinically more effective and more cost effective to select a patient by Harada's scoring system and, where a score of four or more was obtained, to administer a single 2 g/kg intravenous dose of gamma-globulin for acute KD.", "nan", "nan", "In an initial study, three groups of patients with Kawasaki disease received either aspirin alone or alkylated immunoglobulin G intravenous preparation (IGIV) 200 mg/kg daily x 3 days + aspirin, or 400 mg/kg alkylated IGIV daily x 3 days + aspirin. In a second study, three groups of patients were treated with either 100, 200 or 400 mg/kg of native IGIV in combination with aspirin daily for 5 days. While the regimen of 200 mg/kg native IGIV daily x 5 days was found to be effective, the incidence of coronary artery lesions (CAL) was even less on a regimen of 400 mg/kg daily x 5 days. It is therefore suggested that a better therapeutic effect can be achieved with a 400 mg/kg dose of native IGIV. Based on the results from these two studies, it is assumed that native IGIV is more effective in inhibiting CAL formation and persistence than the chemically modified preparation in which the biological activity of the Fc region in the immunoglobulin G molecule is altered.", "Because intravenously administered immune globulin (IVIG) is effective in reducing the incidence of coronary artery aneurysms in Kawasaki syndrome when given at a dose of 400 mg/kg daily for 4 days, we undertook a multicenter clinical trial comparing two dosage regimens of IVIG. Patients were randomly assigned to receive IVIG at either 400 mg/kg daily for 4 days (22 patients) or 1 gm/kg as a single dose (22 patients). All patients received aspirin therapy, and all were enrolled within 7 days of onset of fever. The presence of coronary artery aneurysms was evaluated by means of two-dimensional echocardiography before infusion; at days 4 to 6, 14 to 21, and 42 to 49 after infusion; and at 1 year. Coronary artery aneurysms were detected in 3 of the 44 patients, including one patient receiving 400 mg/kg and two patients receiving 1 gm/kg (p value not significant). No giant aneurysms were detected. No major side effects occurred with either dosage regimen. Patients receiving the 1 gm/kg dose had a faster resolution of fever and were discharged from the hospital approximately 1 day sooner than the 400 mg/kg group (p = 0.01). Although the relatively small sample size in this trial does not allow for a more definitive statement regarding the occurrence of coronary artery aneurysms, it appears that the 1 gm/kg dose is associated with a more rapid clinical improvement and a shorter hospital stay.", "To evaluate the effectiveness of gammaglobulin in decreasing the incidence of coronary artery lesions in Kawasaki disease, a randomized controlled study in 136 patients was conducted using high doses of gammaglobulin 400 mg/kg/d for 3 days plus aspirin 30 mg/kg/d (gammaglobulin group) and aspirin alone at the same dosage (aspirin group). The total febrile period and the duration of fever after treatment were significantly shorter in the gammaglobulin group than in the aspirin group (P less than 0.001). The incidence of coronary artery lesions and of coronary artery aneurysms was significantly lower in the gammaglobulin group than in the aspirin group up to 30 days after the onset of Kawasaki disease (P less than 0.01 and P less than 0.05, respectively). In 16 of 69 patients given gammaglobulin, fever persisted for longer than 3 days, and there was a higher incidence of coronary artery lesions among them. The effectiveness of high doses of gammaglobulin in preventing coronary artery lesions has been demonstrated, but the indications and the optimal dose of gammaglobulin remain to be determined." ]

[ "17891409", "12351250", "15352967", "11307656", "15790675", "15976212", "9161740", "12631041", "12905750", "19487950", "16480474", "15845675", "11375848", "9542555", "17146383", "16085437", "19562533", "16238896", "15791113", "12594143", "10072016", "18419721", "18581586", "14693612", "7541435", "17022854", "11464348", "11412156", "9540151", "19105251", "18580346" ]

[ "Intravenous paracetamol is highly effective in pain treatment after tonsillectomy in adults.", "Propacetamol as adjunctive treatment for postoperative pain after cardiac surgery.", "Propacetamol and diclofenac alone and in combination for analgesia after elective tonsillectomy.", "Intravenous tramadol compared to propacetamol for postoperative analgesia following thyroidectomy.", "Onset of acetaminophen analgesia: comparison of oral and intravenous routes after third molar surgery.", "Intravenous acetaminophen (paracetamol): comparable analgesic efficacy, but better local safety than its prodrug, propacetamol, for postoperative pain after third molar surgery.", "Postoperative analgesia with i.v. propacetamol and ketoprofen combination after disc surgery.", "Analgesic effect of i.v. paracetamol: possible ceiling effect of paracetamol in postoperative pain.", "[A randomized, double blind, and controlled clinical trial of the non-addictive propacetamol in postoperative analgesia].", "Paracetamol versus metamizol in the treatment of postoperative pain after breast surgery: a randomized, controlled trial.", "Analgesic efficacy of parenteral paracetamol (propacetamol) and diclofenac in post-operative orthopaedic pain.", "A randomized, double-blind comparison between parecoxib sodium and propacetamol for parenteral postoperative analgesia after inguinal hernia repair in adult patients.", "Propacetamol versus ketorolac for treatment of acute postoperative pain after total hip or knee replacement.", "Efficacy of propacetamol in the treatment of postoperative pain. Morphine-sparing effect in orthopedic surgery. Italian Collaborative Group on Propacetamol.", "Acetaminophen is highly effective in pain treatment after endoscopic sinus surgery.", "Analgesic efficacy and safety of intravenous paracetamol (acetaminophen) administered as a 2 g starting dose following third molar surgery.", "Preemptive analgesic effects of intravenous paracetamol in total abdominal hysterectomy.", "A comparison between IV paracetamol and IV metamizol for postoperative analgesia after retinal surgery.", "Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic surgery.", "Adjunctive analgesia with intravenous propacetamol does not reduce morphine-related adverse effects.", "A double-blinded evaluation of propacetamol versus ketorolac in combination with patient-controlled analgesia morphine: analgesic efficacy and tolerability after gynecologic surgery.", "Effect of paracetamol and coxib with or without dexamethasone after laparoscopic cholecystectomy.", "Comparison of parecoxib and proparacetamol in endoscopic nasal surgery patients.", "Assessing analgesia in single and repeated administrations of propacetamol for postoperative pain: comparison with morphine after dental surgery.", "The morphine-sparing effect of propacetamol in orthopedic postoperative pain.", "Clinical equivalence of IV paracetamol compared to IV dipyrone for postoperative analgesia after surgery for breast cancer.", "Diclofenac and/or propacetamol for postoperative pain management after cesarean delivery in patients receiving patient controlled analgesia morphine.", "Analgesic efficacy and safety of nefopam vs. propacetamol following hepatic resection.", "[Comparison of propacetamol and morphine in postoperative analgesia].", "[Analgesic and opioid-sparing effects of intravenous paracetamol in the early period after aortocoronary bypass surgery].", "Intravenous paracetamol improves the quality of postoperative analgesia but does not decrease narcotic requirements." ]

[ "Tonsillectomy in adults is associated with significant postoperative pain. Intravenous paracetamol injection (Perfalgan) is marketed for the management of acute pain. This prospective placebo-controlled study was performed to evaluate the analgesic efficacy and safety of intravenous paracetamol in 76 adult patients undergoing elective standard bipolar diathermy tonsillectomy. After tonsillectomy was performed under general anesthesia, the patients were randomized to receive either intravenous paracetamol 1 g (Perfalgan) (n = 38) or 0.9% normal saline as a placebo (n = 38) at 6-h intervals. No other analgesic medication was permitted for postoperative pain during the study. Need for rescue analgesic during the first 24 h after surgery as well as all adverse events were recorded. The intravenous paracetamol group differed significantly from the placebo group regarding pain relief and median time to pethidine rescue. Intravenous paracetamol significantly reduced pethidine consumption over the 24-h period. The worst pain after surgery was also more severe in the placebo group than that in the paracetamol group. There was no significant difference between groups in the incidence of adverse events. Intravenous paracetamol administered regularly in adult patients with moderate to severe pain after tonsillectomy provided rapid and effective analgesia and was well tolerated.", "Postoperative pain management after cardiac surgery has been mainly based on parenteral opioids. However, because opioids have numerous side effects, coadministration of non-opioid analgesics has been introduced as a method of reducing opioid dose. In this prospective, randomized, double-blinded study, we evaluated the efficacy of propacetamol, an IV administered prodrug of acetaminophen (paracetamol), as an adjunctive analgesic after cardiac surgery. Seventy-nine patients scheduled for elective coronary artery bypass grafting were randomized to receive either propacetamol 2 g (n = 40) or placebo (n = 39) IV in 6-h intervals for 72 h. From the time of extubation, patients had access to an opioid (oxycodone) via a patient-controlled analgesia device. Pain was evaluated on a visual analog scale four times daily, whereas respiratory function tests (forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow, and arterial blood gas measurements) were performed once a day. The prespecified primary efficacy variable (cumulative oxycodone consumption at the end of the 72-h postoperative period) was 123.5 mg (51.3 mg) (mean [SD]) in the propacetamol group and 141.8 mg (57.5 mg) in the placebo group (difference in mean, 18.3 mg = 13%; 95% confidence interval, 6.1-42.7 mg; P = 0.15). Pain scores did not differ between the groups at rest (P = 0.65) or during a deep breath (P = 0.72). The groups were also similar in terms of pulmonary function tests, postoperative bleeding, and hepatic function tests, and no significant differences were noted in the incidences of adverse effects. After completion of the study, apost hoc analysis was also performed analyzing the first 24 h as split into 6-h intervals. This analysis showed a significantly (P = 0.036) smaller consumption of oxycodone in the propacetamol group at 24 h (47.1 mg [20.7 mg] versus 57.9 mg [23.9 mg]; difference in mean, 10.8 mg; 95% confidence interval, 0.7-20.9 mg). In conclusion, propacetamol did not enhance opioid-based analgesia in coronary artery bypass grafting patients, nor did it decrease cumulative opioid consumption or reduce adverse effects within 3 days after surgery. However, post hoc analysis showed that oxycodone requirement was reduced within the first 24 h in the propacetamol group.\n This is the first placebo-controlled study to investigate the efficacy of propacetamol as a complementary analgesic to opioids after cardiac surgery. Propacetamol did not enhance analgesia, nor did it decrease cumulative opioid consumption or reduce adverse effects in a dose of 2 g given every sixth hour for 3 days after surgery.", "Diclofenac and paracetamol have different mechanisms and sites of action. Therefore, we tested if their combination is more effective for analgesia after tonsillectomy than either drug alone with respect to rescue analgesic consumption and visual analog scale values.\n The analgesic effects of intravenously administered propacetamol (injectable pro-drug of paracetamol) and diclofenac or a combination on postoperative pain were compared in 71 adult elective tonsillectomy patients in a randomized, double-blind study. After induction of anesthesia the patients received monotherapy with 2 g propacetamol (n = 25) or 75 mg diclofenac (n = 25), or a combined treatment with 2 g propacetamol and 75 mg diclofenac (n = 21) in physiologic saline as an infusion. Postoperatively the propacetamol dosage was repeated twice and diclofenac once on the ward. Oxycodone (0.03 mg kg(-1)) was used as a rescue analgesic by patient-controlled analgesia.\n On average the patients needed oxycodone 15.3, 13.2 and 10.6 times in the propacetamol, diclofenac and combination groups, respectively (NS). A verbal rating scale and a visual analog scale were employed for assessing post-tonsillectomy pain, nausea and patient satisfaction in all groups. No statistically significant differences were found between the groups. Twelve of the 25 (48%) patients having received propacetamol complained of pain at the cannulation site.\n Combined treatment with propacetamol and diclofenac with the dosages used provided clinically only a minor advantage over monotherapy with propacetamol or diclofenac with respect to postoperative analgesia or the incidence of side-effects in adult tonsillectomy patients.", "We compared the efficacy and side effects of propacetamol (P), an injectable prodrug of acetaminophen, 2 g and tramadol (T), a weak synthetic opioid, 1.5 mg.kg-1, given intravenously following thyroidectomy. 80 patients were randomly assigned to blindly receive one dose of P or T on request in the PACU. Residual pain was treated with i.v. PCA morphine. Pain and patient satisfaction were assessed with Visual Analog Scales. Demographic and peroperative data were comparable in both groups. Although the morphine consumption was comparable (p = 0.71), the decrease in VAS pain scores was significantly higher following tramadol (p = 0.03). More patients complained of nausea and vomiting (p = 0.01) during the first two hours following injection of tramadol, but there was no difference throughout the whole study. Oversedation was not observed in any group. We conclude that a single dose of tramadol provides a better quality of analgesia than propacetamol during the first six hours after thyroidectomy, but fails to ensure optimal analgesia, since VAS pain scores failed to fall below 3 despite the use of supplemental morphine.", "The purpose of this randomized double-blind study was to compare the efficacy and safety of propacetamol 2 g (an i.v. acetaminophen 1 g formulation) administered as a 2-min bolus injection (n=50) or a 15-min infusion (n=50) with oral acetaminophen 1 g (n=50) or placebo (n=25) for analgesia after third molar surgery in patients with moderate to severe pain after impacted third molar removal.\n All patients were evaluated for efficacy during the initial 6 h period after treatment administration (T(0)) and for safety during the entire week after T(0).\n The onset of analgesia after propacetamol was shorter (3 min for bolus administration, 5 min for 15-min infusion) than after oral acetaminophen (11 min). Active treatments were significantly better for all parameters (pain relief, pain intensity, patient's global evaluation, duration of analgesia) than placebo (P<0.05). Adverse events were more frequent after propacetamol, especially pain at the injection site. Propacetamol bolus resulted in a much higher incidence of local adverse events than the infusion (propacetamol bolus 90% vs propacetamol infusion 52%) with no clinically significant benefits in terms of analgesic efficacy.\n I.V. propacetamol, administered as a 15-min infusion, is a fast-acting analgesic agent. It is more effective in terms of onset of analgesia than a similar dose of oral acetaminophen.", "We compared an acetaminophen (paracetamol) 1 g (n = 51) formulation for infusion with propacetamol 2 g (n = 51) and placebo (n = 50) in a randomized, controlled, double-blind, parallel group trial in patients with moderate-to-severe pain after third molar surgery. Treatment efficacy was assessed in house for 6 h after starting the 15-min infusion. Significant effects versus placebo (P < 0.01) were obtained with both active treatments on pain relief, pain intensity difference on a 100-mm visual analog scale, and on a categorical scale (except for propacetamol at 6 h). No significant differences were noted between active groups except at 1 h. Six-hour weighted sums of primary assessments showed significantly better efficacy than placebo (P < 0.0001) and no difference between active treatments. Median stopwatch time to onset of pain relief for active treatment was 6-8 min after infusion start. Active treatments showed comparable efficacy with a significantly longer duration of analgesia and better patients' global evaluation compared with placebo. The incidence of patients reporting local pain at the infusion site was significantly less frequent after IV acetaminophen or placebo (0%) in comparison with propacetamol (49%). In conclusion, acetaminophen 1 g and propacetamol 2 g were superior to placebo regarding analgesic efficacy, with a more frequent incidence of local pain at the infusion site for propacetamol.", "The concept of balanced analgesia suggests that a combination of analgesic drugs may enhance analgesia and reduce side effects after surgery. This study evaluated the effect of the combination of propacetamol (Prodafalgan) and ketoprofen (Profenid) after surgery of a herniated disc of the lumbar spine.\n After randomization, 60 patients received: placebo (group 1); 2 g propacetamol (group 2); 50 mg ketoproten (group 3); or a combination of 2 g propacetamol and 50 mg ketoprofen (group 4). Drugs were administered every six hours for two days after surgery. The patients used morphine with patient controlled analgesia pumps (bolus 1 mg; lock out time 10 min) and were evaluated with a visual analogue scale (VAS) at rest and movement every six hours for two days. Side effects were noted.\n The patient characteristics and surgery were identical for each of the four groups. The VAS scores throughout the study were lower in group 4 than in groups 1, 2 and 3 both at rest (P < 0.05) and on movement (P < 0.01). The cumulative dose of morphine at 48 hr was lower in group 4 than in group 1 (23.4 +/- 5 mg vs. 58.9 +/- 9 mg; P < 0.01) or group 2 (23.4 +/- 5 mg vs 43.4 +/- 6.6 mg; P < 0.05) and similar to that in group 3 (34.2 +/- 4.5 mg). The incidence of side effects was similar in all groups.\n The combination of propacetamol and ketoprofen reduced pain scores both at rest and on movement. The drug combination did not reduce the morphine consumption and incidence of side effects.", "Despite the widespread use of paracetamol for many years, the analgesic serum concentrations of paracetamol are unknown. Therefore the correlation between serum paracetamol concentrations and the analgesic effect was studied.\n Sixty-four women undergoing laparoscopic sterilization were included in a double-blind, placebo-controlled, randomized study. Patients were given i.v. propacetamol 40 mg kg(-1) (group H), 20 mg kg(-1) (group I), 10 mg kg(-1) (group L) or placebo after surgery. Alfentanil was available via patient-controlled analgesia (PCA) during the 4-h postoperative study period. The patients' self-reported pain was registered on the visual analog scale (VAS). A pharmacokinetic model was fitted to the paracetamol data.\n One to 3 h after injection of propacetamol the alfentanil consumption was significantly (P = 0.01-0.04) higher in the placebo group compared with groups H, I, and L receiving propacetamol. There were no significant differences between the amounts of alfentanil consumed in groups H, I, and L. Initial VAS-scores were moderate (5.4-6.2), and declined significantly (P < 0.0001) over time, with no difference between groups. Paracetamol followed an open two-compartment model with i.v. administration and first order elimination. The estimated concentrations immediately (t = 0) after injection were 56 mg l(-1) (H), 28 mg l(-1) (I) and 14 mg l(-1) (L).\n We showed a significant opioid-sparing effect of paracetamol in the immediate postoperative period. Pharmacokinetic data were in accordance with other studies. Our results suggest that a ceiling effect of paracetamol may be present at i.v. doses of 5 mg kg(-1), i.e. a serum concentration of 14 mg l(-1), which is a lower dose than previously suggested.\n Copyright Acta Anaesthesiologica Scandinavica 47 (2003)", "To compare the postoperative analgesic efficacy and safety of the non-addictive propacetamol hydrochloride (Pro-Bufferin) injection and dolantin in a prospective, randomized, double blind and controlled clinical trial.\n After the pain intensity was assessed when the patients were undergone thoracic and abdominal selective surgery became fully conscious, 40 consecutive patients with moderate to severe postoperative pain (equivalent to Pain Grade I and II of American Anesthesia Association classification) were randomized into the study against the control groups. The two groups were similar for age, sex, height/weight, disease categories, operation categories, anesthesia methods and duration, vital signs, hepatorenal function, and blood cell count (P = 0.06-0.93). In the study group, 2 g propacetamol in 100 ml normal saline (NS) intravenously with 1.0 ml NS intramuscularly as the placebo control to dolantin were administered. In the control group, 1.6 g mannitose in 100 ml NS intravenously as the placebo control to propacetamol with 50 mg dolantin (1.0 ml) intramuscularly as the positive control to propacetamol were administered. The intensity change of postoperative pain was then evaluated 10 times with visual analog scale and verbal describing scale during 6 h from the beginning of propacetamol infusion. Vital signs and adverse reactions were also documented. After all data were put into the computer, the blinding codes were decoded and the statistic analysis was then made.\n There was no significant difference (P = 0.93) about the area under the curve of \"Pain Relieve Score vs. Time\". The \"starting to effect\" time (15-30 min), analgesic duration (6 h) and the percentage of excellent or good analgesic effect (90%) in the two groups were the same. Adverse reactions didn't reached the statistic different level (P = 0.35).\n Propacetamol HCL injection 2 g intravenously could be an alternative to dolantin 50 mg intramuscularly for moderate to severe postoperative pain with its advantage of being non-addictive.", "Intravenously administered paracetamol is an effective analgesic in postoperative pain management. However, there is a lack of data on the effect of intravenous (i.v.) paracetamol on pain following soft tissue surgery.\n Eighty-seven patients undergoing elective breast surgery with total i.v. anaesthesia (propofol/remifentanil) were randomized to three groups. Group para received 1 g i.v. paracetamol 20 min before and 4, 10 and 16 h after the end of the operation. Group meta and plac received 1 g i.v. metamizol or placebo, respectively, scheduled at the same time points. All patients had access to i.v. morphine on demand to achieve adequate pain relief.\n No significant difference in total morphine consumption between groups was detectable. The proportion of patients who did not receive any morphine in the postoperative period was significantly higher in group para (42%) than in group plac (4%). Ambulation was significantly (P < 0.05) earlier in group para (4.0 +/- 0.2 h) than in groups meta (4.6 +/- 0.2 h) and plac (5.5 +/- 1.0 h). No differences were observed between groups meta and plac. There were no differences between groups with regard to incidence of postoperative nausea and vomiting or changes in vigilance.\n Neither i.v. paracetamol nor i.v. metamizol provided a significant reduction in total postoperative morphine consumption compared with placebo in the management of postoperative pain after elective breast surgery. Administration of paracetamol resulted in a significant reduction in the number of patients needing opioid analgesics to achieve adequate postoperative pain relief.", "Propacetamol is an injectable pro-drug of paracetamol (acetaminophen) with analgesic and antipyretic activities, especially used in the post-operative period. The aim of this study was to assess the analgesic efficacy and safety of intravenous paracetamol, administered as propacetamol, in comparison with placebo and intramuscular diclofenac in patients with post-operative pain.\n This was a randomized, double-blind, double-dummy study. One hundred and twenty patients with moderate to severe pain following total hip arthroplasty received either two administrations of propacetamol 2 g intravenously, 5 h apart (n = 40), one single administration of diclofenac 75 mg intramuscularly (n = 40) or placebo (n = 40). Efficacy measures were assessed before each drug administration, for the 5 h following each study treatment administration and for the total study duration of 10 h. Safety was assessed by reporting adverse events and changes in vital signs, electrocardiogram (ECG) and biochemical investigations before and 24 h after dosing.\n Both active treatments were effective and statistically superior to placebo over the whole study period, as indicated by the total pain relief score. No significant differences were found between propacetamol and diclofenac for any measures of analgesic activity. Only minor and common adverse events were reported, with no overall differences between the groups.\n Both active treatments were superior to placebo, and the overall efficacy of two intravenous infusions of propacetamol 2 g (equivalent to 1 g of paracetamol), 5 h apart, was not statistically different from that provided by a single intramuscular injection of diclofenac 75 mg over the first 5 h post-dose and over the total 10-h study period. The safety was good.", "The newly injectable cyclooxygenase-2 selective nonsteroidal antiinflammatory drug, parecoxib, has never been compared with propacetamol, a parenteral formulation of acetaminophen. In this prospective, randomized, double-blind, double-dummy study, we randomly assigned 182 patients scheduled for initial inguinal hernia repair under general anesthesia to receive a single injection of 40 mg parecoxib or 2 injections of 2 g propacetamol within the first 12 h after surgery. The study variables were morphine consumption, pain at rest and while coughing, and patient satisfaction throughout the first 12 h postoperatively. For statistical analysis, we used the Student's t-test, chi(2), and covariance analysis. Total morphine consumption did not differ between the two groups. Pain was less intense in the parecoxib group at rest (P = 0.035) but did not differ for pain while coughing. The incidence of side effects was similar. Significantly more patients in the parecoxib group rated their pain management as good or excellent (87% versus 70% in the propacetamol group, P = 0.001). Within the first 12 h after inguinal hernia repair in adult patients, a single injection of parecoxib 40 mg compares favorably with 2 injections of propacetamol 2 g.", "We assessed the analgesic efficacy of IV propacetamol and ketorolac in a double-blinded, placebo-controlled study involving patients undergoing total hip or knee replacement procedures. On the first morning after major joint replacement surgery, 164 patients experiencing moderate-to-severe pain were randomly assigned to receive an IV infusion of propacetamol (2 g), ketorolac (15 or 30 mg), or placebo (saline). Patient-controlled analgesia with morphine was made available as a \"rescue\" analgesic on patient's request during the 6-h postdosing evaluation period. The median time to onset of analgesia with propacetamol (8 [95% confidence interval 6,10] min) was shorter than ketorolac 15 mg (14 [7,16] min), and placebo (16 [8; not estimable] min) although the differences did not reach statistical significance. However, compared with ketorolac 30 mg, propacetamol had a shorter duration of analgesia (3.5 [2;5.4] vs 6 [3.3; not estimable] h). Analysis of pain intensity and pain relief scores demonstrated that propacetamol produced a significantly greater improvement in pain relief than saline from 45 min until 5 h after the injection. Propacetamol was not significantly different from ketorolac 15 mg and 30 mg with respect to the main analgesic efficacy variables during the 6-h assessment period. The most frequently reported adverse event with propacetamol was injection site pain (28% vs 19% for ketorolac 15 mg, 29% for ketorolac 30 mg, and 10% for placebo, respectively). In conclusion, propacetamol (2 g IV) possesses a similar analgesic efficacy to ketorolac (15 or 30 mg IV) after total hip or knee replacement surgery.", "Combined analgesic regimens have been suggested to improve the treatment of postoperative pain. The aim of our study was to evaluate the analgesic efficacy and tolerability of propacetamol, in combination with morphine.\n Four i.v. infusions of propacetamol 2 g or placebo were administered, in a double-blind fashion, after orthopedic surgery (n = 97). Morphine was administered by a patient-controlled analgesia (PCA) device. The total dose of morphine, pain intensity and global efficacy of treatment were evaluated. Tolerability was assessed by monitoring blood pressure, heart and respiratory rate, sedation scores, adverse events, and renal and hepatic parameters.\n The total dose of morphine was significantly decreased in the propacetamol group compared to placebo (9.4 +/- 8.5 mg vs 17.6 +/- 12 mg; P < 0.001), arriving at a sparing effect of 46%. The evolution of pain intensity showed a similar pattern in the two groups. Global efficacy of treatment was rated significantly better by patients receiving the combination propacetamol + PCA morphine (87% of \"good\"/\"excellent\" ratings vs 65%; P = 0.01). Tolerability was comparable in the two groups. Eight patients in the propacetamol and 4 patients in the placebo group reported adverse events, of mild/moderate intensity, most commonly nausea/vomiting. Renal and hepatic parameters were also seen to be comparable.\n These results confirm a significant morphine-sparing effect, significantly better scores in the final assessment by patients, and a good tolerability of propacetamol after orthopedic surgery. The drug may, therefore, represent a useful alternative to NSAIDs, as complementary drug to opioids, in the management of moderate/severe postoperative pain.", "Endoscopic sinus surgery (ESS) is increasingly performed by otorhinolaryngologists. However, the early recovery and pain management after ESS is still largely unexplored. In the present study, we have evaluated the incidence and severity of pain and the efficacy and safety of acetaminophen (paracetamol) for pain management in patients undergoing ESS.\n The authors conducted a prospective, double-blind, placebo-controlled clinical trial.\n Seventy-four patients with ESS were randomized to receive either 1 g intravenous acetaminophen (Perfalgan) (n = 36) or 0.9% normal saline as a placebo (n = 38) after ESS was performed under local anesthesia. No other analgesic medication was permitted during the study. Need for rescue analgesic during the first 4 hours after surgery as well as all adverse events were recorded.\n Most patients, 27 of 38 (71%), in the placebo group needed rescue analgesics but significantly fewer patients in the acetaminophen group required rescue analgesia, i.e., only nine of 36 (25%) patients needed oxycodone. The worst pain after surgery was also more severe in the placebo group than that in the acetaminophen group. There was no significant difference between groups in the incidence of adverse events. The most common adverse events were vomiting, nausea, and headache.\n ESS is associated with significant postoperative pain. Acetaminophen provides adequate pain relief in most patients who have undergone ESS. However, the analgesic efficacy of acetaminophen alone is insufficient in some patients, and hence all patients with ESS must be followed closely to identify those patients in need of more efficient analgesia during the early phase of recovery.", "The recommended dose for intravenous (IV) paracetamol injection in adults is 1g, however pharmacokinetic and pharmacodynamic findings suggest that a better analgesia could be obtained with a 2 g starting dose.\n A single-centre, randomised, double-blind, placebo-controlled, 3-parallel group study was performed to demonstrate the analgesic efficacy and safety of IV paracetamol 2 g. Following third molar surgery, patients reporting moderate to severe pain received a single 15-min infusion of either IV paracetamol 2 g, IV paracetamol 1g or placebo. Efficacy and safety were evaluated over 8 h. Laboratory tests were performed before and 48 h after drug administration.\n Two hundred and ninety seven patients (132 = IV paracetamol 2g; 132 = IV paracetamol 1g; 33 = placebo) were randomised and completed the study. The summed pain relief over 6h (TOTPAR6) was significantly superior with IV paracetamol 2 g as compared to IV paracetamol 1g and placebo (p < 0.0001). Pain relief scores of IV paracetamol 2g were significantly superior to IV paracetamol 1g and to placebo from T30' to T8h (p < 0.0001). Median duration of analgesia was significantly longer following IV paracetamol 2 g compared to IV paracetamol 1g and placebo (p < 0.0001). Adverse events occurred with the same frequency in the 3 treatment groups. No clinically significant changes from baseline were observed for vital signs or laboratory tests.\n The analgesic efficacy of a 2 g starting dose of IV paracetamol was superior over the recommended dose of 1g in terms of magnitude and duration of analgesic effect for postoperative pain following third molar surgery, with no significant difference between groups regarding safety.", "Paracetamol is primarily thought to be a cyclooxygenase inhibitor acting through the central nervous system. Indirect effects of paracetamol are through the serotoninergic system as a non-opioid analgesic. In this study, total abdominal hysterectomy patients were given intravenous (iv) paracetamol 1 g preoperatively or intraoperatively to assess its postoperative analgesic effects.\n 90 patients undergoing total abdominal hysterectomy were enrolled into the study. Patients were randomized into three groups: in Group I, iv paracetamol 1 g was given 30 minutes prior to induction. In Group II, iv paracetamol 1 g was given prior to skin closure. Group III served as the control group and received saline as placebo. Postoperatively, all patients received morphine via patient-controlled analgesia pump. Postoperatively, rest and activity pain scores, sedation scores, hemodynamic parameters, postoperative morphine consumption, side effects, patient satisfaction, and total hospital stay were recorded.\n In the control group, at rest and movement pain scores and total morphine consumption via patient-controlled analgesia were higher than in Groups I and II. When Groups I and II were compared, total morphine consumption was much greater in Group II. Intravenous paracetamol intraoperatively and postoperatively did not result in any hemodynamic effects.\n In total abdominal hysterectomy, preemptive iv paracetamol 1 g provided good quality postoperative analgesia, with decreased consumption of morphine and minimal side effects.", "To assess clinical efficacy of IV paracetamol 1 g and IV metamizol 1 IV metamizol 1 g on a 24-h dosing schedule in this randomized, double-blinded, placebo-controlled study of 38 ASA physical status I-III patients undergoing retinal surgery.\n General anaesthesia using remifentanil, propofol, and desflurane was performed for surgery. The patients were randomly allocated to three groups, receiving infusions of paracetamol 1 g/100 mL (Para Group), of metamizol 1 g/100 mL (Meta Group), or of 100 mL of saline solution as placebo control (Plac Group) 30 min before arrival in the recovery area and every 6 h up to 24 h postoperatively. All patients had unrestricted access to intravenous opioid rescue medication.\n The primary efficacy variables were pain scores at rest over 30 h postoperatively analysed by using repeated ANOVA measurement. Secondary efficacy variables were pain scores on coughing, also analysed by repeated ANOVA measurement.\n Five patients in the Plac Group and one patient in the Meta Group interrupted the study protocol. Regarding pain scores at rest, Mauchly-test of sphericity was significant (p = 0.03). For the p time effects a significant result was detected (p < 0.001). The main effect between the three treatment groups was significantly different (p = 0.01). The Bonferroni adjusted pair wise comparisons between p the Plac Group and the Para Group showed a significant difference in favour of IV paracetamol (p = 0.024; mean difference 14.8; p 95% CI 1.6-28.0), between the Plac Group and the Meta Group in favour of IV metamizol (p = 0.025; mean difference 14.4; 95% CI p 1.5-27.4), and no significant difference between the Para Group and the Meta Group (p = 1.0; mean difference 0.4; 95% CI-12.8 to 13.6). Pain scores on coughing showed a significant different main effect between the three treatment groups (p = 0.022). The Bonferroni adjusted pair wise comparisons between the Plac Group and the Para Group showed a significant difference in favour of IV paracetamol (p = 0.032; mean difference 17.9; 95% CI 1.3-34.6), a p difference, though not reaching statistical significance, in favour of IV metamizol between the Plac Group and the Meta Group (p = 0.081; p mean difference 15.0; 95% CI -1.4 to 31.4), and no significant difference between the Para Group and the Meta Group (p = 1.0; p mean difference 2.9; 95% CI -13.8 6 to 19.6). None of the patients experienced itching; one patient in the Meta Group developed a mild erythema. There was no statistical difference in the incidence of nausea (Plac vs. Para Group: p = 0.94, Plac vs. Meta Group: p = 0.98, Para vs Meta Group: p = 0.95) or vomiting (Plac vs. Para Group: p = 0.73, Plac vs. Meta Group: p = 0.85, Para vs Meta Group: p = 0.86) between the groups. Patients in the Plac Group experienced significantly more often sedation than patients in the Meta Group (p = 0.049). There was a trend of higher sedation in the Plac Group than in the Para Group, which did not reach statistical significance (p = 0.07). There was no difference in sedation between the Meta and the Para Groups (p = 0.84).\n IV paracetamol 1 g has a similar analgesic potency as IV metamizol 1 g for postoperative analgesia after retinal surgery.", "Intravenous acetaminophen injection (paracetamol) is marketed in Europe for the management of acute pain. A repeated-dose, randomized, double-blind, placebo-controlled, three-parallel group study was performed to evaluate the analgesic efficacy and safety of intravenous acetaminophen as compared with its prodrug (propacetamol) and placebo. Propacetamol has been available in many European countries for more than 20 yr.\n After orthopedic surgery, patients reporting moderate to severe pain received either 1 g intravenous acetaminophen, 2 g propacetamol, or placebo at 6-h intervals over 24 h. Patients were allowed \"rescue\" intravenous patient-controlled analgesia morphine. Pain intensity, pain relief, and morphine use were measured at selected intervals. Safety was monitored through adverse event reporting, clinical examination, and laboratory testing.\n One hundred fifty-one patients (intravenous acetaminophen: 49; propacetamol: 50; placebo: 52) received at least one dose of study medication. The intravenous acetaminophen and propacetamol groups differed significantly from the placebo group regarding pain relief from 15 min to 6 h (P < 0.05) and median time to morphine rescue (intravenous acetaminophen: 3 h; propacetamol: 2.6 h; placebo: 0.8 h). Intravenous acetaminophen and propacetamol significantly reduced morphine consumption over the 24-h period: The total morphine doses received over 24 h were 38.3 +/- 35.1 mg for intravenous acetaminophen, 40.8 +/- 30.2 mg for propacetamol, and 57. 4 +/- 52.3 mg for placebo, corresponding to decreases of -33% (19 mg) and -29% (17 mg) for intravenous acetaminophen and propacetamol, respectively. Drug-related adverse events were reported in 8.2%, 50% (most of them local), and 17.3% of patients treated with intravenous acetaminophen, propacetamol, and placebo, respectively.\n Intravenous acetaminophen, 1 g, administered over a 24-h period in patients with moderate to severe pain after orthopedic surgery provided rapid and effective analgesia and was well tolerated.", "Propacetamol is widely used in the management of postoperative pain. It decreases morphine requirements but its effect on the incidence of morphine-related adverse effects remains unknown.\n Patients (550) were randomly assigned to receive propacetamol or a placebo over the first 24 h after operation in a blinded study. Intravenous morphine titration was performed, after which morphine was administered s.c. every 4 h according to their pain score. Pain was assessed using a visual analogue scale (VAS). The primary end-point was the incidence of morphine-related adverse effects. The main secondary end-points were morphine requirements and VAS score.\n After morphine titration, the VAS score and the number of patients with pain relief did not differ between groups. Morphine requirements were decreased in the propacetamol group (21 vs 14.5 mg, P<0.001) but the incidence of morphine-related adverse effects did not differ between groups (42 vs 46%, not significant). In patients with moderate pain (n=395), morphine requirements decreased by 37% (P<0.001) and the percentage of patients requiring no morphine was greater (21 vs 8%, P=0.002) in the propacetamol group. In patients with severe pain (n=155), morphine requirements decreased by 18% (P=0.04) in the propacetamol group and the number of patients who did not require morphine (3 vs 8%) did not differ significantly.\n Although propacetamol induced a small morphine-sparing effect, it did not change the incidence of morphine-related adverse effects in the postoperative period. Moreover, no benefit could be demonstrated in patients with severe postoperative pain.", "We assessed the relative morphine consumption in a combined analgesic regimen (on-demand morphine plus the nonopioids propacetamol or ketorolac) after gynecologic surgery. Two hundred women randomly received two i.v. doses of propacetamol 2 g or ketorolac 30 mg in a double-blinded, double-dummy trial. Patients were monitored for 12 h, and the following efficacy variables were assessed: total dose of morphine, pain intensity, and global efficacy. Safety and tolerability were evaluated by the occurrence of adverse events, especially the presence and intensity of gastrointestinal symptoms. Hemostatic variables were measured 30 and 60 min after the first infusion; arterial blood pressure, heart and respiratory rates, sedation scores, and renal and hepatic function were also assessed. Total morphine requirements were not significantly different between the propacetamol (10.6 +/- 4.8 mg) and ketorolac (10.2 +/- 4.4 mg) groups. The evolution of pain intensity and the global efficacy also showed similar patterns in the two groups: 70.2% of patients in the propacetamol group rated the efficacy as \"good/ excellent\" compared with 68.2% in the ketorolac group. There were no clinically significant changes in vital signs or laboratory values and no observed differences between the two groups, although ketorolac slightly, but not significantly, prolonged the bleeding time. Epigastric pain was present in 9% and 15% of patients receiving propacetamol and ketorolac, respectively. There were two adverse events in the propacetamol group and four in the ketorolac group. Propacetamol demonstrates an efficacy similar to that of ketorolac and has an excellent tolerability after gynecologic surgery.\n Propacetamol and ketorolac, combined with patient-controlled analgesia morphine, show similar analgesic efficacy after gynecologic surgery. Morphine consumption and pain scores were comparable in the two studied groups. Propacetamol is as effective as ketorolac and has an excellent tolerability after gynecologic surgery.", "Pain after laparoscopic cholecystectomy (LCC) is multifactorial. Effective post-operative pain control is necessary in LCC performed as day-case surgery. We studied the efficacy of paracetamol or valdecoxib with or without dexamethasone after LCC.\n One hundred sixty patients were randomized to four groups of 40 patients. Groups 1 and 3 received parecoxib 40 mg intravenously (IV) during surgery and valdecoxib 40 mg x 1 per os (PO) for 7 post-operative days. Groups 2 and 4 received paracetamol 1 g x 4 IV during surgery and 1 g x 4 PO for 7 days. In addition, Groups 3 and 4 were given dexamethasone 10 mg IV intra-operatively. Propofol and remifentanil were used during surgery. The patients were given oxycodone 0.05 mg/kg IV in phase 1 post-anaesthesia care unit (PACU 1) or 0.15 mg/kg PO in phase 2 post-anaesthesia care unit (PACU 2) as needed to keep visual analogue scale <3/10. The patients were supplied with the study drugs for 7 post-operative days.\n Pain intensity, nausea and the need of oxycodone in phase 1 PACU were similar in all groups. Dexamethasone reduced the need of oral oxycodone in phase 2 PACU (7.0 +/- 1.0 mg vs. 9.1 +/- 1.0 mg, P<0.05). Pain intensity was similar in all groups at home. More patients in the parecoxib/valdecoxib groups needed rescue medication on the 1st post-operative day (P<0.001) than paracetamol-treated patients.\n Paracetamol was as effective as parecoxib/valdecoxib for pain after LCC. Dexamethasone decreased the need of oxycodone in phase 2 PACU. The effect of dexamethasone was similar in paracetamol and parecoxib/valdecoxib patients.", "The aim of the study was to compare the efficacy of parecoxib for postoperative analgesia after endoscopic turbinate and sinus surgery with the prodrug of acetaminophen, proparacetamol.\n Fifty American Society of Anesthesiology (ASA) physical status I-II patients, receiving functional endoscopic sinus surgery (FESS) and endoscopic turbinectomy, were investigated in a prospective, randomized, double-blind manner. After local infiltration with 1% mepivacaine, patients were randomly allocated to receive intravenous (i.v.) administration of either 40 mg of parecoxib (n=25) or 2 g of proparacetamol (n=25) 15 min before discontinuation of total i.v. anaesthesia with propofol and remifentanil. A blinded observer recorded the incidence and severity of pain at admission to the post anaesthesia care unit (PACU) at 10, 20, and 30 min after PACU admission, and every 1 h thereafter for the first 6 postoperative h.\n The area under the curve of VAS (AUC(VAS)) calculated during the study period was 669 (28-1901) cm x min in the proparacetamol group and 635 (26-1413) cm x min in the parecoxib group (p=0.34). Rescue morphine analgesia was required by 14 patients (56%) in the proparacetamol group and 12 patients (48%) in the parecoxib (p >or= 0.05), while mean morphine consumption was 5-3.5mg and 5-2.0 mg in the proparacetamol groups and parecoxib, respectively (p >or= 0.05). No differences in the incidence of side effects were recorded between the 2 groups. Patient satisfaction was similarly high in both groups, and all patients were uneventfully discharged 24 h after surgery.\n In patients undergoing endoscopic nasal surgery, prior infiltration with local anaesthetics, parecoxib administered before discontinuing general anaesthetic, is not superior to proparacetamol in treating early postoperative pain.", "We conducted this double-blinded, randomized study to assess the analgesic effect of repeated administrations of paracetamol, administered as propacetamol, an injectable prodrug formulation of paracetamol, and to compare this with the analgesic effects of morphine. Patients experiencing moderate to severe pain after elective surgical removal of bone-impacted third-molar teeth under general anesthesia were randomly assigned to receive IV propacetamol 2 g (n = 31), IM morphine 10 mg (n = 30), or placebo (n = 34). Five hours later, the treatments were readministered at half of the previous dosages. Standard measures of analgesia were collected repeatedly for 10 h. Propacetamol and morphine were significantly more effective than placebo in all primary measures of analgesia over 5 h after the first administration and globally over 10 h (first and second administrations). After the first dose, 21 of the 34 patients in the placebo group required rescue medication, compared with 6 of the 31 in the propacetamol group (P < 0.0009) and 4 of the 30 in the morphine group (P < 0.0001). No statistically or clinically significant differences were found between propacetamol and morphine for any sum or peak measures of analgesia. No serious adverse events were reported; adverse events were significantly less frequent in the propacetamol group than in the morphine group (P < 0.027). Propacetamol administered IV in repeated doses (2 g followed by 1 g) has a significant analgesic effect that is indistinguishable from that of morphine administered IM (10 mg followed by 5 mg) after dental surgery, with better tolerability.\n After moderately painful surgical procedures, IV paracetamol, administered as propacetamol, may be an asset in the control of acute postoperative pain.", "The analgesic efficacy and safety of propacetamol (Pro-Dafalgan), an injectable prodrug of acetaminophen, in combination with morphine administered by patient-controlled analgesia (PCA) were studied in 60 patients (56 men, 4 women; age 18-40 years; mean age, 26 years) after knee ligamentoplasty. Using a double-blind, randomized, parallel-group design, the effects of four (every 6 hr) intravenous injections of 2 g propacetamol (= 1 g acetaminophen) were compared with four injections of placebo (PL) in the recovery room immediately after surgery. Efficacy was assessed over 24 hr by automatic recording on the PCA device of the cumulative dose of morphine and the number of boluses requested. It was also assessed on pain scores rated on a five-point verbal scale and a visual analogue scale before administration, at 1, 2, 3, and 4 hr, and then every 2 hr until the 24th hr after administration. A five-point global efficacy scale was also administered. Any side effects were recorded throughout the duration of the study, and the ability to tolerate the drug was assessed by recording arterial pressure, cardiac and respiratory frequency, and sedation at the same assessment times as the pain scores. The 24-hr morphine consumption was significantly decreased in the propacetamol group (number of 1 mg boluses: 14.7 +/- 11.3 versus 23.2 +/- 13.8, P = 0.01; PCA usage: 26.4 +/- 12.3 mg versus 34.6 +/- 15.4 mg, P = 0.03; PCA usage + titration: 34.5 +/- 12.7 mg versus 43.1 +/- 15.9 mg, P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)", "To assess clinical efficacy of IV paracetamol 1 g and IV dipyrone 1 g on a 24-h dosing schedule in this randomised, double-blinded study of 40 ASA I-III (American Society of Anesthesiologists classification of physical status) patients undergoing surgery for breast cancer.\n General anaesthesia using remifentanil and propofol was performed for surgery. The patients were randomly allocated to two groups, receiving infusions of paracetamol 1 g/100 mL (Para Group) or of dipyrone 1 g/100 mL (Dipy Group) 30 min before arrival in the recovery area and every 6 h up to 24 h postoperatively. All patients had unrestricted access to opioid rescue medication via an IV patient-controlled analgesia (PCA) device.\n The primary variables for clinical equivalence were the differences between the mean values for pain scores at rest and pain scores on coughing over 30 h postoperatively. The equivalence margin was determined as +/-10 mm on the visual analogue scale (VAS).\n Regarding pain scores at rest, the 90% CI of the mean differences between the treatment groups over 30 h postoperatively was found to be within the predefined equivalence margin [+7.5/-6.2], and the CI values for pain scores on coughing [+7.3/-9.0] were similar. The two groups did not differ in cumulative opioid rescue consumption (Dipy-Group 14.8 +/- 17.7 mg vs. Para Group 12.1 +/- 8.8 mg, p = 0.54) nor in piritramide loading dose (Dipy Group 0.95 +/- 2.8 mg vs. Para Group 1.3 +/- 2.8 mg, p = 0.545). Five patients in the Dipy Group experienced hypotension in contrast to none in the Para Group (p = 0.047). There were no significant between-treatment differences for other adverse events, patient satisfaction scores (p = 0.4) or quality of recovery scores (p = 0.3).\n IV paracetamol 1 g is clinically equivalent to IV dipyrone 1 g for postoperative analgesia after surgery for breast cancer.", "A multimodal approach to postcesarean pain management may enhance analgesia and reduce side effects after surgery. This study evaluates the postoperative analgesic effects of propacetamol and/or diclofenac in parturients undergoing elective cesarean delivery under spinal anesthesia.\n After randomization, 80 healthy parturients received the following: placebo (group M), 100 mg diclofenac rectally every 8 hours (group MD), 2 g propacetamol intravenously every 6 hours (group MP), or a combination of 2 g propacetamol and 100 mg diclofenac (group MDP) as described above. Drugs were administered for 24 hours after surgery. Postoperative pain was controlled with a patient controlled analgesia pump, using morphine. The visual analog scale (VAS) at rest and on coughing, as well as the morphine consumption, were evaluated at 2, 6, and 24 hours postoperatively. Also, the side effects experienced after undergoing the different regimens were compared.\n The patients' characteristics did not differ significantly between the 4 groups. VAS score at 2 hours, both at rest and on coughing were lower in group MDP and MD compared with group M (P <.05). At 24 hours, there was still a tendency toward lower pain scores in the groups MDP and MD; however, this difference was only statistically significant at rest between the MDP group and the MP and M groups. Morphine consumption at 2, 6, and 24 hours was lower in the MDP and MD groups compared with the MP and M groups (P <.05). The morphine-sparing effect was higher in groups MDP and MD compared with group MP (57% and 46%, respectively, v 8.2%, P <.05). The incidence of side effects was similar in all groups. However, the power of the study was too low to permit an evaluation of potential side effects.\n Diclofenac after cesarean delivery improves analgesia and has a highly significant morphine-sparing effect. We were unable to demonstrate significant morphine-sparing effect of propacetamol or additive effect of propacetamol and diclofenac in this group of patients.", "In order to compare the morphine-sparing effect, analgesic efficacy and tolerance of nefopam and propacetamol given at their highest recommended doses, 120 patients undergoing elective hepatic resection were randomly assigned to receive postoperative intravenous patient-controlled analgesia with morphine alone, or in combination with nefopam (20 mg.4 h-1) or propacetamol (2 g.6 h-1). Compared with the control group (43 [7-92] mg), median [range] cumulative morphine consumption for 24 h after the study started was halved in the nefopam group (21 [3-78] mg, p <0.001) and 20% lower in the propacetamol group (35 [6-84] mg, p = 0.15). Analgesia was superior in the nefopam group despite the lower morphine consumption. Adverse effects were comparable in the three groups, except for significantly more nausea in the control group (39% vs. 17 and 26% in the nefopam and propacetamol groups, respectively) and more sweating in the nefopam group (17% vs. 0 and 3% in the control and propacetamol groups, respectively). Overall patient satisfaction was better (p < 0.001) in patients given nefopam (97%) than those receiving morphine alone (82%) or propacetamol (74%).", "To compare the analgesic efficacy and tolerance of propacetamol and morphine, 80 patients in good clinical condition were included in a prospective, parallel, randomized double blind trial after elective surgery expected to elicit light to moderate postoperative pain. At the end of general anesthesia, 40 patients received 30 mg/kg propacetamol and 40 0.2 mg/kg morphine, as a 15-min intravenous infusion. The groups were similar for age, weight and duration of anesthesia. Supplemental analgesia had to be given in 7 cases from the propacetamol group vs. 2 cases from the morphine group. The postoperative pain, evaluated 7 times during 4 h from the end of infusion with a visual analog scale, revealed a modest advantage for morphine at 0.5 and 4 h (p = 0.05). The respiratory rate was slightly lower after morphine (p = 0.02). No significant differences were observed in blood oxygen saturation, blood pressure, heart rate, body temperature and vigilance evaluated by the trailmaking test. Nausea was present in 4 cases under propacetamol and 3 under morphine, and pruritus in 2 and 7 cases, respectively. In conclusion, propacetamol may represent an alternative to morphine for pain prevention after mildly to moderately painful surgery in situations where the use of opioids is unsuitable.", "The study was to evaluate the analgesic and opioid-sparing effect of intravenous paracetamol injections in cardiosurgical patients in the early postoperative period. Adequate analgesia within the first 12-18 hours of the early postoperative period is very important for a good prognosis of the further course of pain syndrome and for the reduction of a risk for its progression to its chronic form. In early studies, propacetamol lowered morphine use after orthopedic and gynecological operations. The efficacy of paracetamol used in cardiac surgery has been little studied and the results of the studies are conflicting. The randomized, blind, placebo-controlled study included patients after aortocoronary bypass surgery, of them 22 patients received paracetamol and 23 had placebo. The test drug (perfalgan 100 ml or placebo) was intravenously injected 30 min before extubation and then every 6 hours within succeeding 18 hours. The intensity of the pain syndrome was rated by a 5-score verbal scale every 2 hours. With pain score of 2 or more, promedol was intramuscularly administered in a dose of 10 mg. Inspiratory volume was recorded before extubation and the first administration of a drug just after extubation and then every 2 hours. The baseline indices did not differ in both groups. Throughout the observation, the inspiratory volume was lower in the paracetamol group than in the placebo group; however, there was a statistically significant difference (p = 0.012) in the reduction in the manifestations of the pain syndrome (by 81%) only just after tracheal extubation. During this period, inspiratory volume values were higher in the paracetamol group; however, a statistically significant (39%) difference between the groups in the mean values was obtained only during and 2 hours after extubation. In the perfalgan group, the mean total use of promedol was 36% less than in the placebo-group, which was statistically significant (p = 0.019). The early postoperative use of paracetamol after myocardial revascularization reduces the intake of opioids and diminishes the intensity of the pain syndrome within the first hours after extubation, which promotes a higher thoracic excursion, as confirmed by a statistically significant increase in the maximum inspiratory capacity.", "Paracetamol, a centrally acting inhibitor of cyclooxygenase, has less gastrointestinal and platelet-inhibiting side effects and is clinically better tolerated than nonsteroidal anti-inflammatory drugs. Therefore, it will be ideally suited for postoperative pain relief. In this prospective, double-blind, randomized, placebo-controlled study, we evaluated the analgesic efficacy, opioid-sparing effect and effects on opioid-related adverse effects of intravenous (IV) paracetamol in combination with IV morphine after lumbar laminectomy and discectomy. Forty patients were divided into 2 groups (n=20 each) to receive either paracetamol 1 g (group 1) or 0.9% NaCl 100 ml (group 2) at the end of the operation and at 6-hour intervals over 24 hours. IV patient-controlled analgesia with morphine was used as a rescue analgesic in both groups. Pain was evaluated at rest and on movement at the 1st, 2nd, 4th, 6th, 12th, 18th, and 24th hours using a visual analog scale. Hemodynamic parameters, morphine usage, patient satisfaction, and probable side effects were also evaluated. Pain scores at rest and on movement at the 12th, 18th, and 24th hours were significantly lower in group 1 (P<0.001). Morphine consumption was not statistically significantly different between the groups (P>0.05). Vomiting in group 2 was significantly higher (P=0.027). Significantly more patients in the paracetamol group rated their pain management as excellent (45% vs. 5%). Although repeated IV paracetamol usage after lumbar laminectomy and discectomy did not demonstrate a significant opioid-sparing effect, it did decrease visual analog scale scores at certain evaluation times and incidence of vomiting and increase patient satisfaction." ]

[ "8822429", "7720911", "1553169", "8671376", "8671270", "8224258", "16220761", "7675371" ]

[ "Prevention of de-novo adhesion formation after laparoscopic myomectomy: a randomized trial to evaluate the effectiveness of an oxidized regenerated cellulose absorbable barrier.", "Expanded polytetrafluoroethylene (Gore-Tex Surgical Membrane) is superior to oxidized regenerated cellulose (Interceed TC7+) in preventing adhesions.", "Use of Interceed(TC7) absorbable adhesion barrier to reduce postoperative adhesion reformation in infertility and endometriosis surgery. The Obstetrics and Gynecology Adhesion Prevention Committee.", "Post-operative adhesions after laparoscopic electrosurgical treatment for polycystic ovarian syndrome with the application of Interceed to one ovary: a prospective randomized controlled study.", "Reduction of postoperative adhesion formation after laparoscopic ovarian cystectomy.", "Adhesion formation after laparoscopic ovarian cautery for polycystic ovarian syndrome: lack of correlation with pregnancy rate.", "Adhesion-prevention effects of fibrin sealants after laparoscopic myomectomy as determined by second-look laparoscopy: a prospective, randomized, controlled study.", "Reduction of adhesion reformation after laparoscopic endometriosis surgery: a randomized trial with an oxidized regenerated cellulose absorbable barrier." ]

[ "To evaluate the effectiveness of the oxidized regenerated cellulose absorbable barrier (Interceed, TC7) in the prevention of de-novo adhesion formation after laparoscopic myomectomy, a prospective and randomized study was performed at the Department of Obstetrics and Gynaecology of the University of Cagliari, Cagliari, Italy. A total of 50 pre-menopausal non-pregnant women, aged 23-42 years, who submitted to laparoscopic myomectomy from January 1993 to June 1994, were randomized to surgery alone (control group, n = 25) or surgery and oxidized regenerated cellulose barrier (Interceed group, n = 25). Neither group received any other treatment for adhesion prevention. A second-look laparoscopy was performed 12-14 weeks after laparoscopic myomectomy. The incidence of adhesion-free patients was assessed at second-look laparoscopy by an investigator not informed of the treatment. The numbers of adhesion-free patients were three out of 25 (12%) in the control group and 15 out of 25 (60%) in the treatment group (P < 0.05). In conclusion, the oxidized regenerated cellulose absorbable barrier significantly reduced de-novo adhesion formation after laparoscopic myomectomy.", "To compare the impact of expanded polytetrafluoroethylene (PTFE; Gore-Tex Surgical Membrane; W. L. Gore & Associates, Inc., Flagstaff, AZ) and oxidized regenerated cellulose (Interceed TC7, Johnson & Johnson Medical, Inc., Arlington, TX) on the development of postsurgical adhesions.\n A multicenter, nonblinded, randomized clinical trial.\n University medical centers.\n Each barrier was allocated randomly to the left or right sidewall of every patient.\n Thirty-two women with bilateral pelvic sidewall adhesions undergoing reconstructive surgery and second-look laparoscopy.\n Adhesion score (on a 0- to 11-point scale), the area of adhesion (cm2), and the likelihood of no adhesions.\n The use of both barriers was associated with a lower adhesion score and area of adhesion postoperatively. However, those sidewalls covered with PTFE had a significantly lower adhesion score (0.97 +/- 0.30 versus 4.76 +/- 0.61 points, mean +/- SEM) and area of adhesion (0.95 +/- 0.35 versus 3.25 +/- 0.62 cm2). Overall, more sidewalls covered with PTFE had no adhesions (21 versus 7) and, when adhesions were present on the contralateral sidewall, the number of sidewalls covered with PTFE without adhesions was greater than those covered with oxidized regenerated cellulose (16 versus 2).\n Expanded polytetrafluoroethylene was associated with fewer postsurgical adhesions to the pelvic sidewall than oxidized regenerated cellulose.", "Interceed(TC7) is a fabric composed of oxidized, regenerated cellulose that was designed to reduce the formation of postsurgical adhesions. We evaluated Interceed(TC7) in a randomized, multicenter clinical study. Sixty-three infertility patients had bilateral pelvic sidewall adhesions removed at laparotomy. One pelvic sidewall was covered by Interceed(TC7) and the other was left uncovered. The deperitonealized areas (N = 205) of all sidewalls were divided into three groups: less than 100 mm2, N = 72; 100-1000 mm2, N = 95; and more than 1000 mm2, N = 38. The effectiveness of Interceed(TC7) was evaluated at laparoscopy 10-98 days after laparotomy. Significantly more adhesions were observed at laparoscopy on the control pelvic sidewalls (48 of 63, 76%) than on the treated sides (26 of 63, 41%) (P less than .0001). The Interceed(TC7)-treated sidewalls also had significantly less area involved with adhesions at laparoscopy (P less than .05, P less than .001, and P less than .001 in the three groups, respectively). Twenty-eight women with severe endometriosis also had significantly more adhesions on the control side (23 of 28, 82%) than on the treated side (14 of 28, 50%) (P less than .05). We conclude that Interceed(TC7) effectively reduced the incidence and extent of postoperative adhesions, even in patients with severe endometriosis.", "In this prospective, randomized, controlled clinical study, 21 women underwent a second-look laparoscopy 2-11 weeks after standardized laparoscopic electrosurgical treatment for polycystic ovarian syndrome (PCOS). Following bilateral ovarian treatment, one ovary was randomly chosen to have Interceed applied to its surface using a specially designed applicator, with the other ovary serving as a control. Peri-adnexal adhesions of significant extent and severity developed in 57% of the women and 38% of the adnexa. The incidence of adhesions on the Interceed-treated side was 43%, while on the control side it was 33%. In addition, the extent and severity of the adhesions appeared to be similar on the Interceed-treated and control side. However, larger numbers would be required to determine statistically the effects of Interceed on de-novo adhesion formation after laparoscopic electrosurgical treatment of PCOS, as described here.", "The purpose of this randomized, open-label study was to assess the efficacy of the product Interceed absorbable adhesion barrier in the prevention of adhesion formation on the ovary after laparoscopic ovarian cystectomy. A total of 25 patients requiring laparoscopic bilateral ovarian cystectomy were enrolled into this study. After removal of ovarian cysts, peri-adnexal adhesions, and peritoneal irrigants, and the attainment of meticulous haemostasis, the random assignment of one ovary for wrapping with Interceed was revealed to the surgeon. The other ovary served as the untreated control. A follow-up laparoscopy was performed 8-30 weeks after the initial procedure in 17 patients. Significantly fewer adhesions formed at the Interceed treated ovaries compared with the control (untreated) ovaries (P < 0.05). In terms of adhesion-free outcome, 76% (13/17) of Interceed treated ovaries and 35% (6/17) of control ovaries were free of adhesions. A significant reduction was observed in the area of the sutured ovaries involved with adhesions when Interceed (6%) was used, compared with controls (20%). The reduction of adhesion formation was not related to the size of the cysts at the initial procedure. No adverse events were reported by any patient during the study. In conclusion, Interceed was found to be safe and effective in reducing the incidence of postoperative adhesion formation in patients undergoing laparoscopic ovarian cystectomy.", "To assess adhesion formation after laparoscopic ovarian cautery in women with polycystic ovarian syndrome (PCOS) and the efficacy of Interceed Adhesion Barrier (Ethicon, Summerville, NJ) in their prevention.\n Prospective, randomized, blinded, clinical study of laparoscopic ovarian cautery with application of Interceed to one ovary, followed by short interval second-look laparoscopy, scoring of adhesions, and clinical follow-up.\n Tertiary care clinic at a University teaching hospital.\n Eight infertile women with PCOS who failed to conceive with previous clomiphene citrate (CC) therapy.\n Periovarian adhesions of varying severity developed in all women after laparoscopic ovarian cautery. Interceed showed no protective effect. Despite this finding, all women initiated regular menses after laparoscopic ovarian cautery and seven of eight women spontaneously conceived eight singleton pregnancies without any further therapy.\n Laparoscopic ovarian cautery should be considered in infertile women with PCOS who fail to respond to CC therapy. These women must be counseled with respect to the possible complication of postoperative adhesion formation.", "To examine the adhesion prevention effects of 2 types of fibrin sealant after laparoscopic myomectomy (LM).\n A prospective, randomized study (Canadian Task Force I) was conducted at a University-affiliated hospital. A total of 91 patients showing a minimal myoma > 5 cm, excluding pedunculated myomas, underwent LM alone: 32 patients in the control group, 29 in the fibrin gel group and 30 patients in the fibrin sheet group. After LM, postoperative adhesions were evaluated by second-look laparoscopy. The frequency of postoperative adhesions was the main outcome.\n The frequency of postoperative adhesions of the uterus was significantly lower (p < 0.05) in the fibrin gel group, with 20/32 (62.5%) in the control group, 10/29 (34.5%) in the fibrin gel group and 20/30 (67.7%) in the fibrin sheet group. Although no significant differences were found in the incidence of de novo adnexal adhesions, the lowest rate was found in the fibrin gel group, with 4/32 patients (12.5%) in the control group, 2/29 patients (6.8%) in the fibrin gel group and 5/30 patients (16.7%) in the fibrin sheet group. No bilateral adnexal adhesions were observed in the 3 groups.\n After LM for myomas as large as > or = 5 cm, postoperative adhesions were observed in > or = 50% of patients. The use of fibrin gel after LM is recommended.", "To evaluate the effectiveness of an oxidized regenerated cellulose absorbable barrier (Interceed [TC7] Absorbable Adhesion Barrier) in the reduction of adhesion reformation after laparoscopic surgery for endometriosis.\n Thirty-two premenopausal nonpregnant women who had severe endometriosis and complete posterior cul-de-sac obliteration and were undergoing laparoscopic surgery were randomly assigned to either surgery alone or surgery and Interceed. None of the subjects received any other treatment for adhesion prevention. Second-look laparoscopy was performed 12-14 weeks after laparoscopic surgery by an investigator blinded to the treatment, and the incidence of adhesion-free subjects was assessed.\n Twelve of 16 (75%) women treated with the oxidized regenerated cellulose barrier were free of adhesions, compared with two of 16 (12.5%) controls, a statistically significant difference (P < .05).\n The oxidized regenerated cellulose absorbable barrier significantly reduces adhesion reformation after laparoscopic surgery for endometriosis." ]

[ "6116952", "1606398", "3242186", "2878174", "7908570", "10740301" ]

[ "Ethamsylate reduces the incidence of periventricular haemorrhage in very low birth-weight babies.", "Prophylaxis of patent ductus arteriosus using ethamsylate in preterms treated with exogenous surfactant.", "The effect of ethamsylate on neonatal mortality in preterm infants.", "Multicentre trial of ethamsylate for prevention of periventricular haemorrhage in very low birthweight infants.", "Ethamsylate in the prevention of periventricular-intraventricular hemorrhage in premature infants.", "Role of ethamsylate in preventing periventricular-intraventricular hemorrhage in premature infants below 34 weeks of gestation." ]

[ "nan", "nan", "nan", "The effectiveness of ethamsylate in the prevention of periventricular haemorrhage (PVH) in very low birthweight infants was evaluated by means of a multicentre, placebo-controlled, double-blind trial. In 330 infants without evidence of PVH on initial cranial ultrasound examination there was little difference between ethamsylate and placebo groups with respect to subependymal haemorrhage, but intraventricular and parenchymal haemorrhages developed in 30/162 infants (18.5%) in the treated group, compared with 50/168 (29.8%) in the control group (p less than 0.02). The incidence of intraventricular and parenchymal haemorrhage in survivors was 20/137 (14.6%) in the ethamsylate group and 37/146 (25.3%) in the controls (p less than 0.05). In 30 infants with evidence of PVH on the initial scan, ethamsylate treatment seemed to limit parenchymal extension. Analysis of the total cohort of 360 infants showed that the proportion of infants in whom an increase of two or more grades of severity of PVH was recorded during the trial was lower in the treated than in the placebo group (p less than 0.01). No adverse effects were attributed to ethamsylate therapy. The reported incidence of patent ductus arterious was lower in the treated than in the placebo group (p less than 0.02). Mortality was similar in the two groups.", "A random and controlled trial was conducted to evaluate the efficacy and safety of ethamsylate in the prevention of periventricular-intraventricular hemorrhage (PIVH) in premature infants. Between January 1990 and July 1992, 171 premature infants with a birth weight of < 1,751 g who displayed no PIVH on initial cranial ultrasound scan, performed within an hour of delivery, were randomly divided into two groups. Group 1 consisted of 86 premature infants with a mean birth weight of 1.4 +/- 0.5 kg and a mean gestational age of 30.1 +/- 2.4 weeks. The first dose of ethamsylate 12.5 mg/kg (0.1 mL/kg from 250 mg/2mL ampoules) was given to group 1 intravenously within an hour of delivery and was followed by doses at six-hourly intervals for four days (total dose 200 mg/kg). Group 2 consisted of 85 premature infants with mean birth weight of 1.4 +/- 0.3 kg and mean gestational age of 30.4 +/- 2.2 weeks. Group 2 received 0.1 mL/kg normal saline intravenously in a similar fashion as the ethamsylate-treated group. Cranial ultrasound examinations were performed on postnatal days one, two, three, five, seven and 14. The incidence of PIVH in the ethamsylate-treated group was 24/86 (27.9%) and 39/85 (45.9%) in the control group (p < 0.02). In addition, the incidence of severe PIVH in the ethamsylate-treated group was 9/86 (10.5%) and 20/85 (23.5%) in the control group (p < 0.05). No adverse effects were attributed to ethamsylate therapy in this study.", "To determine the role of ethamsylate in prevention of PVH-IVH in premature infants <34 weeks gestational age.\n Prospective, randomized, controlled study.\n Infants less than 34 weeks gestational age were included in the trial. Neonates with congenital malformations, family history of bleeding disorders and with Apgar scores <5 at 5 minutes were excluded. Subjects were randomized into two groups--Group A infants received intravenous ethamsylate (12.5 mg/kg) six hourly for four days and Group B infants served as a control group. Regular cranial ultrasounds to detect the presence of PVH-IVH were done between days 3-5, 10-14 and 28-30 of post natal age, and before hospital discharge in all infants and weekly in infants detected to have PVH-IVH on earlier scans. Various antenatal and postnatal factors known to affect the incidence of PVH-IVH were recorded.\n A total of 192 infants underwent the trial, 93 in Group A and 99 in Group B. Antenatal corticosteroids (1 or 2 doses) were administered to 32 ( 34.4%) and 36 (36.3%) women in Group A and Group B, respectively. None of the mothers received phenobarbitone, vitamin K or indomethacin antenatally and none of the infants received phenobarbitone, vitamin E or indomethacin postnatally during the study period. PVH-IVH was seen in 26 infants in Group A, of which Grade I IVH occurred in 9, Grade II in 14, Grade III in 2 and Grade IV in one infant. Twenty-nine infants had PVH-IVH in Group B of which 11 had Grade I, 15 Grade II and 3 Grade III. None of the differences were statistically significant.\n Postnatal administration of ethamsylate did not decrease the incidence of PVH-IVH in the study infants." ]

[ "4952467", "4893890", "17003397", "19329003", "6992856", "16522834", "9114186", "17005549", "8102427", "5325465", "4780349", "8637698", "17255240", "4570291", "6025181" ]

[ "Gantrisin and madribon in trachoma.", "Controlled trials with trisulfapyrimidines in the treatment of chronic trachoma.", "Impact of annual targeted treatment on infectious trachoma and susceptibility to reinfection.", "Assessment of herd protection against trachoma due to repeated mass antibiotic distributions: a cluster-randomised trial.", "Family-based suppressive intermittent therapy of hyperendemic trachoma with topical oxytetracycline or oral doxycycline.", "Effect of a single mass antibiotic distribution on the prevalence of infectious trachoma.", "A comparison of oral azithromycin with topical oxytetracycline/polymyxin for the treatment of trachoma in children.", "Efficacy and safety of short duration azithromycin eye drops versus azithromycin single oral dose for the treatment of trachoma in children: a randomised, controlled, double-masked clinical trial.", "Randomised controlled trial of single-dose azithromycin in treatment of trachoma.", "Trachoma therapy: a controlled study.", "Clinical assessment of the comparative effect of terramycin and GS 2989 in the mass treatment of trachoma.", "Single-dose azithromycin in the treatment of trachoma. A randomized, controlled study.", "Chlamydia on children and flies after mass antibiotic treatment for trachoma.", "Doxycycline treatment of chronic trachoma.", "Failure of trachoma treatment with ophthalmic antibiotics and systemic sulfonamides used alone or in combination with trachoma vaccine." ]

[ "nan", "nan", "The World Health Organization developed the SAFE strategy (Surgery for trichiasis; Antibiotics for Chlamydia trachomatis infection; Facial cleanliness; and Environmental improvement) to eliminate blinding trachoma globally by the year 2020. Despite a number of studies using various intervals of treatment for different prevalence rates, there has been a lack of sufficient follow-up beyond the final treatment point to determine rates of recurrence of disease and infection and the risk factors that may contribute to each.\n To evaluate the impact of 2 annual targeted azithromycin treatments on active trachoma and C trachomatis infection rates over 3 years in Vietnam.\n Three communes were randomly selected for a longitudinal study in Vietnam from November 2000 through November 2003. Individuals (n = 3186) were graded for trachoma followed by conjunctival sampling to detect chlamydiae by commercial polymerase chain reaction. Grading and chlamydial detection were repeated every 6 months for 3 years.\n Azithromycin was given to children aged 5 through 15 years with active trachoma and their household members in SAFE and SA communes at baseline and 12 months; these communes were compared with the S-only control commune that did not receive azithromycin targeted treatment.\n Prevalence and incidence of active trachoma and C trachomatis infection in all communes at baseline, 6, 12, 18, 24, and 36 months. Subgroup analysis evaluated new infection, continuing infection, and reinfection at 6, 12, 18, 24, and 36 months and risk factors for each.\n Reinfection rates increased significantly between 12 and 36 months for SAFE (from 1.6 to 29.3 per 1000; P<.001) and SA (5.1 to 25.3 per 1000; P = .002) communes but not for the S-only commune (13.4 to 6.7 per 1000; P = .55) after 24 months. Compared with the S-only commune, mixed-effects and generalized estimating equations (GEE) logistic models showed that reinfection risk was significantly higher for SAFE (odds ratio [OR], 4.1; 95% confidence interval [CI], 1.5-9.8; P = .005) and SA (OR, 4.2; 95% CI, 1.1-17.3; P = .04) communes at 36 months.\n Increasing reinfection rates suggest that treatment may interrupt the duration of infection required for developing immunity, increasing the number of individuals susceptible to reinfection and adversely affecting disease prevalence over time. Additional research is needed to determine optimal trachoma control strategies, including evaluation of the \"F\" and \"E\" components.\n www.actr.org.au Identifier: 12606000360516.", "Trachoma-control programmes distribute oral azithromycin to treat the ocular strains of chlamydia that cause the disease and to control infection. Theoretically, elimination of infection is feasible if untreated individuals receive an indirect protective effect from living in repeatedly treated communities, which is similar to herd protection in vaccine programmes. We assessed indirect protection against trachoma with mass azithromycin distributions.\n In a cluster randomised trial, 24 subkebeles (government-defined units) in Amhara, Ethiopia, were randomised, with use of a simple random sample, to distribution four times per year of single-dose oral azithromycin to children aged 1-10 years (12 subkebeles, 4764 children), or to delayed treatment until after the study (control; 12 subkebeles, 6014 children). We compared the prevalence of ocular chlamydial infection in untreated individuals 11 years and older between baseline and 12 months in the treated subkebeles, and at 12 months between the treated and control subkebeles. Health-care and laboratory personnel were blinded to study group. Analysis was intention to treat. The study is registered with clinicaltrials.gov, number NCT00322972.\n At 12 months, 637 children aged 1-10 years and 561 adults and children aged 11 years and older were analysed in the children-treated group, and 618 and 550, respectively, in the control group. The mean prevalence of infection in children decreased from 48.4% (95% CI 42.9-53.9) to 3.6% (0.8-6.4) after four mass treatments. At 12 months, the mean prevalence of infection in the untreated age group (>/=11 years) was 47% (95% CI 33-57) less than baseline (p=0.002), and 35% (95% CI 1-57) less than that in untreated communities (p=0.04).\n Frequent treatment of children, who are a core group for transmission of trachoma, could eventually eliminate infection from the entire community. Herd protection is offered by repeated mass antibiotic treatments, providing a strategy for elimination of a bacterial disease when an effective vaccine is unavailable.\n National Institutes of Health.", "A controlled double-blind stratified trial was carried out in a village in Southern Iran to assess the efficacy of family-based intermittent therapy of hyperendemic trachoma with topical oxytetracycline oily suspension twice daily for 7 days each month, or oral doxycycline 5 mg per kilogram of body weight once a month, in comparison with a control group which received vitamin pills once a month. In addition all other members of the selected children's families were also treated with the same regimen of therapy. The treatment was given for a period of 1 year by 3 field technicians, each responsible for one regimen of therapy. Examining the whole conjunctiva 4 months after the start of therapy, we observed no marked difference in the cure rate or the number of patients with moderate to severe trachoma between the groups treated with antibiotics and the control group. When treatment was continued for 12 months, a marked decrease in the prevalence of trachoma and in the grades of intensity of inflammatory responses as well as the positivity rate for Chlamydia trachomatis was observed in the groups treated with the topical oxytetracycline or oral doxycycline compared with the control group. While there was no marked difference between the efficacy of these 2 regimens of mass chemotherapy, the monthly intermittent therapy with a single dose of doxycycline offers the advantage of being more practical and less expensive for mass control of trachoma by requiring approximately one-tenth of the staff, transport, and other facilities required for the intermittent topical therapy with tetracycline eye ointment.", "The World Health Organization recommends mass antibiotic distributions in its strategy to eliminate blinding trachoma as a public health concern. Some hypothesize that a single distribution is sufficient to control the ocular strains of chlamydia that cause trachoma. Others believe infection will inevitably return and periodic treatments or other measures are essential.\n To determine whether ocular chlamydial infection returns to the community up to 24 months after a single mass antibiotic distribution in a hyperendemic region of Ethiopia.\n Longitudinal cohort study conducted March 2003 to March 2005 in the Gurage Zone of Ethiopia. Eight randomly selected villages were assessed for ocular chlamydial infection. Fifteen untreated villages were randomly chosen at 12 months to allow assessment of a secular trend.\n A single dose of oral azithromycin was offered to all residents of the 8 selected villages who were aged 1 year or older.\n Prevalence of ocular chlamydial infection in all children aged 1 to 5 years from each intervention village prior to treatment and 2, 6, 12, 18, and 24 months after mass antibiotic treatment, and also in untreated villages enrolled at 12 months.\n Five hundred fifteen children were examined for ocular chlamydial infection at baseline. For the follow-up examinations, the mean participation rate was 83%. The mean prevalence of infection in children aged 1 to 5 years decreased from 43.5% (95% confidence interval [CI], 35.0%-52.0%) to 5.1% (95% CI, 1.1%-9.2%) after treatment. On average, infection returned gradually over 24 months to 11.3% (95% CI, 4.5%-18.1%; P = .001). In 7 of 8 villages, infection was higher at 24 months than at 2 months. In the remaining village, no infection could be identified at any point after treatment. Villages enrolled at 12 months had significantly fewer infections than those enrolled 12 months earlier, suggesting a secular trend (P<.001).\n Ocular chlamydial infection was not eliminated in children aged 1 to 5 years after a single mass azithromycin distribution; it slowly returned over 24 months, although not to baseline levels. Repeated treatments or other effective measures will be necessary for elimination.", "Trachoma, an infectious keratoconjunctivitis caused by Chlamydia trachomatis, is a leading cause of preventable blindness in developing countries. In this study we compared oral azithromycin with oxytetracycline/polymyxin eye ointment (once daily for 5 days every 4 weeks; total of six treatment cycles) for the treatment of active endemic trachoma in 168 rural Egyptian children. A suspension of azithromycin was administered to children as a dose of 20 mg/kg by one of three schedules: a single dose, one dose a week for 3 weeks, and one dose every 4 weeks for a total of six doses. The children's clinical status and chlamydial infection rates were evaluated for 1 year. The clinical cure rates were 35% 2 months after initial treatment, 16% at 8 months (during the annual autumn epidemic of purulent conjunctivitis), and 47% at 1 year. The pretreatment chlamydial infection rate of 33% (determined by direct immunofluorescence) decreased to 5% at 2 months and was 9% at 12 months. There were no significant clinical or laboratory differences among the four treatment groups. Thus, 1-6 doses of azithromycin were equivalent to 30 days of topical oxytetracycline/polymyxin ointment and may offer an effective alternative means of controlling endemic trachoma.", "Efficacy and safety of a short-duration treatment of azithromycin 1.5% eye drops versus oral azithromycin to treat active trachoma.\n Randomised, controlled, double-masked, double-dummy, non-inferiority explanatory study including 670 children from Guinea Conakry and Pakistan if: 1-10 years old; active trachoma (TF+TI0 or TF+TI+ on simplified World Health Organisation (WHO) scale). Three groups received either: azithromycin 1.5% eye drops twice daily for 2 days, for 3 days or azithromycin single 20 mg/kg oral dose. Patients' contacts were treated whenever possible. Clinical evaluation was performed using a binocular loupe. Primary efficacy variable was the cure (no active trachoma (TF0)) at day 60. Non-inferiority margin for difference between cure rates was 10%.\n Cure rate in per protocol set was as follows: 93.0%, 96.3% and 96.6% in 2-day group 3-day group, and oral treatment group, respectively. Azithromycin 1.5% groups were non-inferior to oral azithromycin. The intend to treat (ITT) analysis supported the results. Clinical re-emergence rate was low: 4.2%. Ocular tolerance was similar for all groups. No treatment related adverse events were reported. Logistic regression analyses found prognostic factors such as: country (p<0.001) and trachoma severity (p = 0.003).\n In active trachoma, azithromycin eye drops twice daily for 2 or 3 days are as efficient as the WHO's reference treatment and represent an innovative alternative to oral azithromycin.", "Blindness due to trachoma is a serious public health issue world wide. The currently recommended treatment of active trachoma with repeated doses of tetracycline eye ointment has many disadvantages. The new azalide antibiotic azithromycin is effective as a single oral dose in the chemotherapy of genital Chlamydia trachomatis infections, and we have assessed its efficacy for trachoma treatment. We carried out a randomised single-blind comparison of azithromycin (a single oral dose of 20 mg/kg) with conventional treatment (6 weeks of topical tetracycline plus erythromycin for severe cases) in two villages with endemic trachoma in The Gambia. The patients were followed up for 26 weeks from the start of treatment by an observer unaware of treatment allocation. By 6 months' follow-up, trachoma had resolved in 76 (78%) of 97 subjects who received azithromycin compared with 70 (72%) of 97 who were treated conventionally (95% CI for difference -6% to 18%). Compliance with both treatments was good, but that for conventional treatment could probably not be achieved outside the research setting. There were no significant differences in treatment effect, baseline characteristics, or re-emergent disease between the treatment groups. Azithromycin was well tolerated. As a systemic treatment effective in a single dose it has important potential for trachoma control.", "nan", "nan", "To compare the safety and efficacy of single oral-dose azithromycin with a 7-week topical tetracycline ointment course in the treatment of active trachoma.\n A total of 64 patients with active trachoma were selected randomly to receive azithromycin (20 mg/kg) in a single dose or topical tetracycline eye ointment for 6 weeks. Clinical assessments were made before and at 4, 8, 12, and 24 weeks after treatment. Conjunctival scrapings were obtained before and after 24 weeks after treatment and fixed for Giemsa and direct immunofluorescence staining.\n Trachoma resolved in 17 (63.3%) patients who received azithromycin compared with 19 (65.4%) who were treated with tetracycline ointment. There were no significant differences in treatment effect or baseline characteristics between the treatment groups. Both treatments were well tolerated, and no adverse events were noted.\n Single-dose azithromycin is as effective as a 6-week course of topical tetracycline ointment in the treatment of active trachoma. The findings may help establish high compliance in treating trachoma and could contribute to the control of trachoma worldwide.", "There are various approaches to control trachoma. These include the elimination of the ocular strains of Chlamydia trachomatis that cause the disease and to decrease the spread of infection by other measures such as fly control. Here, we examined how these two are related (i.e., how treating children with antibiotics affects carriage of Chlamydia by flies). Flies were collected in villages that had received mass oral azithromycin distribution and were compared with flies in untreated villages. Polymerase chain reaction (PCR) was performed to detect chlamydial DNA on the flies. Conjunctival swabs were also taken to assay for chlamydial prevalence in the children. Chlamydia was found on 23% of the flies in the untreated villages but only 0.3% in treated villages. Prevalence of trachoma in children proved to be an excellent predictor of the prevalence on flies (correlation coefficient, 0.89). Thus, treating children with antibiotics may drastically reduce the role of flies as a vector.", "nan", "nan" ]

[ "19398797", "17585259", "18388724", "19700984", "10513357", "18539675", "19350335", "21357965", "20419009", "17323092", "17596049" ]

[ "Conservative management of idiopathic clubfoot: Kite versus Ponseti method.", "Is it hazardous or mandatory to release the talocalcaneal interosseous ligament in clubfoot surgery?: a preliminary report.", "Treatment of clubfoot with the Ponseti method: a comparison of casting materials.", "The effectiveness of botulinum A toxin as an adjunct to the treatment of clubfeet by the Ponseti method: a randomized, double blind, placebo controlled study.", "Clubfoot surgical treatment: preliminary results of a prospective comparative study of two techniques.", "Is there a role for lengthening flexor hallucis and flexor digitorum longus tendons in surgery for club foot?: a preliminary report.", "Comparison of Ponseti versus surgical treatment for idiopathic clubfoot: a short-term preliminary report.", "An accelerated Ponseti versus the standard Ponseti method: a prospective randomised controlled trial.", "Comparison of Ponseti and Kite's method of treatment for idiopathic clubfoot.", "Ponseti's vs. Kite's method in the treatment of clubfoot--a prospective randomised study.", "Comparison of modified posteromedial release and complete subtalar release in resistant congenital clubfoot: a randomized controlled trial." ]

[ "To compare the long-term results of the Kite and Ponseti methods of manipulation and casting for clubfoot.\n 42 patients (with 64 idiopathic clubfeet) were equally randomised to Kite or Ponseti treatments in the early weeks of life. 14 males and 7 females (34 clubfeet) were treated by the Kite method, whereas 13 males and 8 females (30 clubfeet) were treated by the Ponseti method. All the clubfeet were manipulated, casted, and followed up (for a mean of 3 years) by one experienced orthopaedic surgeon. The final results were compared.\n The success rates for the Kite and Ponseti treatments were similar (79% vs 87%). With the Ponseti method, the number of casts was significantly fewer (7 vs 10); the duration of casting required to achieve full correction was significantly shorter (10 vs 13 weeks); the maximum ankle dorsiflexion achieved was significantly greater (12 vs 6 degrees); and the incidence of residual deformity and recurrence was slightly lower.\n The Ponseti method can achieve more rapid correction and ankle dorsiflexion with fewer casts, without weakening the Achilles tendon.", "Extreme overcorrection and avascular necrosis are recognized complications in clubfoot surgery and are thought to be the result of division of the talocalcaneal interosseous ligament (TCIL). This is a preliminary report of a prospective study of the cases of 46 patients with 66 idiopathic clubfeet treated by means of soft tissue release using a posteromedial approach at a mean age of 9 months. The deformity was very severe in 51 feet and severe in 15. The feet were divided into 2 equal groups (33 feet each). In group A feet, the TCIL was released, whereas in group B, the ligament was left intact. At a mean follow-up period of 28 months, the result was satisfactory (excellent and good) in 96.9% of feet in group A and in 87.9% of feet in group B. When the mean overall clinical and radiological score was investigated, group A graded excellent whereas group B graded good. In feet with satisfactory outcome, group A showed statistically significant improvement of the anteroposterior and lateral talocalcaneal angles, talocalcaneal index, and lateral calcaneus-first metatarsal angles when compared with group B. This was reflected clinically on better hind foot correction with the release of the TCIL, with no evidence of significant overcorrection. Magnetic resonance imaging of the ankle and foot confirmed no evidence of talar avascular necrosis or extreme overcorrection in 40 feet (60.1%), 20 in each group. We conclude that it is advisable to release the TCIL in severe and very severe clubfeet.", "Popular initial treatment for congenital clubfoot includes the use of serial manipulations and casting as described by Ponseti et al. Plaster of Paris and semirigid fiberglass are 2 materials commonly used for casting. To our knowledge, no study to date has compared the clinical results of these 2 materials. The objective of this randomized prospective study was to compare the effectiveness of these materials in the initial management of clubfoot.\n All clubfeet presenting to the 2 senior authors' outpatient clinics over a 15-month period were offered enrollment. Patients were randomly assigned for treatment with either plaster or semirigid fiberglass casts. The severity of the clubfoot deformity was documented using the scoring system devised by Diméglio et al. Serial casts were applied according to the technique described by Ponseti et al. At the completion of nonsurgical treatment, the final clubfoot severity was documented.\n A total of 42 clubfeet in 34 patients were enrolled in the study. After exclusion of 3 patients, 13 patients (16 feet) received fiberglass, and 18 patients (23 feet) received plaster casts. The mean baseline severity scores of the 2 groups were not significantly different. The mean final severity score was significantly higher in the feet treated with fiberglass than those treated with plaster (6.4 vs 4.1; P = 0.037). There was a trend toward higher scores for cast tolerance, durability, and parent satisfaction in the fiberglass group, but this did not reach significance.\n This study supports the use of plaster casting with the Ponseti technique. The use of plaster casts resulted in a statistically lower Diméglio-Bensahel score at the completion of serial casting. There was a trend toward higher patient satisfaction in the fiberglass-treated group. Whether this difference has an effect on long-term outcomes and recurrence remains to be studied.\n Level II. Nonblinded randomized controlled prospective study.", "The Ponseti method has been shown to be a highly effective way to correct congenital clubfeet nonoperatively. Children treated with the technique frequently require percutaneous Achilles tenotomies, however, and until recently have experienced frequent relapses of their deformity. The purpose of this study was to see if Botulinum a A toxin (BTX-A) (manufactured by Allergan, Irvine CA) and administered before starting treatment with the Ponseti method might decrease the time in cast to correction, reduce the need for percutaneous Achilles tenotomy, and reduce the frequency of relapse.\n After IRB approval and informed consent, 20 newborns (age 0 to 30 d) with Dimeglio lll congenital clubfeet (N=32) were randomized into either BTX-A or placebo groups. All clubfeet underwent serial manipulation and casting according to the Ponseti technique. Outcomes measured were days in cast to correction of deformity (judged clinically and radiographically), and the need for percutaneous Achilles tenotomy to achieve correction. Recurrence requiring further treatment after initial correction was also recorded.\n We were unable to demonstrate a significant difference (t test and chi2 procedures) between the BTX-a group and the placebo group in the outcomes measured.\n We were not able to demonstrate that BTX-A as administered in this study speeds correction, reduces the need for percutaneous Achilles tenotomy, or decreases the chance of relapse after treatment when used as an adjunct to serial manipulation and casting for congenital clubfoot. It is possible that BTX-A could have a treatment effect that due to the power of our study would not have been detected by our study.\n Level 1b.", "Twenty patients with 30 idiopathic resistant clubfeet were operated on by the same surgeon. The mean patient age was 7.7 months (range, 3.5-19 months). Two different surgical techniques (15 posteromedial release and 15 complete circumferential subtalar release) were used during a prospective randomized study. Average follow-up was 2 years 3 months. None of the children had received previous conservative treatment. Radiologic assessment on lateral and anteroposterior radiographs included preoperative and follow-up measurements of tibiotalar, tibiocalcaneal, talocalcaneal, talo-I meta, and calcaneo-V meta angles, as well as physis morphology, talocalcaneal divergence, and location of the navicular. Before surgery, both groups were statistically similar as assessed by the Student t test. Follow-up results were also statistically similar between the groups. Functional assessment, according to Magone's score, showed global average excellent and good results in 23 feet (76.7%), with a slight but not significant difference (P = 0.77) between the two techniques. At short-term follow-up, no significant differences were found in radiologic and functional results between the two surgical procedures for idiopathic clubfoot.", "Most cases of club foot (congenital talipes equinovarus) respond to non-operative treatment but resistant cases may need surgery. It is broadly accepted that lengthening of tendo Achillis, the tendon of tibialis posterior and capsulotomy of the ankle and subtalar joints are necessary during surgical release, but there is no consensus as to whether lengthening of the tendons of flexor hallucis longus and flexor digitorum longus is required. We randomised 13 children with severe bilateral club foot deformities to undergo lengthening of the flexor hallucis longus and flexor digitorum longus tendons on one side and simple decompression on the other. We found no difference in the deformities of the toes between the lengthened and non-lengthened sides at a mean follow-up of four years (2 to 6). We conclude that routine lengthening of the tendons of flexor hallucis longus and flexor digitorum longus during soft-tissue surgery for resistant club foot is not necessary.", "The Ponseti method of treatment for congenital clubfeet has gained widespread clinical acceptance. We have used manipulation, serial casting, and surgery to treat congenital clubfeet for almost 3 decades. Considering the Ponseti method of treatment to replace our traditional treatment method, we conducted a randomized, controlled trial evaluating the short-term outcome of the two treatment protocols. We evaluated foot function and applied a standardized measure of health status for children with orthopaedic problems. Nineteen patients (28 feet) were included in the trial. Nine infants (12 feet) were assigned to the Ponseti treatment group, and 10 (16 feet) were assigned to a group with initial casting and posteromedial release at the age of 6 to 8 months. The minimum followup was 3.3 years (mean, 3.5 years; range 3.3-3.8 years). Outcome measures included the Functional Rating System of Laaveg and Ponseti, the Pediatric Outcomes Data Collection Instrument (PODCI), and standardized radiographic measurements. At last followup the mean Functional Rating score was higher in the Ponseti group. Passive dorsiflexion and passive inversion-eversion were better in the Ponseti group. PODCI scales were comparable and radiographic outcome measures were similar in both groups. This trial has documented a favorable short-term outcome for the Ponseti method when compared with a traditional treatment protocol. Level of Evidence: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.", "We conducted a prospective randomised controlled trial to compare the standard Ponseti plaster method with an accelerated method for the treatment of idiopathic congenital talipes equinovarus. The standard weekly plaster-change method was accelerated to three times per week. We hypothesised that both methods would be equally effective in achieving correction. A total of 40 consecutive patients (61 feet) were entered into the trial. The initial median Pirani score was 5.5 (95% confidence interval 4.5 to 6.0) in the accelerated group and 5.0 (95% confidence interval 4.0 to 5.0) in the standard control group. The scores decreased by an average 4.5 in the accelerated group and 4.0 in the control group. There was no significant difference in the final Pirani score between the two groups (chi-squared test, p = 0.308). The median number of treatment days in plaster was 16 in the accelerated group and 42 in the control group (p < 0.001). Of the 19 patients in the accelerated group, three required plaster treatment for more than 21 days and were then assigned to the standard control method. Of the 40 patients, 36 were followed for a minimum of six months. These results suggest that comparable outcomes can be achieved with an accelerated Ponseti method. The ability to complete all necessary manipulations within a three-week period facilitates treatment where patients have to travel long distances.", "The manipulation and corrective cast application for club foot was known to be done by Kite's method. The Kite's method of manipulation (center of rotation of malaligned foot and fulcrum on cuboid) was modified by Ponseti (fulcrum on head of talus). Recently, Ponseti's method has gained popularity and vastly improved results are reported. We report randomized controlled trial where manipulation of club foot was done by Ponseti's and Kite's method and correction evaluated by Pirani score to compare the outcome of treatment.\n Sixty feet in 38 patients, 22 with bilateral and 16 with unilateral clubfeet in children less than two years of age and without any prior manipulation or surgical treatment were randomly allocated to the Ponseti (30 feet) and Kite (30 feet) methods of manipulation. This process resulted in the right and left feet of the same patient in 12 bilateral cases being compared with one another (Paired analysis). In the remaining 10 bilateral cases, four patients had both feet treated by Ponseti and six had both feet treated by Kite (unpaired analysis). Finally, in 16 unilateral cases, 10 feet were allocated to the Ponseti and six to Kite methods of manipulation (unpaired analysis). Feet were followed up weekly for 10 weeks for change of cast and recording of hindfoot, midfoot and total Pirani scores. Correction was measured as a difference between hindfoot, mid foot and total Pirani scores weekly from weeks 1 to 10 and corresponding baseline scores. Absolute correction and rate of correction in (i) bilateral clubfeet treated by Ponseti's method on one side and Kite's method on the other side in the same patient were compared using paired Student's t test and (ii) patients with unilateral clubfoot (where either of the methods was used) or those with bilateral clubfoot (where both feet treated by either of the two methods on both the sides) were compared using difference between means (mean correction by Ponseti minus mean correction by Kite) for magnitude of difference and unpaired Student's t test (if data was normally distributed) or Mann Whitney U statistics (otherwise) for significance of difference.\n In 12 bilateral clubfeet, where one foot received Kite's method and the other Ponseti's manipulation, feet treated by Ponseti's technique showed faster rates of decrease in Pirani score (improvement) as compared to feet treated by Kite's method with the mean of difference between baseline and follow up scores showing significantly greater (P<0.05) difference from zero from fourth week onwards to up to 10 weeks. In unpaired analysis, both for unilateral or bilateral clubfeet, regardless of side, mean Pirani scores in Ponseti feet improved much faster than Kite feet but the difference achieved statistical significance only at the 10(th) week from the start of treatment.\n Hind foot, midfoot and total Pirani scores reduce much faster with Ponseti than the Kite's method of manipulation of clubfoot. In paired analysis the difference becomes statistically significant at fourth week and in unpaired analysis at 10(th) week from the start of treatment.", "Ponseti's and Kite's methods of conservative management in idiopathic congenital clubfoot were compared in a prospective randomised study consisting of 45 infants (67 feet) younger than 3 months, from March 2003 through February 2004. There were 36 and 31 feet that underwent treatment by Ponseti's and Kite's methods, respectively. After an average follow-up of 27.24 months in the Ponseti group, correction was achieved in 33 feet (91.7%), with only three patients requiring surgical management. There were seven relapses (21.1%), all of which were corrected conservatively. However, two of these required surgical intervention on showing a relapse again in the second year. In the Kite group, we achieved correction in 21 feet (67.7%) after an average follow-up of 24.8 months, with ten patients requiring surgical intervention. There were eight relapses of which only four could be corrected conservatively. We could also achieve correction in very severe feet (Dimeglio classification) in a significantly higher percentage using Ponseti's method, in significantly lesser time and with fewer casts. We are of the opinion that Ponseti's method is superior to Kite's method in achieving correction in idiopathic clubfeet in a relatively shorter period of time when used to treat young infants.", "To compare the surgical results of modified posteromedial release with modified complete subtalar release in resistant congenital clubfoot in a randomized controlled trial\n Eighty six children with 128 clubfeet, at an average of 5.9 months old (3-12 months) were operated on between 1996 and 2006 by a single surgeon. They were randomized into two groups. Group A, the modified posteromedial release was performed on 47 children with 69 clubfeet from 26 boys and 21 girls. Group B, the modified complete subtalar release was performed on 39 children with 59 clubfeet from 22 boys and 17 girls. Both groups received the same postoperative protocols. The mean follow up time was 15.1 months in group A (3-90 months) and 23.7 months in group B (3-120 months).\n There were no statistically significant differences of both groups between age, sex, side, bilaterality, and Dimeglio pre-operative evaluation. Most of the children ended up with satisfactory appearance of feet without major complications, neurovascular injuries, talonavicular dislocation, or avascular necrosis of the talus. Mild forefeet adduction was found in 10 feet in group A and in 5 feet in group B but allfeet were flexible and reducible to normal alignment of the feet. Two feet in group A and one foot in group B were re-operated by soft tissue release without bone surgery and had fair results. Four feet in group A and two feet in group B got soft tissue infection and resolved in a few weeks by dressing and antibiotics. The postoperative mean Ponseti score was 89.6 (75-100) points in group A and 88.2 (70-98) points in group B without statistically significant difference (p = 0.25). The Turco postoperative evaluation of both groups was not statistically significantly different (p = 0.17). The good and excellent results from Ponseti score was 85.5% in group A and 89.9% in group B. The correlation coefficient (r) between Ponseti and Turco evaluation was 0.81.\n The clinical and statistical significant difference were not found in the surgical results of modified posteromedial release and modified complete subtalar release in resistant clubfeet." ]

[ "8441139", "17276548", "7966077" ]

[ "Comparison of triamcinolone acetonide with indomethacin in the treatment of acute gouty arthritis.", "Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol combination therapy in the treatment of acute goutlike arthritis: a double-blind, randomized, controlled trial.", "Comparison of adrenocorticotropic hormone and triamcinolone acetonide in the treatment of acute gouty arthritis." ]

[ "Twenty-seven patients presenting within 5 days of the onset of crystalline proven acute gout were prospectively treated with either indomethacin 50 mg tid or triamcinolone acetonide 60 mg intramuscularly. Patients with contraindications to therapy with indomethacin received triamcinolone acetonide. They were followed for 30 days. Resolution of all symptoms occurred at an average of 8 days for the indomethacin patients and 7 days in the triamcinolone patients. No side effects or episodes of rebound gout attacks occurred with the triamcinolone acetonide therapy. It is as safe and effective as indomethacin in the treatment of acute gout, and is particularly useful in patients with contraindications to therapy with nonsteroidal antiinflammatory drugs.", "We compare the analgesic efficacy and adverse effects of oral prednisolone/acetaminophen and oral indomethacin/acetaminophen combination therapy in the treatment of acute goutlike arthritis in patients presenting to an emergency department (ED).\n This is a double-blind, randomized, controlled study in a university hospital emergency department (ED) in the New Territories of Hong Kong. Patients older than 17 years and presenting between February 1, 2003, and June 30, 2004, with a clinical diagnosis of goutlike arthritis were randomized to receive either oral prednisolone/acetaminophen or oral indomethacin/acetaminophen combination therapy. Primary outcome measures were pain scores, time to resolution of symptoms and signs, and adverse effects. Secondary outcome measures were the need for additional acetaminophen and relapse rate.\n There were 90 patients randomized: 46 patients to the indomethacin group and 44 patients to the prednisolone group. Baseline characteristics, including pain scores, were similar in the 2 groups. Both treatment groups had a similar decrease in pain score in the ED. The mean rate of decrease in pain score with activity for indomethacin was -1.7+/-1.6 (SD) mm per day and for prednisolone was -2.9+/-2.0 (SD) mm per day (mean difference 1.2 mm/day; 95% confidence interval 0.4 to 2.0 mm/day; P=.0026). Although these differences were statistically significant, at no time was the difference in mean pain score greater than 13 mm. Therefore, it is unclear whether these differences are clinically significant. The mean total dose of acetaminophen consumed by the prednisolone group was significantly more than in the indomethacin group (mean 10.3 g, range 1 to 21 g versus mean 6.4 g, range 1 to 21 g). Twenty-nine patients in the indomethacin group and 12 patients in the prednisolone group experienced adverse effects (P<.05). The commonest adverse effects in the indomethacin group were nausea, indigestion, epigastric pain, dizziness, and gastrointestinal bleeding (N=5; 11%). None of the patients in the prednisolone group developed gastrointestinal bleeding. The relapse rate for both groups was similar.\n In the treatment of acute goutlike arthritis, oral prednisolone/acetaminophen combination is as effective as oral indomethacin/acetaminophen combination in relieving pain but is associated with fewer adverse effects.", "To determine the best alternative therapy for acute gouty arthritis when nonsteroidal antiinflammatory drugs or colchicine are contraindicated.\n Thirty-one patients with crystal proven gout presenting with an acute attack of < 5 days' duration were treated prospectively with either a single intramuscular injection of adrenocorticotropic hormone (ACTH) 40 IU or triamcinolone acetonide 60 mg. The patients were followed for 30 days.\n Resolution of all symptoms occurred at an average of 8 days for both groups. No adverse reactions were noted in either group; however, there were 11 reinjections in the ACTH group and 5 reinjections in the triamcinolone acetonide group. Two patients from the ACTH arm were transferred to the triamcinolone acetonide arm because of rebound arthritis.\n Although recent studies of ACTH and triamcinolone acetonide have demonstrated efficacy and safety comparable to indomethacin, in a direct comparison of the 2 at the doses used, triamcinolone acetonide resulted in fewer rebound attacks and treatment failures than ACTH and required fewer reinjections." ]

[ "4947381" ]

[ "An evaluation of azathioprine in severe chronic asthma." ]

[ "nan" ]

[ "8641230", "10612342", "12225311", "10999555", "10227615", "8764816", "8649570", "8956919", "8649569" ]

[ "Double-blind, placebo-controlled trial of topiramate as add-on therapy in patients with refractory partial seizures.", "Topiramate in medically intractable partial epilepsies: double-blind placebo-controlled randomized parallel group trial. Korean Topiramate Study Group.", "Low-dose topiramate in adults with treatment-resistant partial-onset seizures.", "A double-blind, placebo-controlled study of topiramate in adult patients with refractory partial epilepsy.", "A double-blind, randomized trial of topiramate as adjunctive therapy for partial-onset seizures in children. Topiramate YP Study Group.", "Double-blind, placebo-controlled trial of topiramate (600 mg daily) for the treatment of refractory partial epilepsy.", "Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 200-, 400-, and 600-mg daily dosages. Topiramate YD Study Group.", "Double-blind, placebo-controlled study of topiramate in patients with refractory partial epilepsy.", "Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 600-, 800-, and 1,000-mg daily dosages. Topiramate YE Study Group." ]

[ "In a double-blind, randomized, parallel-group trial, we compared topiramate (TPM) with placebo as add-on therapy in patients with refractory partial epilepsy. TPM was titrated either to the target dosage of 800 mg/ day [400 mg twice daily (b.i.d)] or to the maximal tolerated dose if lower. Twenty-eight (28) patients were randomized to each treatment group. In the intent-to-treat analysis, the net median percent reduction relative to placebo in average monthly seizure rate was 54% for patients in the TPM group (p < 0.001). None of the placebo-treated patients and 43% of the patients treated with TPM experienced > or = 50% reduction in seizures (p = 0.001), and 36% of patients assigned to TPM had a 75-100% reduction in seizures (p < 0.01). Secondarily generalized seizures were also significantly reduced in the TPM group (p = 0.044). The most common adverse events (AE) reported in the TPM group were fatigue, impaired concentration, weight loss, dizziness, and paresthesias. AE occurring either during the rapid titration of TPM or at high dosages led 21% of TPM-treated patients to withdraw from the study. Half of these occurred during the titration study period. No serious AE or clinically important changes in clinical laboratory measures were observed. The present study further establishes the favorable profile and good benefit/risk ratio of TPM in resistant partial epilepsy.", "To evaluate the efficacy and safety of topiramate (TPM) as add-on therapy in medically intractable partial epilepsies.\n We used a multicenter double-blind placebo-controlled randomized parallel-group trial consisting of 12 weeks of baseline phase, 10 weeks of titration phase, and 8 weeks of stabilization phase. The primary efficacy variable was the median seizure frequency reduction rate (MSFRR), and the other efficacy variables included responder rate, seizure-free rate, and global evaluations by the patient and the physician. The patient should have partial epilepsies refractory to the maximally tolerable doses of one to two antiepileptic drugs (AEDs) and should have two or more episodes of clinical seizures every 4 weeks during the baseline phase. The target dose of study drugs was 600 mg/day. The study drugs were started at the initial dose of 50 mg/day and gradually increased to the target dose over a 10-week period.\n A total of 177 patients was randomized into the TPM group (n = 91) and the placebo (PLC) group (n = 86). Baseline median seizure frequencies were 5.6 episodes/4 weeks in the TPM and the PLC groups. Among those who were randomized, 174 patients (TPM, 89 patients; PLC, 85 patients) were available for the efficacy measurement by intention-to-treat analysis. The MSFRR was 51.3% for TPM and 9.1% for PLC, which was highly in favor of TPM (p = 0.0001). The responder rate was 50.6% for TPM and 12.9% for PLC (p = 0.001). Seven (7.9%) of 89 patients taking TPM became seizure free compared with one (1.2%) of 85 patients taking PLC (p = 0.004). The global evaluation greatly favored TPM (p = 0.001). The incidence of adverse events (AEs) was higher in the TPM (81.3%) than in the PLC (48.9%) group, with central nervous system (CNS)-related AEs being the most frequent. Among individual AEs, anorexia (20.9%) and abdominal pain or discomfort (20.9%) were the most common AEs in the TPM group. AEs precipitated early drop-out in seven (7.6%) patients taking TPM and three (3.5%) patients taking PLC. No serious systemic AEs were observed.\n TPM was highly effective and safe as add-on therapy in medically intractable partial epilepsies. Slower titration of TPM might be responsible for the lesser drop-out rate than previous trials, but the incidence of AEs was still high. The AE profile of TPM in Koreans was different from that in whites.", "Based on dose predictions from animal and human volunteer studies, most patients enrolled in initial randomized controlled trials of topiramate as adjunctive therapy in adults with partial-onset seizures were randomized to >or= 600 mg/day topiramate. Subsequent experience suggests that dosage needs were overestimated. This double-blind, placebo-controlled study evaluated 200 mg/day topiramate in adults with treatment-resistant partial-onset seizures receiving a concurrent enzyme-inducing antiepileptic agent (carbamazepine).\n After a 4-week baseline, 263 adults receiving carbamazepine who had at least three partial-onset seizures during the baseline period were randomized to placebo or one of two topiramate 200 mg/day treatment arms: topiramate escalated weekly 25 mg/day(8-week escalation) or 50 mg/day(4-week escalation). Therapy was then maintained for the remainder of the 12-week double-blind study.\n Median percent reduction in seizure frequency from baseline to study end was 44% with topiramate and 20% with placebo (P <or= 0.001). A significant therapeutic effect was present at 2 weeks with a dose of 100 mg/day. The most common adverse events (>or=10% incidence in topiramate-treated patients) were somnolence, fatigue, paresthesia, nervousness and anorexia; 8% of topiramate-treated patients and 2% of placebo-treated patients discontinued because of adverse events. As a result of the low incidence of adverse events, differences between titration rates in terms of tolerability were not detected.\n Topiramate 200 mg/day is an appropriate target dose as adjunctive therapy in adults with treatment-resistant partial-onset seizures, even when receiving an enzyme-inducing agent; 100 mg/day also appears to be effective. A significant therapeutic effect may be seen in the second week of treatment with a dose of 100 mg/day.", "The efficacy and safety of topiramate (TPM) as adjunctive therapy in the treatment of adult Chinese patients with refractory partial epilepsy were investigated in a randomized, double-blind, placebo-controlled study.\n A total of 46 patients who had four or more complex partial seizures with or without secondary generalization within an 8-week baseline phase were enrolled. Patients were assigned randomly to receive TPM (n = 23) or placebo (n = 23). TPM or placebo was titrated to target doses of 300 mg/d for 6 weeks and maintained at stabilized levels for another 8 weeks. Concomitant antiepileptic drugs remained at constant previous levels during the trial.\n In all, 41 patients completed the trial (TPM group, n = 20; placebo group, n = 21). The proportion of patients with a > or =50% reduction from baseline in complex partial seizures was 11 of 23 (47.8%) in the TPM group and 3 of 23 (13.0%) in the placebo group (p = 0.01). In addition, patients treated with TPM had significantly better investigator (p = 0.014) and patient (p = 0.0005) global assessment scores than patients in the placebo group. Adverse events were mostly mild and transient, with no significant differences between treatment groups. Two patients with TPM therapy complained of weight loss. Routine blood cell counts and other laboratory results showed no significant changes from baseline in either treatment group.\n TPM 300 mg/d is effective and well tolerated as treatment for refractory partial epilepsy in adults.", "To evaluate the efficacy and safety of topiramate 6 mg/kg/day in children (age 2 to 16 years) as adjunctive therapy for uncontrolled partial-onset seizures with or without secondarily generalized seizures in a multicenter, randomized, double-blind, placebo-controlled trial.\n Patients with at least six partial-onset seizures during the 8-week baseline phase were treated with either topiramate (n = 41) or placebo (n = 45) for 16 weeks.\n Topiramate-treated patients had a greater median percent reduction from baseline in average monthly partial-onset seizure rate than placebo-treated patients (33.1% versus 10.5%, p = 0.034), a greater proportion of treatment responders (i.e., patients with a > or = 50% seizure rate reduction; 16 of 41 [39%] versus 9 of 45 [20%], p = 0.080), and patients with a > or = 75% seizure rate reduction (7 of 41 [17%] versus 1 of 45 [2%], p = 0.019), and better parental global evaluations of improvement in seizure severity (p = 0.019). Emotional lability (12% versus 4%), fatigue (15% versus 7%), difficulty with concentration or attention (12% versus 2%), and forgetfulness/impaired memory (7% versus 0%) were more frequent among topiramate-treated than placebo-treated patients. Most treatment-emergent adverse events were mild or moderate in severity. No topiramate-treated patients discontinued the study due to adverse events.\n Topiramate was safe and effective in the treatment of partial-onset seizures in children.", "We wished to evaluate adjunctive therapy for partial-onset seizures with topiramate (TPM) for efficacy and safety in a double-blind, placebo-controlled, randomized, parallel-group study.\n Sixty outpatients with epilepsy (47 men and 13 women, mean age 32.9 years) were studied. All had a documented history of partial-onset seizures with or without secondarily generalized seizures. After an 8-week baseline during which patients had at least one seizure per week, 30 patients each were randomized to TPM 300 mg twice daily (b.i.d.) or placebo for 12 weeks.\n TPM was significantly superior to placebo, as indicated by all efficacy assessments: greater median percent reduction from baseline in the average monthly seizure rate (46 vs. -12%, p = 0.004); greater number of treatment responders (patients with > or = 50% reduction in seizure rate) (47 vs. 10%, p = 0.001), and better investigator (p = 0.002) and patient (p = 0.010) global assessments of treatment. Among TPM-treated patients, the most commonly reported adverse events (AE) were headache, somnolence, fatigue, dizziness, and abnormal thinking. Most AE were mild or moderate in severity.\n The results of the present trial indicate that TPM 600 mg/day is effective in the treatment of refractory partial-onset seizures with or without secondarily generalized seizures.", "We conducted a randomized double-blind comparison of three doses of the novel antiepileptic drug (AED) topiramate (200, 400, and 600 mg/day) and placebo as adjunctive therapy in patients with refractory partial onset epilepsy receiving one or two other AEDs at therapeutic concentrations. A total of 181 patients completed the 12-week baseline phase and were randomized to double-blind therapy. Median percent reductions from baseline in average monthly seizure rate, the principal efficacy evaluation, were 13% for placebo, 30% for topiramate 200 mg/day, 48% for topiramate 400 mg/day, and 45% for topiramate 600 mg/day. For the seizure rate comparison of active drug to placebo p values were: topiramate 200 mg/day, p = 0.051; topiramate 400 mg/day, p = 0.007; topiramate 600 mg/day, p < 0.001. Percent responders ( > or = 50% reduction in seizure rates) were 18% for placebo, 27% for topiramate 200 mg/day, 47% for topiramate 400 mg/day (p = 0.013), and 46% for topiramate 600 mg/day (p = 0.027). A significant (p = 0.003) reduction in secondarily generalized seizures compared with placebo treatment was also documented with topiramate. Topiramate plasma concentrations were closely related to dosage, and there were no significant interactions between topiramate and other AEDs. The minimal effective dose of topiramate in this study population was approximately 200 mg/day. Mild or moderate CNS symptoms were the primary treatment-emergent adverse events, but treatment-limiting adverse events occurred in only 9% of patients given topiramate compared with 7% given placebo. Results of this initial well-controlled study in patients indicate that topiramate is a very promising new AED.", "The efficacy and safety of topiramate 400 mg/day as adjunctive therapy to traditional antieleptic drugs for partial onset seizures with or without secondary generalization were assessed in a double-blind, parallel-group, placebo-controlled trial. Forty-seven patients with at least one seizure per week during an 8 week baseline were randomly assigned to topiramate (N = 23) or placebo (N = 24) double-blind treatment for a 3 week titration and an 8 week stabilization period. Median percent reduction from baseline in monthly seizure frequency during the double-blind phase was not significantly greater in the topiramate group than in the placebo group (41% vs. 1%; P = 0.065). Nevertheless, other efficacy variables evidenced statistically significant differences in favor of topiramate: a greater number of treatment responders (> or = 50% reduction in seizures; 35% vs. 8%; P = 0.033); better investigator (P = 0.002) and patient (P = 0.021) global assessments; and greater reductions in secondarily generalized seizures compared to placebo (P = 0.002). The most commonly reported topiramate treatment-emergent adverse events were somnolence, fatigue, abnormal vision, weight decrease, and anxiety. Most adverse events were mild or moderate in severity. Among 7 withdrawals due to limiting adverse events, 6 were CNS-related (in 5 topiramate-treated patients). Results of this trial strongly suggest that topiramate 400 mg/day is effective and well tolerated in the treatment of refractory partial epilepsy.", "We conducted a multicenter, double-blind, randomized, parallel, placebo-controlled trial in 190 patients to evaluate the safety and efficacy of three dosages of topiramate (600, 800, and 1,000 mg/day) as adjunctive therapy for patients with refractory partial epilepsy. During an 18-week double-blind treatment period, median percent reductions from baseline in average monthly seizure rates were 1% for placebo, 41% for topiramate 600 mg/day and topiramate 800 mg/day, and 38% for topiramate 1,000 mg/day. There was a 50% or greater reduction from baseline in seizure frequency in 9% of patients in the placebo group and in 44% for topiramate 600 mg/day, 40% for topiramate 800 mg/day, and 38% for topiramate 1,000 mg/day. No placebo patients were improved by 75 to 100% in seizure frequency, whereas 20% of the topiramate patients were improved to this degree. All intent-to-treat drug-placebo comparisons including seizure reduction, percent responders, and investigator and patient global evaluations significantly (p < or = 0.02) favored topiramate. Treatment-emergent adverse events consisted mainly of neurologic symptoms commonly observed during antiepileptic drug (AED) therapy. Sixteen percent of patients on topiramate discontinued therapy due to adverse events. Results of this study indicate that topiramate is a highly efficacious and generally well tolerated new AED. When large groups of patients are compared, incremental efficacy in the add-on setting is not observed at topiramate dosages above 600 mg/day; however, higher doses may prove beneficial to individual patients who tolerate them." ]

[ "9647148", "9241305", "12080483", "11476777", "11214131", "16487195", "16045528", "3685399", "12694974", "9552948" ]

[ "Randomised comparative trial of the levonorgestrel intrauterine system and norethisterone for treatment of idiopathic menorrhagia.", "Levonorgestrel-releasing intrauterine device versus hysteroscopic endometrial resection in the treatment of dysfunctional uterine bleeding.", "A randomized controlled trial of levonorgestrel releasing IUD and thermal balloon ablation in the treatment of menorrhagia.", "Treatment of menorrhagia with the levonorgestrel intrauterine system versus endometrial resection.", "Quality of life and cost-effectiveness of levonorgestrel-releasing intrauterine system versus hysterectomy for treatment of menorrhagia: a randomised trial.", "A randomised trial comparing the levonorgestrel intrauterine system and thermal balloon ablation for heavy menstrual bleeding.", "Randomised comparative trial of the levonorgestrel intrauterine system and mefenamic acid for the treatment of idiopathic menorrhagia: a multiple analysis using total menstrual fluid loss, menstrual blood loss and pictorial blood loss assessment charts.", "The effects of danazol, mefenamic acid, norethisterone and a progesterone-impregnated coil on endometrial prostaglandin concentrations in women with menorrhagia.", "Comparison between the levonorgestrel intrauterine system (LNG-IUS) and thermal balloon ablation in the treatment of menorrhagia.", "Open randomised study of use of levonorgestrel releasing intrauterine system as alternative to hysterectomy." ]

[ "To compare the efficacy and acceptability of the levonorgestrel intrauterine system and norethisterone for the treatment of idiopathic menorrhagia.\n A randomised comparative parallel group study.\n Gynaecology outpatient clinic in a teaching hospital.\n Forty-four women with heavy regular periods and a measured menstrual blood loss exceeding 80 ml.\n Twenty-two women had a levonorgestrel intrauterine system inserted within the first seven days of menses, and 22 women received norethisterone (5 mg three times daily) from day 5 to day 26 of the cycle for three cycles.\n The main outcome measure was the change in objectively assessed menstrual blood loss after three months of treatment.\n When menstrual blood loss at three months was expressed as a percentage of the control, the levonorgestrel intrauterine system reduced menstrual blood loss by 94% (median reduction 103 ml; range 70 to 733 ml), and oral norethisterone by 87% (median reduction 95 ml; range 56 to 212 ml). After three cycles of treatment 76% of the women in the levonorgestrel intrauterine system group wished to continue with the treatment, compared with only 22% of the norethisterone group.\n Both the levonorgestrel intrauterine system and oral norethisterone in this regimen provided an effective treatment for menorrhagia in terms of reducing menstrual blood loss to within normal limits. The levonorgestrel intrauterine system was associated with higher rates of satisfaction and continuation with treatment, and thus offers an effective alternative to currently available medical and surgical treatments for menorrhagia.", "To compare the effect of a levonorgestrel-releasing intrauterine device with that of endometrial resection on menstrual bleeding, patient satisfaction, and quality of life in menorrhagic women during 12 months of follow-up.\n Seventy premenopausal women with dysfunctional uterine bleeding were enrolled in a prospective, open, parallel-group, controlled trial. They were randomized to either insertion of an intrauterine system releasing 20 micrograms/day of levonorgestrel (n = 35) or endometrial resection (n = 35). The women were evaluated at baseline, and thereafter, uterine bleeding was assessed monthly with a pictorial blood loss assessment chart. Clinical gynecologic examination was performed bimonthly, and the hematologic variables were measured at 6 and 12 months. On the latter occasion, the women were requested to rate the degree of satisfaction with the effect of their treatment and to complete the Short Form 36 General Health Survey questionnaire.\n Recurrent menorrhagia was observed at 12 months in four women in the intrauterine device group (including two with partial expulsion of the device) and in three women in the resection group. Compared with baseline values, at 1 year, the pictorial blood loss assessment chart score was reduced by 79% in the former group and by 89% in the latter. Amenorrhea or hypomenorrhea at 12 months was reported by 65% of the women with an intrauterine device compared with 71% who underwent endometrial resection. The degree of satisfaction with treatment was high in both groups, with 29 of 34 (85%) women being satisfied or very satisfied in the intrauterine device group versus 33 of 35 (94%) in the resection group. Health-related quality of life perception was not significantly different in the two treatment groups.\n Somewhat less satisfactory results were obtained with a levonorgestrel-releasing intrauterine system compared with endometrial resection for dysfunctional uterine bleeding at 1 year of follow-up.", "Our aim was to compare the treatment of menorrhagia either with a levonorgestrel-releasing intrauterine device or with endometrial thermal balloon ablation. The primary endpoints of evaluation were menstrual blood flow reduction and the increase in hemoglobin values, while the secondary end points were adverse side effects; health related quality of life. After randomization, 36 women underwent outpatient thermal balloon ablation under local anesthesia and an intrauterine device releasing 20 microgram/day of levonorgestrel, were inserted within the first 7 days of menses to 36 women. Both techniques were found to be significantly effective in reducing the menstrual blood loss but in comparison thermal balloon ablation was more effective in Deltamean +/- SD decrease of pictorial sores (388.2 +/- 21 vs 343 +/- 27; p < 0.001). We noted a significant but similar increases in Deltamean +/- SD hemoglobin values (3.9 +/- 1.7 vs 3.7 +/- 1.4; p:.21). Patients treated by thermal balloon ablation reported fewer side effects and perceived a higher health related quality of life in physical role functioning. At one year of follow-up, the medicated device was effective but not as effective as thermal balloon ablation in reducing the menstrual blood loss. However it was found to be as effective as thermal balloon ablation in increasing the hemoglobin values. The side effect profile of the medicated device may alter its acceptability by reducing the perceived health related quality of life in menorrhagic women with no desire for further childbearing.", "Treatment of menorrhagia with levonorgestrel intrauterine system (LNG IUS) and transcervical resection.\n An open, therapeutic, randomized study.\n Central county hospital specializing in hysteroscopy.\n Two parallel groups of 30 subjects each.\n Thirty patients had a LNG IUS inserted within the first 7 days of menses; 29 patients underwent endometrial resection.\n A 12-month follow-up of menstrual blood loss and adverse events were evaluated.\n LNG IUS group: 13 patients reported one or more pelvic adverse events, bleeding disorders (n = 6), abdominal pain (n = 4), breast tenderness (n = 3), headache, acne (n = 2), and mood changes (n = 1). Six patients discontinued treatment because of irregular bleeding (n = 3), pain (n = 2), and acne (n = 1). In both groups, general feeling of genital health increased with Visual Analogue Scale score. Nine patients reported adverse events. This included pelvic pain indicating inflammation (n = 4), bleeding (n = 3), vaginitis (n = 1), and ulceration (n = 1). Treatment success at 12 months was achieved in 20 (67%) of the 30 patients in the LNG IUS group and in 26 (90%) of the 29 patients in the transcervical resection group. Adverse events were more often reported in the LNG IUS group.\n Both treatments effectively reduced the menstrual blood loss. Furthermore, the LNG IUS treatment is reversible and has no operative hazards.", "Heavy menstrual blood loss is a common reason for women to seek medical care. The levonorgestrel-releasing intrauterine system (IUS) is an effective medical treatment for menorrhagia. We report a randomised comparison of this approach with hysterectomy in terms of the quality of life of women with menorrhagia and cost-effectiveness.\n Of 598 women referred with menorrhagia to five university hospitals in Finland, 236 were eligible and agreed to take part. They were randomly assigned treatment with the levonorgestrel-releasing IUS (n=119) or hysterectomy (n=117). The amount of menstrual blood loss was objectively measured. The primary outcome measure was health-related quality of life at 12-month follow-up. Analyses were by intention to treat.\n In the group assigned the levonorgestrel-releasing IUS, 24 (20%) women had had hysterectomy and 81 (68%) continued to use the system at 12 months. Of the women assigned to the hysterectomy group, 107 underwent the operation. Health-related quality of life improved significantly in both the IUS and hysterectomy groups (change 0.10 [95% CI 0.06-0.14] in both groups) as did other indices of psychological wellbeing. There were no significant differences between the treatment groups except that women with hysterectomy suffered less pain. Overall costs were about three times higher for the hysterectomy group than for the IUS group.\n The significant improvement in health-related quality of life highlights the importance of treating menorrhagia. During the first year the levonorgestrel-releasing IUS was a cost-effective alternative to hysterectomy in treatment of this disorder.", "To compare the levonorgestrel intrauterine system (LNG-IUS) (Mirena); Schering Co., Turku, Finland) and thermal balloon ablation (Thermachoice; Gynecare Inc., Menlo Park, CA, USA) for the treatment of heavy menstrual bleeding.\n An open, pragmatic, prospective randomised trial.\n A menstrual disorders clinic at National Women's Hospital, Auckland, New Zealand.\n Seventy-nine women with heavy menstrual bleeding randomised to the LNG-IUS (40 women) or the thermal balloon ablation (39 women).\n Women were randomised to treatment with the LNG-IUS or thermal balloon ablation and followed up by a postal and telephone questionnaire.\n Menstrual loss measured by a pictorial bleeding assessment chart (PBAC) at 3, 6, 12 and 24 months. Patient satisfaction, quality of life and menstrual symptoms were assessed by questionnaire administered at 3, 6, 12 and 24 months. Treatment side effects and treatment failures were also recorded.\n Both the treatments resulted in a significant reduction in PBAC scores. At 12 and 24 months, median PBAC scores were significantly lower in women treated with the LNG-IUS compared with women treated by thermal balloon ablation (11.5 versus 60.0 at 12 months [P= 0.002]; 12.0 versus 56.5 [P= 0.002] at 24 months). At 24 months, nine (35%) women still using the LNG-IUS had amenorrhoea compared with one (5%) woman successfully treated by thermal balloon ablation (P = 0.025). There were no significant differences in patient satisfaction between two treatments during follow up. Treatment failed in 11 (28%) women using the LNG-IUS and in 10 (26%) women treated with thermal balloon ablation. Overall, women in both groups showed an increased quality of life as a result of the treatment, with Short Form-36 scores increasing from 63.7 at randomisation to 76.1 at 24 months.\n At 12 and 24 months of follow up, women with heavy menstrual bleeding treated with the LNG-IUS have significantly lower PBAC scores than women treated with thermal balloon ablation. Both the treatments resulted in a significant increase in overall quality of life, but there were no significant differences between either treatment in quality of life, patient satisfaction or the number of women requesting an alternative treatment during 24 months of follow up.", "To compare the efficacy and tolerability of the levonorgestrel intrauterine system (LNG IUS) with mefenamic acid in the management of objective idiopathic menorrhagia.\n Phase III, Single centre, open, randomised, comparative, parallel group study.\n District General Hospital in the United Kingdom.\n Fifty-one women with objective menorrhagia.\n Twenty-five women randomised to receive the LNG IUS and 26 to oral mefenamic acid for six cycles.\n Change from baseline in menstrual blood loss (MBL), total menstrual fluid loss (TMFL) and pictorial blood loss assessment chart (PBAC) score at the third and sixth cycle of treatment.\n After six cycles the median menstrual blood loss was 5 mL in the LNG IUS group and 100 mL in the mefenamic acid group (P < 0.001). Median TMFL was 27 mL in the LNG IUS group and 157 mL in the mefenamic acid group (P < 0.001). Median PBAC score was 25 in the LNG IUS group and 159 in the mefenamic acid group. Changes in menstrual blood loss correlated strongly to changes in TMFL (r= 0.88) but PBAC correlated less well to blood loss and total fluid loss (r= 0.53 and r= 0.58).\n Both the LNG IUS and mefenamic acid significantly decreased menstrual blood loss, TMFL and PBAC scores. The LNG IUS produced greater reductions in all parameters than mefenamic acid. Comparison of the different measurements suggests that TMFL assessment may be an easier and a more relevant measure of symptom severity than menstrual blood loss.", "The effects of four medical treatments have been assessed on menstrual blood loss (MBL) and endometrial prostaglandin (PG) concentrations in 30 women with objectively confirmed menorrhagia. Patients were randomly treated with danazol, 200 mg daily (n = 6), mefenamic acid, 500 mg three times daily during menses (n = 8), norethisterone, 5 mg twice daily from day 15-25 of the cycle (n = 8) or a progesterone-impregnated coil releasing 65 micrograms progesterone daily (n = 8). Endometrial biopsies were obtained in the mid-luteal phase before and after treatment in 23 cases, and assayed for PG content using radioimmunoassay. Treatment with norethisterone had no effect on either MBL or the concentration of PGs in the endometrium. MBL was significantly reduced after treatment with mefenamic acid (P = 0.05, n = 6) and the progesterone coil (P less than 0.05, n = 6), and was reduced in each of 4 cases treated with danazol in whom endometrial biopsies were available. Although there was no consistent change in endometrial PG concentrations in either the mefenamic acid or danazol groups, the lower MBL after insertion of the progesterone coil was associated with a reduced endometrial content of PGE, PGF2 alpha and \"total\" PG (6oxo PGF1 alpha + PGE + PGF2 alpha)-P = 0.05. Whereas the cyclooxygenase inhibitor mefenamic acid is likely to exert its effect on endometrial PGs at the time of menstruation itself, the continuous administration of progesterone throughout the menstrual cycle could result in both an impairment in estrogen receptor generation leading to reduced estrogen-mediated cyclooxygenase activity, and an increase in endometrial PG metabolism.", "To compare the effectiveness of endometrial thermal ablation and the levonorgestrel intrauterine system (LNG-IUS) in the management of menorrhagia.\n Fifty women attending a gynaecology clinic at a District General Hospital in south-west England were randomised to either surgical treatment using thermal ablation (Thermochoice, Gynecare) or medical treatment using a LNG-IUS (Mirena, Schering Healthcare). A pictorial menstrual chart was completed pre-insertion/operatively and again at 6 months post-insertion/operatively. Non-parametric tests (Mann-Whitney) were used for statistical analysis.\n Follow-up analysis was possible in 23 women in the Thermochoice group and 21 women in the Mirena group. The menstrual scores were slightly higher in the Thermochoice group (median 101) than the Mirena group (median 75) (P=0.025) pre-insertion/operatively but this difference was lost post-insertion/operatively (P=0.689) with median menstrual scores of 27 for the Thermochoice group and 19 for the Mirena group, respectively.\n Both Thermochoice endometrial ablation and a Mirena LNG-IUS are equally effective in the management of menorrhagia. The choice of treatment should be tailored to the woman's needs and preferences.", "To assess whether the levonorgestrel intrauterine system could provide a conservative alternative to hysterectomy in the treatment of excessive uterine bleeding.\n Open randomised multicentre study with two parallel groups: a levonorgestrel intrauterine system group and a control group.\n Gynaecology departments of three hospitals in Finland.\n Fifty six women aged 33-49 years scheduled to undergo hysterectomy for treatment of excessive uterine bleeding.\n Women were randomised either to continue with their current medical treatment or to have a levonorgestrel intrauterine system inserted.\n Proportion of women cancelling their decision to undergo hysterectomy.\n At 6 months, 64.3% (95% confidence interval 44.1 to 81.4%) of the women in the levonorgestrel intrauterine system group and 14.3% (4.0 to 32.7%) in the control group had cancelled their decision to undergo hysterectomy (P < 0.001).\n The use of the levonorgestrel intrauterine system is a good conservative alternative to hysterectomy in the treatment of menorrhagia and should be considered before hysterectomy or other invasive treatments." ]

[ "2666120", "16140593", "18401024", "10371538", "1957968", "11407953", "10210023", "9400037", "1920391", "8347179", "9596201" ]

[ "Double-blind, placebo-controlled evaluation of cinromide in patients with the Lennox-Gastaut Syndrome. The Group for the Evaluation of Cinromide in the Lennox-Gastaut Syndrome.", "A randomized, double-blind, placebo-controlled trial of topiramate in adults with epilepsy and intellectual disability: impact on seizures, severity, and quality of life.", "Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome.", "A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Topiramate YL Study Group.", "Double-blind placebo-controlled trial of flunarizine as add-on therapy in refractory childhood epilepsy.", "A randomized open-label study of gabapentin and lamotrigine in adults with learning disability and resistant epilepsy.", "The efficacy of felbamate as add-on therapy to valproic acid in the Lennox-Gastaut syndrome.", "Lamotrigine for generalized seizures associated with the Lennox-Gastaut syndrome. Lamictal Lennox-Gastaut Study Group.", "Treatment of epilepsy in mentally retarded patients with a slow-release carbamazepine preparation.", "Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut syndrome). The Felbamate Study Group in Lennox-Gastaut Syndrome.", "The efficacy of lamotrigine in children and adolescents with refractory generalized epilepsy: a randomized, double-blind, crossover study." ]

[ "This study evaluated the effects of cinromide in patients with Lennox-Gastaut Syndrome. No difference between cinromide and placebo was shown in terms of seizure reduction or global evaluations. This study is important, however, because it represents an effort to overcome methodologic difficulties inherent in evaluating this population, and because a substantial placebo response was demonstrated. The need for well-designed, placebo-controlled clinical studies of potential antiepileptic drugs, even in an especially refractory and mentally impaired population, is underscored by the study's outcome.", "This randomized, double-blind, placebo-controlled UK trial evaluated the effect of topiramate as add-on therapy on seizure frequency, seizure severity, and quality of life in patients with epilepsy and intellectual disability. There were three phases: 4 weeks baseline, 18 weeks titration to 200-400 mg topiramate/day (adults) or 5-9 mg/kg/day (children), 12 weeks maintenance. Recruitment was low (88/120); analyses were underpowered. Seizure frequency varied enormously (median 17.7, maximum 1706.2). There was no significant difference in reduction in mean total seizure frequency or number of responders between the groups. Topiramate reduced seizure frequency by >30% from baseline (placebo 1%); post hoc analyses showed a trend toward significance (R ratio, P=0.052). There were no significant differences between the groups with respect to mean seizure severity or other outcome measures. Topiramate was generally well tolerated; body weight (P=0.015) and systolic blood pressure (P=0.043) were reduced. The study suggests that topiramate reduces seizure frequency in patients with epilepsy and intellectual disability without the added burden of behavior effects, and was potentially advantageous to physical well-being.", "Lennox-Gastaut syndrome is a catastrophic pediatric epilepsy syndrome characterized by multiple types of treatment-resistant seizures and high rates of seizure-related injury. Current available treatments are inadequate, leaving patients with few treatment options and opportunities.\n We conducted a double-blind, randomized, placebo-controlled trial of the antiepileptic drug rufinamide in patients with Lennox-Gastaut syndrome. Eligible patients between 4 and 30 years of age had multiple types of seizures (including tonic-atonic and atypical absence seizures) with a minimum of 90 seizures in the month before baseline and a recent history of a slow spike-and-wave pattern on EEG.\n After a 28-day baseline period, 139 eligible patients were randomized; 138 patients received either rufinamide (n = 74) or placebo (n = 64) in addition to their other antiepileptic drugs. The median percentage reduction in total seizure frequency was greater in the rufinamide therapy group than in the placebo group (32.7% vs 11.7%, p = 0.0015). There was a difference (p < 0.0001) in tonic-atonic (\"drop attack\") seizure frequency with rufinamide (42.5% median percentage reduction) vs placebo (1.4% increase). The rufinamide group had a greater improvement in seizure severity (p = 0.0041) and a higher 50% responder rate compared with placebo for total seizures (p = 0.0045) and tonic-atonic seizures (p = 0.002). The common adverse events (reported by >or=10% of patients receiving rufinamide) were somnolence (24.3% with rufinamide vs 12.5% with placebo) and vomiting (21.6% vs 6.3%).\n Rufinamide was an effective and well-tolerated treatment for seizures associated with Lennox-Gastaut syndrome.", "To evaluate the efficacy and safety of topiramate as adjunctive therapy for Lennox-Gastaut syndrome in a multicenter, double-blind, placebo-controlled trial.\n Conventional antiepileptic drugs are frequently ineffective against multiple-seizure types of Lennox-Gastaut syndrome.\n Ninety-eight patients >1 year to <30 years of age, with slow spike-and-wave patterns on EEG, seizure types including drop attacks, and either a history of or active atypical absence seizures, were assigned to an 11-week, double-blind treatment phase with either topiramate or placebo. Topiramate was titrated to target doses of approximately 6 mg/kg/d.\n For drop attacks, the most severe seizures associated with this syndrome, the median percentage reduction from baseline in average monthly seizure rate was 14.8% for the topiramate group and -5.1% (an increase) for the placebo group (p = 0.041). Topiramate-treated patients demonstrated greater improvement in seizure severity than did placebo-treated patients based on parental global evaluations (p = 0.037). The percentage of patients with a > or = 50% reduction from baseline in major seizures (drop attacks and tonic-clonic seizures) was greater in the topiramate group (15/46 or 33%) than in the control group (4/50 or 8%; p = 0.002). The most common adverse events in both groups were CNS related; there were no discontinuations from topiramate therapy due to adverse events.\n Topiramate adjunctive therapy was effective in reducing the number of drop attacks and major motor seizures and in improving seizure severity as determined by parental global evaluation.", "Flunarizine (FLN) has been suggested as an add-on treatment in drug-resistant epilepsy patients. In view of the discordant experiences and of the paucity of controlled trials in children, we studied its effectiveness in 20 patients aged 6 to 18 years (10 males and 10 females), affected by drug-resistant epilepsy. 14 had symptomatic generalized epilepsy (the Lennox-Gastaut syndrome in 10; other forms in 4); 3 had cryptogenic generalized epilepsy (the Lennox-Gastaut syndrome in 2; myoclonic absences epilepsy in 1); 3 had symptomatic partial epilepsy (temporal lobe epilepsy). 7 of them were withdrawn: only 1 because of side effects. An initial four-month baseline pretrial period was followed by two four-month periods of administration of FLN or a placebo, under double blind conditions, in a randomized sequence. Preexisting antiepileptic (AEDs) medication was maintained at a constant dose throughout the study. FLN was administered as drops in a single evening dose of 5 mg (patients less than 10 years) or 10 mg. (patients greater than 10 years). During the pretrial phase, after phase 1 and phase 2, a waking EEG was recorded and blood samples were taken for hematology, hepatic-function tests, and AED serum levels. The evaluation of the activity of FLN was based on the total number of seizures. A 30-60% reduction in seizure frequency was found in 5 out of the 13 patients completing the trial (no changes occurred in the remainders). This result did not appear to be due to changes in the plasma levels of the AEDs. No significant differences were seen in the EEG paroxysmal activity in the three phases of the study. Side effects were rare. The serum FLN levels ranged between 16.4 and 109 ng/ml. It seems that the antiepileptic properties of FLN need further validation, particularly in childhood.", "The aim of this study was to evaluate the efficacy and safety of gabapentin in patients with learning disabilities and resistant epilepsy, comparing the effects of gabapentin with lamotrigine on efficacy, behaviour and mood. An open-label, randomized, parallel group, multicentre add-on study comparing gabapentin with lamotrigine in 109 patients with drug-resistant localization-related epilepsy and learning disabilities was conducted: 39 patients were randomized to gabapentin and 44 to lamotrigine. The study population had a range of learning disabilities and severe partial epilepsy. The percentage of patients achieving a greater than or equal to 50% reduction in seizure frequency on gabapentin was 50%, (mean reduction in seizures was 51%). Compared to 48.6% of lamotrigine patients, no statistically significant treatment differences could be identified. The safety profile of both drugs was consistent with that seen in previous clinical trials. Carer-rated visual analogue scales detected significant improvements (P< 0.05) for the gabapentin-treated patients in seizure severity, attention, general health and sleeping pattern, while for lamotrigine seizure severity improved significantly. For learning disabled patients with resistant epilepsy, gabapentin and lamotrigine provide safe and effective treatment, with positive benefits on behaviour.", "We studied the efficacy of felbamate (FBM) in combination with valproic acid (VPA) in 13 patients with the Lennox-Gastaut syndrome and evaluated the contribution of each drug. Following stabilization on VPA monotherapy, FBM or placebo titration was performed for two observation periods lasting 7 weeks with a washout period between them. 6-h video-electroencephalography was recorded following each observation period. In addition to examining the effects of the drugs with parental reports and video-EEG, we compared video-EEG data with families' seizure reports. Based on parental counts for the 7-week observation periods, patients had 40% fewer drop attacks (p < 0.03, Wilcoxon rank sum test) and 60% fewer total seizures (p < 0.02) on VPA and FBM. VPA level rose by 12.7% when FBM was added (p < 0.01). When the effect of FBM was factored out, VPA had a significant effect on drop attack frequency, although not total number of seizures. FBM's therapeutic effect on drop attacks is due in part to increased VPA levels, although the combination may be synergistic for the effect on total seizure number.", "The Lennox-Gastaut syndrome, a severe form of epilepsy that usually begins in early childhood, is difficult to treat. Dose-related drug toxicity is common.\n We conducted a double-blind, placebo-controlled trial of the antiepileptic drug lamotrigine in patients with the Lennox-Gastaut syndrome. Eligible patients had more than one type of predominantly generalized seizure, including tonic-clonic, atonic, tonic, and major myoclonic, and had seizures on average at least every other day. After a 4-week base-line period in which all participants received placebo, we randomly assigned 169 patients (age range, 3 to 25 years) to 16 weeks of lamotrigine (n= 79) or placebo (n=90) in addition to their other antiepileptic drugs.\n The median frequency of all major seizures changed from base-line levels of 16.4 and 13.5 per week in the lamotrigine and placebo groups, respectively, to 9.9 and 14.2 per week after 16 weeks of treatment (P=0.002). Thirty-three percent of the patients in the lamotrigine group and 16 percent of those in the placebo group had a reduction of at least 50 percent in the frequency of seizures (P= 0.01). There were no significant differences between groups in the incidence of adverse events, except for colds or viral illnesses, which was more common in the lamotrigine group (P=0.05).\n Lamotrigine was an effective and well-tolerated treatment for seizures associated with the Lennox-Gastaut syndrome.", "Pharmacokinetic properties and efficacy of a conventional (C) carbamazepine (CBZ) preparation divided into three daily doses and a slow-release CBZ preparation (SR) divided into two daily doses were evaluated in a randomized, double-blind, cross-over study. The trial started with a 8-week baseline period followed by the two treatment periods each 10 weeks long. At the end of each period, a 24-h blood sample series for determination of serum CBZ and carbamazepine-10,11-epoxide (CBZE) was collected. The occurrence of seizures was monitored day and night during the whole study period by experienced nurses. The mean age of the 20 evaluable patients was 24.9 and the duration of epilepsy 19.2 and carbamazepine treatment 7.0 years. The bioavailability of CBZ from the two preparations was similar. The mean fluctuation of serum CBZ concentration (Cmax-Cmin/Css) was 16% smaller during SR. The mean serum CBZ concentration in the morning samples was significantly (P less than 0.001) higher during SR treatment. The mean total number of seizures was approximately four per week and did not differ between the two treatments, but during the last 2 weeks of the study period the occurrence of seizures was significantly smaller during SR (P = 0.02).", "The Lennox-Gastaut syndrome is a childhood disorder characterized by multiple types of seizures, mental retardation, characteristic electroencephalographic abnormalities, and resistance to standard antiepileptic drugs. Felbamate is an investigational antiepileptic drug with a preclinical profile that suggests it would be effective in patients with multiple types of seizures. In controlled clinical trials, felbamate was superior to placebo in reducing the frequency of refractory partial-onset seizures.\n We studied the efficacy of felbamate in 73 patients ranging in age from 4 to 36 years who had the Lennox-Gastaut syndrome. During a 28-day base-line phase, the patients received their usual antiepileptic therapies. At the end of this phase, felbamate or placebo was administered for 70 days in addition to the current antiepileptic medications. The dosage of felbamate was titrated during the first 14 days of the treatment phase to a maximum of 45 mg per kilogram of body weight per day or 3600 mg per day, whichever was less. The primary efficacy variables were the total number of seizures counted during a four-hour period of video recording, parents' or guardians' global evaluations of the patients' quality of life, and the total number of atonic seizures, as reported by parents or guardians.\n The patients treated with felbamate had a 34 percent decrease in the frequency of atonic seizures, as compared with a 9 percent decrease in the patients who received placebo (P = 0.01). The felbamate-treated patients had a 19 percent decrease in the total frequency of seizures, as compared with a 4 percent increase in the placebo group (P = 0.002). The global-evaluation scores were significantly higher in the felbamate group than in the placebo group from day 49 to the end of the study. There were no significant differences in the frequency of seizures occurring during video monitoring, but there was a significant reduction (P = 0.017) in the number of tonic-clonic seizures during the maintenance period in the felbamate group. The types and frequency of side effects were similar in the two treatment groups.\n Felbamate is beneficial in patients with the Lennox-Gastaut syndrome.", "We report a double-blind, placebo-controlled crossover study of lamotrigine (LTG) as add-on treatment in therapy-resistant, generalized epilepsy in children and adolescents (n = 30).\n Twenty patients had Lennox-Gastaut syndrome. Each patient acted as his or her own control. LTG and placebo were randomly added to existing antiepileptic medication (AEDs). The LTG dosage was individualized in an open phase preceding the placebo/treatment phase. Patients who responded to LTG in the open phase went on to the double-blind phase. \"Responders \" were defined as patients with a >50% seizure reduction or less severe seizures or both, or improved behavior or improved motor skills or both. \"Nonresponders\" were defined as children who showed no positive effects of LTG with plasma levels of < or = 10 microg/ml or children who had adverse events during the open phase.\n There was a clear statistically significant reduction of seizure frequency in LTG compared with placebo treatment. None of the children studied showed abnormal biochemical or hematologic findings, or changes in plasma levels of concomitantly administered AEDs.\n LTG is a well-tolerated and effective treatment in children with intractable generalized epilepsies, including those with Lennox-Gastaut syndrome. The study design allowed a double-blind placebo-controlled assessment of LTG although the participating children used 19 different AED combinations at entry." ]

[ "14625698", "17510766" ]

[ "Lichtenstein vs anterior preperitoneal prosthetic mesh placement in open inguinal hernia repair: a prospective, randomized trial.", "Pain after open preperitoneal repair versus Lichtenstein repair: a randomized trial." ]

[ "Male veterans with unilateral primary inguinal hernia, classified intraoperatively as Gilbert Type III or IV, were randomized to subaponeurotic (Lichtenstein, n=126) or preperitoneal (Read-Rives, n=121) repair under general or spinal anesthesia. The two groups of patients were comparable in age, body weight index, comorbidities, and size and type of hernia. Of the 247 patients enrolled, 224 were followed for at least 2 years (median 82 months, range 24-110 months), 16 were lost to follow-up, and seven died from causes unrelated to the surgery. The average operative time of the Read-Rives repair was 9 min longer than that of the Lichtenstein repair. There were no wound infections, and the frequencies of other short- and long-term complications were low and similar in the two groups. Six patients developed hernia recurrence, five in the Lichtenstein group (4.3%), and one in the Read-Rives group (<1%), ( P=0.21). Both anterior repairs are associated with low postoperative morbidity and recurrence rates. The Lichtenstein repair is technically easier and less time consuming. There is no statistically significant difference in the recurrence rate between the two repairs.", "The open preperitoneal approach in inguinal hernia repair might have the benefit of a mesh in the preferred space without the disadvantages of an endoscopic procedure.\n A total of 172 patients with primary inguinal hernia were randomized to undergo the open preperitoneal Kugel or the standard open anterior Lichtenstein procedure in a teaching hospital. The main outcome measures were operating variables, visual analog scale (VAS) pain scores, and consumed analgesics during the first 2 weeks postoperatively and at 3 months, neurological examination, and complications.\n In the Lichtenstein group the operation took longer (54 min versus 41 min; p < .001). There were no clinically important differences in VAS pain score or number of analgesics during the first 2 weeks postoperatively. In the Kugel group the mean VAS pain score at 3 months was less (0.3 versus 0.9; p = .002), as was the proportion of patients reporting pain (21 versus 40%; p = .007). Pain was merely described as neuropathic, especially in the Lichtenstein group. With the anterior repair significantly more nerves were encountered, numbness reported, and cutaneous sensory changes found with neurological examination (all p < .001).\n For those surgeons preferring an open approach, the Kugel procedure is a feasible alternative for the standard Lichtenstein procedure and is associated with less chronic pain at three months. Most likely the neuropathic pain and numbness with the Lichtenstein technique are results of more nerves at risk with the anterior approach." ]

[ "11866001", "18536860", "16484769", "18686739", "18836213", "20714373", "20620037", "17996436", "12728159", "17504798", "17693107", "16761228", "16144890", "17920256", "18060091", "17605774", "16305289", "21503263", "16507855", "21103404" ]

[ "A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease.", "Bronchodilator efficacy of tiotropium in patients with mild to moderate COPD.", "The effect of tiotropium on hyperinflation and exercise capacity in chronic obstructive pulmonary disease.", "Effect of tiotropium on health-related quality of life as a primary efficacy endpoint in COPD.", "A 4-year trial of tiotropium in chronic obstructive pulmonary disease.", "Efficacy and safety of tiotropium Respimat SMI in COPD in two 1-year randomized studies.", "A one-year trial of tiotropium Respimat plus usual therapy in COPD patients.", "A randomized study of tiotropium Respimat Soft Mist inhaler vs. ipratropium pMDI in COPD.", "Health outcomes following treatment for six months with once daily tiotropium compared with twice daily salmeterol in patients with COPD.", "Effect of tiotropium on sputum and serum inflammatory markers and exacerbations in COPD.", "Tiotropium improves FEV1 in patients with COPD irrespective of smoking status.", "[Efficacy of tiotropium bromide (Spiriva) in patients with chronic-obstructive pulmonary disease (COPD) of different severities].", "Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial.", "Improvements with tiotropium in COPD patients with concomitant asthma.", "A randomized controlled trial to assess the efficacy of tiotropium in Canadian patients with chronic obstructive pulmonary disease.", "Efficacy and safety of tiotropium in COPD patients in primary care--the SPiRiva Usual CarE (SPRUCE) study.", "Absence of electrocardiographic findings and improved function with once-daily tiotropium in patients with chronic obstructive pulmonary disease.", "Assessing the Impact of Tiotropium on Lung Function and Physical Activity in GOLD Stage II COPD Patients who are Naïve to Maintenance Respiratory Therapy: A Study Protocol.", "The effect of tiotropium on exacerbations and airflow in patients with COPD.", "Development and implementation of treadmill exercise testing protocols in COPD." ]

[ "Currently available inhaled bronchodilators used as therapy for chronic obstructive pulmonary disease (COPD) necessitate multiple daily dosing. The present study evaluates the long-term safety and efficacy of tiotropium, a new once-daily anticholinergic in COPD. Patients with stable COPD (age 65.2+/-8.7 yrs (mean+/-SD), n=921) were enrolled in two identical randomized double-blind placebo-controlled 1-yr studies. Patients inhaled tiotropium 18 microg or placebo (mean screening forced expiratory volume in one second (FEV1) 1.01 versus 0.99 L, 39.1 and 38.1% of the predicted value) once daily as a dry powder. The primary spirometric outcome was trough FEV1 (i.e. FEV1 prior to dosing). Changes in dyspnoea were measured using the Transition Dyspnea Index, and health status with the disease-specific St. George's Respiratory Questionnaire and the generic Short Form 36. Medication use and adverse events were recorded. Tiotropium provided significantly superior bronchodilation relative to placebo for trough FEV1 response (approximately 12% over baseline) (p<0.01) and mean response during the 3 h following dosing (approximately 22% over baseline) (p<0.001) over the 12-month period. Tiotropium recipients showed less dyspnoea (p<0.001), superior health status scores, and fewer COPD exacerbations and hospitalizations (p<0.05). Adverse events were comparable with placebo, except for dry mouth incidence (tiotropium 16.0% versus placebo 2.7%, p<0.05). Tiotropium is an effective, once-daily bronchodilator that reduces dyspnoea and chronic obstructive pulmonary disease exacerbation frequency and improves health status. This suggests that tiotropium will make an important contribution to chronic obstructive pulmonary disease therapy.", "Evaluation of tiotropium efficacy in patients with mild chronic obstructive pulmonary disease (COPD) defined by the 2003 Swedish Society of Respiratory Medicine guidelines (post-bronchodilator FEV1/FVC <70%; FEV1 >60% predicted).\n In this 12-week, randomised, double-blind, placebo-controlled study of tiotropium 18 mcg once daily versus placebo, respiratory function was assessed on Days 1, 15 and 85 (baseline: pre-dose Day 1).\n Mean+/-SD baseline FEV1 (% predicted) was 73.4+/-12.5 (tiotropium, n=107; placebo, n=117). Tiotropium significantly improved change from baseline in area under the curve from pre-dose to 2 hours post-dose (AUC0-2 h) FEV1 versus placebo, by 166+/-26 mL (mean+/-SE) at study end (p<0.0001). With tiotropium, there were significant increases in the change in AUC0-2 h FVC versus baseline, and trough FEV1 and FVC, versus placebo, on all test days (p<0.01). Adverse event rates were similar.\n Compared with placebo, tiotropium improved lung function in patients with mild COPD.", "Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation, which results in the progressive development of dyspnea and exercise limitation.\n To compare the effect of tiotropium with placebo on forced vital capacity (FVC) in patients with moderate-to-severe COPD and lung hyperinflation, using exercise endurance, dyspnea and health-related quality of life (HRQoL) as secondary endpoints. One hundred patients were randomized to receive either tiotropium 18 mug once daily or placebo for 12 weeks.\n Trough (predose) FVC was significantly improved with tiotropium compared to placebo on day 42 (0.27 +/- 0.08 liters) and 84 (0.20 +/- 0.08 liters; p < 0.05 for both). Trough inspiratory capacity (IC) was also significantly improved with tiotropium compared to placebo on day 42 (0.16 +/- 0.07 liters) and 84 (0.15 +/- 0.07 liters; p < 0.05 for both). Tiotropium increased the mean distance walked during the shuttle walking test by 33 +/- 12 (day 42) and 36 +/- 14 m (day 84) compared to placebo (p < 0.05 for both). On day 84, 59% of the patients in the tiotropium group and 35% of the patients in the placebo group had significant and clinically meaningful improvements in the St. George's Respiratory Questionnaire total score (p < 0.05). Numerical decreases in the focal score in the Transition Dyspnea Index in patients receiving tiotropium versus placebo suggest that tiotropium also improved dyspnea during activities of daily living.\n Tiotropium 18 mug once daily reduced hyperinflation with consequent improvements in walking distance and HRQoL in patients with COPD and lung hyperinflation.", "Clinical manifestations of chronic obstructive pulmonary disease (COPD), including airflow limitation, dyspnea, and activity limitation, ultimately lead to impaired health-related quality of life (HRQoL). This 9-month, randomized, double-blind, multicenter study compared the effect of once-daily tiotropium 18 microg and placebo on HRQoL, spirometric parameters, and exacerbations in 554 patients with moderate-to-severe COPD. HRQoL was assessed using the St. George's Respiratory Questionnaire (SGRQ) and the new 8-item Visual Simplified Respiratory Questionnaire (VSRQ), which is currently being validated. The primary efficacy endpoint was the proportion of patients achieving a reduction of at least 4 units in the SGRQ total score at study end (Month 9). Mean +/- SD baseline SGRQ total score was 47.4 +/- 18.1. Significantly more tiotropium-treated patients achieved a reduction of at least 4 units in the SGRQ score vs placebo at study end (59.1% vs 48.2%, respectively; p = 0.029). Tiotropium significantly improved spirometric parameters (forced expiratory volume in 1 second [FEV1]: 0.11 +/- 0.02 L vs 0.01 +/- 0.02 L; between-group difference: 0.10 +/- 0.03 L, p = 0.0001) and reduced exacerbations vs placebo. Maintenance treatment with tiotropium provided significant and clinically relevant improvements in HRQoL, as measured by the SGRQ.", "Previous studies showing that tiotropium improves multiple end points in patients with chronic obstructive pulmonary disease (COPD) led us to examine the long-term effects of tiotropium therapy.\n In this randomized, double-blind trial, we compared 4 years of therapy with either tiotropium or placebo in patients with COPD who were permitted to use all respiratory medications except inhaled anticholinergic drugs. The patients were at least 40 years of age, with a forced expiratory volume in 1 second (FEV(1)) of 70% or less after bronchodilation and a ratio of FEV(1) to forced vital capacity (FVC) of 70% or less. Coprimary end points were the rate of decline in the mean FEV(1) before and after bronchodilation beginning on day 30. Secondary end points included measures of FVC, changes in response on St. George's Respiratory Questionnaire (SGRQ), exacerbations of COPD, and mortality.\n Of a total of 5993 patients (mean age, 65+/-8 years) with a mean FEV(1) of 1.32+/-0.44 liters after bronchodilation (48% of predicted value), we randomly assigned 2987 to the tiotropium group and 3006 to the placebo group. Mean absolute improvements in FEV(1) in the tiotropium group were maintained throughout the trial (ranging from 87 to 103 ml before bronchodilation and from 47 to 65 ml after bronchodilation), as compared with the placebo group (P<0.001). After day 30, the differences between the two groups in the rate of decline in the mean FEV(1) before and after bronchodilation were not significant. The mean absolute total score on the SGRQ was improved (lower) in the tiotropium group, as compared with the placebo group, at each time point throughout the 4-year period (ranging from 2.3 to 3.3 units, P<0.001). At 4 years and 30 days, tiotropium was associated with a reduction in the risks of exacerbations, related hospitalizations, and respiratory failure.\n In patients with COPD, therapy with tiotropium was associated with improvements in lung function, quality of life, and exacerbations during a 4-year period but did not significantly reduce the rate of decline in FEV(1). (ClinicalTrials.gov number, NCT00144339.)\n 2008 Massachusetts Medical Society", "Two 1-year studies evaluated the long-term efficacy and safety of tiotropium 5 or 10 microg versus placebo, inhaled via the Respimat Soft Mist Inhaler (SMI). The two studies were combined and had 4 co-primary endpoints (trough FEV(1) response, Mahler Transition Dyspnea Index [TDI] and St George's Respiratory Questionnaire scores all at week 48, and COPD exacerbations per patient-year). A total of 1990 patients with COPD participated (mean FEV(1): 1.09 L). The mean trough FEV(1) response of tiotropium 5 or 10 microg relative to placebo was 127 or 150 mL, respectively (both P < 0.0001). The COPD exacerbation rate was significantly lower with tiotropium 5 microg (RR = 0.78; P = 0.002) and tiotropium 10 microg (RR = 0.73; P = 0.0008); the health-related quality of life and Mahler TDI co-primary endpoints were significantly improved with both doses (both P < 0.0001). Adverse events were generally balanced except anticholinergic class effects, which were more frequent with active treatment. Fatal events occurred in 2.4% (5 microg), 2.7% (10 microg), and 1.6% (placebo) of patients; these differences were not significant. Tiotropium Respimat SMI 5 microg demonstrated sustained improvements in patients with COPD relative to placebo and similar to the 10 microg dose but with a lower frequency of anticholinergic adverse events.", "In this randomised double-blind study, patients >or=40 years old with COPD, a smoking history of >or=10 pack-years, a pre-bronchodilator FEV(1) of <or=60% predicted and an FEV(1)/FVC of <or=70% received tiotropium 5 microg or placebo via Respimat inhaler once daily for 48 weeks. Other medications were permitted except inhaled anticholinergics. Co-primary endpoints were trough FEV(1) and the time to first exacerbation. Adverse events were followed and vital status regularly assessed. In all, 3991 patients (mean age, 65 years [SD, 9 years]) were evaluable. Mean baseline FEV(1) was 1.11 L (0.40 L) or 40% (12%) of predicted normal. Adjusted mean differences in trough FEV(1) and trough FVC at Week 48 (tiotropium minus placebo) were 102 and 168 ml respectively (p < 0.0001, both). Tiotropium delayed time to first exacerbation relative to placebo (hazard ratio [HR], 0.69 [95% CI, 0.63-0.77]) and time to first hospital-treated exacerbation (HR, 0.73 [0.59-0.90]). SGRQ score at Week 48 was 2.9 units lower with tiotropium (p < 0.0001). Adverse and serious adverse events were balanced across treatment groups and similar in profile to previous tiotropium trials. The rate ratio for a major adverse cardiovascular event during the treatment period + 30 days was 1.12 (0.67-1.86). By the end of planned treatment (Day 337) 52 patients on tiotropium (incidence rate per 100 years, 2.94) and 38 on placebo (2.13) had died (HR = 1.38 [0.91-2.10]; p = 0.13). Lung function, exacerbations and quality of life were improved by tiotropium 5 microg Respimat but a numerical imbalance was seen in all-cause mortality. The protocol is registered on the European Clinical Trials Database as trial number 2006-001009-27 and in the ClinicalTrials.gov database as NCT00387088.", "The aim of these studies was to compare the efficacy and the safety of tiotropium, delivered via Respimat Soft Mist Inhaler (SMI), a novel multi-dose, propellant-free inhaler, with ipratropium pressurized metered-dose inhaler (pMDI) in chronic obstructive pulmonary disease (COPD) patients. Two identical, 12-week, multi-national, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled studies were performed. COPD patients were randomized to treatment with either inhaled tiotropium (5 or 10 microg) via Respimat SMI administered once daily, ipratropium (36 microg) pMDI QID or placebo. The primary endpoint was the mean trough forced expiratory volume in 1s (FEV(1)) response after 12 weeks of treatment. Secondary endpoints included other spirometry measures and rescue medication use. A total of 719 patients were randomized; the majority were male (69%) with a mean pre-bronchodilator FEV(1) (% predicted) of 40.7%. The mean treatment differences between tiotropium 5 and 10 microg and placebo for the primary endpoint (mean trough FEV(1) response at week 12) were 0.118 and 0.149L, respectively (both P<0.0001). Treatment differences between tiotropium 5 and 10 microg and ipratropium were 0.064L (P=0.006) and 0.095L (P<0.0001). The increases in peak FEV(1), FEV(1) AUC((0-6h)) and FVC for both tiotropium doses were statistically superior to placebo (P<0.01) and higher than ipratropium. All active treatments significantly reduced the rescue medication use compared with placebo, but only tiotropium 10 microg was statistically superior to ipratropium (P=0.04). The incidence of adverse events was comparable across groups. In conclusion, tiotropium 5 and 10 microg daily, delivered via Respimat SMI, significantly improved lung function compared with ipratropium pMDI and placebo.", "A study was undertaken to record exacerbations and health resource use in patients with COPD during 6 months of treatment with tiotropium, salmeterol, or matching placebos.\n Patients with COPD were enrolled in two 6-month randomised, placebo controlled, double blind, double dummy studies of tiotropium 18 micro g once daily via HandiHaler or salmeterol 50 micro g twice daily via a metered dose inhaler. The two trials were combined for analysis of heath outcomes consisting of exacerbations, health resource use, dyspnoea (assessed by the transitional dyspnoea index, TDI), health related quality of life (assessed by St George's Respiratory Questionnaire, SGRQ), and spirometry.\n 1207 patients participated in the study (tiotropium 402, salmeterol 405, placebo 400). Compared with placebo, tiotropium but not salmeterol was associated with a significant delay in the time to onset of the first exacerbation. Fewer COPD exacerbations/patient year occurred in the tiotropium group (1.07) than in the placebo group (1.49, p<0.05); the salmeterol group (1.23 events/year) did not differ from placebo. The tiotropium group had 0.10 hospital admissions per patient year for COPD exacerbations compared with 0.17 for salmeterol and 0.15 for placebo (not statistically different). For all causes (respiratory and non-respiratory) tiotropium, but not salmeterol, was associated with fewer hospital admissions while both groups had fewer days in hospital than the placebo group. The number of days during which patients were unable to perform their usual daily activities was lowest in the tiotropium group (tiotropium 8.3 (0.8), salmeterol 11.1 (0.8), placebo 10.9 (0.8), p<0.05). SGRQ total score improved by 4.2 (0.7), 2.8 (0.7) and 1.5 (0.7) units during the 6 month trial for the tiotropium, salmeterol and placebo groups, respectively (p<0.01 tiotropium v placebo). Compared with placebo, TDI focal score improved in both the tiotropium group (1.1 (0.3) units, p<0.001) and the salmeterol group (0.7 (0.3) units, p<0.05). Evaluation of morning pre-dose FEV(1), peak FEV(1) and mean FEV(1) (0-3 hours) showed that tiotropium was superior to salmeterol while both active drugs were more effective than placebo.\n Exacerbations of COPD and health resource usage were positively affected by daily treatment with tiotropium. With the exception of the number of hospital days associated with all causes, salmeterol twice daily resulted in no significant changes compared with placebo. Tiotropium also improved health related quality of life, dyspnoea, and lung function in patients with COPD.", "Chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations demonstrate increased stable-state airway inflammation. Tiotropium has been shown to reduce exacerbation frequency, but its effect on airway inflammation is unknown. The aim of the present study was to investigate the effect of tiotropium on sputum inflammatory markers and exacerbation frequency. Patients (n = 142) were randomised to receive tiotropium or placebo in addition to their usual medication for 1 yr. Sputum and serum cytokines were assayed by ELISA and exacerbation frequency calculated using a symptom-based diary. There was no difference in the area under the curve for sputum interleukin (IL)-6 or myeloperoxidase between the groups, but sputum IL-8 level was increased in the tiotropium arm. There was no difference between start and end of study in serum IL-6 or C-reactive protein level. Tiotropium was associated with a 52% reduction in exacerbation frequency (1.17 versus 2.46 exacerbations.yr(-1)). Of patients on tiotropium, 43% experienced at least one exacerbation, compared with 64% on placebo. The total number of exacerbation days was reduced compared with placebo (17.3 versus 34.5 days). Tiotropium reduces exacerbation frequency in chronic obstructive pulmonary disease, but this effect does not appear to be due to a reduction in airway or systemic inflammation.", "This study evaluated whether the effect of tiotropium on the change in trough forced expiratory volume in 1s (FEV1), vs. placebo, is affected by smoking status. In a 3-month, double-blind study in 31 centres in Portugal, 311 (289 completed) patients were randomised to tiotropium 18 microg once daily or placebo. Baseline mean (standard deviation (SD)) FEV1 was 1.11 (0.39) l in the tiotropium group and 1.13 (0.39) l in the placebo group. Patients had an average smoking history of 55 (25.7) pack-years; 80 (26%) were smokers and 224 (74%) were ex-smokers. The primary end-point was change in morning pre-dose (i.e. trough) FEV1 after 12 weeks. Trough FEV1 at 12 weeks was significantly improved with tiotropium vs. placebo: the difference in means was 102 ml, P=0.0011, 95% confidence interval (CI) (41, 164). The difference in means in smokers was 138 ml, P=0.0105, CI (32, 244); in ex-smokers it was 66 ml, P=0.0375, CI (3, 129). The difference between smokers and ex-smokers was not statistically significant (P=0.6982) and may be due to greater variability and differences in disease severity. The significant improvement in lung function in patients treated with tiotropium vs. placebo in both smokers and ex-smokers suggests that tiotropium is an effective and well-tolerated therapy in chronic obstructive pulmonary disease (COPD), regardless of smoking status.", "Aim of this study was to evaluate the efficacy of inhaled Tiotropium bromide in COPD patients of different severities in pneumological practices during a three months clinical trial.\n A randomized, double blind, placebo controlled study including COPD-patients (FEV1/FVC < 70 %, FEV1 < or = 70 % predicted; age > or = 40 years; > or = 10 pack years) of different severities was performed. The efficacy of 18 microg Tiotropium bromide once daily on lung function and exacerbations over 12 weeks was evaluated by respective pulmonary function tests (spirometry) before (trough value) and 2 hours after inhalation of study medication.\n 1639 patients (1236 Tiotropium bromide, 403 placebo; FEV1 reversibility after 200 microg Ipratropium bromide + 200 microg Fenoterol: 7.9 +/- 7.5 % predicted [mean +/- sd]) were randomized. After 12 weeks of treatment Tiotropium bromide led to significant increases of trough FEV1 (23 - 24 h after last inhalation; + 79 +/- 17 ml), and 2 h after Tiotropium bromide inhalation (+ 128 +/- 19 ml) (all values vs. placebo, adjusted mean +/- se, p < 0.0001). FVC and IVC were also improved significantly. In mild COPD (FEV1 > or = 50 - 70 %) improvements were most pronounced (trough FEV1 + 113 +/- 29 ml, 2 h post-inhalation + 181 +/- 33 ml; all values vs. placebo., p < 0.0001). 14.6 % of patients treated with Tiotropium bromide had a COPD exacerbation vs. 19.9 % of patients treated with placebo (p = 0.0151). The time to first exacerbation was prolonged (p = 0.0092 vs. placebo).\n Tiotropium bromide 18 microg once daily led to a persistent improvement of lung function and a reduction of exacerbations in patients with COPD of different severities.", "Patients with chronic obstructive pulmonary disease (COPD) frequently develop exacerbations, leading to major clinical and health resource use ramifications.\n To prospectively evaluate the effectiveness of a long-acting inhaled anticholinergic bronchodilator, tiotropium, in reducing COPD exacerbations and exacerbation-related health care utilization.\n Randomized, double-blind study.\n 26 Veterans Affairs medical centers.\n 1829 patients with moderate to severe COPD (mean baseline FEV(1), 36% predicted).\n Once-daily tiotropium (18 microg) or placebo for 6 months. Patients otherwise received usual care, except for other anticholinergic bronchodilators.\n The coprimary end points were the percentage of patients with a COPD exacerbation and the percentage of patients with a COPD-related hospitalization.\n Tiotropium significantly reduced the percentage of patients experiencing 1 or more exacerbations compared with placebo (27.9% vs. 32.3%, respectively; difference, -5.7 percentage points [95% CI, -10.4 to -1.0 percentage points]; P = 0.037). Fewer tiotropium patients were hospitalized because of COPD exacerbation (7.0% vs. 9.5%, respectively; difference, -3.0 percentage points [CI, -5.9 to -0.1 percentage points]; P = 0.056), although this difference was of borderline statistical significance. Analysis of secondary outcomes indicates that tiotropium may lengthen the time to first COPD exacerbation (P = 0.028) and reduce health care utilization for exacerbations, including the frequency of hospitalizations (P = 0.047), unscheduled clinic visits (P = 0.019), and days of antibiotic treatment (P = 0.015). Tiotropium did not statistically significantly reduce all-cause hospitalization rates.\n Trial participants were enrolled from 1 health care system, and 99% were men. The follow-up period extended for only 6 months.\n Tiotropium reduces COPD exacerbations and may reduce related health care utilization in patients with moderate to severe COPD.", "Chronic obstructive pulmonary disease (COPD) and asthma have different diagnostic criteria and treatment paradigms. Both are common and can occur in the same patient. We sought to determine the spirometric effects of tiotropium in COPD patients with concomitant asthma.\n A 12-week randomized, double-blind, placebo-controlled, parallel group trial with tiotropium 18 mcg daily was performed. Patients continued usual respiratory medications except for inhaled anticholinergics. Inclusion criteria: Physician diagnosis of COPD and asthma, age >or= 40 years, smoking >10 pack years, post-bronchodilator forced expiratory volume in 1s (FEV(1))<80% predicted, FEV(1)/forced vital capacity (FVC)<70%, >or= 12%, and >or= 200 ml increase in FEV(1) following inhaled bronchodilator, treatment with inhaled steroids >or= 1 year. Spirometry was measured serially for 6h on days 1, 29 and 85.\n Four hundred and seventy-two patients were randomized. Baseline characteristics were balanced. Mean age=59.6 years, 61.4% were men, and FEV(1)=1.55l (53.0% predicted). Improvements at 12 weeks with tiotropium were observed for the primary endpoint FEV(1) area under the curve (AUC) from 0 to 6h (difference=186+/-24 ml, p<0.001) and for morning pre-dose FEV(1) (difference=98+/-23 ml, p<0.001). Significant differences in favor of tiotropium were observed for pre-dose FVC (difference=128+/-34 ml, p<0.001) and FVC AUC 0-6h (difference=232+/-35 ml, p<0.001). Compared to baseline, the mean weekly number of daily puffs of prn salbutamol was reduced by 0.05+/-0.12 puffs/day in the placebo group and by 0.50+/-0.12 puffs/day in the tiotropium group at week 12 (p<0.05).\n Patients with COPD and concomitant asthma achieve spirometric improvements with tiotropium along with symptomatic benefit as seen by reduced need for rescue medication.", "Patients with chronic obstructive pulmonary disease (COPD) who smoke have a greater annual rate of decline in forced expiratory volume in 1 s (FEV(1)) than those patients who have stopped smoking.\n To assess the effect of tiotropium on pre-dose (trough) FEV(1) in patients with COPD followed in Canada.\n A total of 913 patients were randomly assigned to receive either tiotropium 18 mug once daily (n=608) or placebo (usual care minus inhaled anticholinergics) (n=305) for 48 weeks in the present randomized, double-blind, parallel-group study. The effect of tiotropium on measurements of lung function (FEV(1), FEV(6) and forced vital capacity), symptoms, health-related quality of life (St George's Respiratory Questionnaire) and exacerbations were examined.\n Tiotropium improved trough FEV(1) in both current and ex-smokers compared with placebo. Baseline FEV(1) in smokers and ex-smokers was 1.03 L and 0.93 L, respectively (P<0.001). At week 48, the mean difference between the tiotropium and placebo groups was 0.14+/-0.04 L (P<0.001) in the smoker group and 0.08+/-0.02 L (P<0.0001) in the ex-smoker group. Tiotropium also significantly improved trough forced vital capacity and FEV(6) compared with placebo throughout the treatment period (P<0.05, for all). Furthermore, tiotropium significantly improved the St George's Respiratory Questionnaire total score compared with placebo at week 48 (40.9 versus 43.7 units, P<0.005).\n Compared with the placebo group, tiotropium provides sustained improvements in lung function in patients with COPD, with improvements for smokers and ex-smokers.", "Clinical trials of tiotropium have principally recruited patients from secondary care with more severe chronic obstructive pulmonary disease (COPD), and typically had included limitation of concomitant medication. In primary care, which is the most common setting for COPD management, many patients may have milder disease, and also may take a broad range of concomitant medication.\n This randomised, placebo-controlled, parallel-group, 12-week, 44-centre study investigated the efficacy (trough forced expiratory volume in 1 second [FEV1] response) and safety of additional treatment with once-daily tiotropium 18 mug via the HandiHaler in a primary care COPD population (tiotropium: N = 191, FEV1 = 1.25 L [47.91% predicted]; placebo: N = 183, FEV1 = 1.32 L [49.86% predicted]). Secondary endpoints included: trough forced vital capacity (FVC) response, weekly use of rescue short-acting beta-agonist, and exacerbation of COPD (complex of respiratory symptoms/events of >3 days in duration requiring a change in treatment). Treatment effects were determined using non-parametric analysis.\n At Week 12, median improvement in trough FEV1 response with tiotropium versus placebo was 0.06 L (p = 0.0102). The improvement was consistent across baseline treatment and COPD severity. Median improvement in FVC at 2, 6 and 12 weeks was 0.12 L (p < 0.001). The percentage of patients with > or =1 exacerbation was reduced (tiotropium 9.5%; placebo 17.9%; p = 0.0147), independent of disease severity. Rescue medication usage was significantly reduced in the tiotropium group compared with placebo. Adverse event profile was consistent with previous studies.\n Tiotropium provides additional benefits to usual primary care management in a representative COPD population.\n The identifier is: NCT00274079.", "To examine electrocardiographic findings after short- and long-term tiotropium therapy in patients with chronic obstructive pulmonary disease (COPD), and to establish previously reported symptomatic efficacy.\n Randomized, double-blind, placebo-controlled, parallel-group study.\n Twelve outpatient investigational centers in the United States.\n One hundred ninety-six patients with COPD.\n Patients received either tiotropium 18 mug once/day or placebo, delivered by the HandiHaler device.\n Electrocardiography (predose and 5 min postdose) and 24-hour Holter monitoring were performed at baseline and after 8 and 12 weeks of treatment with tiotropium 18 microg once/day or placebo. Efficacy measures (spirometry, global COPD ratings, scores on the EuroQol Health Questionnaire [EQ-5D], albuterol inhaler as needed) were included to demonstrate that the study population exhibited the characteristic improvements observed in previous tiotropium studies. Mean baseline forced expiratory volume in 1 second (FEV1) was 1.03 L. Mean changes in heart rate from baseline were similar in both groups. No differences were noted in the percentage of patients developing rhythm or conduction abnormalities detected with electrocardiography or Holter monitoring. Frequency of premature beats and mean maximal changes in PR, QRS, QT, QTcB, and QTcF intervals were similar in both groups. No patients developed new-onset QT or QTc intervals greater than 500 msec, and no differences were noted in the percentage of patients developing new QT prolongation less than 30 msec, 30-60 msec, or greater than 60 msec. At 12 weeks, predose and postdose improvements in FEV1 were 184 and 265 ml, respectively, with tiotropium versus placebo (p<0.001). Physician and patient global COPD ratings and the EQ-5D visual analog scale scores were improved with tiotropium (p<0.05); as-needed albuterol was reduced by 25% relative to placebo (p<0.05).\n Tiotropium provided spirometric and symptomatic benefits in patients with COPD and was not associated with evidence of electrocardiographic changes in heart rate, rhythm, QT intervals, or conduction.", "Physical activity status is increasingly recognized as a reliable predictor of mortality and hospitalization in patients with chronic obstructive pulmonary disease (COPD). The reduction in physical activity occurs earlier in the clinical course of COPD than previously appreciated, possibly arising from breathlessness, reduced exercise tolerance, and adoption of a more sedentary lifestyle. To date, no clinical trial has evaluated the impact of pharmacotherapy on both lung function and physical activity. We recently designed a study that evaluates the impact of tiotropium (a once-daily inhaled anticholinergic) on lung function and physical activity in a maintenance/treatment-naïve Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage II COPD cohort. Previous studies have demonstrated that tiotropium improves lung function and exercise tolerance; whether these benefits translate into improvements in physical activity is the focus of the current work. Here we describe the rationale and challenges in developing and implementing this study and review its unique features and novel design, including: utility of direct activity monitoring in multicenter clinical trials; importance of behavioral-modification techniques (including motivational interviewing to improve patient self-efficacy and adherence for a healthy, more active lifestyle); utility of individualized activity plans that provide an integrated approach with pharmacotherapy and behavioral modification to help patients achieve a more active lifestyle.", "This randomised, double-blind, parallel-group, 1-yr study compared the effect of tiotropium 18 microg once daily (n=500) and placebo (n=510) on exacerbations, associated health resource use (HRU) and airflow limitation in chronic obstructive pulmonary disease (COPD) patients. The mean+/-sd number of exacerbations during the past year was 2.14+/-1.40, the mean weekly morning peak expiratory flow (PEF) was 259.6+/-96.1 L.min-1 and the mean forced expiratory volume in one second (FEV1) was 1.37+/-0.45 L. Tiotropium significantly delayed the time to first exacerbation by approximately 100 days, reduced the proportion of patients experiencing more than one exacerbation by 17%, and decreased the number of exacerbations by 35% and exacerbation days by 37% versus placebo. Tiotropium also decreased HRU versus placebo, as indicated by the significant reductions in the use of concomitant respiratory medications, antibiotics and oral steroids, and the number of unscheduled physician contacts. Mean weekly morning PEF improved significantly with tiotropium versus placebo from week 1 until the end of the study. At the end of the study, tiotropium significantly improved trough (pre-dose) FEV1, forced vital capacity, slow vital capacity and inspiratory capacity versus placebo. In conclusion, tiotropium reduced exacerbations and associated health resource use, and improved airflow over 1 yr in chronic obstructive pulmonary disease patients.", "Because treadmill exercise testing is more representative of daily activity than cycle testing, we developed treadmill protocols to be used in various clinical settings as part of a two-year, multicenter, chronic obstructive pulmonary disease (COPD) trial evaluating the effect of tiotropium on exercise.\n We enrolled 519 COPD patients aged 64.6 ± 8.3 years with a postbronchodilator forced expiratory volume in one second (FEV(1)) of 1.25 ± 0.42 L, 44.3% ± 11.9% predicted. The patients performed symptom-limited treadmill tests where work rate (Ẇ) was increased linearly using speed and grade adjustments every minute. On two subsequent visits, they performed constant Ẇ tests to exhaustion at 90% of maximum Ẇ from the incremental test.\n Mean incremental test duration was 522 ± 172 seconds (range 20-890), maximum work rate 66 ± 34 watts. For the first and second constant Ẇ tests, both at 61 ± 33 watts, mean endurance times were 317 ± 61 seconds and 341 ± 184 seconds, respectively. The mean of two tests had an intraclass correlation coefficient of 0.85 (P < 0.001). During the second constant Ẇ test, 88.2% of subjects stopped exercise because of breathing discomfort; 87.1% for Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage II, 88.5% for GOLD Stage III, and 90.2% for GOLD Stage IV.\n The symptom-limited incremental and constant work treadmill protocol was well tolerated and appeared to be representative of the physiologic limitations of COPD." ]

[ "21191095", "19296055", "18486203", "12781165", "19141661" ]

[ "Eating for pleasure or profit: the effect of incentives on children's enjoyment of vegetables.", "Results from a dietary intervention study in preschools \"Beastly Healthy at School\".", "High 5 for Kids: the impact of a home visiting program on fruit and vegetable intake of parents and their preschool children.", "Increasing children's acceptance of vegetables; a randomized trial of parent-led exposure.", "Effectiveness of a social support intervention on infant feeding practices: randomised controlled trial." ]

[ "Parents commonly use rewards to encourage children to eat healthfully, but this practice remains controversial because rewards are suspected of undermining children's intrinsic motivation. A cluster-randomized trial examined children's acceptance of a disliked vegetable over 12 daily taste exposures. These exposures were paired with a tangible reward, a social reward, or no reward, and the findings were compared with the results from a no-treatment control condition. Liking and intake of the vegetable were assessed in a free-choice consumption task at preintervention, postintervention, 1 month after intervention, and 3 months after intervention. Liking increased more in the three intervention conditions than in the control condition, and there were no significant differences between the intervention conditions. These effects were maintained at follow-up. Children in both reward conditions increased consumption, and these effects were maintained for 3 months; however, the effects of exposure with no reward became nonsignificant by 3 months. These results indicate that external rewards do not necessarily produce negative effects and may be useful in promoting healthful eating.", "Applying the Intervention Mapping Protocol, an intervention was developed to assist Belgian preschools in the implementation of a healthy school food policy. In the present study the impact of the intervention on children's food consumption is investigated.\n Teachers and parents from 16 schools (8 intervention; 8 control) were asked to participate in the study. Teachers registered the children's available food and beverages during the morning and afternoon breaks (data of baseline and follow-up was matched for 618 intervention and 445 control children). Parents were asked to complete a food frequency questionnaire on their children's general consumption (308 intervention and 168 control matches).Linear mixed model analyses were used to investigate the intervention effect.\n Both assessment methods indicate an increased fruit consumption for intervention children in comparison with control children, although the effect was only significant for the parental reported fruit consumption. Additionally the results suggest that the change is mainly due to increased availability at school. No significant associations were found for the other food items (snacks, vegetables and different types of beverages).\n The results indicate that a healthy food policy at school can improve young children's diet.", "The High 5 for Preschool Kids (H5-KIDS) program tested the effectiveness of a home based intervention to teach parents how to ensure a positive fruit-vegetable (FV) environment for their preschool child, and to examine whether changes in parent behavior were associated with improvements in child intake.\n A group randomized nested cohort design was conducted (2001 to 2006) in rural, southeast Missouri with 1306 parents and their children participating in Parents As Teachers, a national parent education program.\n When compared to control parents, H5-KIDS parents reported an increase in FV servings (MN=0.20, p=0.05), knowledge and availability of FV within the home (p=0.01), and decreased their use of noncoercive feeding practices (p=0.02). Among preschoolers, FV servings increased in normal weight (MN=0.35, p=0.02) but not overweight children (MN=-0.10, p=0.48), relative to controls. The parent's change in FV servings was a significant predictor of child's change in FV in the H5-KIDS group (p=0.001).\n H5-KIDS suggests the need for, and promise of, early home intervention for childhood obesity prevention. It demonstrates the importance of participatory approaches in developing externally valid interventions, with the potential for dissemination across national parent education programs as a means for improving the intake of parents and young children.", "Despite considerable epidemiological evidence of the health benefits of a diet high in fruit and vegetables, consumption in pre-school children remains well below recommended levels. This study evaluated the effectiveness of an exposure-based intervention, carried out by parents in the home, in increasing children's liking for a previously disliked vegetable. 156 parents of 2-6 year old children were randomly assigned to Exposure, Information or Control groups after a pre-intervention taste test at which a 'target' vegetable was selected. Parents in the Exposure group gave their child a taste of this vegetable daily for 14 days, parents in the Information group were given nutritional advice and a leaflet, and parents in the Control group received no further intervention. All participants took part in a post-intervention taste test. Greater increases in liking, ranking and consumption of the 'target' vegetable from pre- to post-intervention occurred in the Exposure group than in either of the other two groups. Only the Exposure group showed significant increases across all three outcomes. It can be concluded that a parent-led, exposure-based intervention involving daily tasting of a vegetable holds promise for improving children's acceptance of vegetables. These findings suggest a parental advice strategy which could be disseminated directly to parents or by health professionals.", "To assess whether monthly home visits from trained volunteers could improve infant feeding practices at age 12 months, a randomised controlled trial was carried out in two disadvantaged inner city London boroughs.\n Women attending baby clinics with their infants (312) were randomised to receive monthly home visits from trained volunteers over a 9-month period (intervention group) or standard professional care only (control group). The primary outcome was vitamin C intakes from fruit. Secondary outcomes included selected macro and micro-nutrients, infant feeding habits, supine length and weight. Data were collected at baseline when infants were aged approximately 10 weeks, and subsequently when the child was 12 and 18 months old.\n Two-hundred and twelve women (68%) completed the trial. At both follow-up points no significant differences were found between the groups for vitamin C intakes from fruit or other nutrients. At first follow-up, however, infants in the intervention group were significantly less likely to be given goats' or soya milks, and were more likely to have three solid meals per day. At the second follow-up, intervention group children were significantly less likely to be still using a bottle. At both follow-up points, intervention group children also consumed significantly more specific fruit and vegetables.\n Home visits from trained volunteers had no significant effect on nutrient intakes but did promote some other recommended infant feeding practices.\n Current Controlled Trials ISRCTN55500035." ]

[ "18242413", "17050891", "20739054", "18046028", "21067381" ]

[ "Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial.", "AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP.", "Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study.", "Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura.", "Romiplostim or standard of care in patients with immune thrombocytopenia." ]

[ "Chronic immune thrombocytopenic purpura (ITP) is characterised by accelerated platelet destruction and decreased platelet production. Short-term administration of the thrombopoiesis-stimulating protein, romiplostim, has been shown to increase platelet counts in most patients with chronic ITP. We assessed the long-term administration of romiplostim in splenectomised and non-splenectomised patients with ITP.\n In two parallel trials, 63 splenectomised and 62 non-splenectomised patients with ITP and a mean of three platelet counts 30x10(9)/L or less were randomly assigned 2:1 to subcutaneous injections of romiplostim (n=42 in splenectomised study and n=41 in non-splenectomised study) or placebo (n=21 in both studies) every week for 24 weeks. Doses of study drug were adjusted to maintain platelet counts of 50x10(9)/L to 200x10(9)/L. The primary objectives were to assess the efficacy of romiplostim as measured by a durable platelet response (platelet count > or =50x10(9)/L during 6 or more of the last 8 weeks of treatment) and treatment safety. Analysis was per protocol. These studies are registered with ClinicalTrials.gov, numbers NCT00102323 and NCT00102336.\n A durable platelet response was achieved by 16 of 42 splenectomised patients given romplostim versus none of 21 given placebo (difference in proportion of patients responding 38% [95% CI 23.4-52.8], p=0.0013), and by 25 of 41 non-splenectomised patients given romplostim versus one of 21 given placebo (56% [38.7-73.7], p<0.0001). The overall platelet response rate (either durable or transient platelet response) was noted in 88% (36/41) of non-splenectomised and 79% (33/42) of splenectomised patients given romiplostim compared with 14% (three of 21) of non-splenectomised and no splenectomised patients given placebo (p<0.0001). Patients given romiplostim achieved platelet counts of 50x10(9)/L or more on a mean of 13.8 (SE 0.9) weeks (mean 12.3 [1.2] weeks in splenectomised group vs 15.2 [1.2] weeks in non-splenectomised group) compared with 0.8 (0.4) weeks for those given placebo (0.2 [0.1] weeks vs 1.3 [0.8] weeks). 87% (20/23) of patients given romiplostim (12/12 splenectomised and eight of 11 non-splenectomised patients) reduced or discontinued concurrent therapy compared with 38% (six of 16) of those given placebo (one of six splenectomised and five of ten non-splenectomised patients). Adverse events were much the same in patients given romiplostim and placebo. No antibodies against romiplostim or thrombopoietin were detected.\n Romiplostim was well tolerated, and increased and maintained platelet counts in splenectomised and non-splenectomised patients with ITP. Many patients were able to reduce or discontinue other ITP medications. Stimulation of platelet production by romiplostim may provide a new therapeutic option for patients with ITP.", "Most current treatments for chronic immune thrombocytopenic purpura (ITP) act by decreasing platelet destruction. In a phase 1-2 study, we administered a thrombopoiesis-stimulating protein, AMG 531, to patients with ITP.\n In phase 1, 24 patients who had received at least one treatment for ITP were assigned to escalating-dose cohorts of 4 patients each and given two identical doses of AMG 531 (0.2 to 10 microg per kilogram of body weight). In phase 2, 21 patients were randomly assigned to receive six weekly subcutaneous injections of AMG 531 (1, 3, or 6 microg per kilogram) or placebo. The primary objective was to assess the safety of AMG 531; the secondary objective was to evaluate platelet counts during and after treatment.\n No major adverse events that could be attributed directly to AMG 531 occurred during the treatment period; 4 of 41 patients had transient post-treatment worsening of thrombocytopenia. In phase 1, a platelet count that was within the targeted range (50,000 to 450,000 per cubic millimeter) and at least twice the baseline count was achieved in 4 of 12 patients given 3, 6, or 10 mug of AMG 531 per kilogram. Overall, a platelet count of at least 50,000 per cubic millimeter was achieved in 7 of 12 patients, including 3 with counts exceeding 450,000 per cubic millimeter. Increases in the platelet count were dose-dependent; mean peak counts were 163,000, 309,000, and 746,000 per cubic millimeter with 3, 6, and 10 microg of AMG 531 per kilogram [corrected], respectively. In phase 2, the targeted platelet range was achieved in 10 of 16 patients treated with 1 or 3 mug of AMG 531 per kilogram per week for 6 weeks. Mean peak counts were 135,000, 241,000, and 81,000 per cubic millimeter in the groups that received the 1-mug dose, the 3-mug dose, and placebo, respectively.\n AMG 531 caused no major adverse events and increased platelet counts in patients with ITP. (ClinicalTrials.gov number, NCT00111475 [ClinicalTrials.gov].).\n Copyright 2006 Massachusetts Medical Society.", "Eltrombopag is an oral thrombopoietin receptor agonist for the treatment of thrombocytopenia. We aimed to compare the response to once daily eltrombopag versus placebo in patients with chronic immune thrombocytopenia during a 6-month period.\n We undertook a phase 3, double-blind, placebo-controlled study in adults with previously treated immune thrombocytopenia of more than 6 months' duration who had baseline platelet counts lower than 30,000 per μL. Patients were randomly allocated (in a 2:1 ratio) treatment with local standard of care plus 50 mg eltrombopag or matching placebo once daily for 6 months. Randomisation was done centrally with a computer-generated randomisation schedule and was stratified by baseline platelet count (≤ 15,000 per μL), use of treatment for immune thrombocytopenia, and splenectomy status. Patients, investigators, and those assessing data were masked to allocation. Dose modifications were made on the basis of platelet response. Patients were assessed for response to treatment (defined as a platelet count of 50,000-400,000 per μL) weekly during the first 6 weeks and at least once every 4 weeks thereafter; the primary endpoint was the odds of response to eltrombopag versus placebo. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT00370331.\n Between Nov 22, 2006, and July 31, 2007, 197 patients were randomly allocated to treatment groups and were included in the intention-to-treat analysis (135 eltrombopag, 62 placebo). 106 (79%) patients in the eltrombopag group responded to treatment at least once during the study, compared with 17 (28%) patients in the placebo group. The odds of responding were greater in patients in the eltrombopag group compared with those in the placebo group throughout the 6-month treatment period (odds ratio 8·2, 99% CI 3·59-18·73; p<0·0001). 37 (59%) patients receiving eltrombopag reduced concomitant treatment versus ten (32%) patients receiving placebo (p=0·016). 24 (18%) patients receiving eltrombopag needed rescue treatment compared with 25 (40%) patients receiving placebo (p=0·001). Three (2%) patients receiving eltrombopag had thromboembolic events compared with none in patients on placebo. Nine (7%) eltrombopag-treated patients and two (3%) in the placebo group had mild increases in alanine aminotransferase concentration, and five (4%) eltrombopag-treated patients (vs none allocated to placebo) had increases in total bilirubin. Four (7%) patients taking placebo had serious bleeding events, compared with one (<1%) patient treated with eltrombopag.\n Eltrombopag is effective for management of chronic immune thrombocytopenia, and could be particularly beneficial for patients who have not responded to splenectomy or previous treatment. These benefits should be balanced with the potential risks associated with eltrombopag treatment.\n GlaxoSmithKline.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "The pathogenesis of chronic idiopathic thrombocytopenic purpura (ITP) involves antibody-mediated platelet destruction and reduced platelet production. Stimulation of platelet production may be an effective treatment for this disorder.\n We conducted a trial in which 118 adults with chronic ITP and platelet counts of less than 30,000 per cubic millimeter who had had relapses or whose platelet count was refractory to at least one standard treatment for ITP were randomly assigned to receive the oral thrombopoietin-receptor agonist eltrombopag (30, 50, or 75 mg daily) or placebo. The primary end point was a platelet count of 50,000 or more per cubic millimeter on day 43.\n In the eltrombopag groups receiving 30, 50, and 75 mg per day, the primary end point was achieved in 28%, 70%, and 81% of patients, respectively. In the placebo group, the end point was achieved in 11% of patients. The median platelet counts on day 43 for the groups receiving 30, 50, and 75 mg of eltrombopag were 26,000, 128,000, and 183,000 per cubic millimeter, respectively; for the placebo group the count was 16,000 per cubic millimeter. By day 15, more than 80% of patients receiving 50 or 75 mg of eltrombopag daily had an increased platelet count. Bleeding also decreased during treatment in these two groups. The incidence and severity of adverse events were similar in the placebo and eltrombopag groups.\n Eltrombopag increased platelet counts in a dose-dependent manner in patients with relapsed or refractory ITP. (ClinicalTrials.gov number, NCT00102739.)\n 2007 Massachusetts Medical Society", "Romiplostim, a thrombopoietin mimetic, increases platelet counts in patients with immune thrombocytopenia, with few adverse effects.\n In this open-label, 52-week study, we randomly assigned 234 adult patients with immune thrombocytopenia, who had not undergone splenectomy, to receive the standard of care (77 patients) or weekly subcutaneous injections of romiplostim (157 patients). Primary end points were incidences of treatment failure and splenectomy. Secondary end points included the rate of a platelet response (a platelet count >50×10(9) per liter at any scheduled visit), safety outcomes, and the quality of life.\n The rate of a platelet response in the romiplostim group was 2.3 times that in the standard-of-care group (95% confidence interval [CI], 2.0 to 2.6; P<0.001). Patients receiving romiplostim had a significantly lower incidence of treatment failure (18 of 157 patients [11%]) than those receiving the standard of care (23 of 77 patients [30%], P<0.001) (odds ratio with romiplostim, 0.31; 95% CI, 0.15 to 0.61). Splenectomy also was performed less frequently in patients receiving romiplostim (14 of 157 patients [9%]) than in those receiving the standard of care (28 of 77 patients [36%], P<0.001) (odds ratio, 0.17; 95% CI, 0.08 to 0.35). The romiplostim group had a lower rate of bleeding events, fewer blood transfusions, and greater improvements in the quality of life than the standard-of-care group. Serious adverse events occurred in 23% of patients (35 of 154) receiving romiplostim and 37% of patients (28 of 75) receiving the standard of care.\n Patients treated with romiplostim had a higher rate of a platelet response, lower incidence of treatment failure and splenectomy, less bleeding and fewer blood transfusions, and a higher quality of life than patients treated with the standard of care. ( ClinicalTrials.gov number, NCT00415532.)." ]

[ "4068085", "3673975", "8426771", "9655549", "7826118" ]

[ "Management of BCG adenitis in infancy.", "Is medical therapy effective for regional lymphadenitis following BCG vaccination?", "Evaluation of oral erythromycin and local isoniazid instillation therapy in infants with Bacillus Calmette-Guérin lymphadenitis and abscesses.", "Comparison of oral erythromycin, local administration of streptomycin and placebo therapy for nonsuppurative Bacillus Calmette-Guérin lymphadenitis.", "Needle aspiration for suppurative post-BCG adenitis." ]

[ "nan", "We describe 120 patients with regional lymphadenitis following intradermal BCG vaccination. Seventy-eight of the patients were given medical therapy to prevent drainage and suppuration, and 42 patients were followed up without such treatment. The medical therapy group is divided into three subgroups: 36 were given erythromycin stearate, 21 isoniazid, and 21 isoniazid plus rifampin. No statistical difference in the incidence of spontaneous drainage and suppuration was found between the \"no therapy\" and the \"medical therapy\" groups. No significant superiority of any specific therapy was shown. If lymphadenitis develops rapidly (in two months), the incidence of spontaneous drainage and suppuration is significantly higher than in patients with slowly developing lesions. Total surgical excision is recommended to prevent spontaneous drainage and chronic suppuration in these rapidly evolving instances.", "A randomized placebo-controlled prospective trial was conducted to evaluate the efficacy of erythromycin therapy in 69 patients affected with Bacillus Calmette-Guérin lymphadenitis. When patients who developed subsequent regional abscesses were excluded, erythromycin caused significantly earlier resolution of lymphadenitis (5.1 months vs. 5.7 months for placebo; P < 0.01) compared with placebo. There was no significant difference in the proportion of patients who developed subsequent regional abscesses between the 2 groups (47% for erythromycin, 60% for placebo, P = 0.14). When the entire group of 69 patients was evaluated for \"duration to heal\" (regardless of subsequent abscess formation), erythromycin therapy (4.1 +/- 1.5 SD months) did not differ significantly from the placebo group (3.5 +/- 1.3 months, P = not significant). Patients who developed subsequent abscess (n = 36) along with those with B. Calmette-Guérin regional abscesses at presentation (n = 27) were further studied to compare oral erythromycin therapy with that of single dose 50-mg intranodal isoniazid instillation. Local isoniazid therapy caused significantly earlier resolution of the abscesses (3.9 months) compared with erythromycin therapy (5.2 months; P < 0.001).", "nan", "The effect of needle aspiration in suppurative post-BCG adenitis was studied. Nodes that had been aspirated (43 patients) regressed in 25 (58%) and 41 (95%) patients two and six months after aspiration. In the control group (34 patients) regression occurred in three (9%) and 22 (65%) patients. Spontaneous drainage with sinus tract formation was also significantly less in the aspirated group at six months (7% v 44%)." ]

[ "2945109", "7546872", "11797655", "20054944", "7823996", "6450448", "9971865", "2931153", "12131705" ]

[ "How many days of bed rest for acute low back pain? A randomized clinical trial.", "Does 48 hours' bed rest influence the outcome of acute low back pain?", "Westeinde sciatica trial: randomized controlled study of bed rest and physiotherapy for acute sciatica.", "How many days of bed rest for acute low back pain? Objective assessment of trunk function.", "The treatment of acute low back pain--bed rest, exercises, or ordinary activity?", "Acute low-back pain. An objective analysis of conservative therapy.", "Lack of effectiveness of bed rest for sciatica.", "Clinical trial of common treatments for low back pain in family practice.", "Bed rest or normal activity for patients with acute low back pain: a randomized controlled trial." ]

[ "Bed rest is usually recommended for acute low back pain. Although the optimal duration of bed rest is uncertain, a given prescription may directly affect the number of days lost from work or other activities. In a randomized trial, we compared the consequences of recommending two days of bed rest (Group I) with those of recommending seven days (Group II). The subjects were 203 walk-in patients with mechanical low back pain; 78 percent had acute pain (less than or equal to 30 days), and none had marked neurologic deficits. Follow-up data were obtained at three weeks (93 percent) and three months (88 percent). Although compliance with the recommendation of bed rest was variable, patients randomly assigned to Group I missed 45 percent fewer days of work than those assigned to Group II (3.1 vs. 5.6 days, P = 0.01), and no differences were observed in other functional, physiologic, or perceived outcomes. For many patients without neuromotor deficits, clinicians may be able to recommend two days of bed rest rather than longer periods, without any perceptible difference in clinical outcome. If widely applied, this policy might substantially reduce absenteeism from work and the resulting indirect costs of low back pain for both patients and employers.", "Bed rest is a traditional treatment for back pain, yet only in recent years has the therapeutic benefit of this been questioned.\n The aim of this pilot study was to ascertain whether or not 48 hours' bed rest had an effect on the outcome of acute low back pain.\n The study was conducted as a randomized controlled trial to compare a prescription of 48 hours' strict bed rest with controls; the control subjects were encouraged to remain mobile and to have no daytime rest. Nine general practitioners from practices in the West Midlands recruited patients in the age range 16-60 years who presented with low back pain of less than seven days' duration, with or without pain radiation. The outcome measures assessed were: change in straight leg raise and lumbar flexion after seven days, Oswestry and Roland-Morris disability scores after seven days and 28 days, and time taken from work.\n Forty two patients were recruited: 20 were allocated to bed rest and 22 as controls. Compared with the bed rest group the control group had statistically better Roland-Morris scores at day seven (P < 0.05) but not at day 28. At day seven, there were no statistically significant differences between groups in straight leg raise or lumbar flexion measurements although the control group had a better mean lumbar flexion than the bed rest group. The improvement in disability scores at day seven compared with day one was similar for the two groups but more of the control group had fully recovered (defined as scores of one or zero on the Roland-Morris disability scale and five or less on the Oswestry disability scale) by day seven. Remaining mobile did not appear to cause any adverse effects. The number of days lost from work in both groups was equal. A large number of self-remedies and physical therapies were recorded by subjects from both groups.\n The results of this pilot study did not indicate whether bed rest or remaining mobile was superior for the treatment of acute low back pain; however, the study sample was small. Subjects in the control group possibly fared better as they appeared to have better lumbar flexion at day seven. It appears that 48 hours' bed rest cannot be recommended for the treatment of acute low back pain on the basis of this small study. Large-scale definitive trials are required to detect clinically significant differences.", "The authors conducted a study to compare the efficacies of three nonsurgical treatment strategies in patients with sciatica. Their hypothesis was that bed rest, physiotherapy, and continuation of activities of daily living (ADLs) (control treatment) are each of equivalent efficacy.\n This randomized controlled trial was designed for comparison of bed rest, physiotherapy, and continuation of ADLs. The setting was an outpatient clinic. General practitioners were asked to refer patients for treatment as soon as possible. The authors enrolled 250 patients (< 60 years of age) with sciatica of less than 1-month's duration and who had not yet been treated with bed rest or physiotherapy. Primary outcome measures were radicular pain (based on a visual analog pain scale [VAPS]) and hampered ADLs (Quebec Disability Scale [QDS]). Secondary outcome measures were the rates of treatment-related failure and surgical treatment. Measures were assessed at baseline and during follow up at 1, 2, and 6 months. Mean differences in VAPS and QDS scores between bed rest and control treatment were 2.5 (95% confidence interval [CI] -6.4 to 11.4) and -4.8 (95% CI -10.6 to 0.9) at 1 month and 0.9 (95% CI -8.7 to 10.4) and -2.7 (95% CI -9.9 to 4.4) at 2 months, respectively. The respective differences between physiotherapy and control treatment were 0.8 (95% CI -8.2 to 9.8) and -0.5 (95% CI -6.3 to 5.3) at 1 month and -0.3 (95% CI -9.4 to 10) and 0.0 (95% CI -7.2 to 7.3) at 2 months. The respective odds ratios for treatment failure and surgical treatment of bed rest compared with control treatment were 1.6 (95% CI 0.8-3.5) and 1.5 (95% CI 0.7-3.6) at 6 months. When physiotherapy was compared with control treatment, these ratios were 1.5 (95% CI 0.7-3.2) and 1.2 (95% CI 0.5-2.9) at 6 months, respectively.\n Bed rest and physiotherapy are not more effective in acute sciatica than continuation of ADLs.", "Bed rest is usually considered an efficient treatment for acute low back pain. However, the optimal duration of bed rest is still being discussed. The recommended periods vary from 2 days to 2 weeks. The duration of optimum length is an important topic given the economical and physiological drawbacks of prolonged inactivity. The purpose of this work is to measure objectively the efficacy of two different durations of bed rest through a dynamometric measure of trunk function. Some 51 male patients, students or self-employed, being treated for acute low back pain were randomized into two groups. Group I was prescribed a bed rest period of 3 days and group II, a period of 7 days. We used a multi-axis isoinertial trunk testing dynamometric device (Isostation B200, Isotechnologies, USA). Patients were all assessed on day 1 and also on day 5 for group I or on day 9 for group II. The variables measured in the sagittal plane were isometric torques in flexion and extension, unresisted range of motion, average dynamic torques and average velocities. Patients were also asked to fill in a visual analogue pain scale on both assessment days. The improvement of all performance measures were important and highly significant (P < 0.001) in both groups. The results of the functional testing and the visual analogue pain scale showed no significant differences between the groups. In these relatively young and motivated patients, a duration of bed rest of 3 days resulted in the same objective functional improvement of trunk function and pain rating as a period of 7 days. This shorter duration should be considered as preferable, given the same objective results but important physiological and economical advantages.", "Bed rest and back-extension exercises are often prescribed for patients with acute low back pain, but the effectiveness of these two competing treatments remains controversial.\n We conducted a controlled trial among employees of the city of Helsinki, Finland, who presented to an occupational health care center with acute, nonspecific low back pain. The patients were randomly assigned to one of three treatments: bed rest for two days (67 patients), back-mobilizing exercises (52 patients), or the continuation of ordinary activities as tolerated (the control group; 67 patients). Outcomes and costs were assessed after 3 and 12 weeks.\n After 3 and 12 weeks, the patients in the control group had better recovery than those prescribed either bed rest or exercises. There were statistically significant differences favoring the control group in the duration of pain, pain intensity, lumbar flexion, ability to work as measured subjectively, the Oswestry back-disability index, and number of days absent from work. Recovery was slowest among the patients assigned to bed rest. The overall costs of care did not differ significantly among the three groups.\n Among patients with acute low back pain, continuing ordinary activities within the limits permitted by the pain leads to more rapid recovery than either bed rest or back-mobilizing exercises.", "The roles of bedrest, antiinflammatory medication, and analgesic medication in the treatment of acute back strain were objectively analyzed to determine whether they have a measurable effect on the return of patients to full daily activities as well as on the relief of pain. Two hundred patients were studied prospectively. Each patient had the diagnosis of acute back strain, which was defined as nonradiating low-back pain. The results of the patient's neurologic examination, straight leg raising test, and lumbosacral spine roentgenograms had to be within normal limits for the patient to be included in the study. The results showed that bedrest, as compared with ambulation, will decrease the amount of time lost from work by 50%. Bedrest will also decrease the amount of discomfort by 60%. Analgesic medication, when combined with bedrest, will further decrease the amount of pain incurred, particularly when used in the first three days of the healing process. However, analgesic medication will not allow a more prompt return to work. Antiinflammatory medication, when added to bedrest in the treatment of lumbago, does not provide an advantage over bedrest alone.", "Bed rest is widely advocated for sciatica, but its effectiveness has not been established. To study the effectiveness of bed rest in patients with a lumbosacral radicular syndrome of sufficient severity to justify treatment with bed rest for two weeks, we randomly assigned 183 subjects to either bed rest or watchful waiting for this period. The primary outcome measures were the investigator's and patient's global assessments of improvement after 2 and 12 weeks, and the secondary outcome measures were changes in functional status and in pain scores (after 2, 3, and 12 weeks), absenteeism from work, and the need for surgical intervention. Neither the investigators who assessed the outcomes nor those involved in data entry and analysis were aware of the patients' treatment assignments.\n After two weeks, 64 of the 92 patients in the bed-rest group (70 percent) reported improvement, as compared with 59 of the 91 patients in the control (watchful-waiting) group (65 percent) (adjusted odds ratio for improvement in the bed-rest group, 1.2; 95 percent confidence interval, 0.6 to 2.3). After 12 weeks, 87 percent of the patients in both groups reported improvement. The results of assessments of the intensity of pain, the bothersomeness of symptoms, and functional status revealed no significant differences between the two groups. The extent of absenteeism from work and rates of surgical intervention were similar in the two groups.\n Among patients with symptoms and signs of a lumbosacral radicular syndrome, bed rest is not a more effective therapy than watchful waiting.", "The results of a multicentered randomised clinical trial are reported of bed rest and of a physiotherapy and education programme for patients who presented in family practice with an acute episode of low back pain. No beneficial effect of either treatment was observed on several clinical outcome measures, including straight leg raising, lumbar flexion, activities of daily living, and pain. In fact the results favoured early mobilisation over bed rest and suggested that the physiotherapy and education programme was doing more harm than good. Moreover, additional analyses, which focused on clinically interesting patient subgroups, discovered no subset of patients who benefited from either of the treatments under study. Having failed to identify any clinically important benefits, or other explanations for these negative results, we can only conclude that family doctors have little reason to prescribe either bed rest or isometric exercises to patients who suffer from low back pain.", "The management of common low back pain has two principal objectives: to relieve acute pain and to attempt prevention of transition to chronicity. Several studies have shown the ineffectiveness of prolonged periods of bed rest.\n To compare 4 days of bed rest with continued normal daily activity in acute low back pain, taking into account the type of work (physical or sedentary labor).\n This open, comparative multicenter study enrolled 281 ambulatory patients, ages 18 to 65 years, with low back pain (onset < 72 hours). The subjects did not have pain radiating below the buttocks and did not have work-related injuries. They were randomized into two treatment groups: one instructed to continue normal activity (insofar as the pain allowed), and the other prescribed 4 days of bed rest. After inclusion, patients were seen at three visits: on day 6 or 7, after 1 month, and after 3 months.\n On day 6 or 7, pain intensity was similar for both groups, as was the overall judgment of the treatment by patients and physicians. At 1 and 3 months, the groups again had equivalent intensity of back pain, functional disability, and vertebral stiffness. A higher proportion of patients in the bed rest group than in the normal activity group had an initial sick leave (86% vs 52%; P < 0.0001). This difference was greater for the patients whose work was sedentary.\n For patients with acute low back pain, normal activity is at least equivalent to bed rest. The findings of this study indicate that prescriptions for bed rest, and thus for sick leaves, should be limited when the physical demands of the job are similar to those for daily life activities." ]

[ "19194671", "19729582", "20434603" ]

[ "Dynamic splinting after treatment with botulinum toxin type-A: a randomized controlled pilot study.", "Combined botulinum toxin type A with modified constraint-induced movement therapy for chronic stroke patients with upper extremity spasticity: a randomized controlled study.", "Cyclic functional electrical stimulation does not enhance gains in hand grasp function when used as an adjunct to onabotulinumtoxinA and task practice therapy: a single-blind, randomized controlled pilot study." ]

[ "Over 1.5 million Americans are diagnosed with a stroke each year, and excessive flexion or extension (hypertonia) of upper extremity joints are common secondary conditions. The purpose of this study was to compare the efficacy of botulinum toxin type-A and manual therapy, with the adjunct treatment of dynamic splinting on range of motion, spasticity, and elbow flexor hypertonia, in a randomized trial.\n Thirty-six subjects were recruited for this pilot study and all exhibited hypertonia in elbow flexion. Six patients were excluded due to noncompliance. Testing was done with pre/post active range of motion in elbow extension, and the Modified Ashworth Scale (extension) for spasticity. All patients received the current standard of care: botulinum toxin type-A injections and manual therapy. Experimental patients were randomly assigned adjunct treatment with Elbow Extension Dynasplint.\n Thirty patients completed the study (mean age [SD] 52+/-17 years). The percentage of change in active range of motion in elbow extension was greater for the experimental than for control subjects (33.5% vs. 18.7%). The Modified Ashworth Scale (extension) scores showed comparable changes of a mean 9.3% improvement for experimental versus 8.6% for the control subjects.\n This study confirmed the efficacy of botulinum toxin type-A in tone management and occupational therapy in contracture reduction. It also showed the value of dynamic splinting in maintaining gains in range of motion.", "Botulinum toxin type A (BtxA) injection and modified constraint-induced movement therapy (mCIMT) are both promising approaches to enhance recovery after stroke. The combined application of these 2 promising modalities has rarely been studied. The aim was to investigate whether combined BtxA and mCIMT would improve spasticity and upper extremity motor function more than BtxA plus conventional rehabilitation in chronic stroke patients with upper extremity spasticity.\n In a prospective, randomized controlled, observer-blinded trial with 6-month follow-up, 32 patients (>or=1 year after stroke) with ability to actively extend >10 degrees at metacarpophalangeal and interphalangeal joints and 20 degrees at wrist of the affected upper limb were randomized to receive BtxA + mCIMT (combination group) or BtxA + conventional rehabilitation (control group) for 2 hours/day, 3 days/week for 3 months.The primary outcome assessed spasticity on the Modified Ashworth Scale. Secondary outcomes assessed real-world arm function (Motor Activity Log), laboratory motor activity (Action Research Arm Test), and patients' global satisfaction.\n A total of 32 stroke patients were recruited, and 29 completed the study. Spasticity significantly improved in all subjects at 4 weeks and 3 months postinjection without between-group differences.The combination group showed significantly greater improvements in elbow, wrist, and finger spasticity (P = .019, P = .019, and P < .001, respectively), affected upper extremity real-world arm function (P < .001) and laboratory motor activity (P < .001) than the control group at 6-month postinjection. Patients reported considerable satisfaction and no serious adverse events occurred.\n Combining BtxA and mCIMT is an effective and safe intervention for improving spasticity and motor function in chronic stroke patients. The results are promising enough to justify further studies. We recommend future research to address the likely need for including rehabilitation with BtxA to improve function in patients with poststroke spasticity.", "To determine whether onabotulinumtoxinA injections and task practice training with or without functional electrical stimulation (FES) improve upper limb motor function in chronic spastic hemiparesis.\n Randomized controlled trial.\n Outpatient spasticity clinic.\n Participants (N=23) had chronic spastic hemiparesis with moderate-severe hand impairment based on Chedoke-McMaster Assessment greater than or equal to 2.\n OnabotulinumtoxinA injections followed by 12 weeks of postinjection task practice. Participants randomly assigned to FES group were also fitted with an orthosis that provided FES.\n Motor Activity Log (MAL)-Observation was the primary outcome. Secondary outcomes were Action Research Arm Test (ARAT) and MAL-Self-Report.\n For the entire cohort, MAL-Observation mean item scores improved significantly from baseline to week 6 (P=.005) but did not remain significant at week 12. MAL-Self-Report mean item scores improved significantly (P=.009) from baseline to week 6 and remained significantly higher (P=.014) at week 12. ARAT total scores also improved significantly from baseline to week 6 (P=.018) and were sustained at week 12 (P=.032). However, there were no significant differences between the FES and no-FES groups for any outcome variable over time.\n Rehabilitation strategies that combine onabotulinumtoxinA injections and task practice therapy are feasible and effective in improving upper-limb motor function and reducing spasticity in patients with chronic spastic hemiparesis. However, the cyclic FES protocol used in this study did not increase gains achieved with the combination of onabotulinumtoxinA and task practice alone." ]

[ "8817707", "8353699", "11236818" ]

[ "The cost of treatment of psychiatric emergencies: a comparison of hospital and community services.", "A controlled trial of home-based acute psychiatric services. I: Clinical and social outcome.", "A randomized controlled trial of community-oriented and hospital-oriented care for discharged psychiatric patients: influence of personality disorder on police contacts." ]

[ "This study aimed to compare the costs of treatment by community-based and hospital-based psychiatric services. The design entailed random allocation of patients presenting with psychiatric emergencies over a subsequent 3-month period to one of two services, followed by retrospective quantification of service use and its cost for each group. One hundred patients with emergency presentations to the psychiatric service via the Accident and Emergency Department, liaison psychiatrist and approved social worker were included in the study. Their use of a range of terms of service was recorded and disaggregated costings of these items of service was calculated. The use of non-psychiatric services was similar for both groups, but the use of psychiatric services differed, with the hospital group making greater use of in-patient beds and the community group employing more frequent home-based interventions. The total cost of treatment for the community group (pound 56,000) was much lower than for the hospital group (pound 130,000), although the median patient cost was 50% higher in the community group (pound 938 v. pound 610), and a greater proportion of the community service expenditure (10% v. 2%) was due to failed contacts. Taken together with clinical outcome, which showed no advantages for the hospital-based service over the community-based service, our findings suggest that this form of community psychiatric service is a cost-efficient alternative to hospital-based care for this group of patients.", "While research has shown community-based psychiatric care to be as good as, or better than, hospital-based care, generalisation to clinical practice has been difficult. This prospective, randomised controlled study examined a community-based approach feasible within NHS conditions. Ninety-four patients were randomly allocated to experimental and 78 to control treatments and followed for one year. The groups were well matched apart from an excess of psychotic control patients. No differences in clinical or social functioning outcome were found. Both groups improved substantially on clinical measures in the first six weeks, with some slow consolidation thereafter. There were three suicides in the control group and one in the experimental group. Access to care was better in the experimental group (93% attended assessment) than in the control group (75% attended assessment).", "An important forensic psychiatric measure, contacts with police, was compared in a randomized, controlled trial of 155 patients with severe mental illness with a previous admission within the past two years. The patients, who also had their personality status addressed formally before randomization, were allocated to community multidisciplinary teams or to hospital-based care programs after discharge from in-patient care and were followed up for one year. A total of 138 patients (89%) had at least one post-baseline assessment and of these patients, 16 (12%) had at least one police contact in the year of the study, most of which were emergency assessments. The data showed significantly greater numbers of police contacts in patients with increasing severity of personality disturbance. Patients with such disturbance were six times more likely to have police contacts than those with no personality disorder. There were significantly more contacts in patients with borderline and antisocial (dissocial) personality disorder allocated to community-oriented care compared with hospital-oriented care. These findings have important implications for risk assessment in severe mental illness." ]

[ "6624427", "13954597", "6726466", "13907465", "13836053" ]

[ "Effects of an antenatal load of pyridoxine (vitamin B6) on the blood oxygen affinity and prolactin levels in newborn infants and their mothers.", "Pyridoxine supplementation during pregnancy. Clinical and laboratory observations.", "Effect of maternal pyridoxine X HCl supplementation on the vitamin B-6 status of mother and infant and on pregnancy outcome.", "The effects of pyridoxine supplements on the dental caries experience of pregnant women.", "Vitamin B6, serum lipids and placental arteriolar lesions in human pregnancy." ]

[ "The effects of a loading dose of pyridoxine (100 mg) given intramuscularly or per os to 24 earlier non-supplemented pregnant women at term was investigated. The in vitro oxygen affinity (P50) and the prolactin level in both maternal and newborn blood was sampled. The blood P50 values were measured by a variant of \"mixing method\". Blood prolactin levels were determined by RIA. After pyridoxine administration, the maternal P50 values increased moderately and the newborns' cord blood P50 values increased significantly when compared with the control group's (number of cases 12) values. The decrease of blood oxygen affinity was most pronounced in the supplemented groups in newborns' capillary blood at the age of five days. The pyridoxine supplementation had no effect on the maternal and the newborns' cord blood prolactin level or on the daily amount of breast milk. Pyridoxine supplementation of the mother at labour may influence favourably the oxygen transport function of the newborn's blood and it may be especially advantageous in early postnatal adaptation disturbances of newborns.", "nan", "The effect of maternal pyridoxine X HCl (PN-HCl) supplementation on the vitamin B-6 status of pregnant women and their infants at birth and on pregnancy outcome was investigated. Volunteer subjects were randomly assigned a daily vitamin B-6 supplement containing 0, 2.6, 5, 7.5, 10, 15 or 20 mg of PN-HCl in a double-blind study. The mean dietary vitamin B-6 intake of the group was 1.43 +/- 1.28 mg/day as estimated from 24-hour dietary recalls. Maternal plasma pyridoxal 5'-phosphate (PLP) levels were positively correlated with vitamin B-6 supplementation at 30 weeks gestation (r = 0.55, P less than 0.0005) and at delivery (r = 0.54, P less than 0.01). Cord plasma PLP levels reached a maximum when maternal PN-HCl supplementation was 7.5 mg and greater. Supplemental PN-HCl at the 7.5-mg level was required to prevent a decrease in maternal plasma PLP at delivery. Apgar scores at 1 minute after birth were higher (P less than 0.05) for infants whose mothers took 7.5 mg or more supplemental PN-HCl than for infants of mothers who took 5 mg or less. These findings indicate that a vitamin B-6 intake between 5.5 and 7.6 mg/day (diet plus supplement as pyridoxine equivalents) was required to maintain maternal plasma PLP levels at term at a level comparable to initial values.", "nan", "nan" ]

[ "1608408", "9434669", "16543297", "9033521" ]

[ "A randomized trial of a program to reduce the use of psychoactive drugs in nursing homes.", "The impact of regular multidisciplinary team interventions on psychotropic prescribing in Swedish nursing homes.", "Effect of enhanced psychosocial care on antipsychotic use in nursing home residents with severe dementia: cluster randomised trial.", "Predictors of antipsychotic withdrawal or dose reduction in a randomized controlled trial of provider education." ]

[ "Although psychoactive medications have substantial side effects in the elderly, these drugs are used frequently in nursing homes. Few interventions have succeeded in changing this situation, and little is known about the clinical effects of such interventions.\n We studied six matched pairs of nursing homes; at one randomly selected nursing home in each pair, physicians, nurses, and aides participated in an educational program in geriatric psychopharmacology. At base line we determined the type and quantity of drugs received by all residents (n = 823), and a blinded observer performed standardized clinical assessments of the residents who were taking psychoactive medications. After the five-month program, drug use and patient status were reassessed.\n Scores on an index of psychoactive-drug use, measuring both the magnitude and the probable inappropriateness of medication use, declined significantly more in the nursing homes in which the program was carried out (experimental nursing homes) than in the control nursing homes (decrease, 27 percent vs. 8 percent; P = 0.02). The use of antipsychotic drugs was discontinued in more residents in the experimental nursing homes than in the control nursing homes (32 percent vs. 14 percent); the comparable figures for the discontinuation of long-acting benzodiazepines were 20 percent vs. 9 percent, and for antihistamine hypnotics, 45 percent vs. 21 percent. In the experimental nursing homes residents who were initially taking antipsychotic drugs showed less deterioration on several measures of cognitive function than similar residents in the control facilities, but they were more likely to report depression. Those who were initially taking benzodiazepines or antihistamine hypnotic agents reported less anxiety than controls but had more loss of memory. Most other measures of clinical status remained unchanged in both groups.\n An educational program targeted to physicians, nurses, and aides can reduce the use of psychoactive drugs in nursing homes without adversely affecting the overall behavior and level of functioning of the residents.", "To evaluate the impact of regular multidisciplinary team interventions on the quantity and quality of psychotropic drug prescribing in Swedish nursing homes.\n A randomized controlled trial.\n 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 long-term care residents with an average age of 83 years. Seventy percent of the residents were women, and 42% had a documented diagnosis of dementia. An additional 5% had a psychotic disorder, and 7% had a diagnosis of depression.\n Experimental homes participated in an outreach program that was designed to influence drug use through improved teamwork among physicians, pharmacists, nurses, and nurses' assistants. Multidisciplinary team meetings were held on a regular basis throughout the 12-month study period.\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 with any psychotropic drug, polymedicine, and therapeutic duplication and proportion of residents with nonrecommended and acceptable drugs in each psychotropic drug class, as defined by current Swedish guidelines.\n Baseline results show extensive psychotropic drug prescribing, with the most commonly prescribed drugs being hypnotics (40%), anxiolytics (40%), and antipsychotics (38%). After 12 months of team meetings in the experimental homes, there was a significant decrease in the prescribing of psychotics (-19%), benzodiazepine hypnotics (-37%), and antidepressants (-59%). Orders for more acceptable antidepressants also increased in the experimental homes. In the control homes there was increased use of acceptable antidepressants, but there were no significant reductions in other drug classes.\n There is excessive prescription of psychotropic drugs in Swedish nursing homes. Improved teamwork among caregivers can improve prescribing as defined by clinical guidelines.", "To evaluate the effectiveness of a training and support intervention for nursing home staff in reducing the proportion of residents with dementia who are prescribed neuroleptics.\n Cluster randomised controlled trial with blinded assessment of outcome.\n 12 specialist nursing homes for people with dementia in London, Newcastle, and Oxford.\n Residents of the 12 nursing homes; numbers varied during the study period.\n Training and support intervention delivered to nursing home staff over 10 months, focusing on alternatives to drugs for the management of agitated behaviour in dementia.\n Proportion of residents in each home who were prescribed neuroleptics and mean levels of agitated and disruptive behaviour (Cohen-Mansfield agitation inventory) in each home at 12 months.\n At 12 months the proportion of residents taking neuroleptics in the intervention homes (23.0%) was significantly lower than that in the control homes (42.1%): average reduction in neuroleptic use 19.1% (95% confidence interval 0.5% to 37.7%). No significant differences were found in the levels of agitated or disruptive behaviour between intervention and control homes.\n Promotion of person centred care and good practice in the management of patients with dementia with behavioural symptoms provides an effective alternative to neuroleptics.", "To evaluate the effects of an educational program to reduce antipsychotic use in nursing homes that had high use rates post-OBRA-87 and to identify factors that predicted antipsychotic withdrawal or 50% or greater dose reduction.\n A randomized controlled trial (RCT) of the educational program (nursing home the unit of randomization and analysis) was conducted in 12 Tennessee nursing homes (6 education/6 control). Cohort analysis in baseline antipsychotic users identified factors predicting withdrawal or dose reduction.\n The RCT analysis included 1152 patients in the homes at baseline and 6 months. The cohort analysis included 133 baseline antipsychotic users in the five education homes able to implement the recommendations of the educational program.\n Change in days of antipsychotic use per 100 days of nursing home residence, withdrawal from antipsychotics, reduction in antipsychotic dose by 50% or more.\n Following the educational intervention, use of antipsychotics in the six education homes decreased from 25.3 days per 100 at baseline to 19.7 days per 100 by month 6, a 23% reduction relative to control homes (P = .014). In the withdrawal analysis, 44 (33%) of 133 baseline antipsychotic users were withdrawn. Factors at baseline predicting successful withdrawal were low antipsychotic dose, no use of benzodiazepines or antidepressants, and behavioral symptoms score below the median. However, although an additional 22 patients had dose reductions > or = 50%, none of the predictors of withdrawal were associated with dose reductions.\n Focused provider education programs may facilitate antipsychotic reduction above and beyond that attributable to regulatory changes. Patients who are poor candidates for total antipsychotic withdrawal may tolerate substantial dose reductions, which should reduce their risk of adverse antipsychotic effects." ]

[ "22475493" ]

[ "Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial." ]

[ "Most previous studies of the use of cervical pessaries were either retrospective or case controlled and their results showed that this intervention might be a preventive strategy for women at risk of preterm birth; no randomised controlled trials have been undertaken. We therefore undertook a randomised, controlled trial to investigate whether the insertion of a cervical pessary in women with a short cervix identified by use of routine transvaginal scanning at 20-23 weeks of gestation reduces the rate of early preterm delivery.\n The Pesario Cervical para Evitar Prematuridad (PECEP) trial was undertaken in five hospitals in Spain. Pregnant women (aged 18-43 years) with a cervical length of 25 mm or less were randomly assigned according to a computer-generated allocation sequence by use of central telephone in a 1:1 ratio to the cervical pessary or expectant management (without a cervical pessary) group. Because of the nature of the intervention, this study was not masked. The primary outcome was spontaneous delivery before 34 weeks of gestation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00706264.\n 385 pregnant women with a short cervix were assigned to the pessary (n=192) and expectant management groups (n=193), and 190 were analysed in each group. Spontaneous delivery before 34 weeks of gestation was significantly less frequent in the pessary group than in the expectant management group (12 [6%] vs 51 [27%], odds ratio 0·18, 95% CI 0·08-0·37; p<0·0001). No serious adverse effects associated with the use of a cervical pessary were reported.\n Cervical pessary use could prevent preterm birth in a population of appropriately selected at-risk women previously screened for cervical length assessment at the midtrimester scan.\n Instituto Carlos III.\n Copyright © 2012 Elsevier Ltd. All rights reserved." ]

[ "8159193" ]

[ "Discontinuing antiepileptic drugs in children with epilepsy. A comparison of a six-week and a nine-month taper period." ]

[ "The optimal regimen for discontinuing antiepileptic medications in children with epilepsy is unknown.\n We randomly assigned 149 children to either a six-week or a nine-month period of drug tapering, after which therapy was discontinued. Each group was composed of patients who had been seizure-free for either two or four years before drug tapering was begun. Most patients were receiving one antiepileptic drug; none were taking more than two. The children were evaluated periodically during and after the taper period. Sixteen patients were lost to follow-up before the beginning of the taper period. Proportional-hazards regression analysis was used to assess the risk of seizure recurrence among the remaining 133 patients.\n Seizures recurred in 53 patients (40 percent). The mean duration of follow-up was 39 months (range, 11 to 105) for the patients who did not have a recurrence of seizures. Neither the length of the taper period (six weeks vs. nine months, P = 0.38) nor the length of time the patients were free of seizures before the taper period was begun (two years vs. four years, P = 0.20) significantly influenced the risk of seizure recurrence. The presence of mental retardation (relative risk, 3.1, 95 percent confidence interval, 1.5 to 6.2) or spikes in the electroencephalogram at the time of tapering (relative risk, 1.9, 95 percent confidence interval, 1.0 to 3.4) increased the risk of seizure recurrence.\n The risk of seizure recurrence during drug tapering and after the discontinuation of antiepileptic drug therapy in children with epilepsy is not different whether the medications are tapered over a six-week or a nine-month period." ]

[ "8746601", "2001777", "3440987", "1925430", "1538559", "7936332", "7795830", "6599665" ]

[ "Diet and exercise intervention have favourable effects on blood pressure in mild hypertensives: the Oslo Diet and Exercise Study (ODES).", "Weight reduction in obese hypertensive patients.", "How useful is weight reduction in the management of hypertension?", "The effect of a weight reduction program on cardiovascular risk factors among overweight hypertensives in primary health care.", "Renin predicts diastolic blood pressure response to nonpharmacologic and pharmacologic therapy.", "[The effect on left ventricular mass of treatment with amlodipine and diet therapy in obese patients with arterial hypertension].", "Trial of Nonpharmacologic Intervention in the Elderly (TONE). Design and rationale of a blood pressure control trial.", "Effect of dietary change on the return of hypertension after withdrawal of prolonged antihypertensive therapy (DISH). Dietary Intervention Study of Hypertension." ]

[ "The purpose of this study was to investigate the effect of 1-year diet intervention, exercise intervention and both combined on blood pressure (BP) in normotensives and mild hypertensives. Two hundred and nineteen sedentary middle aged men and women with slightly deranged coronary heart disease (CHD) risk factors were randomised to a control, a diet, an exercise and a diet + exercise group. Based on baseline diastolic BP, participants were divided into tertiles, giving baseline average BP of 141.4/96.7 in tertile 1, 130.7/87.6 in tertile 2 and 121.9/79.0 in tertile 3. The 1-year net-difference in BP between the intervention groups and the control group decreased across the tertiles; in tertile 1 being -11.2/-6.7 (p < 0.05), -11.3/-6.7 (p < 0.05 for systolic BP only) and -7.0/-5.1 (NS) in the combined, diet and exercise group respectively. Triglycerides, HDL cholesterol, and insulin variables were significantly and favourably changed, the changes being most marked in the combined group. The results show that diet and diet + exercise are about equally effective in reducing BP, and the effects may be dependent on the baseline level. Within the upper tertile of baseline BP, the decline in BP in the combined intervention and the diet group are almost comparable to those obtained with drug treatment. In addition, other important CHD risk factors were all changed in a beneficial direction.", "This study tested the feasibility of a low-technology office-based approach to weight reduction in obese hypertensive patients. Family practice residents were randomly assigned to either an experimental or a control group. Physicians in the experimental group were instructed in methods of weight reduction, which they then passed on to their patients. Patients of experimental physicians were seen monthly, their diets were discussed, and improvements were suggested. The control group patients received their usual care. After six months the experimental patients had lost significantly more weight than the controls and had significantly reduced the number of antihypertensive drugs while maintaining blood pressure control. After 12 months there was no significant difference between the two groups with respect to weight loss, blood pressure, or number of antihypertensive drugs. Experimental and control patients who lost weight had visited their physicians more frequently than those who did not and had reduced the number of antihypertensive medications they were taking. This educationally oriented intervention trial is an example of the type of research that is practical to perform in a family practice center and is applicable in family physicians' offices.", "A group of previously untreated obese hypertensive patients were started on a weight reduction programme supervised by two dietitians working in a general practice surgery. It was stressed from the beginning of the programme that reducing blood pressure was the purpose of the diet. The results of follow-up after six months are presented together with results for a control group of obese hypertensive patients not receiving dietary advice or drug therapy, but being followed by the general practitioner. The weight, systolic blood pressure and diastolic blood pressure of the dieting hypertensive group were significantly lower than those of the non-dieting group after six months. However, the drop-out rate was significantly higher for the dieting group than for the non-dieting group.The results of a separate comparison between a control group of obese normotensive patients following the same dietary programme and the group of dieting obese hypertensive patients are also presented. Attendance rates and weight loss achieved were significantly better for the hypertensive group than for the normotensive group after 12 months.Weight reduction appears to be an effective first-line therapy for approximately 50% of obese patients with mild to moderate hypertension, and raised blood pressure appears to provide motivation for such patients to attend a dietitian's clinic and to lose weight.", "The aim of the study was to test the effect of a nonpharmacological weight reduction program on cardiovascular risk factors among overweight hypertensives in a primary health care setting. Forty-nine overweight hypertensive patients completed the 12-month program. The patients were randomly allocated into either intervention or control groups. The examinations included interviews by a nutritionist, pertinent laboratory tests, and a medical examination. The intervention involved an individually planned energy-restricted diet of 1000-1500 kcal per day, weekly discussions, and various leaflets on diet modification and on increase of physical activity. The mean body weight was reduced by 5 kg in the intervention group, but remained unchanged in the control group. The intervention group reduced their fat intake by 14 g/day while the control group increased it by 9 g/day on the average. In the intervention group, the total serum cholesterol decreased, HDL-cholesterol increased and triglycerides decreased significantly. The systolic blood pressure fell by 8 mm Hg and 15 mm Hg in the intervention and control groups, respectively. The diastolic blood pressure fell on average by 11 mm Hg in both groups. The results demonstrate the comprehensive weight reduction program to be effective in the control of cardiovascular risk factors.", "Plasma renin activity was measured at baseline and 6 months in a trial of nonpharmacologic therapy of mild hypertension to determine whether plasma renin activity predicts the diastolic blood pressure (DBP) response to nonpharmacologic therapy.\n Randomized controlled trial of volunteers from the general community with mild hypertension (DBP between 90 and 100 mm Hg), off all antihypertensive therapy at baseline, treated in special research clinics (n = 593).\n Subjects were randomly assigned to usual, weight loss, or low sodium/high potassium diet and then randomly assigned to receive placebo, chlorthalidone, or atenolol.\n Renin was analyzed as plasma renin activity and as a renin index (logarithm of 24-hour urinary sodium excretion times logarithm of plasma renin activity) (593 patients at baseline and 6 months) to correct for varied sodium intakes. The DBP was measured using the random zero device.\n Change in DBP at 6 months could be predicted from baseline plasma renin activity or renin index. The DBP was decreased after 6 months of therapy by 2 mm Hg for each unit increase in baseline plasma renin activity and by 0.16 mm Hg for each unit increase in baseline renin index. Patients in the highest renin index quartile had a greater DBP response to atenolol therapy, and patients in the lowest renin index quartile had a greater DBP response to chlorthalidone therapy. Weight loss diet achieved a greater reduction in DBP in patients with higher baseline renin index and had an additive effect on DBP response in both of the drug groups. Patients on a weight loss diet receiving placebo in the highest baseline renin index quartile had a reduction in DBP of 12.4 mm Hg, compared with 4.4 mm Hg in the lowest baseline renin index quartile (P = .009). A low sodium/high potassium diet had a lesser effect than a weight loss diet on pharmacologic therapy. As with the weight loss diet, patients on a low sodium/high potassium diet in the highest baseline renin index quartile had a greater reduction in DBP than patients in the lowest baseline renin index quartile.\n These data suggest a significant relationship between baseline levels of plasma renin index and the likelihood of success of nonpharmacologic treatment of hypertension.", "Increased parietal stress, in hypertensive obese patients, produces a left ventricular hypertrophy. In this study we demonstrated that the association of amlodipine with hypocaloric diet can decrease the parietal stress. MATERIALS AND METHODS. From February to July 1993 32 hypertensive obese patients (17 males, 15 females) were treated with amlodipine 10 mg/day for six months. Sixteen patients were treated with amlodipine 10 mg/day (Group A) and 16 patients were treated with amlodipine 10 mg/day and hypocaloric diet (Group B). All patients included had a Body Mass Index > 30 and diastolic blood pressure > 100 mmHg. The patients were studied with 2D guided M-mode echocardiogram before treatment and after 6 months. RESULTS. In Group A the septal thickness, the posterior wall thickness and the left ventricular mass decreased significatively (p < 0.05). In the Group B also the left ventricular diastolic diameter and the left atrial diameter decreased. CONCLUSION. The association of a hypocaloric diet with amlodipine therapy, in hypertensive obese patients, improves the effect of the drug on ventricular hypertrophy.", "National and international policy-making organizations advocate nonpharmacologic therapies to reduce blood pressure (BP). However, data to support such recommendations in older persons are virtually nonexistent. The Trials of Nonpharmacologic Intervention in the Elderly (TONE) is a randomized, controlled trial that will test whether weight loss or a reduced sodium (Na) intake or both can maintain satisfactory BP control, without unacceptable side effects, after withdrawal of antihypertensive drug therapy. Medication-treated hypertensives (aged 60 to 80 years) with a systolic BP less than 145 mm Hg and a diastolic BP less than 85 mm Hg who are taking one antihypertensive medication are randomly assigned to one of four groups: (1) weight loss alone, (2) reduced Na intake alone, (3) combined weight loss and reduced Na intake, or (4) usual life-style (control group). Overweight participants are randomized to one of these four groups, while nonoverweight individuals are assigned to either the reduced Na intake or the usual life-style group. The interventions, tailored to the needs of older persons, use behavioral approaches to accomplish intervention-specific goals (weight loss > or = 10 lb, daily Na intake < or = 80 mEqa). Three months after the start of intervention, antihypertensive drug therapy is withdrawn. The primary trial end point is a BP of 150/90 mm Hg or higher, resumption of antihypertensive drug therapy, or the occurrence of a BP-related clinical complication during 2 to 3 years of follow-up. It is anticipated that TONE findings may identify an effective and acceptable nonpharmacologic approach to control hypertension in the increasingly large number of older persons treated with antihypertensive drug therapy.", "The possibility exists that dietary modification may increase the number of patients who remain normotensive after drug withdrawal. In an effort to resolve this question, former Hypertension Detection and Follow-up Program Stepped Care participants (n = 496) were randomized into four major groups at the end of the programme (greater than 5 years antihypertensive therapy): controls (continue medication); discontinue medication, no dietary intervention; discontinue medication and weight loss; discontinue medication and reduce sodium. Groups 1, 2 and 4 were further divided into obese (greater than or equal to 120% ideal weight, and non-obese groups). The weight reduction group (greater than or equal to 120% ideal weight) lost 10.1 +/- 11 lbs without changing dietary sodium (n = 87). The sodium restriction group reduced urine sodium excretion from 145 to 97 mEq per day (n = 169). Sixty per cent of the weight loss group were normotensive at 56 weeks compared to 35% withdrawn from medication without dietary intervention. The highest 56 weeks success rates were in the mild non-overweight hypertensives on sodium restriction (78%), and the mild overweight hypertensives on weight reduction (72%). Randomization to either weight loss group or sodium restriction group increased the likelihood of remaining off drugs (adjusted odds ratio of 3.43 for the weight group and 2.17 for the sodium group (P less than 0.05). Age, severe hypertension greater than 5 years previous to entry into Dietary Intervention Study of Hypertension (DISH) or need for several drugs increased the chance of failure." ]

[ "7044462", "797427" ]

[ "Treatment of T3 bladder cancer: controlled trial of pre-operative radiotherapy and radical cystectomy versus radical radiotherapy.", "The management of deeply infiltrating (T3) bladder carcinoma: controlled trial of radical radiotherapy versus preoperative radiotherapy and radical cystectomy (first report)." ]

[ "nan", "The preliminary results are presented of a multicentre, co-operative randomised trial, sponsored by the Institute of Urology, London, in which radical irradiation (6,000 rads in 6 weeks) is compared with preoperative irradiation (4,000 rads in 4 weeks) plus radical cystectomy for deeply infiltrating carcinoma of the bladder (Stage T3 or B2C). 189 of the 199 cases entered into the trial between 1966 and 1975 were eligible for study. The overall 3- and 5-year survival rates for combined treatment were 41% and 33%, respectively, compared with 28% and 21% for radical radiotherapy. The operative mortality was 7.8%. The difference between the two treatments in favour of the combined treatment has not yet reached the generally accepted level of significance (P less than 0.05), the p factors for the 3- and 5-year results being 0.064 and 0.077, respectively. Of patients receiving the protocol combined treatment, reduction in tumour stage was found in the surgical specimen in 47% of cases. The overall incidence of nodal metastases was 23% (against the usual figure of 40-50%), and in the presence of a good response of the primary tumour to irradiation, only 8%. The 3- and 5-year survival rates for the down-staged cases were 66% and 55%, respectively, compared with 29% and 22% for patients showing no stage reduction in the surgical specimen. The aim of our future studies is to find effective radiosensitising and cytotoxic agents with which to try and increase the incidence and degree of tumour response to pre-operative irradiation in the combined modality treatment of T3 bladder cancers." ]

[ "7032378", "4603999", "2040103", "13492604", "3538487", "11001866", "13970249", "6383740", "3902388", "8625660", "9616526", "6758833", "6347233", "3465581", "8511727", "2180105", "1412119", "10095821", "3514164", "1521875" ]

[ "Steroid response in stable chronic obstructive pulmonary disease.", "A controlled trial of prednisone, in low dosage, in patients with chronic airways obstruction.", "Prediction of nonresponse to corticosteroids in stable chronic airflow limitation.", "Long-continued treatment with tetracycline and prednisolone in chronic bronchitis; a controlled trial.", "Value of serial peak expiratory flow measurements in assessing treatment response in chronic airflow limitation.", "Additive effects of prednisolone and beclomethasone dipropionate in patients with stable chronic obstructive pulmonary disease.", "A controlled study of the effect of prednisone on air-flow obstruction in severe pulmonary emphysema.", "Treatment of chronic obstructive pulmonary disease with corticosteroids. Comparison of daily vs alternate-day therapy.", "Effect of steroid therapy on exercise performance in patients with irreversible chronic obstructive pulmonary disease.", "Effects of long-term treatment with corticosteroids in COPD.", "The effect of oral corticosteroids on bronchodilator responses in COPD.", "The use of the 12 minute walking test in assessing the effect of oral steroid therapy in patients with chronic airways obstruction.", "Response to oral corticosteroids in chronic airflow obstruction.", "A double-blind comparison of oral prednisolone 40 mg/day with inhaled beclomethasone dipropionate 1500 ug/day in patients with adult onset chronic obstructive airways disease.", "Effects of high dose inhaled beclomethasone dipropionate, 750 micrograms and 1500 micrograms twice daily, and 40 mg per day oral prednisolone on lung function, symptoms, and bronchial hyperresponsiveness in patients with non-asthmatic chronic airflow obstruction.", "Corticosteroid trials in non-asthmatic chronic airflow obstruction: a comparison of oral prednisolone and inhaled beclomethasone dipropionate.", "Effects of corticosteroids on bronchodilator action in chronic obstructive lung disease.", "The response to inhaled and oral steroids in patients with stable chronic obstructive pulmonary disease.", "Corticosteroids in COPD. A clinical trial and reassessment of the literature.", "Role of corticosteroids in the management of chronic obstructive lung disease: factors predicting response." ]

[ "We compared a 2-week course of 32 mg/d methylprednisolone with placebo in a double-blind crossover trial in 46 well-characterized patients with stable chronic obstructive pulmonary disease. Placebo and steroid trials were separated by 2 weeks when no tablets were given. Response was assessed by measuring forced expiratory volume in 1 second (FEV1.0). Placebo responses were normally distributed (mean, 0.8% change in FEV1.0; range, -30% to 33%). Six patients showed a greater than 50% increase of FEV1.0 in response to steroid; a seventh showed a 36% increase and an eighth, a 29% increase. Because of these patients the group as a whole showed a significantly greater FEV1.0 after steroid than after placebo. The eight steroid responders did not differ from nonresponders in age, sex, smoking history, or duration and intensity of symptoms including wheeze. Baseline lung function and eosinophilia of blood or sputum did not differ between the two groups. Patients who responded to steroids also responded to inhaled beta agonists: Acute bronchodilator response averaged 25% in steroid responders and 13% in nonresponders, a difference that was statistically significant although there was overlap between the two groups.", "nan", "The efficacy of corticosteroids in chronic airflow limitation is variable and nonpredictable. We believe that the corticosteroid-induced improvement seen in a few subjects with chronic airflow limitation indicates coexistent bronchial asthma. Therefore, we hypothesize that by carefully excluding all features (other than corticosteroid response), either objective or subjective, that might be consistent with coexisting asthma, we could predict non-response to corticosteroids. Twenty patients with chronic airflow limitation related to cigarette smoking were chosen. Features that might suggest coexisting asthma were carefully excluded; these included rhinitis, nocturnal symptoms, atopy, large response to bronchodilator, and sputum or blood eosinophilia. Eighteen of these 20 subjects completed a double-blind random-order cross-over placebo-controlled trial of 30 mg of prednisone for 14 d (with a 14 d washout between treatments). There were no significant differences, individually or collectively, in objective or subjective determinations. Based on a greater than or equal to 250 mL improvement in FEV1, there were two placebo responders and two prednisone responders. Although it may be difficult to predict corticosteroid response in chronic airflow limitation, it appears that careful exclusion of 'asthmatic tendencies' may predict nonresponse to corticosteroids.", "nan", "A double blind, randomised, placebo controlled, crossover trial of prednisolone (40 mg/day for 14 days) was carried out in 33 patients with chronic airflow limitation (mean age 62 years, mean FEV1 1.01 litres, mean FEV1/FVC ratio 44%), to assess the value of serial peak expiratory flow (PEF) measurements, taken five times daily in evaluating treatment response by comparison with other objective measurements and with measurements of symptoms. The mean serial PEF after a one week run in period was 189 1 min-1, during the second week of placebo 193 1 min-1, and during the second week on prednisolone 231 1 min-1. The difference in mean PEF values between placebo and prednisolone was significant (p less than 0.01). With regard to the response to steroids of the individual patients, 13 of the 33 had a detectable trend of improvement on visual inspection of serial PEF measurements during prednisolone treatment but only one during placebo administration. Of all the objective measurements made after the run in and after each treatment phase (12 minute walking distance, FEV1, forced vital capacity (FVC), serial PEF), the serial PEF chart provided the best discrimination between placebo and prednisolone treatment. There was no statistically significant association between steroid induced improvement in serial PEF measurements and in breathlessness, partly because of placebo improvements in symptoms in those who had no improvement in serial PEF values. This study indicates the importance of making objective measurements to identify a genuine steroid response rather than relying on symptomatic improvement alone. The best simple measurement to make is serial PEF during steroid trials. This is more sensitive in detecting a steroid response than are the 12 minute walking distance, FEV1, or FVC, and is also less likely than these measurements to show spurious placebo responses.", "It remains unclear whether inhaled corticosteroids can produce the maximum benefits of corticosteroids in patients with chronic obstructive pulmonary disease (COPD). To assess the additive effects of 30 mg/day prednisolone to high-dose, inhaled beclomethasone dipropionate (BDP), we conducted a randomised double-blind, placebo-controlled cross-over trial. The study population consisted of 21 men with stable COPD. The mean age of the patients was 69.1 +/- 6.8 years, and FEV(1)was 0.86 +/- 0.28 l. Seventeen out of the 21 patients (81%) were considered susceptible to steroids in a previous trial (FEV(1)increased at least 15% from baseline after receiving 14 days of 30 mg/day prednisolone). All of the patients had been on 1600 microg/day BDP for more than 3 months. Spirometry was performed before the entry, and at the end of 3-week placebo and prednisolone periods. The peak expiratory flow (PEF), symptoms, and Guyatt's Chronic Respiratory Disease Questionnaire (CRQ) as a disease specific health-related quality of life over the last seven days of each period were also evaluated. Although a marginal increase in PEF was found during the prednisolone period, no significant differences in FEV(1), FVC, symptoms or CRQ scores were observed between the two treatment periods. We conclude that the therapeutic effects of steroid therapy may be achieved by the long-term use of high-dose, inhaled corticosteroid in some patients with stable COPD.\n Copyright 2000 Academic Press.", "nan", "We compared the efficacy of corticosteroid therapy initiated as an alternate-day regimen to that of a four-times-daily regimen in patients with stable chronic obstructive pulmonary disease. In this double-blind study, 44 patients with moderate to severe COPD (mean FEV1 740 +/- 310 ml) were hospitalized and randomly allocated to receive methylprednisolone, 8 mg qid, 64 mg qod, or placebo for a ten-day period. The mean FEV1 and FVC improved significantly to a comparable degree in both steroid-treated groups, but not in the placebo-treated group. Eight of the 29 steroid-treated patients (28 percent) had improved FEV1 of more than 25 percent compared with only one of the 15 placebo-treated patients. Those in the qod group also had notable improvement in SaO2. Although the correlation between the improvement after the administration of nebulized bronchodilators and that after corticosteroid therapy was significant, some patients had more than a 25 percent improvement in their FEV1 with corticosteroids, but less than a 10 percent improvement after nebulized bronchodilators. We conclude that a substantial proportion of all patients with stable COPD will have a greater than 25 percent improvement in their flow rates with corticosteroid administration. Since the response to a qod regimen is comparable to that of a qid regimen, and since the qod regimen is associated with fewer side effects, we recommend that a qod regimen be tried initially.", "Many patients with irreversible chronic obstructive pulmonary disease (COPD) claim symptomatic improvement with steroid therapy, despite a lack of objective improvement in their spirometric data. To determine if steroids actually increase the exercise capacity of these individuals, 13 clinically stable patients (mean age, 63 +/- 4 years; 12 male patients) were given methylprednisolone (32 mg once daily) or placebo in a randomized double-blind crossover fashion. Spirometric data and minute ventilation, oxygen consumption (VO2), carbon dioxide production, and heart rate during incremental exercise were measured at each visit. Methylprednisolone did not produce a significant change in any of the measured parameters. Three patients had an increase in maximal VO2 of greater than 2 ml/kg/min during therapy with methylprednisolone, while two experienced a decline in maximal VO2 of similar magnitude. The change in exercise capacity was unrelated to the change in the forced expiratory volume in one second in individual patients (r = 0.08). We conclude that in the absence of any improvement in the usual tests of airway mechanics, steroid therapy does not improve exercise performance in patients with COPD.", "To determine the effectiveness of treatment with corticosteroids in patients with COPD.\n In this study, we investigated the effect of a 2-year treatment with corticosteroids on clinical symptoms and the decline of lung function in 58 nonallergic patients with COPD. Subjects were treated in a double-blind, randomized, placebo-controlled, parallel way with inhaled budesonide (bud), 1,600 micrograms/d; inhaled budesonide, 1,600 micrograms/d, plus oral prednisolone, 5 micrograms/d (bud + pred); or placebo (plac). Clinical assessment (history, physical examination, and spirometry) was carried out every 2 months. The rate of decline in FEV1 was assessed by calculating individual regression co-efficients from linear regression of FEV1 on time for each subject.\n Eleven patients dropped out. The number of withdrawals due to pulmonary problems was significantly higher in the plac group (n = 5 out of 18) than in the actively treated groups (n = 2 out of 40). Treatment with corticosteroids significantly reduced pulmonary symptoms. Median decline of FEV1 was 60 mL/yr in the plac group, 40 mL/yr in the bud + pred group, and 30 mL/yr in the bud group. Variation was large and differences were not statistically significant. No treatment effect was found on frequency or duration of exacerbations, possibly because of the high number of withdrawals due to pulmonary deterioration in the plac group. Treatment with a combination of inhaled plus oral corticosteroids was not more effective than inhaled corticosteroids alone. Morning plasma cortisol levels remained within the normal range in all three groups.\n Our study shows beneficial effects of long-term daily treatment with inhaled corticosteroids in patients with COPD with regard to symptoms and drop out due to pulmonary problems. Lung function decline tends to decrease during treatment with inhaled corticosteroids. The observed effects are limited but warrant further studies on the effectiveness of corticosteroids in larger numbers of patients with COPD.", "There have been suggestions that corticosteroid treatment might improve bronchodilator responses in chronic obstructive pulmonary disease (COPD). We have studied bronchodilator responses to salbutamol and to oxitropium bromide in 20 patients with stable moderate to severe COPD. Dose responses to the two bronchodilators were tested before and after 3 week courses of placebo and 30 mg prednisolone. Thirteen patients were taking inhaled corticosteroids. There were no significant changes in numbers of responses or maximum bronchodilator effects from either bronchodilator, although there was a trend towards higher maximum levels after 3 weeks of prednisolone. Spirometry measured at home each morning before and after oxitropium bromide showed no difference between prednisolone and placebo periods. This study provides no evidence for a significant effect on bronchodilator responses to beta-agonists or anticholinergic agents from 3 weeks of oral prednisolone in moderately severe COPD.", "The reproducibility of the 12 minute walking distance (12 MD) was assessed in ten men with chronic airways obstruction, and the 12 MD was used, together with spirometry, transfer factor and three subjective assessments of breathlessness to evaluate the effects on respiratory function of prednisone 30 mg daily given orally in double-blind placebo-controlled fashion for two weeks. Like others, we found the 12 MD reproducible on a single day with a mean variation of 3.1%. Tests performed two weeks apart showed greater variability ranging from 0.2% to 30.9%, (mean 9.1%). During placebo and prednisone therapy the 12 MD and assessments of breathlessness correlated significantly with each other and with TLCO, but not with spirometry. Following steroid therapy there was a significant increase in mean TLCO but no significant change in 12 MD, spirometry or subjective assessments. Changes in 12 MD and TLCO correlated significantly with each other and with changes in subjective assessments. Changes in FEV1 correlated with changes in breathlessness, and also with variability in FEV1 while receiving placebo. Individuals with the greatest changes in 12 MD and FEV1 were those with the greatest variability on placebo. The variability of the 12 MD and FEV1 should be measured in individuals before using these tests to assess response to steroid therapy.", "Sixteen Chinese patients with chronic fixed airflow obstruction (mean age 62.5 years; mean forced expiratory volume in 1 second (FEV1) of 0.85 litres, and mean ratio FEV1/forced vital capacity (FVC) of 0.45) entered a randomized double-blind crossover trial comparing prednisolone 40 mg orally daily for 2 weeks with placebo. Nine of the 16 patients (56%) had an increase in FEV1 of 15% or more after prednisolone. Compared with placebo, prednisolone significantly improved objective measurements (mean FEV1 by 21.4%, mean FVC by 11.9%, mean daily peak expiratory flow rate by 22.6%), subjective measurement (mean dyspnoea score by 16%) and exercise performance assessed by the distance walked in 12 minutes (12MD, by 5.5%). Objective improvements in FEV1 and PEFR were correlated with subjective upgrading of the dyspnoea score, but were not paralleled by an improvement in 12MD. Changes in FVC correlated with neither. FEV1 was thus the best index of objective measurement. The following characteristics were examined for reliability in predicting steroid responsiveness: variability of symptoms, wheezing score, prick skin test positivity, initial bronchodilator response, peripheral blood and sputum eosinophilia, and serum and sputum immunoglobulin E (IgE) level. None was found to be useful. A therapeutic trial of oral corticosteroid should be considered in patients with chronic fixed airflow obstruction on an individual basis.", "A double-blind cross-over trial was carried out on 83 sequential out-patients presenting with adult onset chronic airflow obstruction who were not clearly asthmatic. The study consisted of three treatment phases each lasting two weeks with a two week interval between each phase. The treatment phases were prednisolone 40 mg daily, beclomethasone dipropionate 500 ug three times a day and placebo, administered in a random order. FEV1 and FVC were measured at the end of each of the treatment phases and peak expiratory flow rate five times a day throughout. Over the study period 25 (30%) patients responded with an improvement of greater than or equal to 20% in at least one of the parameters measured as compared with the best of either baseline or placebo measurements. A further eight patients were classified as partial responders with an improvement of greater than 15% in any single parameter or greater than 10% in any two parameters. A similar number responded to beclomethasone [15] as responded to prednisolone [16]. Only six patients, however, responded fully to both forms of steroid therapy. A number of patients responded to one form of steroid treatment only which was also comparable between the two groups (prednisolone 10, beclomethasone 9). For full and partial responders mean improvement in FEV1, FVC and PEFR was greater during the prednisolone phase than during the beclomethasone phase, however, the difference did not achieve statistical significance.", "The effect of treatment with inhaled corticosteroids in patients with non-asthmatic chronic airflow obstruction is still disputed. Whether any physiological improvements seen are accompanied by changes in bronchial responsiveness and symptoms and quality of life is also still unclear.\n A sequential placebo controlled, blinded parallel group study investigating the effect of three weeks of treatment with inhaled beclomethasone dipropionate (BDP), 750 micrograms or 1500 micrograms twice daily, and oral prednisolone, 40 mg per day, was carried out in 105 patients with severe non-asthmatic chronic airflow obstruction (mean age 66 years, mean forced expiratory volume in one second (FEV1) 1.05 litres [40% predicted], geometric mean PD20 0.52 mumol). End points assessed were FEV1, forced vital capacity (FVC), and peak expiratory flow (PEF), bronchial responsiveness to inhaled histamine, and quality of life as measured by a formal quality of life questionnaire.\n Both doses of BDP produced equivalent, small, but significant improvements in FEV1 (mean 48 ml), FVC (mean 120 ml), and PEF (mean 12.4 l/min). The addition of oral prednisolone to the treatment regime in two thirds of the patients did not produce any further improvement in these parameters. Inhaled BDP produced a treatment response in individual patients (defined as an improvement in FEV1, FVC, or mean PEF of at least 20% compared with baseline values) more commonly than placebo (34% v 15%). The two doses of BDP were equally effective in this respect and again no further benefit of treatment with oral prednisolone was noted. Treatment with BDP for up to six weeks did not affect bronchial responsiveness to histamine. Small but significant improvements were seen in dyspnoea during daily activities, and the feeling of mastery over the disease.\n High dose inhaled BDP is an effective treatment for patients with chronic airflow obstruction not caused by asthma. Both objective and subjective measures show improvement. Unlike asthma, no improvement in bronchial responsiveness was detected after six weeks of treatment.", "One hundred and twenty seven adults considered on clinical grounds to have non-asthmatic chronic airflow obstruction entered a randomised, double blind, placebo controlled, crossover trial comparing the physiological response to inhaled beclomethasone dipropionate 500 micrograms thrice daily with oral prednisolone 40 mg a day, both given for two weeks. One hundred and seven patients completed the study. Response was assessed as change in FEV1 and FVC measured on the last treatment day, and as change in mean peak expiratory flow (PEF) over the final seven days of treatment from home PEF recordings performed five times daily. A full response to treatment was defined as an increase in FEV or FVC, or an increase in mean daily PEF over the final seven days of treatment, of at least 20% from baseline values. An improvement in one measurement of at least 15%, or of 10% in any two measurements, was defined as a partial treatment response. Response to placebo showed a significant order effect, suggesting a carry over effect of active treatment of at least three weeks. Response to active treatment was therefore related to initial baseline values, and compared with placebo by considering responses in the first treatment phase only. A full response to oral prednisolone (16/38) was significantly more common than to placebo (3/35). The number of full responses to inhaled beclomethasone (8/34) did not differ significantly from the number responding to oral prednisolone or placebo in the first treatment phase, though full and partial responses to inhaled beclomethasone (12/34) were significantly more common than those to placebo (4/35). When all three treatment phases were considered 44/107 patients showed a full response to one or both forms of corticosteroid treatment, a response to prednisolone (39) occurring more frequently than to inhaled beclomethasone (26). Only 21 of the 44 responders showed a response to both forms of treatment. Inhaled beclomethasone dipropionate 500 micrograms thrice daily was inferior to oral prednisolone 40 mg per day, but better than placebo, in producing improvement in physiological measurements in patients thought to have nonasthmatic chronic airflow obstruction. It was, however, an effective alternative in over half of those showing a response to prednisolone.", "Short term treatment with corticosteroids does not usually reduce airflow limitation and airway responsiveness in patients with chronic obstructive lung disease. We investigated whether corticosteroids modulate the effects of inhaled salbutamol and ipratropium bromide.\n Ten non-allergic subjects with stable disease were investigated; eight completed the randomised, double blind, three period cross over study. Treatment regimens consisted of 1.6 mg inhaled budesonide a day for three weeks, 40 mg oral prednisone a day for eight days, and placebo. After each period cumulative doubling doses of salbutamol, ipratropium, a combination of salbutamol and ipratropium, and placebo were administered on separate days until a plateau in FEV1 was reached. A histamine challenge was then performed.\n At the end of placebo treatment mean FEV1 was 55.5% predicted after inhaled placebo, 67.9% predicted after salbutamol and 64.0% predicted after ipratropium. Compared with the results after the placebo period the FEV1 with salbutamol increased by 0.7% predicted after treatment with budesonide and by 0.7% predicted after treatment with prednisone; the FEV1 with ipratropium increased by 0.7% predicted after budesonide and by 4.8% predicted after prednisone; none of these changes was significant. After placebo treatment the geometric mean PC20 was 0.55 mg/ml after placebo, 1.71 mg/ml after salbutamol and 0.97 mg/ml after ipratropium. Compared with the placebo period the PC20 with salbutamol was increased by 0.86 doubling concentrations after treatment with budesonide, and by 0.67 doubling concentrations after prednisone; the PC20 with ipratropium increased by 0.03 and 0.34 doubling concentrations after budesonide and after prednisone respectively compared with placebo; none of these changes was significant.\n In non-allergic subjects with chronic obstructive lung disease short term treatment with high doses of inhaled or oral corticosteroids does not modify the bronchodilator response to salbutamol or ipratropium or the protection provided by either drug against histamine. Salbutamol produces greater protection from histamine induced bronchoconstriction than ipratropium.", "A significant minority of patients with COPD have favourable response to corticosteroid treatment. In addition, the benefit of corticosteroid treatment may be outweighed by the side-effects. Long-term administration of inhaled steroids is a safe means of treatment. However, only a few studies have addressed the role of inhaled steroids in patients with COPD, with conflicting results.\n Forty-four patients with stable COPD were defined as 'responders to bronchodilators' (increase in FEV1 > or = 20% following administration of beta 2-agonist) (group A), and 124 as 'non-responders to bronchodilators' (group B). All patients were randomized to receive a 6-week course of either a daily dose of 800 micrograms of inhaled budesonide or placebo, separated by 4 weeks when no medication was taken; were randomized again to receive a 6-week course of either 1600 micrograms day-1 of inhaled budesonide, or 800 micrograms day-1 of inhaled budesonide plus placebo; and were randomized once again to receive a 6-week course of either 40 mg day-1 of prednisone or placebo. All stages were performed in a double-blind cross-over design.\n Following administration of 800 micrograms day-1 of inhaled budesonide, there was an increase in the mean FEV1 from 1.40 +/- 0.20 to 1.92 +/- 0.22 L (P < 0.001) and a significant decrease in inhaled beta 2 agonist consumption in group A. These changes remained almost stable during the increased dose of inhaled budesonide or during prednisone treatment. The mean FEV1 did not change during the placebo period, or in group B in either treatments.\n Treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about one-quarter of patients with stable COPD, and this rate increased to about three-quarters in patients who responded to beta 2-agonist inhalation. There was no additional benefit in using a higher dose of inhaled budesonide or prednisone.", "A placebo-controlled, double-blind cross-over trial was conducted to assess whether 16 men with chronic obstructive pulmonary disease (COPD) would benefit from orally taken corticosteroids. Two weeks of treatment with 40 mg of prednisone daily did not result in improvement of pulmonary symptoms or function in the group as a whole, although one patient had small improvement in airflow. The baseline spirometric data and beta-agonist responsiveness of the patients in the study were then compared to a reference population consisting of 264 men who fulfilled a criteria for chronic obstruction out of 730 men who comprised a systematic sample drawn from all patients referred for spirometry at three hospitals. Our study subjects and those of five similar trials of corticosteroids in COPD had more severe obstruction than this reference group. Furthermore, the proportion of steroid responders found in each study was inversely related to the baseline FEV1 of the patients examined. It appears that previous studies of corticosteroids in COPD may have overestimated the number of COPD patients who might benefit from corticosteroids, due to a bias resulting from the selection of severely obstructed subjects.", "A double-blind crossover trial of prednisolone was conducted in 70 patients of chronic obstructive lung disease (COLD). Emphysema dominated the clinical picture in 38, rest being chronic bronchitis with varying degrees of air trapping. None of the patients had clinical asthma. All the patients had obtained maximal benefit from an optimal dose of bronchodilators prior to entering the study. Prednisolone in a dose of 0.8 mg/kg was prescribed in a double blind crossover manner with identical appearing placebo tablets. Patients were evaluated on a weekly basis for an objective as well as a subjective response and side effects of therapy. Thirty-four patients demonstrated a statistically significant improvement in pulmonary functions. In 20 others only subjective response was observed. A good objective response was predicted by a pre-study variability in FEV1, disease duration of less than 10 years and a history of smoking less than 50 pack years." ]

[ "16549410", "7501382", "10907384", "12792318" ]

[ "Short-term efficacy of Epley's manoeuvre: a double-blind randomised trial.", "Randomized trial of the canalith repositioning procedure.", "The canalith repositioning procedure for the treatment of benign paroxysmal positional vertigo: a randomized controlled trial.", "A randomized trial of the canalith repositioning procedure." ]

[ "Benign paroxysmal positional vertigo of the posterior canal (PC-BPPV) is a common vestibular disorder and can be easily treated with Epley's manoeuvre. Thus far, the short-term efficacy of Epley's manoeuvre for treatment of PC-BPPV is unknown.\n To evaluate the efficacy of Epley's manoeuvre for treatment of PC-BPPV 24 h after applying the manoeuvre.\n The short-term efficacy of Epley's manoeuvre was compared with a sham procedure in 66 patients with PC-BPPV by using a double-blind randomised study design.\n 24 h after treatment, 28 of 35 (80%) patients in the Epley's manoeuvre group had neither vertigo nor nystagmus on positional testing compared with 3 of 31 (10%) patients in the sham group (p<0.001).\n Epley's manoeuvre is shown to resolve PC-BPPV both effectively and rapidly.", "Thirty-six subjects with confirmed, unilateral benign paroxysmal positioning vertigo of at least 2 months' duration were randomly assigned to one of two treatment groups. After complete informational counseling and explanation of the posttreatment instructions, subjects were randomly assigned to receive either Epley's canalith repositioning procedure or a placebo maneuver. All subjects completed a daily diary for 1 month to document any dizzy spells and their adherence to the posttreatment instructions. Follow-up Dix-Hallpike testing was performed after 1 month by an audiologist who was blinded to the patient's treatment group status. Analysis of Dix-Hallpike results confirmed that those who received the canalith repositioning procedure had significantly more negative responses (88.9%) than did those in the placebo group (26.7%).", "To compare the canalith repositioning procedure (CRP) with a sham maneuver for the treatment of benign paroxysmal positional vertigo.\n We recruited 50 patients with a history of positional vertigo and unilateral positional nystagmus on physical examination (Dix-Hallpike maneuver). Patients were randomized to either the CRP (n = 24) or a sham maneuver (n = 26). Measured outcomes included resolution of vertigo and positional nystagmus at follow-up examination.\n The mean duration of follow-up was 10 days for both groups. Resolution of symptoms was reported by 12 (50%) of the 24 patients in the CRP group and by 5 (19%) of the 26 patients in the sham group (P = .02). The results of the Dix-Hallpike maneuver were negative for positional nystagmus in 16 (67%) of 24 patients in the CRP group and in 10 (38%) of 26 patients in the sham group (P = .046).\n The CRP is effective treatment of benign paroxysmal positional vertigo, and this procedure can be performed by general internists on outpatients with this disorder.", "To compare the effectiveness and complications of our adaptation of the canalith repositioning procedure (CRP) with the expectation treatment for benign paroxysmal positional vertigo.\n A randomized, controlled trial in the setting of a neurotological clinic in Thailand.\n Fifty-eight patients with posterior benign paroxysmal positional vertigo were randomly assigned to treatment and control groups using a block of four. The treatment group was treated with the modified CRP technique until the nystagmus disappeared. A mastoid oscillator was not used, nor were any instructions given for patients after the maneuver. Both groups recorded the daily grading of symptoms and the amount of anti-vertiginous drugs (cinnarizine) taken. Objective and subjective assessments were made weekly until the nystagmus disappeared or until 4 weeks had passed since treatment began.\n The rates of effectiveness of CRP treatment and the control treatment for benign paroxysmal positional vertigo were 75.9% and 48.2%, respectively. There was a significant difference in the treatment outcomes of the CRP and control groups (P =.03). The CRP group used significantly fewer drugs than the control group (P =.001). Complications in the CRP group, such as lateral canalithiasis and fainting, were observed in 13.8% of the patients.\n The CRP was more effective than the expectation treatment for benign paroxysmal positional vertigo insofar as it provided faster recovery and required less dependence on medication. Complications of CRP were limited to 13.8% of patients." ]

[ "2203467" ]

[ "Topical steroids in the treatment of central and paracentral corneal ulcers." ]

[ "During an 18-month period a prospective randomised trial was conducted on 40 selected patients with bacterial corneal ulcers. Two groups were compared: one was treated with antibiotic only and the other with antibiotic plus steroid. Complications were similar in the two groups. No delay in healing rate of the ulcers was seen with the use of topical steroid. Two methods of assessing visual improvement are discussed, but it was not possible to demonstrate a difference in visual outcome between the two groups." ]

[ "285752", "3462964", "1059514", "1547611", "4395021", "1913770", "7004469", "4149310", "359013", "369697", "4154819", "4382492", "7016089", "4385839", "4393333", "4146249", "4149071", "6342787", "4383235", "2052894", "6953125", "1055598", "4148037", "4380623", "170634", "1069175", "295702", "356989", "4392097", "6589669", "9383759", "342181", "234138", "13270998", "6961143", "6754242", "4147708", "4380624", "3269091", "6365424", "2797545", "4400318", "6947332", "4501134", "6572128", "271002", "3865156", "6929082", "6253112", "4608298", "6594021", "4400046", "3905917", "1756217", "4379365", "4394685", "4395304", "321181", "279409", "4151901", "6593805", "3471376", "10445367", "4153291", "4404998", "1890532", "224083", "4405623", "284065", "4404788", "6941001", "4400348", "1623700", "6088166", "4395303", "4149070", "4391820", "7005653", "6944630", "4147760", "4401615", "4561760", "4888451", "4295135", "6337712", "6264506", "6989549", "6943157", "6593146", "4396165", "4502245", "281356", "318958", "9879918", "1069886", "782777", "9017171" ]

[ "A supervised brushing trial of sodium monofluorophosphate dentifrices in a fluoridated area.", "The effectiveness of a 0.2 percent and a 0.05 percent neutral NaF mouthrinsing programme.", "Caries preventive effect of a fluoride-containing varnish (Duraphat) after 1 year's study.", "Efficacy of APF treatments without prior toothcleaning targeted to high-risk children.", "The effect of a fluoride gel used for supervised toothbrushing 15 or 30 times per year.", "Effect of partial substitution of invert sugar for sucrose in combination with Duraphat treatment on caries development in preschool children: the Malmö Study.", "Caries prevention by dentifrices containing a combination of sodium monofluorophosphate and sodium fluoride. Report of a 3-year clinical trial.", "Self-application of fluoride by rinsing.", "Caries prevention by daily supervised use of a MFP gel dentifrice. Report of a 3-year clinical trial.", "A 3-year clinical trial of calcium carbonate dentifrice containing calcium glycerophosphate and sodium monofluorophosphate.", "Studies on the effect of dentifrices with low fluoride content.", "Clinical anticaries effect of repeated topical sodium fluoride applications by mouthpieces.", "The anticaries effect of single and combined topical fluoride systems in school children.", "The use of fluoride dentifrices in the control of dental caries: methodology and results of a clinical trial.", "Final report on the efficacy of a stannous fluoride-calcium pyrophosphate dentifrice.", "The effect on dental caries of weekly rinsing with a neutral sodium fluoride or an acidulated phosphate-fluoride mouthwash.", "Two-year evaluation of a self-administered procedure for the topical application of acidulated phosphate-fluoride; final report.", "A four-year clinical study to determine the caries-inhibiting effect of calcium glycerophosphate and sodium fluoride in calcium carbonate base dentifrices containing sodium monofluorophosphate.", "Field test of a sodium fluoride dentifrice containing acid orthophosphate and an insoluble metaphosphate abrasive--second year report.", "Effects of a chlorhexidine-fluoride-strontium rinsing program on caries, gingivitis and some salivary bacteria among Finnish schoolchildren.", "Confidence intervals for percentage reduction in caries increments.", "A dentifrice containing 0.8 per cent sodium monofluorophosphatein an aluminium oxide trihydrate base. A 3-year clinical trial.", "Clinical evaluation of three concentrations of sodium fluoride in dentifrices.", "Effect of SnF2 dentrifices on caries in children: two-year clinical study of supervised brushing in children's homes.", "A clinical evaluation of a sodium fluoride dentifrice.", "Cariostatic effects of fluoride mouthrinses in a fluoridated community.", "Effect of fluoride varnish (Duraphat) in preschool children.", "A three-year clinical study to determine the separate and combined caries-inhibiting effects of sodium monofluorophosphate toothpaste and an acidulated phosphate-fluoride gel.", "Albany topical fluoride study.", "[3-year clinical tooth cream test with toothpastes of varying fluoride content: 0.8% and 1.2% sodium monofluorophosphate].", "A 24-month study comparing sealant and fluoride varnish in caries reduction on different permanent first molar surfaces.", "Caries-preventive effect of two concentrations of stannous fluoride mouthrinse.", "The clinical cariostatic effectiveness of two concentrations of acidulated phosphate-fluoride mouthwash.", "A comparison between the anticariogenic effects of dentifrices containing stannous fluoride and sodium fluoride.", "Caries-preventive effects of daily and weekly fluoride mouthrinsing in a fluoridated community: final results after 30 months.", "Comparative unsupervised clinical trial on caries inhibition effect of monofluorophosphate and amine fluoride dentifrices after 3 years in Strasbourg, France.", "Caries prevention by daily fluoride mouthrinsing. Report of a three-year clinical trial.", "Effectiveness of a SnF2-Ca2P2O7 dentifrice on dental caries in children whose teeth calcified in a natural fluoride area. II. Results at the end of 24 months.", "[Caries limiting effectiveness of newly developed fluoride-containing gels after 3 years clinical use in preschool years].", "Caries prevention using a 1.2% sodium monofluorophosphate dentifrice in an aluminium oxide trihydrate base.", "Identification and preventive care of high caries-risk children: a longitudinal study.", "Clinical evaluation of neutral sodium fluoride, stannous fluoride, sodium monofluorophosphate and acidulated fluoride-phosphate denifrices.", "[Fluoride mouthwashes in combination with fluoridation of the public water supply for the prevention of dental caries].", "[Effectiveness of a Na2FP03 toothpaste on caries in children].", "Combined effects of a fluoride dentifrice and mouthrinse on the incidence of dental caries.", "Clinical testing of a mouthrinse and a dentifrice containing fluoride. A two-year supervised study in school children.", "The caries-preventive effects of full- and half-strength topical acidulated phosphate fluoride.", "Caries increment and gingival status during 2 years' use of chlorhexidine- and fluoride-containing dentifrices.", "Caries-inhibiting effect of a stannous fluoride silica gel dentifrice: a three-year clinical study.", "Clinical trial among Scottish children of an anti-caries dentifrice containing 2 percent sodium monofluorophosphate.", "The caries-preventive effect of a fluoride varnish in the fissures of the first permanent molar.", "A multiple-examiner clinical evaluation of a sodium fluoride dentifrice.", "Results of a 32-month fluoride varnish study in Sherbrooke and Lac-Megantic, Canada.", "[The caries-protective efficacy of 2 fluoride varnishes in a 2-year controlled clinical trial].", "Comparative study of a fluoride dentifrice containing soluble phosphate and a calcium-free abrasive: second-year report.", "A clinical comparison of fluoride and antienzyme dentifrices.", "The effect on dental caries of topically applied acidulated phosphate-fluoride: results after three years.", "A 3-year clinical trial of the effect on dental caries of a dentifrice containing 2% sodium monoflurophosphate.", "A clinical trial of a calcium carbonate base dentifrice containing 0.76% sodium monofluorophosphate.", "Evaluation of self-administered prophylaxis and supervised toothbrushing with acidulated phosphate fluoride.", "Three-year study of the effect of fluoride varnish (Duraphat) on proximal caries progression in teenagers.", "Clinical cariostatic effectiveness of a NaF rinse in a low prevalence child population.", "Effect of professional flossing with NaF or SnF2 gel on approximal caries in 13-16-year-old schoolchildren.", "Caries-preventive effect of dentifrice containing 2percent sodium monofluorophosphate in a natural fluoride area in Denmark.", "Clinical evaluation of stannous fluoride as an anticaries mouthrinse.", "Effectiveness of fortnightly tooth brushing with amine fluorides in caries-prone subjects.", "The relative caries-inhibiting effects of a stannous fluoride dentifrice in a silica gel base.", "The use of a sodium fluoride mouthwash in reducing the dental caries incresent in eleven year old English school children.", "The caries-preventive effect of amine fluorides and inorganic fluorides in a mouthrinse or dentifrice after 30 months of use.", "Effect on dental caries of self-application of acidulated phosphate fluoride paste and gel.", "A clinical study of the caries preventive effects of an APF solution and APF thixotropic gel.", "Fluorides in community programs; a study of four years of various fluorides applied topically to the teeth of children in fluoridated communities.", "Caries development after termination of a fluoride rinsing program.", "Caries inhibition of a dentifrice containing 0.78% sodium monofluorophosphate in a silica base.", "Incremental rates of dental caries after repeated topical sodium fluoride applications in children with lifelong consumption of fluoridated water.", "The cariostatic effectiveness of a phosphate-fluoride gel administered annually to school children; final results.", "An evaluation of the utility of application and cariostatic effectiveness of phosphate-fluorides in solution and gel states.", "[Cariostatic effect of Fluocaril; controlled clinical research].", "The effect of a preventive programme on dental plaque and caries in school children.", "A clinical evaluation of a stannous fluoride and a sarcosinate dentifrice.", "Clinical evaluation of an aged stannous fluoride-calcium pyrophosphate dentifrice.", "The effect of oral rinsing with sodium fluoride on the gingiva of children.", "[Three years of clinical observations with fluoridated tooth-pastes].", "Cariostatic effect of a stannous fluoride-containing dentifrice on children: two-year report of a supervised toothbrushing study.", "The effects of changing caries prevalence and diagnostic criteria on clinical caries trials.", "A three-year clinical caries evaluation of the effect of a sodium fluoride-silica abrasive dentifrice.", "A 3-year clinical trial into the effect of fluoride content and toothpaste abrasivity on the caries inhibitory properties of a dentifrice.", "Effect of stannous fluoride treatments on the progression of initial lesions in approximal surfaces of permanent posterior teeth.", "Caries clinical trial of fluoride rinses in a Danish Public Child Dental Service.", "Clinical testing of fluoride and non-fluoride containing dentifrices inHounslow school children.", "[Prevention of dental caries by means of mouthwashes with 0.1 solutions of sodium fluoride. Results of a 2 year study].", "Observations on dental caries in primary teeth after frequent fluoride toplications in a program involving other preventives.", "Effect of high-concentration ammonium and sodium fluoride rinses on dental caries in schoolchildren.", "Approximal caries development following intensive fluoride mouthrinsing in teenagers. A 3-year radiographic study.", "Cariostatic effects of fluoride mouthrinses in a non-fluoridated community.", "Clinical study of an amine fluoride gel and acidulated phosphate fluoride gel.", "Effect of supervised use of an alum mouthrinse on dental caries incidence in caries-susceptible children: a pilot study." ]

[ "nan", "nan", "The caries prophylactic effect of semi-annual applications of a fluoride-containing varnish (Duraphat) was tested in 121 15-year-old children. The children were divided into a test (60 subjects). The teeth of the children in the test group were coated with fluoride varnish at the beginning of the experimental period and again 6 months later. A clinical and radiographic examination of all children was performed immediately prior to the first application of varnish and 1 year later. The mean caries increment was 0.9 new DMFS in the test group and 4.0 in the control group. The difference was statistically significant at the 0.1% level. The caries prophylactic effect on different tooth surfaces was statistically significant both on proximal and on occlusal surfaces at the 0.1% level. Analyzing the material with respect to the caries prophylactic effect against the background of caries prevalence at the start of the investigation showed a better effect in the group of children with low and medium initial DMFS values.", "A clinical field trial was conducted, over a 2-yr period, to evaluate the efficacy of bi-annual APF gel topical applications without previous prophylaxis in reducing dental caries among high-risk children living in non-fluoridated communities. 488 children 6 yr old, presenting at least three cavities on proximal surfaces of their primary teeth, were randomly assigned to two groups. The experimental group received bi-annual topical APF gel applications and the control group received a placebo. All treatments were given at school without any prior toothcleaning. The APF gel provided a 34.3% reduction in caries incidence (P-value = 0.03) among the children with 3-14 cavities on their primary teeth at the beginning of the study. However, the treatment did not show any efficacy in reducing caries incidence among the higher-risk children having initially more than 14 cavities. These findings suggest that the efficacy of APF gel applications without previous prophylaxis varies according to the individual risk of the subjects and that more comprehensive programs should be targeted to very high-risk children.", "nan", "The aim was to study the effect of substitution of invert sugar for sucrose, in combination with fluoride varnish (Duraphat) treatment twice a year, on caries development in preschool children. One hundred and eighty-seven 4-years-olds were divided randomly into four sugar groups: (1) sucrose (S), (2) sucrose-Duraphat (SD), (3) invert sugar (I), and (4) invert sugar-Duraphat (ID). All families were asked to buy beverages, biscuits, breakfast cereals, marmalade, ice cream, jam, ketchup, sweets and table sugar, totally 32 different food items, sweetened with invert sugar or sucrose. The substitution was, thus, restricted to a number of sugar-rich between-meal products. The study was carried out double-blind for 2 years. The children of those parents who did not want to participate in the sugar groups were divided randomly into one of the following two groups: (5) Duraphat (D), and control (C). Because of lack of cooperation, only 114 of the 187 children (61%) were considered to have completed the study. The mean caries increment, including initial lesions, was 3.86 dmfs in the combined groups S and SD (n = 63) and 3.10 dmfs in the combined groups I and ID (n = 51) during the 2 years (p = 0.34). The corresponding values for the 2nd year only were 1.84 and 0.67 dmfs, respectively (p = 0.09). The mean caries increment was 2.86 dmfs in group D (n = 113) and 4.10 dmfs (p = 0.08) in group C (n = 93). If initial caries lesions were excluded from the index, the difference between groups D and C was significant (p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)", "nan", "nan", "nan", "nan", "nan", "nan", "nan", "nan", "nan", "nan", "nan", "nan", "nan", "In order to find out if it is possible to prevent caries and gingivitis by periodical use of chlorhexidine-fluoride mouthrinses with or without strontium, and to find out what effects they have on salivary mutans streptococci and lactobacilli counts, a total of 243 schoolchildren aged 11 yr with high DMFS scores were randomly divided into four groups. One group (C) served as a basic control. Subjects in the second group (CXF) rinsed their mouths twice a day every third week with a rinsing solution containing 0.05% chlorhexidine gluconate and 0.04% NaF. In the third group (CXFS) the rinsing solution contained 500 ppm Sr during the first and second year and 15 ppm during the last 6 months, in addition to chlorhexidine and fluoride. In the fourth group (CX) the solution contained only 0.05% chlorhexidine gluconate. All the rinsing solutions had pH 5.8 buffered with succinic acid-NaOH buffer. After 2 yr and 9 months, the mean DMFS (SD) increments in the C, CXF, CXFS, and CX groups were 3.8 (5.7), 2.5 (3.2), 3.5 (4.8), and 3.4 (5.5), respectively. The percentage of subjects with bleeding gingival units had decreased from initial to final values as follows: C, 81-38; CXF, 88-42; CXFS, 89-56; CX, 89-37. The number of lactobacilli and mutans streptococci in saliva remained virtually unchanged throughout the study. For caries increment and gingival bleeding, the differences between groups were not statistically significant. The chlorhexidine-fluoride combination tended to prevent caries, but the effect on gingival bleeding and salivary counts of mutans streptococci and lactobacilli was negligible.", "nan", "nan", "nan", "nan", "A double-blind study to determine the anticaries efficacy of a neutral pH dentifrice containing sodium fluoride and a high Beta-phase calcium pyrophosphate was conducted among elementary school children in Kansas City, Missouri. A sample of 567 children ages 8-13 were recruited and randomly assigned to test and control groups: the test group received a sodium fluoride high Beta-phase calcium pyrophosphate dentifrice, and the control group received a calcium pyrophosphate dentifrice without the active ingredient. The sodium fluoride dentifrice contained fluoride at the level of 1000 ppm. Caried examinations were conducted at initiation, after 12 months, and again after 24 months at the study's termination. All examinations (clinical and radiographic) were performed by the same investigator. At 12 months the sodium fluoride dentifrice demonstrated a caries reduction of 24.1% (DMFS). At 24 months the reduction demonstrated was 30.1% (DMFS); this reduction is significant at alpha = 0.05.", "nan", "The caries-preventive effect of semiannual applications of a fluoride varnish (Duraphat) was tested for 2 years in 225 3-year-old children; 113 children served as a control group. At the baseline examination, 69% of the children in the test group and 75% in the control group were caries-free. The results after 2 years showed an average caries increment of 2.1 surfaces in the test group and 3.7 in the control group. The difference is statistically significant. Thirty-eight percent of the children in the test group and 27% in the control group were still caries-free. The caries reduction was 44%.", "nan", "nan", "nan", "The aim of this study was to determine the separate effects of dental sealants and fluoride varnish on dental caries in fissured and nonfissured surfaces of permanent first molars.\n A clinical trial was conducted with three groups of 6- to 8-year-old schoolchildren: a sealant group (n = 100), in which Delton was applied to first molars; a varnish group (n = 98), in which Duraphat was applied to first molars; and a control group (n = 116), which had no intervention as part of the study. Absolute and percent caries reductions were compared at 24 months.\n Compared to the controls, sealants resulted in a 68 percent and 87 percent reduction on fissured and nonfissured surfaces, respectively. The corresponding figures for varnish were 38 percent and 66 percent.\n Sealant and fluoride varnish are effective in preventing caries in both fissured and nonfissured surface.", "The effectiveness of a stannous fluoride mouthrinse, when used once each school day, was investigated in a 3-year study. Effervescent stannous fluoride tablets of two concentrations were dissolved in 20 ml of water, giving solutions of 100 parts/10(6)F- and 200 parts/10(6)F- respectively. Approximately 1,200 children, with a mean age of 10 years, were divided on a random basis into three groups. Two of the groups rinsed with the two strengths of solution and the third group rinsed with a placebo. Examinations were carried out at the commencement of the study, and at yearly intervals thereafter. The final series was carried out a year after the rinsing procedures were terminated. There were significant reductions in the numbers of new caries in each of the two experimental groups as compared with the controls. The concentration of the solutions appeared to have little influence on the results. More dramatic reductions were noted in the teeth which erupted during the course of the study. A residual effect was demonstrated a year after the rinsing procedures were terminated.", "nan", "nan", "nan", "A randomized, double blind clinical trial of the caries inhibition effects of dentifrices containing respectively monofluorophosphate and amine fluoride was performed. A third control group used a toothpaste without fluoride. A total number of 2008 schoolchildren ranging in age from 6 to 8 years and living in Strasbourg (France) participated in this study. After a baseline examination three groups were constructed with the block randomization technic. The caries inhibition effects of the three dental pastes were compared after 3 years of unsupervised use. The monofluorophosphate dentifrice showed a reduction of 7.02% for DMFT, 5.17% for DMFS and 25.26% for the df rate. The reduction of amine fluoride dentifrice caries was respectively 21.62% for DMFT, 20.94% for DMFS and 48.66% for the df rate.", "nan", "nan", "nan", "A 3-year clinical trial was carried out in France just after fluoride toothpaste was allowed to be sold on the mass market. The aim was to assess the caries preventive effect of a toothpaste containing the maximum fluoride level permitted by the EEC (1.2% SMFP). The trial started with 1318 10-12-yr-old children from a wide socioeconomic background in a typical French community. Test toothpaste was given to 659 children whereas the remaining 659 children obtained the same toothpaste without the fluoride additive. The brushing was unsupervised and performed by the children at home. Dental caries was assessed by clinical and radiographic examinations. 1061 children completed the trial. An interview carried out at the final examination identified a group of 116 uncooperative children (less than five brushings a week on average) who were not included in the statistical analysis. The following mean reductions were found: 26% for DMFT, 27% for DMFS, and 39% for DMFSU. The DMFS index for approximal, buccal-lingual and occlusal surfaces showed caries reductions of 32%, 25%, and 22%, respectively. The trial demonstrated a highly significant effectiveness of the 1.2% SMFP toothpaste in a French population.", "A method of identifying high caries-experience children to participate in a mouthrinsing programme was tested. Children aged 9 to 12 years were assigned into high and low caries-risk groups using caries experience in the deciduous dentition and a clinical lesion on the occlusal surface of a first permanent molar within 2 years of eruption as indicators of risk. There were 273 high caries-risk children (101 in the fluoride rinse group, F, and 172 in the placebo rinse group, P); in the low caries-risk group, L, there were 648 children. After 5 years there were differences in the caries experience in the permanent dentition of the high and low caries-risk groups P and L. The high caries-risk group P had mean DMFT and DMFS scores of 2.7 and 3.2 respectively compared with 0.4 for both indices for the low caries-risk group, L. Most lesions occurred on occlusal surfaces. Caries experience was accurately predicted for 87 percent of the children when a DMFT score equal to or greater than 3 was used as the criterion of high caries experience. Accuracy was greater for the low caries-risk group (96 percent) than for the high caries-risk group (51 percent). Similarly the proportion of low caries-experience children identified in the low caries-risk group was greater than the proportion correctly identified in the high caries-risk group. When a DMFS score equal to or greater than 4 was used, there was little change. This method of prediction provided a practical method of identifying groups of children in need of special preventive care. Fortnightly mouthrinsing with 0.2 percent sodium fluoride solution was tested as a preventive measure for half the high caries-risk children (group F); the control group, P, used a placebo rinse. There were no significant differences in the caries scores of the two groups at the end of the study. Mouthrinsing was an ineffective preventive measure for high caries-risk children in this study.", "nan", "nan", "nan", "751 14- and 15-year old children completed a 3-year, double-blind, caries preventive program. The effects of daily, supervised toothbrushing with an 0.76% sodium monofluorophosphate dentifrice, rinsing with a 0.05% sodium fluoride mouthrinse, and the combined effects of the two treatments were investigated. Both the dentifrice and mouthrinse reduced the incidence of dental caries, but their combined use at the same time had no greater effect than either used alone.", "nan", "nan", "A total of 91 schoolchildren, 13 years of age, were distributed into three groups. Three test dentifrices were used containing 0.1% NaF, 0.1% NaF and 2% chlorhexidine, and 2% chlorhexidine, respectively. The caries increment and gingival conditions over a period of 2 years were recorded. The caries data of the groups were compared and related to two reference groups in order to estimate a possible influence upon the study results by a change in caries incidence general to the area and age groups in question. There was less caries in the group using the dentifrice containing fluoride and chlorhexidine than in the two other test groups. The differences in caries increment between the groups were not statistically significant. The gingival health seemed to improve in all groups, but there were no statistically significant differences between the groups. The caries data from the reference groups indicated that the general trend towards reduced caries incidence was different from that of the study group.", "nan", "nan", "The aim of the present study was to assess the caries-preventive effect of topical application of Duraphat on the occlusal surface of newly erupted first permanent molars. A base-line examination was performed on children aged 5 years and 9 months. The children were randomly divided into a Duraphat group and a control group. In accordance with the anatomy of the fissure system, the molars were divided into shallow and deep fissures, respectively. From the time of eruption, 381 molars were examined every 3rd month during 24 months. Duraphat was applied every 6th month, altogether four times. The results showed that in the Duraphat group 35% of the fissures were decayed compared with 80% in the control group. Caries reduction amounted to 56%, and the caries-preventive effect was found in molars with shallow and deep fissures.", "nan", "nan", "The aim of this randomized, double-blind study was to measure the cariostatic effect of Bifluorid 12 (VOCO GmbH), containing 6% sodium fluoride and 6% calcium fluoride and Laweflour-Schüttellack (LAW), containing 5% sodium fluoride in comparing of placebo varnish. The caries study included 400 schoolchildren, aged 12-14 years. The tests according to the DMFS were carried out by two independent examiners. The 400 children were divided into 3 test and 1 placebo group, each group consisting of 100 subjects. After two years there was a significant inhibition of caries increment in all test groups compared to placebo group. Percentage caries reduction ranged from 25 to 30%. The highest effect was stated at proximal surfaces.", "nan", "nan", "nan", "A clinical trial of a dentifrice containing 2% sodium monofluorophosphate was carried out on 782 schoolchildren in Shropshire, England. After 3 years, a reduction of 23.8% was found in the DMFS increment obtained from clinical examination. The reduction was 38.8% using radiographs. The children were divided into three groups according to baseline DMFS. Those with a \"medium\" caries experience were found to benefit most from using the dentifrice. There was a difference in the effect on individual tooth sites; the approximal surfaces of the posterior teeth received the most benefit and the occlusal surfaces the least.", "nan", "nan", "The effect of sodium fluoride varnish (Duraphat) applications on proximal caries progression was studied during a 3-yr period in 87 teenagers and compared to a control group (n = 107). In the fluoride varnish group the children were treated with fluoride varnish every third month during the experimental period. Caries lesions on the mesial surfaces of first premolars to the mesial surfaces of second molars were recorded annually on radiographs and an individual progression value was calculated. The study showed that topical application of fluoride varnish every third month significantly (P less than 0.05) reduced the progression of proximal caries lesions in premolars and molars. The most obvious reduction of caries progression was observed among children who developed between two and eight new proximal lesions during the test period. In the children with the highest caries activity (greater than nine new proximal lesions) Duraphat treatments did not significantly reduce proximal caries progression in premolars and molars.", "Epidemiologic studies in which oral health in schoolchildren in the nonfluoridated city of The Hague has been monitored, have revealed a substantial decrease in caries prevalence since 1969 in groups of all socioeconomic status (SES). Because of a still significantly higher caries activity in children of lower socioeconomic classes, in 1981 a weekly fluoride mouthrinsing program in these children was started. The purpose of the present study was to investigate the cariostatic effectiveness of a weekly 0.2% neutral NaF rinse in children with low caries prevalence. A sample of 29 schools stratified according to SES and randomly assigned to two groups was selected. One group of schools (14) performed weekly rinsing and the other group (15) served as controls. After 3 yr the number of children available for re-examination had dropped from 501 to 333, of which 62.2% had written parental consent for radiographic examination. Statistical analysis of the data showed that fluoride rinsing could establish a reduction in caries incidence only in children who did not use fluoride tablets. The results of this study are of special interest for health authorities in planning and implementing public dental health measures.", "The aim of this study was to evaluate the effect of professional flossing with NaF and SnF2 gels on caries development on approximal tooth surfaces. Two-hundred-and-eighty 13-year-old schoolchildren were divided into 3 groups: (1) NaF (n = 97), (2) SnF2 (n = 85), and (3) placebo gel group (n = 98). The investigation was carried out double-blind. The children were treated 4 times a year for 3 years with 1% NaF gel, 1% SnF2 gel, or placebo gel. The treatment was carried out by dental nurses and the time required per visit was approximately 10 min. After 3 years, the mean approximal caries increment, including initial caries lesions, was 2.8 in the NaF, 2.4 in the SnF2, and 4.0 in the placebo gel group (P< 0.05 for SnF2 vs placebo); a reduction compared to the placebo of 30% and 39% in the NaF and SnF2 groups, respectively. Thus, professional flossing with NaF or SnF2 gel carried out 4 times a year may be considered as an interesting caries-preventing method for large-scale application in schoolchildren.", "nan", "nan", "The aim of this study was to assess the caries incidence and plaque accumulation in schoolchildren at caries risk, after brushing the teeth fortnightly with gels containing 0, 0.4% F, 1.25% F as amine fluoride (AmF) or the common amine fluoride toothpaste containing 0.125% F. The study was conducted double blind over an 18-month period, and after 6 months discontinuation of brushing. Only the group that brushed with the 1.25% AmF gel showed a significant decrease in caries development compared to the group that brushed with the 0.125% AmF toothpaste. During the 6-month discontinuation period, the incidence of caries increased in all groups; the differences in caries development between all groups were not significant. Plaque indices were significantly lower in the AmF-treated groups. The highest fluoride concentration in the gel reduced the development of caries to zero, probably due to increased fluoride levels in the oral milieu of caries risk children. In order to maintain a positive effect of fluoride over an extended time period, caries-prone subjects should continue an initiated fluoride programme.", "An unsupervised toothbrushing study involving 1,339 children from 5 to 13 years of age conducted for three years compared two stannous fluoride dentifrices, one in a calcium pyrophosphate base and the other in a silica gel base, with a nonfluoride control dentifrice. The test dentifrice, stannous fluoride in a silica gel base, reduced caries to a significant extent when compared with the nonfluoride control dentifrice.The percentage of reductions ranged from 15% to 25% for whole mouth and interproximal surface indexes. There was no significant difference between the two fluoride dentifrices.", "nan", "The study groups using a dentifrice and mouthrinse both containing fluorides, a dentifrice containing stannous fluoride and a mouthrinse containing sodium fluoride, or a mouthrinse containing sodium fluoride with a placebo dentifrice had a 20.7% to 29.0% lower DMF increment than the control group after 30 months. These differences were significant. The study groups using a dentifrice containing amine fluorides and a placebo mouthrinse, a mouthrinse containing amine fluorides and a placebo dentifrice, or a dentifrice containing stannous fluoride and a placebo mouthrinse had a 13.6% to 22.4% lower DMF increment than the control group. These differences were not statistically significant. There was no significant difference in effectiveness against caries between the use of the organic or inorganic fluoride products.", "nan", "nan", "nan", "In a municipality near Copenhagen, Denmark, where fortnightly fluoride rinses with 0.2% neutral sodium fluoride had been performed for more than a decade, 1306 children from kindergarten through 6th grade were stratified by school and grade and randomly distributed into two groups. One group continued the fluoride rinses, the other group had the fluoride solution replaced with distilled water. Both solutions were slightly flavored. 1083 children completed the 3-yr trial. Caries was recorded clinically by the dentists in the municipal dental service using the diagnostic criteria for the Child Dental Health Services, and on bitewing radiographs by one of the authors applying the criteria developed by GRONDAHL et al. Permanent molars and premolars were included in the study. Clinically, caries increment in the two groups was the same with pits and fissures containing 94% of the DMFS. According to the radiographs, caries progression in the water group was higher than in the fluoride group. This difference was statistically significant for the surfaces erupting during the study (P less than 0.05).", "The purpose of this double blind clinical trial was to determine the anticaries activity of a dentifrice containing 0.78% sodium monofluorophosphate in a silica gel abrasive base compared with a placebo under conditions of supervised brushing. 1154 schoolchildren, ages 9-12, were recruited in a non-fluoridated semi-rural area of northeastern Connecticut. Subjects were stratified according to school, grade and sex, and then randomly divided into two groups. Each school day, children brushed their teeth for 1 min under supervision by project personnel. Weekend and vacation usage was ad libitum. Caries examinations and radiographic readings were performed by the same examiner (J.R.). After 12 months, the 996 subjects examined showed that the group using the test dentifrice had significantly (less than 0.05) lower DMFT (25.0%) and DMFS (19.1%) increments than the group using the placebo. After 24 months the 876 subjects examined showed that the test group continued to have significantly lower DMFT (24.5%) and DMFS (24.7%) increments than the placebo group. Surface protection after 24 months ranged from 22.1% for occlusal to 37.1% for interproximal surfaces.", "nan", "nan", "nan", "A controlled, double-blind trial on 42 children showed that a dentrifrice containing 0,25% fluorine clearly prevented caries when used continuously for 2 years. This effects was greater than that of a similar toothpaste containing fluorine. Tolerance was excellent.", "nan", "nan", "nan", "nan", "nan", "nan", "nan", "This study was conducted to determine if the anticaries effectiveness of a 0.243% sodium fluoride-silica abrasive dentifrice is superior to a 0.4% stannous fluoride-calcium pyrophosphate dentifrice. A nonfluoride, calcium pyrophosphate abrasive placebo dentifrice was also included at one-third the sample size of the active treatment groups to estimate the level of efficacy of the sodium fluoride dentifrice. A total of 3,093 schoolchildren were randomly assigned at a ratio of 3:3:1 to the sodium fluoride dentifrice, the stannous fluoride dentifrice, or the placebo dentifrice, respectively. Caries examinations were made by the same examiner initially and after one, two, and three years of ad libitum product usage. After three years, the results showed that the group using the sodium fluoride dentifrice had significantly fewer DMF teeth and DMF surfaces increments than the group using the stannous fluoride dentifrice. The percent reductions for DMF teeth and DMF surfaces were 24.2% and 22.6%, respectively. Both groups using fluoride dentifrices also had significantly fewer DMF teeth and DMF surfaces increments than the group using the placebo dentifrice.", "The effect of reducing the abrasivity of toothpaste on dental caries was observed in a 3-year clinical trial involving 1106 11-13-year-old Berkshire schoolchildren were divided into three groups; Group 1 were allocated a low abrasivity paste containing 0.8% sodium monofluorophosphate, Group 2 a paste of conventional abrasivity also containing 0.8% sodium monofluorophosphate and Group 3 a low abrasivity non-fluoride paste. After 3 years the net DMFS increments (clinical and radiographic scores combined) were 4.22 in Group 1, 4.72 in Group 2 and 6.43 in Group 3. The differences between Groups 1 and 3 and between Groups 2 and 3 were highly significant (P less than 0.001). The mean increment in Group 1 was lower than in Group 2 but did not reach statistical significance. Reducing the abrasivity of the toothpaste had no meaningful effect on the standard of oral hygiene and prevalence of gingivitis as measured by the Gingival and Plaque Indices.", "Bite-wing radiographs were used to determine the effect of three forms of topical SnF2 therapy on the progression of initial lesions in the approximal surfaces of permanent posterior teeth. Radiographs were taken annually over a four-year period. The subjects were schoolchildren, aged 12-14 yr, living in a low fluoride area. The professional application of a 10% SnF2 solution for 30 s, semi-annually for two yr, had no discernible effect on the development of the initial lesions. However, the home use of a SnF2 dentifrice did inhibit caries progression appreciably at all but one of the four time intervals in the study. The professional application of a 10% SnF2 solution for 30 s, semi-annually for two yr, combined with the home use of a SnF2 dentifrice, was the most effective treatment in retarding lesion development. Even without topical fluoride therapy, the rate of progression of initial approximal lesions was generally quite slow. In view of these findings, it would seem sound clinical practice to treat all initial lesions in approximal surfaces with topical fluoride therapy and delay placement of restorations until there is radiographic evidence of lesions reaching dentin.", "365 2nd through 4th graders completed a 3-yr clinical trial on the caries-preventive effect of rinsings every second week during the school year with 10 ml of an 0.2% neutral solution of sodium fluoride. All children received regular dental examinations and treatment in clinics established by the municipality in which the study took place. The trial was performed under double-blind conditions. The caries increment on teeth erupted at baseline was 1.75 DMFS in the fluoride group and 1.83 DMFS in the placebo group (P greater than 0.05; 95% confidence limits for percentage caries reduction: -20.7% and 29.5%). The caries increment on teeth erupting during the trial was 0.73 DMFS in the fluoride group and 0.99 DMFS in the placebo group (P greater than 0.05; 95% confidence limits for percentage caries reduction: 1.0% and 51.6%).", "nan", "nan", "The anticaries effect of repeated toplications with APF gel was assessed in the primary dentition of 2-6-year-olds after 8, 18 and 28 months. Frequent, but less than daily, topical fluoride therapy appeared to have little effect in pre-school children consuming water-borne fluoride and receiving other traditionally recommended modalities of prevention.", "A double-blind clinical trial was conducted in a non-fluoridated community to determine the effect on enamel fluoride and caries experience of daily rinsing in school with 1,000 parts/10(6) solutions of ammonium fluoride or sodium fluoride at pH 4.4. Subjects were 10- to 12-year-old children (n approximately equal to 200/group at baseline), about one-half of whom reported the usage of fluoride supplements. Dental caries (DFS index) and enamel fluoride (in vivo biopsy) were evaluated at baseline, 12 months, and 24 months. Supplement users had higher enamel fluoride levels and less caries experience initially, as well as generally lower caries increments over the study. In year 1, the overall caries reductions (supplement users and non-users combined) were 23 % (ammonium fluoride) and 33 % (sodium fluoride), P less than 0.01. For year 2, treatment effects were significantly greater: 54 % (ammonium fluoride) and 47 % (sodium fluoride). In newly erupted teeth, the effects of the ammonium fluoride (70 % DFS reduction) was significantly greater (P = 0.013) than that of the sodium fluoride (48 % DFS reduction). Enamel fluoride levels at the end of 2 years were 3,124 parts/10(6) (ammonium fluoride), 2,771 parts/10(6) (sodium fluoride), and 2,603 parts/10(6) (placebo), P = 0.025.", "Caries development on approximal surfaces was studied in 139 adolescents for a period of 3 yr. A test group was randomly sampled (n=69) and subjected to a new intensive mode of fluoride (F) mouthrinsings using 10 ml of 0.045% NaF neutral solution once a day for 3 d, twice a year in all, i.e., 6 rinses per year. A control group (n = 70) rinsed in a similar mode using fluoride-free tap water. The two groups received the same basic prophylactic program during the trial. Detection of approximal caries lesions and fillings was based on bitewing radiographs at baseline and after 3 yr. The test group developed an average of 2.75 + 4.76 (mean +/- SD) approximal DFS compared with 3.21 + 4.74 DFS in the control group (n.s.). However, among those teenagers who were caries free (DFS = 0) at baseline, the incidence of approximal carious and filled surfaces was 1.76+/-4.52 in the F-rinsing group (n = 26) compared with 2.76+/-5.01 DFS in the control group (n = 32), a 36% caries reduction which was statistically significant. The intensified mouthrinsing procedure seems to be a promising prophylactic mode for collective caries prevention.", "nan", "This study compared caries inhibition in children by an amine fluoride and an acidulated phosphate fluoride when administered in a topically applied gel. In addition, the effects of applying amine fluoride daily and weekly were compared. Four hundred and sixty-eight children, ages 6 to 13, were randomly assigned to one of five treatment groups and received a total of five, 5-minute treatments. The treatment and interval between each of the five treatments were as follows:(A)acidulated phosphate fluoride daily, (B) amine fluoride daily, (C) amine fluoride weekly, (D) placebo daily, and (E) placebo weekly. When the children were examined for total Decayed, Missing, and Filled Surfaces (DMFS) increments 2 years later, no significant differences were observed. However, when the data were examined for effects of DMFS for specific tooth surface, significant restriction (61%) of occlusal increment was shown in the group which was treated with amine fluoride daily for 5 consecutive days as compared with the control group.", "Aluminum salts have demonstrated anticaries activity in a number of laboratory and animal studies. The aim of this double-blind, pilot, clinical trial was to evaluate the effect of an alum (Al) mouthrinse on dental caries formation both by itself and in combination with an ADA-approved sodium fluoride (F) dentifrice. A total of 260 caries-prone children residing in a low-F area were preselected for the study and scored independently for caries by two experienced examiners. After using gender, age, and initial DMFT(S) scores for baseline stratification, the subjects were assigned to one of three treatment regimens: (1) placebo mouthrinse and F dentifrice, (2) Al mouthrinse and placebo dentifrice, and (3) Al mouthrinse and F dentifrice. The alum mouthrinse contained 500 ppm Al and the sodium fluoride dentifrice contained 1100 ppm F. Rinsing was supervised at school on weekdays for 30 sec/day, while the dentifrices were used ad libitum at home. Subjects were reexamined for caries and oral health after six and twelve months. Both examiners found that children who used Al mouthrinse, in conjunction with either placebo or F dentifrices, had lower caries incidence than those who used placebo mouthrinse/F dentifrice combination; but the differences were statistically significant for only one of the examiners. No evidence of deleterious effects to the oral tissues was observed. The results of this pilot clinical trial demonstrated that daily supervised use of an alum mouthrinse inhibited caries development in decay-prone children at least as effectively as a F dentifrice." ]

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[ "Mirtazapine is more effective than trazodone: a double-blind controlled study in hospitalized patients with major depression.", "A double-blind multicentre comparison of mirtazapine and amitriptyline in elderly depressed patients.", "A double-blind, randomized, group-comparative study of the tolerability and efficacy of 6 weeks' treatment with mirtazapine or fluoxetine in depressed Chinese patients.", "A double-blind study comparing the efficacy and tolerability of mirtazapine and doxepin in patients with major depression.", "A randomized, double-blind, 24-week study comparing the efficacy and tolerability of mirtazapine and paroxetine in depressed patients in primary care.", "A double-blind comparison of Org 3770, amitriptyline, and placebo in major depression.", "The impact of reboxetine and mirtazapine on driving simulator performance and psychomotor function in depressed patients.", "Comparative effects of mirtazapine and fluoxetine on sleep physiology measures in patients with major depression and insomnia.", "Mirtazapine: efficacy and tolerability in comparison with fluoxetine in patients with moderate to severe major depressive disorder. Mirtazapine-Fluoxetine Study Group.", "Double-blind, randomized comparison of mirtazapine and paroxetine in elderly depressed patients.", "Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder.", "Comparison of the effects of mirtazapine and fluoxetine in severely depressed patients.", "Mirtazapine versus venlafaxine in hospitalized severely depressed patients with melancholic features.", "Efficacy and tolerability of mirtazapine versus citalopram: a double-blind, randomized study in patients with major depressive disorder. Nordic Antidepressant Study Group.", "Comparison of mirtazapine and fluoxetine in the treatment of major depressive disorder: a double-blind, randomized trial.", "Mirtazapine orally disintegrating tablet versus sertraline: a prospective onset of action study.", "A multicentre, double-blind, amitriptyline-controlled study of mirtazapine in patients with major depression.", "A comparison of mirtazapine and nortriptyline following two consecutive failed medication treatments for depressed outpatients: a STAR*D report.", "Time course of hypothalamic-pituitary-adrenocortical axis activity during treatment with reboxetine and mirtazapine in depressed patients.", "Mirtazapine orally disintegrating tablets versus venlafaxine extended release: a double-blind, randomized multicenter trial comparing the onset of antidepressant response in patients with major depressive disorder.", "Mirtazapine compared with paroxetine in major depression." ]

[ "Two hundred hospitalized patients with DSM-III diagnosis of moderate to severe major depressive episode were randomized to receive mirtazapine or trazodone for 6 weeks in a double-blind trial. The dosages were 24-72 mg/day for mirtazapine and 150-450 mg/day for trazodone. The improvement on all depression rating scales used was generally greater for mirtazapine, with statistically significant differences over trazodone in the Hamilton Psychiatric Rating Scale for Depression total score and two subscores (the Bech melancholia factor and retardation factor), the Brief Psychiatric Rating Scale total score, the General Psychiatric Impression Global Assessment Scale, the Beck score and responder rates. Mirtazapine was well tolerated, while the trazodone-treated patients experienced somnolence more frequently, particularly during the first 2 weeks of treatment. Furthermore, postural symptoms were a clinical problem in 6% of the trazodone-treated patients. In this trial, mirtazapine showed significant clinical advantages over trazodone in terms of overall efficacy and tolerability.", "A total of 115 elderly patients (60-85 years of age) with DSM III diagnosis of major depressive episode were randomly assigned to 6 weeks of treatment with either mirtazapine, 15-45 mg/day, or amitriptyline, 30-90 mg/day. Efficacy was assessed biweekly, using the Hamilton Rating Scale for Depression (HRSD) and Montgomery and Asberg Depression Rating Scale (MADRS) as primary outcome variables. The treatment with both drugs resulted in a similar reduction of total HRDS and MADRS scores, with no statistically significant differences between treatment groups at any assessment point or at endpoint. Statistically significant differences favouring amitriptyline were present according to CGI-Global Improvement Scale at endpoint, HRDS cognitive disturbance factor at weeks 2, 4 and 6 and endpoint and retardation factor at week 6. Adverse events were reported by a similar number of patients in both treatment groups. Additional research is needed to assess further the efficacy and tolerability of mirtazapine among elderly depressed patients.", "To compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Chinese patients suffering moderate-to-severe depression.\n 133 patients with a diagnosis of major depressive episode (DSM-IV) and scoring 15 or more on the 17-item Hamilton Rating Scale for Depression (HAM-D) were randomly assigned to receive 6 weeks of treatment with either mirtazapine (15-45 mg/day) or fluoxetine (20-40 mg/day). Efficacy was assessed using the HAM-D and Clinical Global Impressions scale, with analyses performed on the intent-to-treat sample using the last-observation-carried-forward method. Safety analysis was based on the all-subjects-treated group.\n Mean daily doses were 34.1 mg for mirtazapine (N = 66) and 30.7 mg for fluoxetine (N = 66). Thirty patients in the mirtazapine group and 22 in the fluoxetine group dropped out. Both drugs proved equally effective for reduction of the overall symptoms of depression throughout the treatment period. At day 42, the mean reductions in HAM-D total score (compared with baseline) were 11.8 and 10.6 for the mirtazapine and fluoxetine groups, respectively; however, the changes were not statistically significant. Both treatments were well tolerated, with more nausea and influenza-like symptoms observed for the fluoxetine group, and greater weight increase and somnolence for the mirtazapine analog.\n Both mirtazapine and fluoxetine were indistinguishable in effectiveness for treatment of depressive symptoms, and both were well tolerated by our population of depressed Chinese patients. In line with analogous Western reports, the safety of mirtazapine and fluoxetine was comparable for our depressed Chinese patients; however, slightly different side effect profiles were noted for the 2 drugs in our study.", "One hundred and sixty-three patients with major depression were randomly assigned to treatment with mirtazapine or doxepin for 6 weeks in a double-blind clinical trial. Initially, patients received mirtazapine 20 mg/day or doxepin 75 mg/day; dosages were then titrated up to a maximum of 60 mg/day and 300 mg/day, respectively. Both drugs produced considerable improvement in depressive symptoms with no statistically significant differences between the two patient groups. In the mirtazapine group only two patients prematurely terminated the study due to adverse drug experiences, as compared to six in the doxepin-treated group. Moreover, doxepin-treated patients complained more frequently of dry mouth and movement disorders. In conclusion, mirtazapine is an effective treatment for major depression and appears to offer advantages in tolerability over doxepin.", "Primary care patients with a major depressive disorder and 17-item Hamilton Rating Scale for Depression (17-HAM-D) score >18 were randomized to 24 weeks of treatment with mirtazapine 30-45 mg/day (n=99) or paroxetine 20-30 mg/day (n=98). Both treatments were efficacious in improving depressive symptomatology, as assessed by group mean 17-HAM-D scores, percentages of HAM-D responders and remitters and Clinical Global Improvement responders. The mirtazapine group showed statistically significantly larger decreases from baseline in group mean 17-HAM-D scores at weeks 1, 2 and 4, and the difference with the paroxetine group reached the level of clinical relevance at weeks 2 and 4. Antidepressant efficacy was maintained throughout both the acute and continuation phase of treatment. Both treatments were well tolerated. The only adverse event with a statistically significantly higher incidence in the mirtazapine group was fatigue. Statistically significantly more paroxetine-treated patients complained of increased sweating, headache and nausea. The results demonstrate that both mirtazapine and paroxetine were efficacious and well tolerated when used for 24 weeks in depressed patients treated in primary care. An observed difference in efficacy favouring mirtazapine between weeks 1 and 4 indicates that mirtazapine patients had improved earlier compared to those on paroxetine, and corroborates similar findings in other comparisons of mirtazapine versus selective serotonin reuptake inhibitors.", "A 6-week, double-blind, dose titration study was performed to evaluate efficacy and safety of the new antidepressant Org 3770 in comparison with amitriptyline and placebo.\n One hundred fifty outpatients of both sexes, 18 years and older, with a DSM-III diagnosis of major depressive episode, were randomly assigned to 6 weeks of treatment with Org 3770, amitriptyline, or placebo.\n At baseline, mean 17-item Hamilton Rating Scale for Depression (HAM-D) scores of all treatment groups were higher than 25, thus indicating that a large proportion of severely depressed patients entered the study. The overall mean daily doses were 22 mg/day for Org 3770, 133 mg/day for amitriptyline, and 4.9 capsules/day for placebo. The majority of times assessments were made, both active drugs produced significantly greater improvements than placebo on all efficacy variables (17-item HAM-D, Montgomery-Asberg Depression Rating Scale, Clinical Global Impressions, and Zung Self-Rating Depression Scale). After 6 weeks of treatment, significantly greater (p < or = .05) proportions of patients in both active treatment groups (70% in the Org 3770- and 58% in the amitriptyline-treatment groups) than in the placebo-treatment group (33%) were HAM-D responders. Org 3770 was well tolerated in this study; dry mouth and somnolence were the only adverse experiences that occurred significantly more frequently with Org 3770- than with placebo-treated patients. By contrast, treatment with amitriptyline was related to significantly higher rates of dry mouth, constipation, and dyspepsia as compared with both Org 3770 and placebo, and significantly higher rates of somnolence as compared with placebo.\n In this study, Org 3770 was as effective as amitriptyline in the treatment of major depression, with advantages regarding improvements of depressed mood (HAM-D Item 1), responder rates, and safety.", "The aim of the present study was to examine the influence of reboxetine and mirtazapine on psychomotor functions related to driving skills and on driving simulator performance in depressed inpatients.\n Forty depressed inpatients diagnosed according to DSM-IV-TR criteria were randomly assigned to treatment with either reboxetine (N = 20) or mirtazapine (N = 20). To control for retest effects in psychomotor measures, a group of 10 healthy controls was examined on the same time schedule. Participants were tested once before pharmacologic treatment and twice after initiation of treatment (days 7 and 14) with computerized tests related to car-driving skills. Data were collected with the Act and React Testsystem ART-90 and the Wiener Testsystem, measuring visual perception, reactivity, stress tolerance, concentration, and vigilance. In addition, patients went through various risk simulations on a static driving simulator. Data were analyzed with nonparametric statistics and repeated-measures analysis of variance. The study was conducted from June 2004 through June 2006.\n Before onset of treatment with antidepressants, about 65% of patients did not reach the threshold criterion according to the German guidelines for road and traffic safety. After 14 days of treatment with reboxetine or mirtazapine, patients improved in driving ability skills. Controlling for retest effects in psychomotor measures, data indicate that both patient groups significantly improved in tests measuring selective attention and reactivity (all p < .01). Furthermore, the frequency of accidents in the risk simulations markedly decreased in patients receiving mirtazapine and reboxetine (all p < .05). Statistically significant differences between treatment groups could not be shown.\n Our results indicate that partially remitted depressed inpatients treated with reboxetine or mirtazapine show a better performance on tasks related to driving skills than do untreated depressives.\n Copyright 2008 Physicians Postgraduate Press, Inc.", "Sleep complaints are common in patients with major depressive disorder (MDD). Both MDD and antidepressant drugs characteristically alter objective sleep measures. This study compares the effects of mirtazapine and fluoxetine on sleep continuity measures in DSM-IV MDD patients with insomnia.\n Patients (N = 19) received initial baseline polysomnography evaluations over 2 consecutive nights. Subjects were randomly assigned to either fluoxetine (20-40 mg/day) or mirtazapine (15-45 mg/day) treatment for an 8-week, double-blind, double-dummy treatment trial. Single-night polysomnograms were conducted at weeks 1, 2, and 8, with depression ratings assessed at baseline and weeks 1, 2, 3, 4, 6, and 8. Statistical analysis was performed by repeated-measures analysis of variance followed by Dunnet's post hoc analyses.\n Patients receiving mirtazapine (N = 8) had significant improvement in objective sleep physiology measures at 8 weeks. Improvements in sleep latency, sleep efficiency, and wake after sleep onset were significant after only 2 weeks of mirtazapine treatment. No significant changes in sleep continuity measures were observed in the fluoxetine group (N = 11). Both groups improved clinically in mood and subjective sleep measures from baseline, with no differences between groups.\n These data demonstrate the differential effects of mirtazapine and fluoxetine, with significant improvement in favor of mirtazapine, on objective sleep parameters in MDD patients with insomnia.", "To compare the efficacy and tolerability of mirtazapine and fluoxetine in depressed inpatients and outpatients.\n Patients with a major depressive episode (DSM-III-R), a baseline score of > or=21 on the 17-item Hamilton Rating Scale for Depression (HAM-D), and > or=2 on HAM-D Item 1 (depressed mood) were randomly assigned to a 6-week treatment with either mirtazapine (N=66, 15-60 mg/day) or fluoxetine (N=67, 20-40 mg/day). The upper limit of the mirtazapine dose range was above the dose range approved in the United States (15-45 mg/day). Efficacy was evaluated by the HAM-D, Clinical Global Impressions, the Visual Analogue Mood Rating Scale (VAMRS), and the Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ). The efficacy analyses were performed on the intent-to-treat group using the last-observation-carried-forward method.\n Mean total 17-item HAM-D scores at baseline were 26.0 for the mirtazapine- and 26.1 for the fluoxetine-treated group. The decrease from baseline on the HAM-D was larger in the mirtazapine than in the fluoxetine group throughout the treatment period, reaching statistical significance at days 21 and 28. At assessments from day 21 and onward, the absolute difference between the 2 study groups favoring mirtazapine ranged from 3.7 to 4.2 points, the magnitude of difference usually seen between an efficacious antidepressant drug and placebo. Mean dosages at weeks 1-4 were 36.5 mg/day for mirtazapine and 19.6 mg/day for fluoxetine; the respective dosages at weeks 5-6 were 56.3 mg and 35.8 mg. Similar numbers of patients dropped out due to adverse events; tolerability profiles were comparable except for changes in body weight from baseline which were statistically significantly more pronounced in the mirtazapine group compared to the fluoxetine group.\n We found that mirtazapine was as well tolerated as fluoxetine and significantly more effective after 3 and 4 weeks of therapy.", "Authors studied the efficacy and tolerability of mirtazapine and paroxetine in elderly patients with major depression during an acute phase (8 weeks) and an extension phase (16 weeks).\n Patients with major depression and without dementia, at least 65 years old, were eligible; they were randomized to mirtazapine or paroxetine once daily, with doses increasing over 42 days. Efficacy was assessed with the Ham-D and Clinical Global Impressions Scale, and tolerability was assessed from adverse events.\n Of 255 patients randomized, 126 on mirtazapine and 120 on paroxetine were included in the efficacy analysis. Differences favoring mirtazapine were observed for the mean change from baseline in Ham-D-17 score. Other significant differences were in the proportion of patients classified as responders (50% decrease from baseline Ham-D-17 scores) at Day 14 and in remission (Ham-D-17 score of 7 or less) at Day 42. The median time to response was 26 days in the mirtazapine group and 40 days in the paroxetine group. The mirtazapine group also showed more reduction in Ham-D Factor I (Anxiety/Somatization) and Factor VI (Sleep Disturbance) scores. Efficacy of both drugs was maintained during the extension phase. Patients on paroxetine were more likely to discontinue therapy in the acute phase because of adverse events.\n During the first weeks of treatment, antidepressant effects were more pronounced in the mirtazapine group, suggesting that mirtazapine has an earlier onset of action. Mirtazapine also demonstrated a better tolerability profile and represents a valuable option for the treatment of depression in elderly patients.", "Patients (n = 150) were randomized to a 6-week, double-blind study to evaluate the relative efficacy and safety of mirtazapine, amitriptyline, and placebo in the treatment of major depressive disorder symptoms. Average daily modal doses were mirtazapine, 18 mg; amitriptyline, 111 mg; and placebo, 4.6 capsules. Mirtazapine- and amitriptyline-treated patients had statistically significantly greater mean Hamilton Rating Scale for Depression (HAM-D) score reductions (weekly visits 1, 2, 4, and endpoint) compared to placebo. These findings were supported by the Montgomery-Asberg Depression Rating Scale (MADRS); the Zung Self-rating Depression Scale (SDS); and the Clinical Global Impressions (CGI) scales. Somnolence and weight gain were the only adverse clinical experiences (ACEs) reported substantially more often by mirtazapine-treated patients than by those in the placebo group. However, more amitriptyline-treated patients reported decreased visual accommodation, dry mouth, dyspepsia, constipation, tachycardia, hypertension, hypotension, discoordination, dizziness, and tremor than mirtazapine- or placebo-treated patients. Results of this study indicate that mirtazapine is more effective than placebo in the treatment of these patients, and superior to amitriptyline in respect to anticholinergic and cardiovascular effects.", "Depression is a major global problem associated with large medical, sociological and economic burdens. Mirtazapine (Remeron, Organon NV, The Netherlands) is an antidepressant with a unique mechanism of action that has similar or superior efficacy to TCAs and SSRIs in moderate-to-severe depression. However, this agent has not yet been tested in patients with severe depression alone.\n To compare the antidepressant efficacy and tolerability of mirtazapine and fluoxetine and their effects on anxiety and quality of life in patients with severe depression (> or = 25 points on the first 17 items of the Hamilton Depression Rating Scale [HDRS-17]).\n In this double-blind study, 297 severely depressed patients were randomised to receive mirtazapine 15-60 mg/day (n = 147) or fluoxetine 20-40 mg/day (n = 152) for 8 weeks. 294 subjects were actually treated and 292 included in the intent-to-treat population. Symptom severity was measured by the HDRS-17, Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) rating scale. Quality of life was self-assessed by patients using the Leeds Sleep Evaluation Questionnaire and the Quality of Life, Enjoyment and Satisfaction Questionnaire. Adverse events were recorded throughout the study.\n No statistically significant differences were noted between the two groups in change from baseline HDRS-17 score at any time point; both treatments were associated with large (approximately 15 points) decreases by study end. However, more mirtazapine-treated patients tended to exhibit a > or = 50% decrease in HDRS score (significant at day 7; 9.0% vs 0.7%, p = 0.002). Significant differences in favour of mirtazapine were also observed at day 14 for changes in MADRS scores (-10.9 vs -8.5, p = 0.006) and the proportion of patients with > or = 50% decrease in MADRS score (21.4% vs 10.9%, p = 0.031). On the CGI, the proportion of 'much/very much improved' patients tended to be greater with mirtazapine (significant at day 7; 9.7% vs 3.4%, p = 0.032). No significant between-group differences were observed for the majority of quality-of-life measures. However, mirtazapine produced significantly better improvements on 'sleeping assessment 1' (14.9 +/- 5.2 vs 13.7 +/- 5.4, p = 0.028) and 'sleeping assessment 2' (p = 0.013) than fluoxetine. Both agents were generally well tolerated but mirtazapine-treated patients experienced a mean weight gain of 0.8 +/- 2.7 kg compared with a mean decrease in weight of 0.4 +/- 2.1 kg for fluoxetine-treated patients (p < 0.001).\n Mirtazapine is as effective and well tolerated as fluoxetine in the treatment of patients with severe depression.", "The aim of this multicenter, randomized, double-blind, 8-week study was to compare the antidepressant efficacy and tolerability of mirtazapine and venlafaxine in the treatment of hospitalized patients with DSM-IV diagnosis of severe depressive episode with melancholic features. Patients with a baseline score of > or = 25 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) were randomly assigned to receive treatment with either mirtazapine (N = 78, 15-60 mg/day) or venlafaxine (N = 79, 75-375 mg/day, twice a day) in a rapid up-titration schedule. Efficacy was assessed with the Montgomery-Asberg Depression Rating Scale (MADRS), HAM-D-17, and Clinical Global Impression scale, and quality of life was assessed with the Quality of Life, Enjoyment, and Satisfaction Questionnaire and Quality of Life in Depression Scale. Tolerability was assessed with the Utvalg for Kliniske Undersogelser (UKU) side effect scale and by reporting adverse events. Both drugs were effective in reducing overall symptoms of depression, showing substantial reductions in group mean MADRS scores (-20.1 for mirtazapine and -17.5 for venlafaxine) and HAM-D-17 scores (-17.1 for mirtazapine and -14.6 for venlafaxine) at the end of the treatment. Although not statistically significant, at all assessment times higher percentages of patients treated with mirtazapine were classified as responders (> or =50% reduction) on the HAM-D (at endpoint, 62% vs. 52%) and MADRS (at endpoint: 64% vs. 58%). Likewise were the percentages of remitters (HAM-D score < or =7; MADRS score < or =12) also higher in the mirtazapine group. A statistically significant difference favoring mirtazapine was found on the HAM-D Sleep Disturbance factor at all assessment points (p < or = 0.03). Both treatments were well tolerated. Although slightly more subjects treated with mirtazapine reported at least one adverse event, a statistically significantly higher percentage of patients treated with venlafaxine (15.3%) than mirtazapine (5.1%) dropped out because of adverse events (p = 0.037). Quality of life improved in both treatment groups. In this study, treatment with mirtazapine resulted in a trend toward more responders and remitters than treatment with venlafaxine and in significantly fewer dropouts as a result of adverse events.", "We aimed to compare the antidepressant and anxiolytic effects, tolerability and effects on quality of life of mirtazapine and citalopram in a randomized, double-blind, multicentre, 8-week study. Patients with a Major Depressive Episode (DSM-IV) and a baseline score of > or = 22 on the Montgomery-Asberg Depression Rating Scale (MADRS) were randomized to 8 weeks treatment with either mirtazapine (n = 137, 15-60 mg/day) or citalopram (n = 133, 20-60 mg/day). Efficacy was evaluated by the MADRS, Hamilton Anxiety Scale (HAM-A), Clinical Global Impression scales (CGI), the Leeds Sleep Evaluation Questionnaire (LSEQ) and Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ). The efficacy analyses were performed on the Intent-To-Treat Group using the Last Observation Carried Forward method. Vital signs and laboratory variables are measured and adverse events recorded at each weekly visit. The magnitude of reduction from baseline in group mean MADRS scores was large in both groups, reaching after 8 weeks of treatment mean scores of 9.1 in the mirtazapine group and 8.9 in the citalopram group. Both treatments also resulted in a substantial improvement in anxiety symptoms, sleep disturbances and quality of life, and high percentage of responders. However, at day 14, statistically significantly larger magnitudes of change favouring mirtazapine were present in the group mean MADRS, HAM-A and CGI-Severity of illness and Quality of life scores. A difference of 2.3 points on MADRS favouring mirtazapine is considered indicative for a clinically relevant superiority between two proven antidepressants. Mirtazapine treatment was also related to faster improvement of sleep, quality of sleep and improved alertness following awakening, as shown by statistically significant differences on the self-rating LSEQ at various time points. There were no differences between two treatment groups on self-rating QLSEQ. Both drugs were well tolerated, with a low number of patients in either group prematurely terminating the study due to adverse events (mirtazapine: 3.6%, citalopram, 3.0%). Sweating and nausea were statistically significantly more frequent in the citalopram group and increased appetite and complaints of weight increase in the mirtazapine group. There were no clinically relevant changes in laboratory parameters and vital sign variables with either treatment, except for clinically relevant increase in body weight, occurring more frequently in mirtazapine patients. In this study, mirtazapine and citalopram were equally effective in reducing symptoms of depression and anxiety, and well tolerated. However, mirtazapine was significantly more effective than citalopram after 2 weeks of treatment on the MADRS, HAM-A and CGI Severity of illness and Quality of life scales. This finding, consistently present at all major efficacy variables, suggests potentially faster onset of efficacy of mirtazapine over citalopram.", "Depression is an international public health problem. The aim of this study was to compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Iranian patients suffering major depressive disorder.\n Thirty-six inpatients and outpatients with a diagnosis of major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders-IV) and a score > or = 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) were randomly assigned to 6 weeks of treatment with mirtazapine (30 mg/day) or fluoxetine (20 mg/day). Efficacy was assessed by HAM-D-17. Information about adverse events was obtained by questioning of participants and/or their examination. Assessments were performed at weeks 0, 1, 2, 3, 4 and 6.\n Sixteen of mirtazapine-treated patients and fifteen of fluoxetine-treated patients completed the 6-week study period. Both treatment groups were well matched at baseline with respect to demographic and disease characteristics. Both drugs showed a significant improvement over the 6 weeks of treatment (P < 0.001). There was no statistically significant difference between the mean +/- SEM HAM-D scores of two groups at weeks 1, 2, 3, 4, and at the end point. There were no significant differences between two groups in terms of response to treatment (> or = 50% decrease from baseline in HAM-D-17 total score) and remission (HAM-D-17 score of < or = 7). None of the differences in reported adverse events was statistically significant.\n In this study, mirtazapine and fluoxetine were equally effective and well tolerated after 6 weeks of treatment in patients with major depressive disorder.", "This multinational, randomized, double-blind study was specifically designed to prospectively compare the onset of antidepressant efficacy of mirtazapine orally disintegrating tablets and sertraline at dosages commonly used in clinical practice. A total of 345 patients with major depressive episode (DSM-IV) received mirtazapine (30-45 mg/d) or sertraline (50-150 mg/d) for 8 weeks. Mirtazapine was administered in the newly developed fast dissolving, orally disintegrating tablet formulation. Assessments were performed at baseline and on days 4, 7, 10, 14, 28, 42, and 56. The primary efficacy variable (mean absolute change from baseline in the Hamilton Depression Rating Scale [HAMD] total score [17 items]) showed that mirtazapine was significantly (P < 0.05) more effective than sertraline at all assessments during the first 2 weeks of the study. After this time, HAMD total scores were similar in both groups. These findings were supported by analysis of the HAMD response rate (ie, > or =50% reduction in HAMD total score from baseline), HAMD remission rate (HAMD total score of < or =7), and the Montgomery-Asberg Depression Rating Scale (MADRS). Both treatments were well tolerated. In addition, mirtazapine had a greater effect than sertraline on sexual functioning. In conclusion, this first prospective onset of action study using the orally disintegrating tablet indicates that mirtazapine has a faster onset of therapeutic effect than sertraline. The orally disintegrating tablet formulation of mirtazapine used in this study is known to enhance the convenience and compliance by the patient.", "Background: the efficacy and tolerability of the new antidepressant mirtazapine were evaluated in a multicentre, randomized, double-blind, amitriptyline-controlled, 5 week clinical study. Method: 156 patients with a DSM-III diagnosis of major depressive episode and 21-item Hamilton Psychiatric Rating Scale for Depression (HPRSD) score ≥ 18, were randomized to treatment with either mirtazapine 20-60 mg/day or amitriptyline 75-225 mg/day. Results: mirtazapine and amitriptyline were equally effective in reducing depressive symptoms, as assessed by the 17-item HPRSD and MADRS scales. Mirtazapine was better tolerated than amitriptyline, with fewer drop-outs due to adverse events and lower incidences of adverse events both at the beginning and at the end of the trial. Conclusion: this study shows that mirtazapine is as effective as amitriptyline in treating major depression, while at the same time better tolerated.", "Few controlled studies have addressed the issue of which antidepressant medications should be recommended for outpatients who have not responded to multiple treatment trials. This study compared the efficacy of switching to mirtazapine to that of switching to a tricyclic antidepressant (nortriptyline) following two prospective, consecutive, unsuccessful medication treatments for nonpsychotic major depressive disorder.\n Following lack of remission or an inability to tolerate an initial trial of citalopram for up to 12 weeks (first step) and a second trial with either monotherapy involving another antidepressant or augmentation of citalopram with bupropion or buspirone (second step), adult outpatients (N=235) with nonpsychotic major depressive disorder were randomly assigned to 14 weeks of treatment with mirtazapine (up to 60 mg/day) (N=114) or nortriptyline (up to 200 mg/day) (N=121). The primary outcome, symptom remission, was defined a priori as a total exit score of </=7 on the 17-item Hamilton Rating Scale for Depression. The 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR(16)), obtained at treatment visits, provided secondary outcomes of remission (score </=5 at exit) and response (>/=50% reduction in score from baseline).\n For mirtazapine, remission rates were 12.3% and 8.0% per the Hamilton and QIDS-SR(16) scores, respectively. For nortriptyline, remission rates were 19.8% and 12.4%, respectively. QIDS-SR(16) response rates were 13.4% for mirtazapine and 16.5% for nortriptyline. Neither response nor remission rates statistically differed by treatment, nor did these two treatments differ in tolerability or adverse events.\n Switching to a third antidepressant monotherapy regimen after two consecutive unsuccessful antidepressant trials resulted in low remission rates (<20%) among patients with major depressive disorder.", "In healthy subjects, cortisol and ACTH secretion are acutely stimulated by reboxetine and inhibited by mirtazapine. However, it was not investigated so far whether reboxetine and mirtazapine may also differ in their impact on hypothalamic-pituitary-adrenocortical (HPA) axis activity in depressed patients and whether these effects are related to clinical outcome.\n In the present study, we investigated the impact of 5-week treatment with reboxetine or mirtazapine on the combined dexamethasone suppression/corticotropin releasing hormone (DEX/CRH) test results in depressed patients.\n Forty drug-free patients suffering from a major depressive episode (Diagnostic and Statistical Manual of Mental Disorders-IV criteria) were treated with either reboxetine (8 mg/day; n=20) or mirtazapine (45 mg/day; n=20) for 5 weeks. Before, after 1 and 5 weeks of therapy, the DEX/CRH test was performed and cortisol and ACTH concentrations were measured.\n During reboxetine treatment, a gradual and significant reduction in HPA axis activity as measured by the DEX/CRH test was seen, which was most pronounced after 5 weeks of treatment. In contrast, mirtazapine significantly reduced the cortisol and ACTH concentrations during the DEX/CRH test within 1 week. However, after 5 weeks of mirtazapine treatment, the cortisol and ACTH responses to the DEX/CRH test partially increased again both in responders and nonresponders.\n This is the first study demonstrating differential effects of various antidepressants on the time course of serial DEX/CRH test results in depressed patients.", "This randomized, multicenter, double-blind study was designed to compare specifically the onset of antidepressant action of mirtazapine orally disintegrating tablets (ODT) with venlafaxine extended-release (XR) formulation in outpatients with major depression. Both treatments were administered in a rapidly escalating dosing regimen. Target doses (mirtazapine ODT, 45 mg OD; venlafaxine XR, 225 mg OD) were reached by day 6 of treatment. On the primary efficacy parameter [the average of the change in HAM-D (17-item) total score on days 5, 8, 11, and 15], mirtazapine ODT was significantly superior to venlafaxine XR (P = 0.008). In addition, calculating the HAM-D score without the sleep items resulted in significant reductions in favor of mirtazapine ODT on days 8 (P = 0.006) and 11 (P = 0.037). The proportion of responders (HAM-D decrease of > or =50% from baseline) was higher in the mirtazapine ODT group on all assessment days, being significant on days 8 (P = 0.002), 11 (P = 0.004), and 22 (P = 0.027). More patients in the mirtazapine ODT group achieved remission (HAM-D total score of < or =7) up to day 29, and the difference was statistically significant on day 15 (P = 0.016). Significant differences in favor of mirtazapine ODT were evident in the CGI of change on days 8 (P = 0.019), 11 (P = 0.004), and 15 (P = 0.031), and the CGI of severity on days 8 (P = 0.014) and 11 (P = 0.033). Both treatments were well tolerated. These results indicate that mirtazapine ODT has a faster onset of antidepressant efficacy than venlafaxine XR in patients with major depressive disorder, and that this effect is independent of its sleep-improving properties.", "The aim was to compare the efficacy and tolerability of mirtazapine with those of paroxetine.\n 275 outpatients with a diagnosis of major depressive episode (DSM-IV) and a score > or = 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) were randomly assigned to 6 weeks of treatment with mirtazapine (15-45 mg/day) or paroxetine (20-40 mg/day). Efficacy was assessed by the HAM-D-17, Hamilton Rating Scale for Anxiety (HAM-A), and Clinical Global Impressions scales (Severity and Improvement), and analyses were performed on the intent-to-treat sample (127 mirtazapine-treated patients and 123 paroxetine-treated patients).\n Mean daily doses were 32.7 mg of mirtazapine and 22.9 mg of paroxetine. Thirty patients in the mirtazapine group and 33 in the paroxetine group dropped out. Both drugs were equally effective in reducing symptoms of depression. At week 1, the mean HAM-D-17 total score was significantly lower in mirtazapine- than paroxetine-treated patients (16.5 vs. 18.8, p = .0032). Similarly, significantly more mirtazapine-treated patients were HAM-D-17 responders (> or = 50% decrease from baseline) at weeks 1 (23.2% vs. 8.9%, p = .002) and 4 (58.3% vs. 44.5%, p = .04). Both treatments were equally effective in reducing anxiety. However, the reduction in mean HAM-A total score was significantly greater with mirtazapine than with paroxetine at week 1 (-5.1 vs. -3.5, p = .0435). Tolerability of both treatments was good, with more nausea, vomiting, tremor, and sweating in the paroxetine group and more weight increase and influenza-like symptoms in the mirtazapine group.\n Mirtazapine and paroxetine were equally effective after 6 weeks of therapy and were both well tolerated. A potentially faster onset of overall therapeutic efficacy of mirtazapine was suggested by significant differences between treatments after 1 week of therapy that were due to slightly larger improvements of several core symptoms of depression as well as distinct prevention of treatment-emergent worsening of anxiety and physical components of depression." ]

[ "8761382", "8784014", "10863061", "11830308", "8696724" ]

[ "The role of post-operative radiotherapy in non-small-cell lung cancer: a multicentre randomised trial in patients with pathologically staged T1-2, N1-2, M0 disease. Medical Research Council Lung Cancer Working Party.", "Postresection irradiation for T2 N0 M0 non-small cell carcinoma: a prospective, randomized study.", "A study of postoperative radiotherapy in patients with non-small-cell lung cancer: a randomized trial.", "Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial.", "Postoperative radiotherapy for radically resected N2 non-small-cell lung cancer (NSCLC): randomised clinical study 1988-1992." ]

[ "The role of post-operative radiotherapy for patients with non-small-cell lung cancer (NSCLC) is unclear despite five previous randomised trials. One deficiency with these trials was that they did not include adequate TNM staging, and so the present randomised trial was designed to compare surgery alone (S) with surgery plus post-operative radiotherapy (SR) in patients with pathologically staged T1-2, N1-2. M0 NSCLC. Between July 1986 and October 1993, 308 patients (154 S, 154 SR) were entered from 16 centres in the UK. The median age of the patients was 62 years, 74% were male, > 85% had normal or near normal levels of general condition, activity and breathlessness, 68% had squamous carcinoma, 52% had had a pneumonectomy, 63% had N1 disease and 37% N2 disease. SR patients received 40 Gy in 15 fractions starting 4-6 weeks post-operatively. Overall there was no advantage to either group in terms of survival, although definite local recurrence and bony metastases appeared less frequently and later in the SR group. In a subgroup analysis, in the N1 group no differences between the treatment groups were seen, but in the N2 group SR patients appeared to gain a one month survival advantage, delayed time to local recurrence and time to appearance of the bone metastases. There is, therefore, no clear indication for post-operative radiotherapy in N1 disease, but the question remains unresolved in N2 disease.", "Stage I nonirradiated T2 N0 non-small cell lung carcinoma has a postoperative prognosis not very different from stage II irradiated T1 N1 carcinoma. The hypothesis was that more locoregional malignant sites are overlooked in T2 N0 M0 than in T1 N0 M0 tumors, considering the better prognosis of this last group, and that T2 N0 cancer might benefit from postresection irradiation.\n From 1985 to 1991, 163 non-small cell lung carcinomas were classified T2 N0 M0 and randomized for irradiation or nonirradiation after operation. After revision of all the cases, 132 were included in this study: 60 were irradiated and 72 were not irradiated. All were followed up. The study was closed in October 1995. Statistical analysis was then performed considering volume, location, cell type, survival, and recurrence in the two groups.\n One hundred thirteen patients were followed up during a minimum of 5 years: the survival was 44.2%. There was no significant difference considering cell type or irradiation. There was no recurrence-free survivor beyond 5 years with a tumor invading the visceral pleura. At the close of the study (follow up, 4 years 3 months to 10 years 1 month), 49 of 132 patients were alive. The median survival was 3 years 11 months. Fifty-nine patients had died of local (21) or distant (40) recurrences (2 patients had both local and distant recurrence). There was again no significant difference considering cell type or irradiation, either in the survival or in the mode of recurrence.\n Stage I T2 N0 M0 non-small cell lung carcinoma tends to manifest distant metastasis. Prospective studies of stratified systemic adjuvant therapy should improve the present moderate result of radical resection in this group of tumors.", "To study the value of postoperative radiotherapy for non-small-cell lung cancer (NSCLC) with positive regional lymph metastases (NI or N2) after radical surgery.\n From February 1982 to October 1995, 366 patients with NSCLC and N1 or N2 disease were randomized into postoperative radiotherapy (S + R) (183 patients) and no further treatment (S alone) (182 patients). Postoperative radiotherapy (RT) was administrated 3-4 weeks after radical operation. Irradiated fields covered the bronchial stump, ipsilateral hilum, and most of the mediastinum. The midplane dose was 6000 cGy/30 fractions/6 weeks, with the spinal cord limited to 4000 cGy/20 fractions/4 weeks or less. One hundred thirty-four patients in S + R group and 162 patients in S alone group were evaluated. Clinical data were comparable in both arms, except for the numbers of N2 patients.\n The 3-year and 5-year overall survival rates were 51.9% and 42.9% in the S + R group and 50.2% and 40.5% in the S alone Group (p = 0.56). The 3-year and 5-year disease-free survival rates were 50.7% +/- 4.7% and 42.9% +/- 5.2% in the S + R group vs. 44.4% +/- 4.3% and 38.2% +/- 4.5% in the S alone group (p = 0.28), respectively. In the patients with NI or T3-4 tumors, there was a trend toward improved survival in the S + R group, especially in the patients with T3-4N1M0. These patients demonstrated 20% improvement in overall survival (p = 0.092) and greater than 20% better disease-free survival (p = 0.057). Postoperative RT reduced local recurrence but had no impact on distant metastases.\n Postoperative RT significantly reduced local relapses, but did not improve overall survival, due to a high frequency of distant metastases in this patient group.", "To evaluate the benefits and the drawbacks of post-operative radiotherapy in completely resected Stage I (a and b) non-small cell lung cancer (NSCLC).\n Patients with pathological Stages Ia and Ib NSCLC have been randomized into two groups: Group 1 (G1) received adjuvant radiotherapy, Group 0 (G0) the control group did not receive any adjuvant therapy. Local control, toxicity and survival have been evaluated.\n Between July 1989 and June 1997, 104 patients with pathological stage I NSCLC have been enrolled in this study. Fifty-one patients were randomized to G1 and 53 to G0. Six patients have been excluded from the study due to incomplete follow-up data. Regarding local control, one patient in the G1 group had a local recurrence (2.2%) while in the G0 12 local recurrences have been observed (23%). Seventy-one percent of patients are disease-free at 5 years in G1 and 60% in G0 (P=0.039). Overall 5-year survival (Kaplan-Meier) showed a positive trend in the treated group: 67 versus 58% (P=0.048). Regarding toxicity in G1, six patients experienced a grade 1 acute toxicity. Radiological evidence of long-term lung toxicity, with no significant impairment of the respiratory function, has been detected in 18 of the 19 patients who have been diagnosed as having a post-radiation lung fibrosis.\n Adjuvant radiotherapy gave good results in terms of local control in patients with completely resected NSCLC with pathological Stage I. Overall 5-year survival and disease-free survival showed a promising trend. Treatment-related toxicity is acceptable.", "In the period 1988-1992, 74 consecutive radically resected patients with NSCLC were randomised to postoperative radiotherapy or surgery alone in order to evaluate the influence of postoperative radiotherapy on survival. There were 61 males and 13 females, aged 35-80 years, median 59 years. Their distribution by stage was as follows: pT1N2 = 19, pT2N2 = 54, pT3N2 = one patient; histology: 32 squamous, 32 adeno and 10 large cell carcinomas; surgery: atypical resection in six, lobectomy in 27, bilobectomy in ten, and pneumonectomy in 31 patients. In 27 patients, only one lymph node in a single mediastinal lymph node site was affected; in 31 patients more than one lymph node in one site; in 16 patients more sites were affected. In 35/74 patients radiotherapy of hilar and mediastinal sites with 3000 cGy in 2 weeks was performed. On December 31, 1994, 19 patients (26%) were still alive; 39/55 patients died of the following causes: locoregional failure-10(26%), distant metastases- 25 (64%), other tumor-unrelated causes-four patients (10%). Five-year survival rates did not show statistically significant differences between the irradiated and surgically treated patients only with respect to sex, pTNM stage, histology and frequency of locoregional failure. The number of metastatic mediastinal lymph nodes was the only significant prognostic factor (P < 0.005) in both randomised groups." ]

[ "3936908", "2122630", "9713029", "6406654", "7844680", "2122016" ]

[ "The metabolic effects of oral L-carnitine administration in infants receiving total parenteral nutrition with fat.", "Parenteral nutrition in preterm neonates with and without carnitine supplementation.", "Randomised controlled trial of L-carnitine as a nutritional supplement in preterm infants.", "Carnitine deficiency in premature infants receiving total parenteral nutrition: effect of L-carnitine supplementation.", "Effects of parenteral L-carnitine supplementation on fat metabolism and nutrition in premature neonates.", "Effect of intravenous L-carnitine on growth parameters and fat metabolism during parenteral nutrition in neonates." ]

[ "beta-Oxidation, an important pathway in the metabolism of free fatty acids, occurs within the mitochondria in mammals. L-Carnitine is an essential cofactor in the transfer of long-chain fatty acids across the inner mitochondrial membrane. Maintenance of normal carnitine concentrations in whole blood and tissues, either through diet or biosynthesis, would appear necessary for adequate utilization of fat as an energy source. Infants, especially premature ones, without an exogenous dietary source of carnitine, have decreased plasma carnitine levels compared with infants receiving carnitine-supplemented feedings. To determine the importance of carnitine supplementation in a total parenteral nutrition program in infants in which a fat emulsion serves as a major calorie source, the following study was undertaken. Twelve infants receiving total parenteral nutrition (TPN) with fat for seven days were divided into two treatment groups. Group 1 was orally supplemented for seven days with carnitine (70 mumol/l/kg/24 h in 24 mL of 5% dextrose), while the second group received seven days of placebo supplementation (dextrose 5%, 24 cc/24 h). Plasma carnitine levels in the carnitine-supplemented group were significantly higher (29 +/- 8 nmol/mL) than in the control group (12.4 +/- 3.5 nmol/mL) after seven days of treatment. However, clearance of serum triglycerides and free fatty acids was not significantly different between the two groups. Baseline triglyceride levels in the carnitine-supplemented group were 96 +/- 42 mg/dL, increased to 242 +/- 101 mg/dL after the lipid challenge and decreased to 121 +/- 47 mg/dL two hours after the lipid infusion.(ABSTRACT TRUNCATED AT 250 WORDS)", "The effects of carnitine supplementation on fat and glucose metabolism and carnitine balance were studied in 12 preterm neonates receiving full or partial parenteral nutrition (PN) for 5 to 21 days. The gestational age ranged from 27 to 32 weeks and the birth weight from 790 to 2090 g. The neonates were assigned at random to receive either L-carnitine 10 mg/kg (n = 6) or saline (n = 6). In the carnitine group, increased concentrations in plasma of total and free carnitine were observed. Less than 50% of the given dose was recovered in urine. In the placebo group no changes in the total plasma carnitine concentration were seen. In all neonates plasma triglycerides, free fatty acids, glycerol, alanine, 3-hydroxybutyrate (BOB), glucose and lactate were measured at predetermined intervals. The only significant difference between the groups was higher BOB-concentrations in the carnitine group 2 days after the start of parenteral nutrition. Elevated BOB concentrations are an indicator of improved fatty acid oxidation in the carnitine group. In this study, only a temporary effect of the carnitine supplementation was found.", "To evaluate the effect of L-carnitine supplementation (25 mg/kg/d) on the growth and incidence of hypoglycaemia in preterm infants.\n A double blind, placebo controlled randomised trial, stratified for gestational age, was conducted of 86 preterm infants between 28 and 34 gestational weeks. The median gestational ages in the carnitine group and placebo groups were 30.7 weeks (range 28.0 to 33.6) and 31.4 weeks (range 28.0 to 33.9), respectively. The median birthweights were 1.557 kg (range 0.944 to 2.275) and 1.645 kg (range 0.885 to 2.545), respectively.\n Mean plasma free carnitine concentrations were below values for normal term infants in both groups on day 1 (carnitine group 44.8 mumol/l, placebo group 25.5 mumol/l) in the placebo group on day 7 (50.7 mumol/l), but in neither group on days 14 and 28. Total, free, and acylcarnitine concentrations were significantly increased in both urine and blood in the L-carnitine group. There was no significant difference between the placebo and carnitine supplemented groups in growth rate, as assessed by weight, length, skinfold thickness and head circumference measurements, or in the incidence of episodes of hypoglycaemia.\n The addition of carnitine as a nutritional supplement at a dose of 25 mg/kg/day did not improve growth in our group of preterm infants nor protect them from episodes of hypoglycaemia.", "To investigate whether L-carnitine supplementation may correct nutritional carnitine deficiency and associated metabolic disturbances in premature infants receiving total parenteral nutrition, an intravenous fat tolerance test (1 gm/kg Intralipid over four hours) was performed in 29 premature infants 6 to 10 days of age (15 receiving carnitine supplement 10 mg/kg . day L-carnitine IV, and 14 receiving no supplement). Total carnitine plasma values were normal or slightly elevated in supplemented but decreased in nonsupplemented infants. In both groups, fat infusion resulted in an increase in plasma concentrations of triglycerides, free fatty acids, D-beta-hydroxybutyrate, and short-chain and long-chain acylcarnitine, but total carnitine values did not change. After fat infusion, the free fatty acids/D-beta-hydroxybutyrate ratios were lower and the increase of acylcarnitine greater in supplemented infants of 29 to 33 weeks' gestation than in nonsupplemented infants of the same gestational age. This study provides evidence that premature infants of less than 34 weeks' gestation requiring total parenteral nutrition develop nutritional carnitine deficiency with impaired fatty acid oxidation and ketogenesis. Carnitine supplementation improves this metabolic disturbance.", "The effects of parenteral L-carnitine supplementation on fat metabolism, nutrient intake, and plasma and erythrocyte carnitine concentrations were studied in 43 very low birth weight infants. Infants were randomly assigned to control or carnitine-supplemented (50 mumol/kg per day) groups within two weight categories: group 1, 750 to 1000 gm, and group 2, 1001 to 1500 gm. Plasma total, free, and acyl carnitine levels, erythrocyte carnitine levels, serum beta-hydroxybutyrate and triglyceride levels, and total fat intake were monitored weekly until 50% of total caloric intake was met enterally. Neonates receiving carnitine had higher plasma carnitine levels than control groups (total carnitine: group 1, 75.2 +/- 22.9 vs 9.6 +/- 2.7 mmol/ml; group 2, 61.6 +/- 31.2 vs 13.0 +/- 9.2 nmol/ml). Levels of beta-OH-butyrate decreased from baseline in control neonates (group 1, 0.12 +/- 0.06 to 0.03 +/- 0.02 mmol/L; group 2, 0.11 +/- 0.03 to 0.05 +/- 0.02 mmol/L); they remained unchanged in supplemented groups. Thus ketogenesis appeared less impaired in infants receiving supplements. Supplemented group 2 tolerated more fat than control group 2; triglyceride levels remained acceptable in all groups. Carnitine group 2 had greater weight gain than control group 2 during the first 2 weeks of life. We conclude that very low birth weight infants requiring prolonged parenteral nutrition have carnitine deficiency with impaired ketogenesis. Parenteral administration of carnitine appears to alleviate this metabolic disturbance.", "To determine whether intravenous carnitine can improve nutritional indices, neonates requiring parenteral nutrition were randomized into carnitine treatment (n = 23) and control (n = 20) groups. Observed plasma lipid indices, carnitine and nitrogen balances, and plasma carnitine concentrations were not different in the prestudy period. Under standardized, steady-state conditions, 0.5 g/kg Intralipid was administered intravenously over 2 hr prior to carnitine administration, after infants received 7 days of 50 mumol/kg/day, and after a second 7 days of 100 mumol/kg/day of continuous intravenous L-carnitine as part of parenteral nutrition. Triglyceride (TGY), free fatty acid (FFA), acetoacetate (AA), beta-hydroxybutyrate (BOB), and plasma carnitine concentrations were measured prior to and at 2, 4, and 6 hr after the initiation of the lipid bolus. Twenty-four-hour urine collections for nitrogen and carnitine balance were obtained on days 7 and 14. Neonates receiving carnitine had significantly greater concentrations of plasma carnitine on days 7 and 14 (p less than 0.001). Greater nitrogen (p less than 0.05) and carnitine (p less than 0.001) balances and weight gain (week 2, p less than 0.05) were found in the carnitine-supplemented group when compared with controls. On day 14, (BOB + AA)/FFA ratios were significantly higher (p less than 0.05), and peak TGY concentrations and 6-hr FFA concentrations were significantly lower (p less than 0.05) in the treatment group. Carnitine supplementation was associated with modest increases in growth and nitrogen accretion possibly by enhancing the neonate's ability to utilize exogenous fat for energy." ]

[ "12819167", "3320325", "6756261", "3981366", "6673482", "676731", "5094252", "556631", "2777499", "325492", "2911997", "2179850", "2881038", "3547300", "6959554", "6407714", "2654350", "7029275", "6546416" ]

[ "Effects of vitamin E supplementation during erythropoietin treatment of the anaemia of prematurity.", "Carboxyhemoglobin concentration as an index of bilirubin production in neonates with birth weights less than 1,500 grams: a randomized double-blind comparison of supplemental oral vitamin E and placebo.", "Effect of vitamin E on the development of oxygen-induced lung injury in neonates.", "Bilirubin production after supplemental oral vitamin E therapy in preterm infants.", "The effect of vitamin E on erythrocyte hemolysis and lipid peroxidation in newborn premature infants.", "Vitamin E requirements of preterm infants.", "Vitamin E-dependent anemia in the premature infant. I. Effects of large doses of medicinal iron.", "The use of intramuscular vitamin E in the premature infant. Optimum dose and iron interaction.", "Vitamin E and selenium in preterm infants: lack of effect on clinical patency of ductus arteriosus.", "Vitamin E and neonatal hemolysis.", "Vitamin E supplementation in very-low-birth-weight infants: long-term follow-up at two different levels of vitamin E supplementation.", "Effect of intramuscular vitamin E on mortality and intracranial hemorrhage in neonates of 1000 grams or less.", "Vitamin E supplementation reduces frequency of periventricular haemorrhage in very preterm babies.", "Tocopherol efficacy and safety for preventing retinopathy of prematurity: a randomized, controlled, double-masked trial.", "Vitamin E and intraventricular hemorrhage in the newborn.", "Protective effect of vitamin E (DL-alpha-tocopherol) against intraventricular haemorrhage in premature babies.", "Effect of sustained pharmacologic vitamin E levels on incidence and severity of retinopathy of prematurity: a controlled clinical trial.", "Retrolental fibroplasia: efficacy of vitamin E in a double-blind clinical study of preterm infants.", "Retrolental fibroplasia and vitamin E in the preterm infant--comparison of oral versus intramuscular:oral administration." ]

[ "To evaluate the effects of vitamin E supplementation on haemoglobin concentration and the requirement for transfusion in premature infants treated with erythropoietin and iron.\n Randomised, double blind, placebo controlled trial. Thirty infants </=32 weeks gestation and </=1250 g birth weight, who were defined as stable based on minimal requirements for respiratory support and phlebotomy, and absence of major congenital anomalies were enrolled. All were treated with erythropoietin and iron, and were randomised to receive, in addition, either vitamin E 50 IU/day or placebo for eight weeks or until discharge, whichever came first.\n Despite higher vitamin E (alpha-tocopherol) levels in the experimental group in weeks 3 (49.0 v 28.1 micro mol/l) and 8 (66.2 v 38.5 micro mol/l), there were no differences in haemoglobin, reticulocyte count, iron concentration, or transfusion requirement.\n Oral vitamin E supplementation at 50 IU/day does not increase the response of preterm infants to erythropoietin and iron. Vitamin E obtained through standard nutrition may have been sufficient or higher doses may be required.", "A randomized double-blind study of the efficacy of oral vitamin E supplementation as a prophylactic treatment for hyperbilirubinemia was undertaken in preterm infants weighing less than 1,500 g. Hemoglobin (Hb) levels, blood carboxyhemoglobin saturation (HbCOc), end-tidal carbon monoxide concentration (ETCO), and serum total bilirubin levels were determined in each subject on the first and third days of the study. We found no differences between the vitamin E-treated and placebo-treated groups with respect to Hb, HbCOc, ETCO, or serum bilirubin levels on day 1 or 3. In addition, we reanalyzed our data to compare those infants who had low vitamin E levels at birth with those who had vitamin E levels greater than 0.4 mg/dl on day 1. We still observed no differences in Hb, HbCOc, ETCO, or serum bilirubin levels on day 1 or 3. The results of our study suggest that supplemental oral vitamin E therapy has no major effect on bilirubin production during the first 3 days of life in premature infants weighing less than 1,500 g at birth.", "nan", "The purpose of this investigation was to determine the influence of early vitamin E supplementation on the rate of heme catabolism (bilirubin production) in healthy preterm infants. Bilirubin production was estimated from the concentration of carbon monoxide in \"end-tidal\" gas. Serum vitamin E, hemoglobin, and bilirubin levels were determined by standard techniques. Thirty infants received supplementation with vitamin E or placebo in a double-blind, randomized fashion. Infants were studied on day 1 of life prior to therapy, and on days 3 and 7 postnatally. Results showed that in both placebo-supplemented and vitamin E-supplemented groups, vitamin E levels were significantly higher on days 3 and 7 compared with day 1. Bilirubin production was not significantly different on day 3 compared with day 1 in either group, but was significantly lower in both groups by day 7 compared with day 1. There were no significant differences in hemoglobin and serum bilirubin levels between the two groups at any point in time. In conclusion, although vitamin E supplementation significantly raises vitamin E levels, placebo-supplemented premature infants also achieve vitamin E sufficiency and a decrease in bilirubin production by day 7 of age.", "The biochemical effect of vitamin E supplementation to mothers with threatened premature delivery and to premature infants after birth has been studied. Although a weak correlation was found between maternal and cord blood vitamin E levels at birth, cord blood levels were not significantly higher in the infants from supplemented mothers than those from unsupplemented mothers. Furthermore, maternal vitamin E treatment did not prevent either erythrocyte hemolysis or lipid peroxide formation in the premature infants after birth. On the other hand, intramuscular vitamin E to infants after birth produced a marked biochemical effect, with both zero erythrocyte hemolysis and low lipid peroxide formation when serum vitamin E increased above 2 mg/100 ml. We conclude that intramuscular vitamin E immediately after birth is necessary to achieve a biochemical effect of vitamin E in the early neonatal period. (No cases of retrolental fibroplasia occurred in the present study.)", "Differences between feeding practices in earlier investigations prompted the present study of iron and vitamin E supplementation in breast milk fed preterm infants. A new and highly sensitive technique for quantitation of alpha-tocopherol in serum was used. Studies on 34 infants with a birth weight below 2000 g or gestational age less than or equal to 35 weeks showed that supplementation with 16.5 mg tocopheryl acetate/day from 10 days of age resulted in a significantly higher haemoglobin concentration and lower reticulocyte count at 8-10 weeks than supplementation with 1.5 mg/day (p is less than 0.05). Studies on 23 infants with a birth weight of 2000-2499 g revealed subnormal alpha-tocopherol levels in 2 of the infants given 1.5 mg tocopheryl acetate/day but there was no effect on the haemoglobin concentration at 8-10 weeks. There were no untoward effects of an early iron supplementation with 2-3 mg Fe++ (as ferrous succinate)/kg/day. It is concluded that extra supplementation with vitamin E is advisable also in breast milk fed preterm infants. A low dosage iron supplementation from 3 weeks of age is safe.", "nan", "nan", "Levels of antioxidant defenses, which include vitamin E and Se-dependent GSH-Px, are generally relatively low in the fetus and neonate. Se-dependent GSH-Px and vitamin E are known to modulate biosynthesis of eicosanoids and therefore could have the potential for affecting patency or closure of the ductus arteriosus after birth. We evaluated some indices of antioxidant defense in sick LBW infants in relationship to one another as well as to clinical PDA, and investigated the effects of producing a rapid rise in serum vitamin E levels in some of these infants. Twenty-nine sick preterm infants (B. W. 750-1750 g) were randomized into control and vitamin E supplemented groups; the latter received dl-alpha-tocopherol IM., commencing within 12 hours of birth, to a total dosage of 175 mg/kg over four weeks. Most E-supplemented infants attained serum tocopherol levels greater than 0.50 mg/dl (12 mumol/l) within 24 hours of the first dose. Vitamin E supplementation did not influence clinical patency or closure of the ductus arteriosus, and no correlation could be established between serum levels of alpha-tocopherol, Se, GSH-Px or NPS and PDA. At 4 weeks vitamin E-supplemented infants had serum levels of the other antioxidant indices that were not significantly different from the non-supplemented babies.", "A study was designed to determine if the presence of vitamin E deficiency during the first week of life played a contributory role in the shortened red cell life span observed in the premature infant. Carboxyhemoglobin values were used as an index of hemolysis. Ten infants received vitamin E administered intramuscularly in a total dose of 125 mg/kg during days 3 to 7 of life; ten infants served as controls. The mean percent carboxyhemoglobin level fell significantly from day 3 to day 8 in the treated group (1.08% to 0.78%) whereas the mean value remained unchanged at 0.96% in the control group. The administration of vitamin E appears to reduce but not eliminate the accelerated red cell destruction that characterizes the preterm infant. Pediatrics, 59:995-997, 1677, VITAMIN E, HEMOLYSIS, PREMATURE INFANT, CARBOXYHEMOGLOBIN.", "This study evaluates the need of vitamin E supplementation in very-low-birth-weight infants by long-term follow-up of plasma vitamin E status during the first 15 mo of life, with two different levels of supplementation. The subjects were 51 newborn infants with birth weights less than or equal to 1520 g. During hospitalization the infants were fed human milk. On the third day of life oral vitamin E supplementation of less than or equal to 10 mg/d was started in all infants. In addition, 23 infants selected at random were given intramuscular vitamin E (20 mg/kg/d) during the first 3 d. The data indicate that the 10 mg/d supplement resulted in an adequate plasma concentration of vitamin E. After cessation of supplementation at age 3 mo, the risk of low plasma vitamin E levels increased. Although intramuscular administration resulted in long-lasting increments in mean plasma vitamin E values, some later levels in these infants were marginal.", "A randomized, double-blind study to determine the effect of intramuscular vitamin E on mortality and intracranial hemorrhage (ICH) was performed. One hundred forty-nine neonates with birth weights less than or equal to 1000 g and less than or equal to 24 hours of age were grouped by weight (501 to 750 g and 751 to 1000 g) and randomized to treatment or control. The treatment group received intramuscular injections of vitamin E (dl-alpha-tocopherol) on days 1, 2, 4, and 6 of life. The control group received intramuscular injections of placebo on the same schedule. All neonates initially received oral vitamin E (100 mg/kg/day dl-alpha-tocopheryl acetate), which was subsequently adjusted to keep serum levels at 0.5 to 3.5 mg/dL. Ultrasonographic examinations of the head were performed as possible on days 1, 5 to 7, and 12 to 14. Hemorrhage was defined as mild if less than or equal to grade II ICH, or severe if grade III or IV. No significant differences in neonatal or total hospital mortality between groups were found. However, all ICH, as well as severe ICH, were significantly less in the vitamin E-treated 501 to 750-g subgroup (all ICH: 60% vs 29%; severe ICH: 32% vs 4%). When survivors were analyzed separately, a significant decrease in severe ICH was seen in the vitamin E-treated neonates (25% vs 5%). Necrotizing enterocolitis and sepsis did not occur more frequently in the neonates treated with intramuscular injections of vitamin E. Other than two cases of mild induration at injection sites, no deleterious side effects of treatment were identified. Vitamin E may have a role in the prevention of severe ICH in premature neonates weighing between 501 and 750 g.", "231 babies, born at less than or equal to 32 weeks' gestation were enrolled in a randomised, controlled trial to assess the efficacy of vitamin E (dl-alpha-tocopherol acetate) in the prevention of periventricular haemorrhage. Daily supplementation with 20 mg/kg vitamin E intramuscularly during the first 3 days of life was associated with a rise in plasma vitamin E concentration and a reduction in hydrogen peroxide haemolysis of red blood cells in vitro. Among babies without haemorrhage on entry to the trial (n = 210), supplemented babies had a lower frequency of intraventricular haemorrhage than controls (8.8% v 34.3%; p less than 0.005) and a lower combined frequency of intraventricular and parenchymal haemorrhage (10.8% v 40.7%; p less than 0.0001) on the final ultrasound brain scan. This protective effect was observed in both inborn and referred babies but was stronger in the former. Supplementation had no effect on mortality, but among survivors fewer supplemented babies than controls had intraventricular or parenchymal haemorrhage (10.7% v 32.6%; p less than 0.001). Possibly, vitamin E scavenges free radicals generated during ischaemic injury of the subependymal region and thereby limits tissue damage and the extent of periventricular haemorrhage on reperfusion.", "To test the efficacy and safety of vitamin E in preventing retinopathy of prematurity, 287 infants with birth weights of less than 1.5 kg or gestational ages of less than 33 weeks were enrolled within 24 hours of birth in a randomized, double-masked trial of IV, followed by oral, placebo v tocopherol (adjusted to plasma levels of 3 to 3.5 mg/dL). In the 196 infants completing ophthalmic follow-up, tocopherol did not prevent retinopathy of prematurity of any stage (28% placebo treated v 26% tocopherol treated) or moderately severe retinopathy of prematurity (8% placebo treated v 11% tocopherol treated). Cicatricial sequelae were not significantly different (1/97 placebo treated v 3/99 tocopherol treated), with one placebo-treated infant and one tocopherol-treated infant having retinal detachments. Among all 232 infants examined, those treated with tocopherol had more retinal hemorrhage than placebo-treated infants (8/121 placebo treated v 16/111 tocopherol treated), and retinal hemorrhage correlated positively (P less than .01) with plasma levels of tocopherol after the first 2 weeks of age. Prospective monitoring of morbidity including late-onset sepsis, necrotizing enterocolitis, etc revealed no differences between groups except that grades 3 and 4 intraventricular hemorrhage occurred more frequently in infants weighing less than 1 kg at birth who had received tocopherol (14/42, 33%) v those who had received placebo (4/43, 9%) (P less than .02). Our data do not support the use of tocopherol for prophylaxis against retinopathy of prematurity in premature infants and suggest that IV tocopherol treatment starting on day 1 may increase the incidence of hemorrhagic complications of prematurity, particularly in infants with birth weights of less than 1 kg.", "nan", "Forty four babies, of less than 32 weeks' gestation, were either randomly given 25 mg/kg vitamin E (DL-alpha-tocopherol acetate) intramuscularly after birth (day 0) and on days 1, 2, and 3 or served as controls. Frequent real time ultrasound examinations of the brain were made in each baby during the first week and less frequently thereafter. In babies under 32 weeks' gestation the incidence of intraventricular haemorrhage was lower in supplemented babies (18.8%) compared with the controls (56.3%). On days 0, 1, 2, and 3 median plasma vitamin E concentrations in babies without haemorrhage and in those with subependymal haemorrhage only were similar. Babies with intraventricular haemorrhage had lower median concentrations on day 1 (p less than 0.002) and day 2 (p less than 0.05) compared with those with subependymal haemorrhage and lower concentrations on day 0 (p less than 0.02) and day 1 (p less than 0.05) compared with those without haemorrhage. These findings suggest that in premature babies vitamin E, an antioxidant, protects endothelial cell membranes from oxidative damage and disruption and limits the magnitude of haemorrhage and its spread from the subependyma into the ventricles.", "The incidence and severity of retinopathy of prematurity (ROP) as affected by vitamin E prophylaxis at pharmacologic serum levels (5 mg/dl) were evaluated in a double-masked clinical trial of infants with a birth weight less than or equal to 2000 gm or a gestational age less than or equal to 36 weeks. The infants were enrolled by age 5 days and randomly assigned to receive parenterally administered, and later orally administered, free alpha-tocopherol (vitamin E) or its placebo. Study medication was continued until retinal vascularization was complete or active ROP had subsided, except in infants with a diagnosis of severe disease, in whom vitamin E was substituted for study medication. Acute ROP data were collected on 755 infants. Logistic regression analysis, with control for immaturity, oxygen exposure, and other illness risk factors, showed a decrease in incidence of ROP in vitamin E-treated infants (p = 0.003, all infants; p = 0.035, infants weighing less than or equal to 1500 gm at birth). Among the 424 infants weighing less than or equal to 1500 gm at birth, the age at enrollment influenced treatment effect (age day 0 to 1, p = 0.006 (n = 288) vs age day 2 to 5, p greater than 0.1 (n = 136]. Overall, 77.6% of infants with ROP had mild disease. Moderate to severe ROP was confined to infants weighing greater than or equal to 1500 gm at birth (25 given placebo, 25 given vitamin E), with progression to severe disease in nine placebo-treated versus three vitamin E-treated infants (p = 0.048). The incidence of severe ROP per se was not significantly decreased (all birth weights, p = 0.086; less than or equal to 1500 gm birth weight, p = 0.080); the sample size was too small, however, to assess this end point adequately. An increased incidence of sepsis and late-onset necrotizing enterocolitis was found among vitamin E-treated infants weighing less than or equal to 1500 gm at birth who received study medication for greater than or equal to 8 days (p = 0.006). Because most ROP is mild in degree and regresses completely, the risk/benefit ratio of pharmacologic prophylaxis for ROP is unfavorable. Treatment of moderate and severe ROP with vitamin E above physiologic serum levels (greater than 3 mg/dl) appears promising and should be further investigated. The interpretation of cicatricial outcome was confounded by the small number of patients involved and by subsequent treatment of severe ROP in placebo-treated infants with vitamin E.", "We performed a double-blind study in 101 preterm infants who weighed less than or equal to 1500 g at birth, who had respiratory distress, and who survived for at least four weeks, to evaluate the efficacy of oral vitamin E in preventing the development of retrolental fibroplasia. Weekly indirect ophthalmologic examinations begun when the infants were three weeks old revealed a significant decrease in the incidence of retrolental fibroplasia greater than or equal to Grade III (P less than 0.03) and greater than or equal to Grade II (P less than 0.05) (McCormick classification) in the 50 infants given 100 mg of vitamin E per kilogram of body weight per day as compared with 51 given 5 mg per kilogram per day (controls). When multivariate analysis was applied to the controls, five risk factors were identified: gestational age, level and duration of administration oxygen, intraventricular hemorrhage, sepsis, and birth weight. When multivariate analysis was applied to both control and treatment groups, the severity of retrolental fibroplasia was found to be significantly reduced in infants given 100 mg of vitamin E (P = 0.012).", "To evaluate the efficacy of four early intramuscular injections of vitamin E given in addition to continuous minimal oral vitamin E supplementation, 168 very low-birth-weight infants (less than or equal to 1,500 g) have enrolled in a randomized, double-masked, clinical study. All infants received vitamin E orally, 100 mg/kg/d. In addition, on days 1, 2, 4, and 6, seventy-nine infants received vitamin E intramuscularly, 15, 10, 10, and 10 mg/kg, respectively. On the same days, 89 control infants received placebo intramuscular injections. Multivariate analysis of the 135 infants who survived greater than or equal to 10 weeks showed no significant difference in the development of severe retrolental fibroplasia between these two supplementation schedules (P = .86). Plasma vitamin E levels never exceeded a mean of 3.3 mg/100 mL, and no toxicity was observed. Ultrastructural analyses of seven pairs of whole eye donations from infants receiving IM vitamin E demonstrated identical kinetics of gap junction formation between adjacent spindle cells as compared with 13 pairs of whole eye donations from control infants (P greater than .3). Therefore, oral vitamin E supplementation affords retinal protection against the development of severe retrolental fibroplasia when initiated on the first day of life and maintained continuously until retinal vascularization is complete." ]

[ "14527527", "17581445", "17075912", "18348595" ]

[ "Treatment of pharmacotherapy-refractory posttraumatic stress disorder among Cambodian refugees: a pilot study of combination treatment with cognitive-behavior therapy vs sertraline alone.", "A pilot randomized controlled trial of combined trauma-focused CBT and sertraline for childhood PTSD symptoms.", "Augmentation of sertraline with prolonged exposure in the treatment of posttraumatic stress disorder.", "Paroxetine CR augmentation for posttraumatic stress disorder refractory to prolonged exposure therapy." ]

[ "Cambodian refugees with posttraumatic stress disorder (PTSD) represent a cohort in severe need of treatment, but little information is available to guide treatment choices. We selected a sample of pharmacotherapy-refractory individuals to test the efficacy of combination treatment with sertraline and cognitive-behavior therapy (CBT) for treating PTSD. Participants in this pilot study were ten Khmer-speaking women who had been at a mean age of 22-26 years during the Pol Pot period (1975-1979). These patients were randomly assigned to either sertraline alone or combined treatment. We found that combined treatment offered additional benefit in the range of medium to large effect sizes for PTSD and associated symptoms. Our findings indicate that substantial gains can be achieved by adding CBT to pharmacotherapy for PTSD, and that a program of CBT emphasizing information, exposure, and cognitive-restructuring can be successfully modified for Khmer-speaking refugees.", "To examine the potential benefits of adding a selective serotonin reuptake inhibitor, sertraline, versus placebo, to trauma-focused cognitive-behavioral therapy (TF-CBT) for improving posttraumatic stress disorder and related psychological symptoms in children who have experienced sexual abuse.\n Twenty-four 10- to 17-year-old female children and adolescents and their primary caretakers were randomly assigned to receive TF-CBT + sertraline or TF-CBT + placebo for 12 weeks.\n Both groups experienced significant improvement in posttraumatic stress disorder and other clinical outcomes from pre- to posttreatment with no significant group x time differences between groups except in Child Global Assessment Scale ratings, which favored the TF-CBT + sertraline group.\n Only minimal evidence suggests a benefit to adding sertraline to TF-CBT. A drawback of adding sertraline was determining whether TF-CBT or sertraline caused clinical improvement for children with comorbid depression. Current evidence therefore supports an initial trial of TF-CBT or other evidence-supported psychotherapy for most children with PTSD symptoms before adding medication.", "The present study was designed to determine whether augmenting sertraline with prolonged exposure (PE) would result in greater improvement than continuation with sertraline alone. Outpatient men and women with chronic PTSD completed 10 weeks of open label sertraline and then were randomly assigned to five additional weeks of sertraline alone (n = 31) or sertraline plus 10 sessions of twice-weekly PE (n = 34). Results indicated that sertraline led to a significant reduction in PTSD severity after 10 weeks but was associated with no further reductions after five more weeks. Participants who received PE showed further reduction in PTSD severity. This augmentation effect was observed only for participants who showed a partial response to medication.", "Little is known about the efficacy of \"next step\" strategies for patients with post-traumatic stress disorder (PTSD) who remain symptomatic despite treatment. This study prospectively examines the relative efficacy of augmentation of continued prolonged exposure therapy (PE) with paroxetine CR versus placebo for individuals remaining symptomatic despite a course of PE.\n Adult outpatients meeting DSM-IV criteria for PTSD were recruited from February 2003 to September 2005 at 4 academic centers. Phase I consisted of 8 sessions of individual PE over a 4- to 6-week period. Participants who remained symptomatic, defined as a score of >or= 6 on the Short PTSD Rating Interview (SPRINT) and a Clinical Global Impressions-Severity of Illness scale (CGI-S) score >or= 3, were randomly assigned to the addition of paroxetine CR or matched placebo to an additional 5 sessions of PE (Phase II).\n Consistent with prior studies, the 44 Phase I completers improved significantly with initial PE (SPRINT: paired t = 7.6, df = 41, p < .0001; CGI-S: paired t = 6.37, df = 41, p < .0001). Counter to our hypothesis, however, we found no additive benefit of augmentation of continued PE with paroxetine CR compared to pill placebo for the 23 randomly assigned patients, with relatively minimal further gains overall in Phase II.\n Although replication with larger samples is needed before definitive conclusions can be drawn, our data do not support the addition of paroxetine CR compared with placebo to continued PE for individuals with PTSD who remain symptomatic after initial PE, suggesting that the development of novel treatment approaches for PTSD refractory to PE is needed.\n ClinicalTrials.gov identifier NCT00215163." ]

[ "10606851", "15183850", "17156002", "16780480" ]

[ "Molluscum contagiosum effectively treated with a topical acidified nitrite, nitric oxide liberating cream.", "Essential oil of Australian lemon myrtle (Backhousia citriodora) in the treatment of molluscum contagiosum in children.", "A prospective randomized trial comparing the efficacy and adverse effects of four recognized treatments of molluscum contagiosum in children.", "Double-blind, randomized, placebo-controlled trial of the use of topical 10% potassium hydroxide solution in the treatment of molluscum contagiosum." ]

[ "A double-blind, group-sequential clinical trial of acidified nitrite was performed to demonstrate the efficacy of this nitric oxide donor in treating molluscum contagiosum. Subjects received either 5% sodium nitrite co-applied with 5% salicylic acid under occlusion, or identical cream with 5% salicylic acid, omitting sodium nitrite. Active and control treatment groups were well matched for the number and duration of lesions and made a similar number of applications. We found a 75% cure rate in the active treatment group and 21% cure with control treatment (P = 0.01). The mean time to cure was 1.83 months. Staining of the skin and irritation were frequent side-effects but did not prevent successful treatment.", "Molluscum contagiosum is a common viral illness of childhood and is increasingly found as a sexually transmitted disease in sexually active young adults. Current treatment options are invasive, requiring tissue destruction and attendant discomfort. Thirty-one children (mean age 4.6 +/- 2.1 years) with the diagnosis of molluscum contagiosum (mean length of time with condition 8.6 +/- 5.3 months) were treated with once daily topical application of a 10% solution (v/v) of essential oil of Australian lemon myrtle (Backhousia citriodora) or vehicle (olive oil). At the end of 21 days, there was greater than 90% reduction in the number of lesions in 9/16 children treated with lemon myrtle oil, while 0/16 children met the same criteria for improvement in the vehicle group (P < 0.05). No adverse events were reported.", "Molluscum contagiosum is a common viral disease of childhood presenting as small, firm, dome-shaped umbilicated papules. Although benign and generally self-limited, this condition is contagious and can lead to complications such as inflammation, pruritus, dermatitis, bacterial superinfection, and scars. No consensus has been established concerning the management of this condition. We conducted a prospective randomized study comparing four common treatments for molluscum contagiosum in 124 children aged 1 to 18 years. One group was treated with curettage, a second with cantharidin, a third with a combination of salicylic acid and lactic acid, and a fourth with imiquimod. Patients needing, respectively, one, two, or three visits for treatment of their mollusca were: 80.6%, 16.1%, and 3.2% for curettage, 36.7%, 43.3%, and 20.0% for cantharidin, 53.6%, 46.4%, and 0% for salicylic acid and glycolic acid, and 55.2%, 41.4%, and 3.4% for imiquimod. The rate of side effects was 4.7% for group 1, 18.6% for group 2, 53.5% for group 3, and 23.3% for group 4. Curettage was found to be the most efficacious treatment and had the lowest rate of side effects. It must be performed with adequate anesthesia and is a time-consuming procedure. Cantharidin is a useful bloodless alternative particularly in the office setting, but has moderate complications due to blisters and necessitated more visits in our experience. The topical keratolytic used was too irritating for children. Topical imiquimod holds promise but the optimum treatment schedule has yet to be determined. Finally, we believe that the ideal treatment for mollusca depends on the individual patient preference, fear, and financial status, distance from the office, and whether they have dermatitis or blood-borne infections.", "Molluscum contagiosum is a common viral infection of the skin that frequently affects children. Lesions take between 6 and 18 months to resolve spontaneously and are a source of great embarrassment to both caretakers and children, often affecting attendance at school and limiting social activity. Treatment options to date have been poorly tolerated by children but recent studies have suggested that potassium hydroxide may be beneficial. This double-blind, randomized, placebo-controlled study compared 10% potassium hydroxide with placebo (normal saline). Twenty patients, aged 2 to 12 years, were recruited. Parents applied a solution twice daily to lesional skin until signs of inflammation appeared. Children were examined by the same observer on days 0, 15, 30, 60, and 90. Seventy percent of children receiving topical potassium hydroxide cleared, compared with 20% in the placebo group. Further dosing studies are required to identify whether weaker concentrations of potassium hydroxide are as efficacious, with less irritancy." ]

[ "11679026" ]

[ "Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam." ]

[ "Passionflower (Passiflora incarnata) is a folk remedy for anxiety. A double-blind randomized trial compared the efficacy of Passiflora incarnata extract with oxazepam in the treatment of generalized anxiety disorder.\n The study was performed on 36 out-patients diagnosed with GAD using DSM IV criteria. Patients were allocated in a random fashion: 18 to the Passiflora extract 45 drops/day plus placebo tablet group, and 18 to oxazepam 30 mg/day plus placebo drops for a 4-week trial.\n Passiflora extract and oxazepam were effective in the treatment of generalized anxiety disorder. No significant difference was observed between the two protocols at the end of trial. Oxazepam showed a rapid onset of action. On the other hand, significantly more problems relating to impairment of job performance were encountered with subjects on oxazepam.\n The results suggest that Passiflora extract is an effective drug for the management of generalized anxiety disorder, and the low incidence of impairment of job performance with Passiflora extract compared to oxazepam is an advantage. A large-scale trial is justified." ]

[ "7673950", "11133794", "11087764", "8145910" ]

[ "Treatment of multifocal motor neuropathy with high dose intravenous immunoglobulins: a double blind, placebo controlled study.", "Intravenous immunoglobulin therapy in multifocal motor neuropathy: a double-blind, placebo-controlled study.", "Multifocal motor neuropathy improved by IVIg: randomized, double-blind, placebo-controlled study.", "Intravenous immunoglobulin treatment in patients with motor neuron syndromes associated with anti-GM1 antibodies: a double-blind, placebo-controlled study." ]

[ "The effect of high dose intravenous immunoglobulin (IVIg) treatment was studied in six patients with multifocal motor neuropathy (MMN). All patients responded to treatment (0.4 g/kg for five consecutive days) in an open trial. The effect of IVIg treatment was confirmed for each patient in a single patient, double blind, placebo controlled trial. Four patients received two IVIg treatments and two placebo treatments, and two patients received one IVIg and one placebo treatment in a randomised order. Five out of six patients responded to IVIg but not to placebo. One patient responded to IVIg in the same manner as to placebo treatment. Thus IVIg treatment can lead to improvement of muscle strength in patients with MMN.", "We conducted a double-blind, placebo-controlled, study of 19 patients fulfilling eligibility criteria for multifocal motor neuropathy with persistent conduction block. They were enrolled and divided into two groups: those who had never been treated previously with intravenous immunoglobulins (IVIg) (Group 1: 10 patients) and those who presented recurrent symptoms after previously successful treatment with IVIg (Group 2: nine patients). They were randomized prospectively to receive either IVIg or placebo at a dose of 500 mg/kg/day for 5 consecutive days, once a month for 3 months. At month 4, patients found to be responders remained on the same treatment for the 3 following months, while non-responders were switched to the alternative study drug for the 3 following months. Clinical assessment was conducted with the MRC score in 28 muscles and a self-evaluation scale (five daily motor activities scored from 0 to 5). In Group 1, nine patients completed the study, of whom initially four received IVIg and five placebo; four patients responded to IVIg (two at months 4 and 7, and a further two at month 7 after switching treatment at month 4), two patients responded to placebo at months 4 and 7, and three patients did not respond to either treatment. In Group 2, nine patients completed the study. Five patients first received IVIg and all responded at months 4 and 7. Four patients first received placebo and none responded at month 4; all were then switched to IVIg and three responded at month 7. When the 18 patients were considered together, seven out of the nine patients who received IVIg first were responders at month 4, compared with two of the nine patients who received placebo first, a difference that was statistically significant (P = 0.03). On the other hand, there was no significant difference in MRC score but a significant difference in the self-evaluation score, at month 4, between IVIg patients and placebo patients. Electrophysiological studies did not show significant differences at month 4 in motor parameters between IVIg patients and placebo patients. IgM anti-GM1 titres did not change significantly in patients treated with IVIg compared with those who received placebo, between baseline, month 4 and month 7. However, of five patients who had significantly high anti-GM1 titres (>3200) at baseline, four responded to IVIg. This trial confirms that IVIg is a promising therapeutic option for multifocal motor neuropathy.", "To determine the effect of IV immunoglobulin (IVIg) on neurologic function and electrophysiologic studies in multifocal motor neuropathy with conduction block (MMN).\n MMN is characterized by progressive, asymmetric, lower motor neuron weakness and is probably immune-mediated. IVIg treatment has been shown to have beneficial effects in several open-label studies and in one small controlled trial. However, larger randomized controlled studies are lacking.\n The authors recruited 16 patients with MMN. All subjects were given each of two treatments (IVIg [0.4 g/kg/d for 5 consecutive days] or placebo [dextrose or saline]) that were assigned according to a randomized, crossover design under double-blind conditions. Patients were evaluated before and about 28 days after trial treatment for subjective functional improvement, neurologic disability score, grip strength, distal and proximal compound muscle action potential amplitude, and conduction block.\n Subjective functional improvement with IVIg treatment was rated as dramatic or very good in nine patients, moderate in one, mild in one, and absent in five patients. This improvement was absent after placebo. The neurologic disability score improved by 6.7+/-3.3 points with IVIg treatment, whereas it decreased by 2.1+/-3.0 with placebo (p = 0.038). Grip strength on the weaker side was increased by 6.4+/-1.9 kg with IVIg treatment; it decreased by 1.0+/-0.8 kg with placebo (p = 0.0021). Conduction block worsened by 12.98+/-6.52 % with placebo, but improved by 12.68+/-5.62 % with IVIg treatment (p = 0.037). Conduction block was reversed in five patients with IVIg but not placebo.\n IVIg improved conduction block as well as subjective and objective clinical measures of function in patients with MMN.", "We studied the effects of intravenous immunoglobulin (IVIg) in 12 patients with motor neuron syndromes associated with high titers of anti-GM1 antibodies. Five of the patients had conduction blocks. The study design was a double-blind, placebo-controlled, crossover trial with IVIg (0.4 g/kg body weight per day injected for 5 consecutive days). We evaluated the patients before and 5, 28, and 56 days after drug administration using a computerized analyzer for muscle strength, the Norris scale for disability, motor nerve conduction velocities for patients with conduction blocks, and measurements of immunologic markers. Compared with placebo, IVIg induced a significant increase in muscle strength only in the patients with conduction blocks." ]

[ "7811160", "7012190", "373665", "12680747", "3555386", "2679483" ]

[ "Pharmacotherapy of impaired affect in recovering schizophrenic patients.", "Viloxazine and the depressed schizophrenic--methodological issues.", "Treatment of secondary depression in schizophrenia. A double-blind, placebo-controlled trial of amitriptyline added to perphenazine.", "A double-blind, placebo-controlled trial of sertraline for depressive symptoms in patients with stable, chronic schizophrenia.", "Adjunctive imipramine in the treatment of postpsychotic depression. A controlled trial.", "Antidepressants in 'depressed' schizophrenic inpatients. A controlled trial." ]

[ "Prominent and persistent anxiety, depression, and/or negative features characterize a substantial minority of recovered or residually psychotic schizophrenic outpatients and contribute to poor outcome. Because extrapyramidal side effects of typical neuroleptic medications often resemble such features, we first systematically studied the contribution of extrapyramidal side effects to these problems and their treatment. For patients who remained distressed, controlled trials of supplemental thymoleptics were undertaken.\n In trial 1, 92 distressed (depressed and/or anxious) patients and 36 patients in a defect state (patients with negative symptoms) participated in a double-blind, intramuscular challenge that compared centrally acting benztropine mesylate with peripherally acting glycopyrrolate. In trial 2, 57 distressed patients and 22 patients in a defect state were randomly assigned to a double-blind, neuroleptic medication dose-reduction group. In trial 3, 57 chronically distressed patients who were maintained on a low dose of fluphenazine decanoate were randomly assigned to a supplemental desipramine hydrochloride, lithium carbonate, or placebo group under double-blind conditions for 12 weeks.\n For patients who were already maintained on antiparkinsonian medication, impaired affect was not resolved by additional benztropine. Only distressed patients with a family history of severe mental disorder (often affective) showed improvement with neuroleptic medication dose reduction. Patients in the defect-state group reported less dysphoria on a reduced neuroleptic medication dose, but negative symptoms persisted. Desipramine improved diverse aspects of mood and residual psychoticism, possibly as a prophylaxis against minor affective exacerbations. Depression improved in women only. Lithium positively affected multiple indexes of anxiety and anxious depression.\n Most often, persistent affective impairments are neither resistant extrapyramidal side effects nor characterological traits. Thymoleptics improve the nonphasic, chronic types of anxiety and depression in contrast to the acute, episodic forms, for which little support can be found in the literature.", "A pilot study of a small group of schizophrenic patients manifesting symptoms of a depressive nature was treated in a double-blind study in which viloxazine or a placebo was administered in combination with either chlorpromazine or haloperidol. There appeared to be no difference between the viloxazine-treated group and the placebo-treated group, although the study raised some question as to the adequacies of the dosage utilized since there was an absence of any apparent side effects. In view of these issues concerning the clinical merit of the combination, this obviously requires further investigation.", "The combination of antidepressants and neuroleptics has been widely recommended and commonly used clinically for the schizophrenic patient who becomes depressed. However, the value of the combination for these patients has not been clearly demonstrated. This report presents results of a double-blind, randomized, placebo-controlled clinical trial designed to evaluate the combination of perphenazine and amitriptyline hydrochloride with that of perphenazine alone in the treatment of 35 ambulatory chronic schizophrenic patients in whom depressive symptoms developed. Results showed that the addition of amitriptyline to perphenazine, when compared with perphenazine alone, was more effective in reducing symptoms of depression after four months of treatment, but less effective in reducing thought disorder. The study concludes that the value of adding an antidepressant to the usual neuroleptic in the treatment of secondary depression in schizophrenia should be reviewed.", "There have been no studies specifically examining the efficacy of selective serotonin reuptake inhibitor antidepressants for the symptoms of depression in schizophrenia. This study aimed to determine the efficacy and safety of sertraline as a treatment for depressive symptoms in patients with stable, chronic schizophrenia. The Beck Depression Inventory (BDI) was used as the principal outcome measure and other measures of depressive symptoms as secondary outcome measures. Twenty-six patients were entered into a double-blind, placebo-controlled, 8-week trial of sertraline and were included in the intent-to-treat (ITT) analysis (13 in each group). Eight patients in the sertraline group and 12 in the placebo group completed at least four weeks in the study and were considered to have had adequate treatment. On the ITT analysis, the mean score on the BDI fell 14.5% for the sertraline group and 5.6% for the placebo group (p > 0.05); the mean score on the Hamilton Depression Rating Scale (HDRS) fell 16.99% for the sertraline group and 8.3% for the placebo group (p > 0.05). When the analysis was repeated for those who had received adequate treatment, the mean BDI score fell by 28% for the sertraline group and 6% for the placebo group (p = 0.1); the mean HDRS score fell 31% for the sertraline group and 8.6% for the placebo group (p = 0.02). On the Clinical Global Impression-Improvement Scale, 10 of the 13 patients on sertraline improved against four of the 13 in the placebo group (p = 0.05). Sertraline-treated patients showed a significant improvement on the anxiety/ depression subscale of the BPRS on ITT analysis (F = 10.1, p = 0.004). There was no significant effect on negative or positive symptoms. Sertraline was well tolerated. The results suggest that sertraline is useful as a treatment for depressive symptoms in schizophrenia.", "The efficacy of adjunctive imipramine hydrochloride treatment for syndromally defined postpsychotic depression was assessed in a six-week, double-blind, placebo-controlled study. All patients had been diagnosed as having schizophrenia or schizoaffective disorder, all were receiving stable doses of fluphenazine decanoate, and all had received benztropine mesylate in an attempt to rule out neuroleptic-induced akinesia. Patients randomized to imipramine therapy fared significantly better in terms of their global improvement and in terms of individual symptoms that are components of the depression syndrome. There were no significant differences in outcome psychosis ratings or side effects. This study indicates the existence of an identifiable syndrome of secondary depression in this patient group that is likely to respond favorably to treatment with adjunctive imipramine.", "Fifty-eight actively psychotic inpatients who initially met criteria for long-standing schizophrenia and subsequently met Research Diagnostic Criteria for a current episode of schizoaffective disorder (mainly schizophrenic) with a depressive syndrome, and who scored at least 30 (mean = 55, SEM = 1.6) on the Brief Psychiatric Rating Scale and 17 (mean = 23, SEM = 0.7) on the Hamilton Rating Scale for Depression, were treated for 5 weeks with haloperidol hydrochloride and benztropine. Haloperidol and benztropine treatment was continued, while those patients who consistently scored greater than 17 on the Hamilton Rating Scale for Depression were randomly assigned to the following double-blind treatment groups for 4 weeks: adjunctive amitriptyline hydrochloride, desipramine hydrochloride, or placebo. Adjunctive desipramine or amitriptyline showed no significant therapeutic advantage, when compared with haloperidol and placebo, on the Brief Psychiatric Rating Scale or the Hamilton Rating Scale for Depression. After 4 weeks of combine therapy, patients receiving adjunctive amitriptyline or desipramine, as compared with those receiving adjunctive placebo, tended to score higher on the Brief Psychiatric Rating Scale hallucinatory behavior item and on the thinking disturbance factor than patients receiving placebo. These results suggest that adjunctive antidepressants are not indicated for the treatment of depressive symptoms in actively psychotic schizophrenic inpatients. Adjunctive antidepressants may retard the rate of resolution of psychosis in this population." ]

[ "16304122", "21570870", "17928625", "8154176", "720236", "11719664", "17145426", "16408299", "2827398", "11666130", "7849445", "18756983", "18482817", "7972781", "8307222", "2140251", "8851268", "17350216", "1824621", "7697845" ]

[ "Adjunctive abciximab improves patency and functional outcome in endovascular treatment of femoropopliteal occlusions: initial experience.", "Batroxobin plus aspirin reduces restenosis after angioplasty for arterial occlusive disease in diabetic patients with lower-limb ischemia.", "Comparison of selective AT1-receptor blockade versus ACE inhibition for restenosis prophylaxis in patients with peripheral occlusive arterial disease after stent angioplasty: a randomized, controlled, proof-of-concept study.", "Acetylsalicylic acid--reocclusion--prophylaxis after angioplasty (ARPA-study). A randomized double-blind trial of two different dosages of ASA in patients with peripheral occlusive arterial disease.", "[Prevention of re-occlusion after recanalisation of occluded arteries by the catheter method (author's transl)].", "Peripheral artery occlusion: treatment with abciximab plus urokinase versus with urokinase alone--a randomized pilot trial (the PROMPT Study). Platelet Receptor Antibodies in Order to Manage Peripheral Artery Thrombosis.", "Low-molecular-weight heparin for prevention of restenosis after femoropopliteal percutaneous transluminal angioplasty: a randomized controlled trial.", "Functional and clinical outcomes of nitinol stenting with and without abciximab for complex superficial femoral artery disease: a randomized trial.", "Combination of suloctidil and anticoagulation in the prevention of reocclusion after femoro-popliteal PTA.", "Potential use of a low-molecular-weight heparin to prevent restenosis in patients with extensive wall damage following peripheral angioplasty.", "Controlled trial of high- versus low-dose aspirin treatment after percutaneous transluminal angioplasty in patients with peripheral vascular disease.", "[A clinical trial of using antiplatelet therapy to prevent restenosis following peripheral artery angioplasty and stenting].", "Cilostazol reduces restenosis after endovascular therapy in patients with femoropopliteal lesions.", "Low-dose aspirin combined with dipyridamole versus anticoagulants after femoropopliteal percutaneous transluminal angioplasty.", "Platelet inhibition with ASA/dipyridamole after percutaneous balloon angioplasty in patients with symptomatic lower limb arterial disease. A prospective double-blind trial. Study group on pharmacological treatment after PTA.", "Reocclusion prophylaxis with dipyridamole combined with acetylsalicylic acid following PTA.", "[The effect of Taprostene on platelet activation and clinical course after percutaneous transluminal angioplasty].", "Adjunctive parenteral therapy with lipo-ecraprost, a prostaglandin E1 analog, in patients with critical limb ischemia undergoing distal revascularization does not improve 6-month outcomes.", "Nd:YAG laser with sapphire tip combined with balloon angioplasty in peripheral arterial occlusions. Long-term results.", "Comparison of effects of high-dose and low-dose aspirin on restenosis after femoropopliteal percutaneous transluminal angioplasty." ]

[ "To prospectively evaluate the safety and effectiveness of adjunctive administration of abciximab observed within 30 days and at 6 months after randomization in patients undergoing endovascular revascularization of long-segment femoropopliteal occlusions.\n The study was approved by the local ethical committee, and patients gave written informed consent. In a prospective, double-blind, placebo-controlled design, patients undergoing percutaneous treatment for long-segment (>5 cm) femoropopliteal occlusions were randomly assigned to receive abciximab or a placebo; all patients also received standard-dose heparin. Effectiveness and safety analyses were based on an intention-to-treat approach. Patency was calculated according to life-table analysis, and P values were derived from the log-rank statistic. The P values for dichotomous safety end points were calculated with the Fisher exact test. Odds ratios were calculated for subgroup analyses. Logistic regression modeling was used for analysis of the safety bleeding data.\n A total of 98 patients (103 limbs) were included: 47 patients received abciximab and 51 received a placebo. Patency with abciximab versus placebo was 95.7% versus 80.4% (relative risk, 0.21; 95% confidence interval: 0.05, 0.96; P = .02) at 30 days and was 61.7% versus 41.2% (relative risk, 0.57; 95% confidence interval: 0.32, 1.01; P = .03), coupled with a better clinical outcome according to the Rutherford score, at the end of follow-up (P = .03). Risk of major bleeding was not significantly increased, while access-site bleeding was significantly higher among patients receiving abciximab (odds ratio, 2.9; 95% confidence interval: 1.04, 8.2; P = .04).\n The data show that adjunctive administration of abciximab has a favorable effect on patency and clinical outcome in patients undergoing complex femoropopliteal catheter interventions not hampered by serious bleeding. Treatment effect of abciximab observed at 30 days was maintained at 6-month follow-up.\n RSNA, 2005", "Aspirin is routinely given to reduce vascular events after angioplasty. Batroxobin has been shown to effectively prevent thrombosis after angioplasty via inhibition of the fibrinogen concentration. In this randomized clinical trial, the hypothesis that batroxobin plus aspirin is more effective than aspirin alone in reducing the incidence of restenosis/reocclusion in patients with diabetes undergoing angioplasty for lower-limb ischemia.\n Patients with diabetes and symptomatic arterial obstructions (N = 129) were randomized to receive aspirin 100 mg/d plus batroxobin 5 IU every other day for six doses (n = 58) or aspirin alone (n = 71). The primary outcome was restenosis documented by magnetic resonance (MR) angiography or duplex imaging at 12 months. Secondary outcomes included amputation above the ankle, death, and cumulative rate of amputation or death. Kaplan-Meier analysis was used to evaluate limb salvage and survival rates.\n After 12 months, restenosis had occurred in 43.1% and 29.7% of patients in the control and batroxobin groups, respectively (P = .0018). MR angiography and duplex imaging revealed an improved restenosis rate for infrapopliteal lesions and for lesions longer than 10 cm (P = .0016). The primary and cumulative secondary outcomes indicated significant improvements in restenosis rate, symptom relief, and amputation rates in the batroxobin group compared with the aspirin-only group. Kaplan-Meier analysis showed limb salvage and survival rates of 78.3% in the aspirin-only group and 92.2% in the batroxobin group 12 months after angioplasty (log-rank test, P = .0414).\n Batroxobin plus aspirin reduced the rate of restenosis after arterial angioplasty, particularly in lesions located below the knee and in those longer than 10 cm, with better clinical symptom relief and improved rate of limb salvage.\n Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.", "Different components of the renin-angiotensin system (RAS) have been demonstrated in atherosclerotic plaques. However, the involvement of the RAS in the complex process of in-stent restenosis is not yet clear. In this prospective, randomized, double-blind, controlled proof-of-concept study, we compared the 2 different pharmacological approaches, selective AT(1)-receptor-blockade with candesartan vs ACE inhibition with quinapril to reduce in-stent restenosis after stent angioplasty of the superficial femoral artery. Twenty-two hypertensive patients with stage IIb peripheral occlusive arterial disease and severe claudication who had been successfully treated with percutaneous transluminal angioplasty (PTA) and stent implantation were randomly assigned to receive daily doses of either candesartan (32 mg) or quinapril (20 mg). Primary end point was restenosis 6 months after intervention, assessed by angiography. Secondary end points were pain-free walking distance, determined by treadmill ergometry; determination of crurobrachial indices; and intima-media thickness (IMT). At 6 months, the rate of restenosis on angiography was 34% in the candesartan group and 71% in the quinapril group (P = .043). Relevant restenosis was found in 3 patients (27%) in the candesartan group and in 7 patients (64%) in the quinapril group. Patients in the candesartan group were able to walk farther on a treadmill (increase: 135 m +/- 20 m) compared with patients in the quinapril group (increase: 83 m +/- 21 m). The IMT at the stent edge was not significantly different in the 2 groups (candesartan: 1.9 mm +/- 0.5 mm; quinapril: 2.0 mm +/- 0.3 mm). This study revealed significant benefit of a pharmacological restenosis regimen using the AT(1)-receptor antagonist candesartan in patients with severe atherosclerosis after superficial femoral artery stenting compared with treatment with the ACE inhibitor quinapril. Further prospective studies in patients are required to confirm these results.", "We report on a randomized controlled clinical trial in patients with peripheral occlusive arterial disease who have been successfully treated with angioplasty. The efficacy and the rate of side effects of two doses of ASA (300 mg vs. 1000 mg daily) have been compared during a treatment period of 6 months after angioplasty. It was planned to include a total of 600 patients in the trial. A predefined interim analysis of 200 patients which was performed after the actual inclusion of 218 patients showed identical reocclusions rates and a very similar frequency of side effects in both treatment groups. The study was then terminated since it was not expected that further continuation would lead to a relevant difference between the two treatment groups concerning efficacy or side effects. Patients already included in the trial at the interim evaluation were included in the final analysis, leading to a total number of 223 patients. Finally 112 patients had been randomized to receive a daily dose of 300 mg ASA and 111 patients to receive 1000 mg ASA. Reocclusions occurred in 18 patients (16%) on 300 mg of ASA/day and in 20 patients (18%) receiving 1000 mg ASA/day. The study was interrupted because of side effects in 27 patients (24%) in the 300 mg/day group and in 27 patients (24%) in the 1000 mg/day group. Mostly subjective gastric complaints were the cause of interruption in 17 patients (15%) in the 300 mg group and in 21 patients (19%) receiving the higher dose regimen. So the reocclusion rate was identical in both dosage-groups.(ABSTRACT TRUNCATED AT 250 WORDS)", "In a double-blind study, prevention of re-thrombosis was tested on 101 patients in whom stenosis or segmental occlusion of a large artery of the lower limbs had been successfully removed by the intraluminal catheter method. The combination of 75 mg dipyridamol and 330 mg acetylsalicylic acid, three times daily by mouth, proved to be slightly more effective than acetylsalicylic acid alone at the same dosage. In the group with the combined treatment 84% of the arteries remained open, compared with 70% on acetylsalicylic acid alone.", "To evaluate the combination of a platelet glycoprotein IIb/IIIa complex receptor inhibitor and urokinase for treatment of recent (<or=6 weeks) arterial occlusion of the legs.\n Seventy patients with lower extremity arterial occlusion of less than 6 weeks duration were randomly separated into two treatment groups: urokinase plus abciximab or urokinase plus placebo. Primary end points were the rate of major complications at 30 days after randomization and the rates of amputation-free survival and survival without open surgery or major amputation at follow-up of 90 days. Two readers unaware of the patients' treatment group assignments analyzed digital subtraction angiograms as they related to the study end points, with a final consensus reading.\n Thrombolysis relative to clot length was faster in the urokinase-plus-abciximab group (odds ratio, 0.52; 95% CI: 0.35, 0.76; P < .001). There were no procedure-related deaths or intracranial hemorrhages, but the rate of nonfatal major bleeding was higher with urokinase plus abciximab (four of 50 patients) than with urokinase alone (none of 20 patients; P = .32). At 90 days, amputation-free survival was 96% (48 of 50 patients) in the urokinase-plus-abciximab group compared with 80% (16 of 20 patients) in the urokinase alone group. The hazard ratio for the two Kaplan-Meier curves was 0.42 (95% CI: 0.16, 0.96; P = .04).\n In patients with lower extremity arterial occlusion who were undergoing urokinase thrombolysis, adjunctive abciximab treatment resulted in faster thrombus dissolution and improved amputation-free survival, despite an increase in major bleeding.", "Restenosis after angioplasty is essentially due to intimal hyperplasia. Low-molecular-weight heparins (LMWHs) have experimentally been shown to have antiproliferative effects in addition to their antithrombotic properties. Their potential in reducing restenosis remains to be established. Therefore, we wanted to test the hypothesis that LMWH plus aspirin is more effective than aspirin alone in reducing the incidence of restenosis/reocclusion in patients undergoing percutaneous transluminal angioplasty (PTA) of femoropopliteal arteries. Further, different effects of LMWH in patients treated for critical limb ischemia (CLI) or claudication only should be investigated.\n After successful PTA, 275 patients with symptomatic peripheral arterial disease (claudication or critical limb ischemia) and femoropopliteal obstructions were randomized to receive either 2500 IU of dalteparin subcutaneously for 3 months plus 100 mg of aspirin daily (n = 137), or 100 mg aspirin daily alone (n = 138). The primary end point was restenosis or reocclusion documented by duplex ultrasonography imaging at 12 months.\n Restenosis/reocclusion occurred in 58 patients (44%) in the dalteparin group and in 62 patients (50%) in the control group (P = .30). In a subgroup analysis according to the severity of peripheral arterial disease, we found that in patients treated for claudication, restenosis/reocclusion developed in 43 (43%) in the dalteparin group, and in 35 (41%) in the control group (P = .70); in patients treated for CLI, restenosis/reocclusion was significantly lower in the dalteparin group (15, 45%) than in the control group (27, 72%; P = .01). No major bleeding events occurred in either group.\n Treatment with 2500 IU dalteparin subcutaneously given for 3 months after femoropopliteal PTA failed to reduce restenosis/reocclusion at 12 months. However, dalteparin may be beneficial in the subgroup of patients with CLI at 12 months follow-up.", "To evaluate the effect of glycoprotein IIb/IIIa inhibition during nitinol stenting, of superficial femoral occlusive disease.\n Stent implantation in the superficial femoral artery has been associated with suboptimal results while Glycoprotein IIb/IIIa inhibitors have shown improved procedural results during coronary intervention. We evaluated abciximab infusion during (Smart Stent) implantation in superficial femoral obstructions.\n We conducted a randomized placebo controlled trial. The two primary end points include: (1) 9-month restenosis defined as a decrease in ankle brachial index and in-stent duplex ultrasound restenosis: (2) adverse events defined as death (30 days) or repeat revascularization within 9 months.\n Twenty-seven patients were randomized to abciximab and 24 patients to control (placebo). The primary end point of cumulative restenosis occurred in 15.4% of patients administered abciximab and in 12% administered placebo (P = 0.873). The primary restenosis endpoint in diabetics and total occlusions were similar at 14.3% and 15.4% respectively. The composite end point of 30-day mortality and 9-month revascularization occurred in 5.8% abciximab and 0% (P = 0.274) placebo with no 30-day deaths. Graded treadmill time and Rutherford class were all significantly improved in both groups, but the abciximab group did not appear to demonstrate any identifiable effect.\n (Smart Stent) nitinol stenting of the superficial femoral artery was associated with favorable functional outcomes at 9 months. Adjunctive abciximab did not appear to demonstrate any identifiable effect.\n 2006 Wiley-Liss, Inc.", "nan", "The long-term outcome of primary successful percutaneous transluminal angioplasty (PTA) for patients with peripheral occlusive arterial disease (POAD) is frequently compromised by the development of restenosis, especially when extensive dissections result from the angioplastic procedure. Unfortunately, prevention of the occlusive process by means of drugs such as antithrombotics, anticoagulants, thrombolytics, corticosteroids, lipid reducers, or cytostatics has not been demonstrated convincingly. The authors sought to clarify whether such patients could benefit from the postsurgical administration of low-molecular-weight heparin. A total of 172 POAD patients with extensive dissections after PTA in the pelvic or upper leg regions were randomized for 7-day post-PTA intravenous treatment with either full heparinization or nadroparin calcium followed by adjunctive oral aspirin for 6 months. The primary outcome measure was the degree of stenosis (normal findings; stenosis < 50%, > 50%, > 80%, occlusion) before and after angioplasty, as well as 3 weeks and 3 and 6 months after dilation; secondary efficacy criteria included changes in the Fontaine stage and in the crurobrachial ratio. No significant treatment-related differences were found at the 3 post-PTA follow-up examinations with regard to the degree of stenosis. This was also the case for the subgroup of patients (n = 62) who had undergone angioplasty in the pelvic region. By contrast, when angioplasty was performed in the superficial femoral artery (n = 110), the degree of restenosis was significantly lower (p<0.01) among patients receiving nadroparin calcium compared to those given heparin at week 3, month 3, and month 6. No intergroup differences emerged for secondary outcome measures in the long term or for safety parameters. These preliminary results indicate that patients with extensive dissections after PTA treatment for POAD in the upper leg region might benefit from a reduction in the rate of restenosis by administration of 7-day weight-adjusted nadroparin calcium.", "Percutaneous transluminal angioplasty of aortoiliac and femoropopliteal atherosclerotic lesions can provide long-lasting hemodynamic improvement. High-dose aspirin is commonly prescribed as reocclusion prophylaxis, but low doses would be preferable because of fewer adverse effects. We performed a double-blind, randomized, controlled clinical trial in patients with peripheral vascular disease with lesions appropriate for angioplasty. We compared the efficacy and side effects of two doses of aspirin (50 mg vs. 900 mg daily) during a period of 12 months after angioplasty. A total of 359 patients were evaluated: 175 were randomly assigned to treatment with 900 mg aspirin daily and 184 to 50 mg aspirin daily. Thirty-nine patients developed restenosis at the angioplasty site; the cumulative percentage of event-free survival after 1 year (patency rate) was 85% in 900 mg group and 84% in 50 mg group. An equivalence test showed the two groups equivalent with respect to restenosis rates (P = 0.0003 for an equivalence region of < 10% difference. Nine patients (5%) in the 900 mg group had serious gastrointestinal side effects (peptic ulcer, 8; erosive gastritis requiring transfusion, 1) compared to two ( peptic ulcer) in the 50 mg group (P = 0.03). The results of our study show that a dose of 50 mg aspirin a day is as effective as 900 mg for the prevention of restenoses after lower limb angioplasty, and that severe gastrointestinal side effects are less frequent.", "To evaluate the clinical effect and restenosis rate of antiplatelet therapy following peripheral artery angioplasty and stenting.\n After successful placement of peripheral artery stents to 103 patients with peripheral arterial occlusive disease (PAOD) in were randomized assigned to 2 groups: antiplatelet therapy group receiving clopidogrel 75 mg plus aspirin 100 mg (n = 56) and control group (n = 47) receiving anticoagulation therapy low molecular weight heparin (LWMH) for 7 d plus long-term warfarin. The patients were followed up 1 day, and 1, 6, 12, and 18 months after the operation to undergo color Doppler ultrasonography, and examinations of blood routine, bleeding time, coagulation time, and ankle-brachial Index. The primary endpoint events included major bleeding rate, and composite rate of restenosis and reocclusion. The secondary endpoint events included cardiovascular events, death, and adverse drug reaction.\n There were no significant differences in the baseline data between these two groups. The thrombotic occlusion rate was 1.8% in the antiplatelet group and 0% in control group, and the restenosis rate was 14.3% in the antiplatelet group and 25.5% in control group (both P > 0.05). The bleeding complication rate of the antiplatelet group was 1.8%, significantly lower than that of the anticoagulation group (19.1%, P < 0.01). There were not significant differences in cardiovascular event rate and mortality 18 months after operation between these two groups.\n Antiplatelet therapy combined with clopidogrel plus aspirin is effective and safe in preventing restenosis following peripheral artery angioplasty and stenting.", "Despite the recent development of endovascular therapy (EVT), a high incidence of restenosis remains as an unsolved issue in patients presenting with femoropopliteal lesions. We investigated whether cilostazol reduces restenosis after successful EVT for de novo femoropopliteal lesions.\n This study was designed as a prospective, randomized, open-label, blinded end point study in a single institution. Between March 2004 and June 2005, we randomized 127 patients who were successfully treated with EVT for de novo femoropopliteal lesions to receive cilostazol (200 mg/d, n = 63) or ticlopidine (200 mg/d, n = 64) in addition to aspirin (100 mg/d). Antiplatelet medications were started at least 1 week before EVT and were continued until the end of follow-up. Patency was defined by duplex ultrasound imaging with peak systolic velocity ratio >2.4.\n There were no significant differences in the patients and lesion characteristics. Sixteen patients dropped out of the study protocol, six of whom were withdrawn due to adverse drug effects (cilostazol, n = 5; ticlopidine, n = 1; P = .09). Ten patients died (cilostazol, n = 4; ticlopidine, n = 6; P = .53) during the follow-up period. Patency rates at 12, 24, and 36 months were 87%, 82%, and 73% in the cilostazol group and 65%, 60%, and 51% in ticlopidine group by intention-to-treat analysis (P = .013) and were 87%, 82%, and 73% in the cilostazol group and 64%, 57%, and 48% in the ticlopidine group (P = .0088) by as-treated analysis. Freedom from target lesion revascularization and all adverse events (restenosis, amputation, and death) was significantly higher in cilostazol group than in ticlopidine group (P = .036, P = .031). No acute, subacute, or chronic thrombotic occlusion was encountered, and bleeding complication rates were similar between the two groups.\n Cilostazol significantly reduces restenosis after EVT in femoropopliteal lesions.", "To investigate whether anticoagulation or platelet inhibition treatment provides better prevention of reobstruction after percutaneous transluminal angioplasty (PTA).\n In a controlled study, 160 patients received either oral anticoagulants or a combination of low-dose acetylsalicylic acid (25 mg) and dipyridamole (200 mg) (ASAD) twice daily for 1 year after successful femoropopliteal PTA. Compliance was comparable. The patients in the two groups had similar clinical and angiographic characteristics. Patency was assessed with noninvasive methods 1 day and then 3, 6, and 12 months after PTA and was confirmed at angiography at the end of the study in 112 patients.\n Patency in patients who received anticoagulants was 53% and was not statistically significantly different from 69% in patients who received ASAD (P = .18). With anticoagulants, there were four bleeding complications (one was fatal); with ASAD, only five minor complications occurred.\n ASAD is at least as effective as anticoagulants for secondary prevention of obstruction after PTA but has less severe side effects.", "A randomised double-blind multicentre trial has been performed comparing the influence of 3 months prophylaxis with acetylsalicylic acid/dipyridamole (50 mg/400 mg daily) or placebo on the outcome following percutaneous transluminal angioplasty for lower limb ischaemia. Two hundred and twenty-three patients were included and followed. There were no differences between the groups regarding results 1, 3, 6 and 12 months following the dilatation treatment. It can be concluded that acetylsalicylic acid at the dose of 50 mg daily combined with dipyridamole does not seem to have a prophylactic effect after transluminal angioplasty during a follow-up period of 1 year.", "After primary successful PTA, 199 patients were randomized into one of three treatment groups, namely, placebo or a combination of 75 mg dipyridamole with either 330 mg (high dose) or 100 mg (low dose) acetylsalicylic acid (ASA) tid. The duration of treatment was six months. Of the 199 patients admitted to the study, 156 completed the six-month trial period. Not all patients had a second angiogram, and in these cases clinical findings were used in the evaluation. Evaluation of the combined angiographic and clinical results showed improvement or no deterioration in 37% of patients in the placebo group compared with 49% in the low-dose and 61% in the high-dose ASA groups respectively. The only statistically significant difference observed was between the placebo group and the group treated with dipyridamole and high-dose ASA (p = 0.01). This difference remained statistically significant at p = 0.039 if only the angiographic findings were considered for group comparison. It cannot, however, be concluded from this study that 75 mg dipyridamole in combination with 100 mg ASA tid is more effective in preventing reocclusion after PTA than in combination with 330 mg ASA tid.", "In a double blind pilot study, we examined the effects of the stable prostacyclin derivate taprostene compared to a combination of aspirin and dipyridamole on platelet uptake and clinical outcome after peripheral percutaneous angioplasty. Taprostene was administered to 19 patients as a continuous intravenous infusion from 2 hours before until 8 (n = 6) or 24 (n = 6) hours after angioplasty; 7 control patients were given a combination of 330 mg aspirin and 75 mg dipyridamole. Uptake of 111-indium labelled platelets at the site of the PTA was measured 3 hours before and 4 and 24 hours after angioplasty. Clinical parameters were obtained one day before PTA, on the following day and 3 months after the procedure. There was a tendency for slightly higher platelet uptake ratios in the taprostene groups as compared to the control group especially in patients requiring technically difficult procedures. There were no differences between the 3 groups with regard to primary success or periinterventional complications. In the taprostene patients, 3 early reocclusions were found up to 72 hours after the procedure and 1 late reocclusion within 3 months. In the control group, no reocclusion was apparent in the observation time. No advantages were found when taprostene was administered during angioplasty as compared to conventional treatment with aspirine and dipyridamole.", "In patients with critical limb ischemia (CLI), distal revascularization remains the procedure of choice for preventing limb loss, but long-term outcomes for pain relief, wound healing, and prevention of amputation remain suboptimal. Prostaglandin drug therapy as an adjuvant to revascularization may improve these outcomes. The current trial was designed to test the hypothesis that the use of lipo-ecraprost, a lipid encapsulated prostaglandin E(1) prodrug, as an adjunctive therapy after distal revascularization would improve amputation-free survival in patients with CLI.\n The study was randomized, multicenter, double blind, and placebo controlled. Patients meeting clinical and hemodynamic criteria for CLI who were undergoing either bypass or endovascular revascularization of the below knee popliteal or more distal arteries were randomized to receive placebo or a 60-microg dose of lipo-ecraprost administered intravenously starting <or=72 hours of the index revascularization and then 5 days per week for 8 weeks. The study primary end point was the composite end point of death or amputation at or above the level of the ankle at 180 days.\n The study randomized 322 patients, and 284 received at least one dose of study medication and were included in the intention-to-treat population. A total of 213 patients underwent surgical bypass, and 71 underwent endovascular revascularization before receiving study medication. The distribution of index revascularization procedures and location of distal target arteries were similar for both placebo and lipo-ecraprost groups. At 180 days, 21 patients (7.4%) were lost to follow-up before reaching the primary end point. Seventy-one percent of the patients taking the placebo completed at least half the doses of the study medication compared with 48% of those taking lipo-ecraprost. Index leg revascularization-assisted primary patency was 82% in the placebo group and 84% in the lipo-ecraprost group (P = .874). Changes in lower extremity hemodynamics as a result of the revascularization during the study period did not differ between the placebo and lipo-ecraprost treatment arms. For the primary event of amputation-free survival, there were no differences between groups: 19 major amputations occurred in the placebo group and 17 in the lipo-ecraprost group; 19 deaths occurred in the placebo group and 13 in the lipo-ecraprost group.\n Eight weeks of parenteral therapy with lipo-ecraprost after distal revascularization in patients with CLI provided no additional benefit in the reduction of major amputation or death at 180 days.", "In 167 patients with complete occlusion (greater than 3 cm) of the femoropopliteal artery, percutaneous transluminal laser angioplasty (PTLA) was performed after an unsuccessful attempt at crossing with a guide wire and was immediately followed by balloon dilatation. An Nd-YAG laser and an optical fiber delivery system with a sapphire tip serving as a contact probe were used for PTLA. In 132 of 167 (79%) patients, the occluded segment was successfully reopened. Clinical symptoms improved in 126 of 167 (75%) patients. PTLA was unsuccessful in 35 patients, and in 15 of these, injury of the vessel wall occurred. In one patient, surgical drainage of a large hematoma became necessary. All patients in whom recanalization had been achieved were randomized to receive long-term treatment with either phenprocumarol or acetylsalicylic acid (ASA) plus dipyridamole to prevent rethrombosis. At 36 months of follow-up, the cumulative patency rate (CPR) was 63%. A complete reobstruction in 32 patients (24%) and a partial reobstruction in 15 patients (11%) were found angiographically. The CPR after 36 months was significantly lower (p less than 0.05) in patients younger than 60 years of age (54%) than in patients older than 60 (68%); it was also significantly lower (p less than 0.05) in patients with reduced peripheral runoff (55%) due to obstructed arteries of the lower leg than in patients with unaffected runoff (73%). The CPR was 65% in recanalized segments shorter than 7 cm and was 62% in recanalized segments longer than 7 cm.(ABSTRACT TRUNCATED AT 250 WORDS)", "Long-term treatment with aspirin is recommended in patients with large-vessel peripheral arterial disease since these patients have a high risk of death from cardiovascular causes. Recent studies have demonstrated the prophylactic effect of low-dose aspirin in reducing the risk of cardiovascular events. Since aspirin is also recommended for prevention of late recurrence after peripheral angioplasty, the present study was undertaken to compare the effects of high-dose (1000 mg/d) and low-dose (100 mg/d) aspirin on long-term patency after femoropopliteal angioplasty.\n Two hundred sixteen patients treated successfully by percutaneous transluminal angioplasty for femoropopliteal lesions were randomly allocated to therapy with either 1000 or 100 mg aspirin daily. The follow-up was 24 months. The long-term results were analyzed using the Kaplan-Meier method, and differences between curves of cumulative patency were determined with the Wilcoxon and log-rank statistics. Complete follow-up information (patency after 24 months, restenosis, and death) was obtained in 207 patients. During the 2-year follow-up period, 72 patients--36 in the high-dose and 36 in the low-dose aspirin group, respectively--developed angiographically verified reobstruction within the recanalized segment. By intention-to-treat analysis, the cumulative patency rates at 24 months were 62.5% in the high-dose and 62.6% in the low-dose aspirin group (Wilcoxon, P = .97; log-rank, P = .97). The cumulative survival at 24 months of follow-up was 86.6% in the high-dose and 87.7% in the low-dose aspirin group. The number of patients discontinuing therapy was 30 in the high-dose and 11 in the low-dose aspirin group (P < .01). Fewer patients receiving 100 mg of aspirin discontinued therapy because of gastrointestinal symptoms (4 versus 20).\n The data indicate that 100 mg aspirin is no less effective in the prevention of restenosis after femoropopliteal PTA than a 1000-mg dose and has fewer side effects." ]

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[ "Vidarabine therapy of simple and IDU-complicated herpetic keratitis.", "Treatment of herpes simplex keratitis: comparison of acyclovir and vidarabine.", "[On the treatment of dendritic keratitis with para-fluorophenylalanine].", "[Studies on the effectiveness of non-specific and virostatic treatment of dendritic keratitis with special reference to the combination of 5-iodo-2-deoxyuridine and para-fluorphenylalanine].", "Combination therapy of recombinant human alpha 2 interferon and acyclovir in the treatment of herpes simplex keratitis.", "Assessment of possible potentiating action of ultraviolet light on 5 iodo-2' deoxyuridine in superficial herpetic keratitis.", "Oral acyclovir in the management of dendritic herpetic corneal ulceration.", "[On the treatment of dendritic keratitis with p-fluorophenylalanine. (Preliminary report)].", "Ganciclovir ophthalmic gel, 0.15%: a valuable tool for treating ocular herpes.", "Proflavine photodynamic viral inactivation in herpes simplex keratitis.", "Human leukocyte and fibroblast interferon in a combination therapy of dendritic keratitis.", "Role of debridement and interferon in the treatment of dendritic keratitis.", "Interferon-beta treatment of herpes simplex keratitis.", "Combination therapy for dendritic keratitis with acyclovir and alpha-interferon.", "Combination therapy for dendritic keratitis with human leucocyte interferon and trifluorothymidine.", "Acyclovir in the treatment of herpetic keratitis.", "[Comparative studies on the effect of cryotherapy and iodization in combination with unspecific and virostatic after-treatment in dendritic keratitis].", "Combination therapy for dendritic keratitis. High-titer alpha-interferon and trifluridine.", "Efficacy of four antiviral agents in the treatment of uncomplicated herpetic keratitis.", "A comparison between acyclovir and trifluorothymidine ophthalmic ointment in the treatment of epithelial dendritic keratitis. A double blind, randomized parallel group trial.", "[Double-blind clinical trial of isoprinosine and placebo in herpetic keratitis].", "Idoxuridine and iodization in the treatment of simple dendritic ulceration.", "Interferon in treatment of dendritic keratitis in humans: a preliminary report.", "Successful treatment of dendritic keratitis with human leukocyte interferon. A controlled clinical study.", "A COMPARISON OF IDU SOLUTION, IDU OINTMENT, AND CARBOLIZATION IN THE TREATMENT OF DENDRITIC CORNEAL ULCER.", "[Acyclovir and trifluorothymidine in herpetic kerato-uveitis. A comparative clinical study. Indications for corticoid therapy].", "Ganciclovir ophthalmic gel (Virgan; 0.15%) in the treatment of herpes simplex keratitis.", "CONTROLLED STUDIES OF IDU IN THE TREATMENT OF HERPETIC KERATITIS.", "Role of débridement and trifluridine (trifluorothymidine) in herpes simplex dendritic keratitis.", "Acyclovir and vidarabine in the treatment of ulcerative herpes simplex keratitis.", "Double controlled comparison of IDU and trifluorothymidine in thirty-three patients with superficial herpetic keratitis.", "A comparison of acyclovir and idoxuridine as treatment for ulcerative herpetic keratitis.", "[Superficial herpes simplex keratitis. Double-blind comparative trial of acyclovir and idoxuridine (author's transl)].", "TREATMENT OF HERPES SIMPLEX OF THE CORNEA WITH IDU. A DOUBLE-BLIND STUDY.", "[Superficial herpetic keratitis: comparative double-blind treatment with iododeoxycytidine and acyclovir].", "Combination therapy for dendritic keratitis with acyclovir and vidarabine.", "The potency of interferon-alpha 2 and interferon-gamma in a combination therapy of dendritic keratitis. A controlled clinical study.", "Clincial experience of human leucocyte interferon in the management of herpetic keratitis.", "[Comparison of the effectiveness of acyclovir and vidarabine in superficial herpes keratitis].", "AN EVALUATION OF DOUBLE-BLIND IDU THERAPY IN 100 CASES OF HERPETIC KERATITIS.", "[Double-blind treatment of ocular herpes simplex: Vira-A and acyclovir].", "Double--blind clinical trial of adenine arabinoside and idoxuridine in herpetic corneal ulcers.", "Clinical evaluation of adenine arabinoside and trifluorothymidine in the treatment of corneal ulcers caused by herpes simplex virus.", "Cryotherapy of epithelial herpes simplex keratitis.", "A double-controlled evaluation of acyclovir and vidarabine for the treatment of herpes simplex epithelial keratitis.", "Comparative study of acyclovir and 5 I.D.U. in the management of viral corneal ulcer.", "Acyclovir and debridement in the treatment of ulcerative herpetic keratitis.", "A controlled trial of oral acyclovir for the prevention of stromal keratitis or iritis in patients with herpes simplex virus epithelial keratitis. The Epithelial Keratitis Trial. The Herpetic Eye Disease Study Group.", "Treatment of herpetic keratitis.", "TREATMENT OF HERPES SIMPLEX KERATITIS WITH 5-IODO-2'-DEOXYURIDINE.", "A double-blind, multicenter clinical trial of acyclovir vs idoxuridine for treatment of epithelial herpes simplex keratitis.", "Acyclovir and trifluorothymidine in herpetic keratitis: a multicentre trial.", "\"Dye/light\" Dye-induced photosensitization of herpes virus. A clinical trial on humans.", "Treatment of amoeboid herpetic ulcers with adenine arabinoside or trifluorothymidine.", "Clinical evaluation of trifluorothymidine in the treatment of herpes simplex corneal ulcers.", "A DOUBLE-BLIND STUDY OF IDU IN HUMAN HERPES SIMPLEX KERATITIS.", "Randomised double-blind trial of acyclovir and idoxuridine in dendritic corneal ulceration.", "Randomised double-blind trial of bromovinyldeoxyuridine (BVDU) and trifluorothymidine (TFT) in dendritic corneal ulceration.", "Randomised double-blind trial of acyclovir (Zovirax) and adenine arabinoside in herpes simplex amoeboid corneal ulceration.", "Oral acyclovir (Zovirax) in herpes simplex dendritic corneal ulceration.", "Bromovinyldeoxyuridine and interferon treatment in ulcerative herpetic keratitis: a double masked study.", "A randomised double-blind clinical trial of acyclovir (Zovirax) and adenine arabinoside in herpes simplex corneal ulceration.", "Combination therapy for dendritic keratitis with human leukocyte interferon and acyclovir.", "Trifluorothymidine versus adenine arabinoside in the treatment of herpes simplex keratitis.", "A controlled trial of adenine arabinoside and trifluorothymidine in herpetic keratitis.", "Acyclovir and idoxiuridine treatment of herpes simplex keratitis--a double blind clinical study.", "Epidermal growth factor in the topical treatment of herpetic corneal ulcers.", "The management of ocular herpes." ]

[ "Large scale, multiclinic evaluations of vidarabine (Ara-A, Vira A, adenine arabinoside) for treating herpetic keratitis have been conducted as double-blind studies (169 patients) in comparison with IDU and open studies (146 patients). In the open studies, the disease in the majority of patients had been refractory to IDU. The effects of vidarabine and IDU were approximately the same in improvement of symptoms (lacrimination, photophobia, sensitivity) and percent of and time for corneal reepithelialization. With vidarabine, significantly more patients had improved distant visual acuity than did with IDU. In the open studies, vidarabine also was effective. Of 116 patients whose ulcers had not responded to IDU, 91 (78%) had reepithelialization within four weeks of treatment with vidarabine. On the basis of results from these studies, vidarabine appears to be a safe and effective drug for treating herpes simplex keratitis.", "At three university centres 66 patients presenting with herpetic dendritic or geographic ulcers participated in a double-blind comparative study of 3% acyclovir and 3% vidarabine ointment. There was healing in 31 (97%) of the 32 patients treated with acyclovir, in a mean time of 6.3 days, and in 30 (88%) of the 34 treated with vidarabine, in a mean time of 7.1 days. The two medications were statistically equally effective, no difference being demonstrated in the healing rate, in the frequency of punctate epithelial keratitis or stromal keratitis, or in the final visual acuity.", "nan", "nan", "No statistical difference was found in both partial and complete healing time in acute epithelial herpetic keratitis between the ACV-recombinant human alpha 2 IFN (both \"eyedrops\" and \"eyerods\") and Buffy coat human leucocyte alpha IFN. A highly significant difference was found in both partial and complete healing time between the ACV-IFN combination versus the ACV-Placebo combination. The combination of ACV and recombinant human alpha 2 arg IFN is a potent anti-herpetic treatment.", "nan", "A controlled trial of oral acyclovir in herpetic dendritic corneal ulcers was carried out on 31 patients. All patients received minimal wiping debridement of the ulcer, following which they were randomly allocated to receive either oral acyclovir or placebo for 7 days. At the end of treatment 67% of dendritic ulcers in patients receiving acyclovir had healed compared with 43% in placebo recipients. The proportion of ulcers healed in the 2 groups at 7 days showed no significant difference (p = 0.18), but the rate of healing was significantly faster in acyclovir group (p = 0.03).", "nan", "Ocular herpes simplex virus (HSV) infection remains a major cause of corneal blindness. Several topical and oral antiviral medications have been used to treat herpetic keratitis. Advances in topical ophthalmic antivirals have been made over the past several decades. The first antivirals that were discovered were cytotoxic, while the antivirals developed more recently, such as acyclovir and ganciclovir, have exceeded these drugs in both efficacy and tolerability. Commercially available outside of the US since 1996, ganciclovir ophthalmic gel, 0.15% (GCV 0.15%, European tradename: Virgan((R))) is sold in more than 30 countries and has become the standard of care in treating acute herpetic keratitis. GCV 0.15% has been studied in animal models of ocular herpes, in healthy volunteers, and in several clinical studies. It has been found to be safe and effective at treating acute superficial herpetic keratitis. Previous preclinical studies of ganciclovir have shown activity against several common adenovirus strains and one recent clinical study demonstrated clinical effect against adenoviral conjunctivitis. This review is intended to provide a comprehensive overview of the GCV 0.15%, including a brief summary of the etiology and available treatments for ocular HSV, an explanation of GCV 0.15% mechanism of action, a compendium of preclinical and clinical GCV 0.15% studies, and an introduction into new areas of interest involving this drug.", "We used the photodynamic inactivation technique with proflavine as the photoactive dye to treat herpetic epithelial keratitis in a preliminary study of patients who had idoxuridine toxicity or resistance. A comparative study with idoxuridine in treating dendritic ulcerations of the cornea showed a good therapeutic effect. But the investigation was suspended when adverse reactions, consisting of a generalized epithelial keratitis and an anterior uveitis, possibly of phototoxic origin, developed in a few patients receiving treatment. The ulcers treated by photodynamic inactivation apparently healed by a process of \"debridement\" followed by subsequent re-epithelialization.", "Thirty-eight patients with virologically proven dendritic keratitis were treated using either debridement plus human leukocyte interferon (HLI) or debridement plus human fibroblast interferon (HFI) in a randomized, double-blind study. We administered one drop of HLI or HFI (1 X 10(6) reference units/ml) daily and found no significant difference in the action of either type of interferon.", "In a controlled clinical study, 42 patients with dendritic keratitis were treated either with thermocautery plus human leukocyte interferon (HLI) or with minimal wiping debridement plus HLI. The results show that the efficiency with which primary debridement was carried out, determined the success of further therapy using interferon. We conclude that interferon works basically as a prophylactic agent and needs the support of further antiviral measures to be effective against dendritic keratitis.", "We tested a new preparation of interferon-beta (IFN-beta) to determine its efficacy and tolerability in the treatment of herpetic keratitis. The 20 patients admitted to the trial were selected from patients who had not received any previous treatment with virustatic agent; they were treated in a comparative, randomised open trial with eye drop containing IFN-beta or iododesoxyuridine (10 vs. 10). Examination of the data show that 10 out of 10 patients treated with IFN-beta respond positively to the treatment, furthermore it showed that IFN-beta produce no local or general toxicity.", "Fifty-nine patients with superficial herpetic keratitis were treated with 3% acyclovir ointment five times a day in combination with alpha-interferon (30 million IU/mL) or albumin-placebo once a day in a stratified double-masked clinical trial. All patients had minimal wiping of the superficial lesion to isolate virus. The healing time of the corneal ulcers was substantially lower with the combination of acyclovir and interferon than with the combination of acyclovir and placebo. Only minor toxic effects were observed. The combination of acyclovir and interferon appears to be the best presently known treatment for dendritic keratitis.", "nan", "Fourty-three eyes with active dendritic keratitis, nearly one third of which had failed to respond to other antiviral agents, were treated with acyclovir with or without preceding debridement. The patients were randomly selected. No statistical difference could be demonstrated between the 2 groups in terms of rate of healing or in efficacy of cure. Acyclovir also seemed to be effective in stromal corneal lesions. There were only minor side effects.", "nan", "Previous studies showed that the combination of trifluridine with human leukocyte interferon in the treatment of dendritic keratitis is effective, and that the best results were obtained with the highest titer then available (30 X 10(6) IU/mL). The present study was undertaken to see if an even higher titer (100 X 10(6) IU/mL) would be more effective. A statistically significant greater effectiveness of the higher titer could not be verified.", "To evaluate the efficacy of four antiviral agents--1% idoxuridine ointment (group 1), 2% trifluorothymidine ointment (group 2), 3% acyclovir ointment (group 3) and 1% bromovinyldeoxyuridine (BVDU) ointment (group 4)--in herpes simplex keratitis.\n Randomized double-blinded clinical trial.\n Tertiary care institution in New Delhi.\n Eighty patients with uncomplicated herpes simplex keratitis of recent onset who had not previously received antiviral treatment.\n Cure rate, frequency and severity of side effects.\n Cure rates of 60%, 90%, 90% and 95% were obtained in groups 1, 2, 3 and 4 respectively. The average healing time was 13.4, 8.9, 8.5 and 7.5 days respectively. Side effects (follicular conjunctivitis, epithelial keratopathy and stinging) were more frequent in group 1 than in the other groups.\n BVDU has a more pronounced therapeutic effect than idoxuridine, trifluorothymidine and acyclovir in uncomplicated epithelial herpetic disease of recent onset that has not previously been treated.", "This report presents the results of a double blind randomized study comprising 50 patients with epithelial herpes simplex keratitis. Twenty-five patients received 3% acyclovir ophthalmic ointment, the other 25 patients 2% trifluorothymidine (TFT) ophthalmic ointment. The mean duration of treatment in the 2 study groups before healing of the epithelial ulceration was obtained was 6.7 days and 5.9 days, respectively (no statistically significant difference). Two patient (8%) in the acyclovir group and 1 patient (4%) in the TFT group failed to heal within 14 days of treatment. No clinically significant adverse effects were recorded.", "nan", "nan", "Seventy-three patients with herpetic epithelial keratitis were randomly divided into three groups and were treated by local applications of human leukocyte interferon, thermocautery plus human leukocyte interferon, or thermocautery plus mock human leukocyte interferon to obtain information on whether therapy with human leukocyte interferon can serve as a substitute for mechanical debridement of the involved epithelium or can improve the results when given as additional therapy. Fifty-five patients (75%) yielded herpes simplex virus before treatment, and only the results in these patients with keratitis of proved viral etiology were included in the analysis. These results indicated that mechanical debridement cannot be replaced with local application of human leukocyte interferon (3-4 X 10(4) units per day). When given in addition to thermocautery, human leukocyte interferon may have been of some value in a number of patients. However, the results were not statistically significant. A more potent dosage of human leukocyte interferon might provide better results.", "There were 40 virologically confirmed cases of dendritic keratitis treated in a randomized double-blind placebo-controlled study. After thermomechanical debridement of the corneal epithelium, the patients received two drops of human leukocyte interferon (HLI) twice daily. The activity was 3 X 10(-6) units/ml. HLI significantly accelerated healing and inhibited virus shedding. It remains to be studied whether HLI will be equally effective in the prophylaxis of late herpes recurrences.", "nan", "The relative efficacy of aciclovir (ACV) and trifluorothymidine (TFT) was evaluated in a randomized, open clinical trial of 37 patients with herpetic kerato-uveitis. Twenty-one patients were treated with ACV and 16 with TFT. Topical steroids were withheld as long as the degree of inflammation permitted. Although both drugs were effective in healing the herpetic corneal ulcers, TFT had a significantly shorter healing time than ACV. However, ACV was more effective in treating the iridocyclitis than TFT. In 5 cases the keratouveitis responded to ACV alone, while only one case was successfully managed with TFT alone. Both drugs seemed to prevent steroid-induced epithelial complications and no significant side-effects were observed with either drug. The treatment of herpetic keratouveitis with single agents such as ACV and TFT is dependent upon rapidly instituting therapy and minimizing the use of topical steroids. The apparently good intraocular penetration of ACV and TFT may decrease the need for adjunctive steroid therapy and thereby minimize the risks of facilitated viral replication and steroid-dependence.", "Ganciclovir is a broad-spectrum virustatic agent. Its efficacy and safety after ocular application have been demonstrated in studies of herpetic keratitis in rabbits. Two strengths of ganciclovir gel (0.05 and 0.15%) were compared with 3% acyclovir ointment in the treatment of superficial herpes simplex keratitis in humans.\n Two multicenter randomized clinical trials were carried out in Africa (Trial 1) and Europe (Trial 2). Sixty-seven patients (Trial 1) and 37 patients (Trial 2) from herpetic ulceration were recruited.\n The results showed no statistically significant difference between the treatment groups, although the healing rates tended to be better in the group receiving 0.15% ganciclovir gel, with healing rates of 85% (Trial 1) and 83% (Trial 2) as compared with 72% (Trial 1) and 71% (Trial 2) in the group receiving acyclovir ointment. Local tolerance was found to be superior with the gel formulation of ganciclovir with fewer complaints of discomfort (stinging, burning) or blurred vision after application of the drug. Systemic absorption of the drug was low. No hematologic changes were detected.\n These findings support the efficacy of ganciclovir gel in the treatment of ulcerative herpes simplex keratitis and demonstrate its superior local tolerance when compared with acyclovir ointment.", "nan", "Thirty-four patients with herpes simplex dendritic keratitis were randomized into three treatment categories: Group A had débridement alone; group B, trifluridine (trifluorothymidine) alone; and group C, débridement and trifluridine. Patients treated with débridement alone had a statistically higher failure rate than did the other two groups. No statistically significant difference was observed between trifluridine treatment alone and débridement combined with trifluridine treatment, with regard to healing time. Our results suggest that débridement alone is suboptimal therapy for herpes simplex dendritic keratitis and that débridement combined with trifluridine appears to offer no advantage over trifluridine alone.", "In a masked controlled study, we treated 41 patients who had active herpes simplex corneal ulcers with either 3% acyclovir of 3% vidarabine ointment five times daily for 14 days. There was no statistically significant difference between the two drugs with reference to mean healing time, efficacy of healing, development of stromal keratitis or iritis, post-treatment visual acuity, or adverse reaction.", "Thirty-three patients were followed in a double controlled study to test the efficacy of IDU and TFT on superficial epithelial herpes simplex virus infection. Sixteen received TFT and 17, IDU. There were four failures in patients on IDU therapy and no failures in the 16 patients using TFT. These results indicate a trend for greater efficacy of TFT than IDU. In those patients who healed with IDU and with TFT, there was no difference in the number of days to heal in each group.", "Sixty patients were treated with either acyclovir 2% ointment or idoxuridine 1% ointment 5 times a day in a stratified randomised double-blind clinical trial. The 2 antiviral agents were equally effective.", "In a double-blind, randomized trial 52 patients with superficial herpes simplex keratitis were treated with a new antiviral compound, acylclovir (ACV) 3% ointment, or with idoxuridine (IDU) 0.5% ointment. No statistically significant difference was found in the number of patients cured with either drug, but healing was achieved more rapidly with ACV than with IDU.", "nan", "nan", "We treated 32 patients with dendritic keratitis with a combination of acyclovir 3% ointment and vidarabine 3% ointment or acyclovir and placebo. Patients with acyclovir alone healed in an average time of 7.7 days, while patients on the combination healed in an average of 6 days. Only one patient in the acyclovir and vidarabine group had a healing time longer than 7 days, whereas six patients in the acyclovir and placebo group had healing times longer than 7 days. By the median test, this difference in healing times was statistically significant (p = 0.035), and the combination prevented cases of prolonged ulceration.", "Forty-five patients with virologically confirmed dendritic keratitis were treated in a randomized, double-blind controlled study with a basic therapy of trifluorothymidine (TFT) eye drops. In addition they received different human recombinant interferon (rHu IFN) eye drops. The following results were obtained for average healing times: TFT plus one drop daily of rHu IFN-alpha 2 arg (30 million iu/ml): 3.3 days, TFT plus rHu IFN-gamma (30 million iu/ml): 3.9 days, TFT plus a mixture of alpha plus gamma (0.3 million iu/ml each): 6.1 days, TFT plus a mixture of alpha plus gamma (1.5 million iu/ml each): 3.3 days. High-titer gamma interferon did not significantly differ from high-titer alpha interferon in the combination therapy of dendritic keratitis. A mixture of alpha plus gamma at a moderate titer (1.5 million iu/ml each) was as effective as a high-titer mono-preparation. Adding a low-titer interferon mixture gave no better therapeutic results than antiviral monotherapy. Thus it seems possible to save about 90% of interferon commonly used in the combination therapy of dendritic keratitis by applying a mixture of different suitable interferons instead of interferon monospecies.", "nan", "In a double-blind clinical trial 28 patients with primary and recurrent herpetic corneal ulcerations were treated either with 3% Acyclovir eye ointment or 3% Adenosine Arabinoside eye ointment. In 11 out of 14 (78%) patients treated with Acyclovir and 8 out of 14 (57%) patients treated with Adenosine Arabinoside the ulcerations healed within a treatment period of 6.5 days and 8 days respectively (no statistical significance). However, the results revealed that Acyclovir was more effective. Both drugs were well tolerated.", "nan", "nan", "The results are reported of a fully controlled randomized double-blind clincial trial of adenine arabinoside and idoxuridine ointment in sixty patients with herpetic ulceration of the cornea. Although both antivirals showed a trend towards superiority over placebo, the therapeutic effect did not reach statistical significance in spite of the known efficacy in laboratory animals. Further studies in rabbits are reported; these indicate that systemic immunity may play a role in combating virus proliferation in recurrent disease, and it is considered this disguises the efficacy of topical antiviral therapy in clinical trials, thus necessitating an estimated requirement for approximately fifty patients per treatment group to obtain significant effects. It is concluded that an antiviral is valuable in the treatment of ulcerative herpetic keratitis, particularly in primary disease and in the presence of systemic and local immunosuppression after the use of topical adrenocorticosteroid. In recurrent disease, where a trigger factor is known, experience has shown that therapy can be profitably administered before the onset of clinical disease.", "One hundred two unselected patients with ulceration of the cornea due to herpes simples virus were treated with either adenine arabinoside or trifluorothymide; the trial was double-blind, stratified, and radomized. The two drugs were given topically five times per day, and the rate of healing was observed and recorded. The series included 87 patients with dendritic ulcers and 15 with amoeboid ulcers. Dendritic ulcers of the cornea can be accurately measured, and the healing process can be easily followed. In this situation no statistically significant difference between the efficacy of adenine arabinoside and that of trifluorothymidine was demonstrated. Amoeboid ulcers are more difficult to evaluate than dendritic ulcers, and their responses to treatment vary considerably; however, data from this small group of patients suggest that trifluorothymodine may be more effective than adenine arabinoside for the treatment of amoeboid ulcers.", "nan", "nan", "Thus, we found that the role of Acyclovir in the treatment of viral corneal ulcer is definitely better and quicker. It takes less time for healing of corneal ulcer and as a result less hospitalisation is needed.", "We treated 25 patients with dendritic keratitis with debridement and 3% acyclovir ointment and another 25 with acyclovir alone. The patients were randomly assigned to the two treatment groups. There were only minimal adverse effects in both groups. The combination of debridement and acyclovir produced a significantly more rapid healing rate than did acyclovir alone. Factors associated with prolonged healing time were duration of symptoms (longer than one week), length of the epithelial defect (greater than 4 mm), proximity of the defect to the corneoscleral limbus (less than 2 mm), and the presence of stromal inflammation.", "To evaluate the efficacy of oral acyclovir in preventing stromal keratitis or iritis in patients with epithelial keratitis caused by herpes simplex virus (HSV).\n Patients with HSV epithelial keratitis of 1-week or less duration were treated with topical trifluridine and were randomly assigned to receive a 3-week course of oral acyclovir, 400 mg 5 times a day (hereafter referred to as the acyclovir group), or placebo (hereafter referred to as the placebo group). The development of HSV stromal keratitis or iritis was assessed during 12 months of follow-up.\n Stromal keratitis or iritis developed in 17 (11%) of the 153 patients in the acyclovir group and in 14 (10%) of the 134 patients in the placebo group. Compared with the placebo group, the adjusted rate ratio for the development of stromal keratitis or iritis in the acyclovir group was 1.16 (95% confidence interval, 0.56-2.43). The development of stromal keratitis or iritis was more frequent in patients with a history of HSV stromal keratitis or iritis than in those without such a history (23% vs 9%; P = .01).\n For patients with HSV epithelial keratitis treated with topical trifluridine, no apparent benefit of a 3-week course of oral acyclovir in preventing HSV stromal keratitis or iritis was seen during the subsequent year. The 1-year rate of development of stromal keratitis or iritis was lower than previously reported in the literature, except in patients with a history of HSV stromal keratitis or iritis.", "Idoxuridine which was first used in 1960 (Kaufman et al., 1962), has been for many years the only antiviral agent available in the treatment of herpetic keratitis. It is however no more successful than is mechanical removal of diseased epithelium (Patterson & Jones, 1967), and furthermore it may give rise to serious toxic side effects. The search for an alternative medication is therefore a pressing one. Trifluorothymidine (F3T) has, in recent years, been shown to be more effective than IDU and to be free from significant toxicity. Both of these drugs are pyrimidine nucleosides. Adenine Arabinoside or Arabinoside-A (Ara-A) is, by contrast, a purine nucleoside. It is thought to exert its antiviral effect by blocking DNA polymerase and ribonucleotide reductase.", "nan", "Thirty patients randomized to the Acyclovir (ACV) group (26 with dendritic lesions, 4 geographic lesions) and 34 patients randomized to the idoxuridine (IDU) treatment group (26 dendritic lesions, 8 geographic lesions) with epithelial herpetic keratitis were evaluated for efficacy and adverse reactions in a multi-center, double-masked, randomized, stratified trial. Patients were treated with either 3% acyclovir ophthalmic ointment or 0.5% idoxuridine ophthalmic ointment five times a day for 14 days. The results of the trial indicated no significant difference between ACV and IDU as antiviral agents in the treatment of epithelial herpetic keratitis. The overall healing patterns of ACV and IDU adjusted for lesion type and prognostic factors, including presenting condition (initial or recurrent disease), duration of symptoms, prior ophthalmic steroid use, and positive pretreatment herpesvirus culture, as well as, the healing patterns within each lesion type adjusted for these factors, were not significantly different between the two treatment groups. There was no significant difference between the two groups in the frequency of development of deeper involvement. The only significant difference (P less than 0.01) in the frequency of development of adverse reactions was found in the incidence of development of superficial punctate epitheliopathy (IDU-42%, ACV-11%).", "nan", "A series of 21 patients with herpetic corneal ulcers was treated by photodynamic inactivation (using a single application of neutral red 1 per cent solution followed by a 15-min exposure to a 40 watt light of 440--550 nm), carbolization, or idoxuridine (IDU) ointment. No significant difference was found in the number that healed, the mean healing time, or the number of recurrences after any of the three treatments.", "In previous studies adenine arabinoside and trifluorothymidine were found to be equally effective treatments for dendritic ulcers of the cornea, but a trend emerged which suggested that in amoeboid ulcers trifluorothymidine was more effective. The collection of additional cases confirms the superiority of trifluorothymidine in such cases.", "nan", "nan", "The results of a randomised double-blind clinical trial of 3% acyclovir and 0.5% idoxuridine (IDU) ophthalmic ointments in 60 patients with corneal dendritic ulceration are presented. Ulcers in all 30 patients treated with acyclovir healed compared with 22 (76%) of 29 patients treated with IDU (P < 0.01). Patients treated with acyclovir healed more rapidly (average 4.4 days) than those who received IDU (average 9.2 days) (P < 0.01). No serious side effects were observed, though transient stinging was recorded in 8 patients receiving acyclovir and in 2 patients receiving IDU. Other side effects in the IDU treated group were watering in 2 patients and superficial punctate erosions in 6 patients.", "The results of a randomised double-blind clinical trial of 0.1% bromovinyldeoxyuridine (BVDU) and 1% trifluorothymidine (TFT) in 60 patients with corneal dendritic ulceration are presented. There was no significant difference between BVDU and TFT in terms of numbers of ulcers healed (p = 0.61), mean healing time (p = 0.065), and cumulative healing rate (p = 0.058). No serious side effects were observed, though transient stinging was recorded in five patients receiving TFT and in three patients receiving BVDU. One patient in the group treated with TFT developed a punctate epitheliopathy.", "Fifty-one patients were treated in a dual-centre, double-blind comparison of acyclovir and adenine arabinoside in herpetic amoeboid (geographic) corneal ulceration. Twenty-four of the 25 patients receiving acyclovir healed in a mean time of 12.2 days, while 24 of the 26 patients treated with adenine arabinoside healed in a mean time of 11.0 days. There was no statistically significant difference between the two groups in terms of healing. A second analysis, excluding any patients who had received antiviral treatment immediately prior to entry into the study, showed that 18 of the 19 who received acyclovir healed in an average of 11.7 days and 18 of the 19 recipients of adenine arabinoside healed in a mean time of 11.2 days. Again the difference was not statistically significant.", "Sixty patients with simple dendritic corneal ulceration were randomly assigned to double blind treatment with either acyclovir tablets (400 mg) or acyclovir ophthalmic ointment administered five times daily. There was no significant difference in the proportions of patients healed in either treatment group (88.9% on oral acyclovir and 96.6% on acyclovir ointment). The median healing time was five days in both groups. No systemic or significant local side effects were noted in either treatment group. Trough levels of acyclovir in the tear fluid of those who received the oral preparation were within or above the range of mean in-vitro ID50 levels for herpes simplex virus type 1. We conclude that oral administration of acyclovir (400 mg, five times daily) may be an effective alternative to topical therapy in selected patients.", "Bromovinyldeoxyuridine is a potent and safe antiherpes compound that in combination with a placebo treatment promoted the partial and complete healing of herpetic epithelial disease in 22 patients in average times of 4-6 days and 8.5 days respectively. However, when BVDU was combined with 1.5 X 10(6) IU of recombinant a 2C interferon, partial and complete healing times for keratitis in 19 patients were reduced to 2-6 days and 4-6 days respectively. No toxic effects of the medications were observed in any patient.", "A double-blind clinical trial of 3% acyclovir (Zovirax) and 3% adenosine arabinoside (ara-A, Vidarabine) in 93 patients with herpetic corneal ulceration is presented. Ulcers in 45 (94%) of acyclovir-treated patients and 37 (82%) ara-A-treated patients healed within 14 days. Patients treated with acyclovir healed more rapidly than those treated with ara-A (p less than 0.01). No serious adverse effects were observed.", "We treated 45 patients with virologically verified dendritic keratitis with a combination of interferon and acyclovir 3% or with placebo and acyclovir 3% in a double-masked study. One drop of human leukocyte interferon (30 X 10(6) IU/ml) or albumin-placebo was administered daily. Acyclovir ointment was applied five times daily. The mean healing time of the corneal ulcers in 24 patients treated with interferon and acyclovir was 3.9 days and the mean healing time in 21 patients treated with placebo and acyclovir was seven days. The difference was significant (P less than .001).", "Trifluorothymidine (TFT) and adenine arabinoside (ara-A) are effective antiviral drugs with a very low toxicity for the cornea. In our study no difference between these 2 drugs in antiviral activity was noted. The average healing time for TFT was 11-14 days and for ara-A 10-54 days. These data differ markedly from those of other studies. This was the result of the use of additional criteria for healing of the lesion. Not only absence of fluorescein staining of the cornea but also the absence of oedema and cystic changes in the epithelium over the previous ulcer were considered criteria for healing. In addition to clearly defined healing criteria and the healing time we found the interval between the first symptoms and the commencement of the therapy of greatest importance in the clinical evaluation of antiviral drug efficacy. An effort was made to approximate this relationship for TFT and ara-A mathematically.", "The effectiveness of two anti-viral agents, adenine arabinoside and trifluorothymidine, were studied in cases of human superficial herpetic keratitis (dendritic ulceration). A highly satisfactory response to each drug was demonstrated in most cases.", "38 patients with herpes simplex keratitis were treated in double blind clinical trial. 18 patients (10 with pure epithelial and 8 with accompanying stromal affection) were treated with 3% acyclovir (ACV) eye ointment, and 20 patients (10 with pure epithelial and 10 with accompanying stromal affection) were treated with 0.5% idoxiuridine (IDU). The cure rate was 94% in the ACV group compared to 70% in the IDU group. This was significantly higher in the ACV group. Only minor adverse reactions were recorded.", "The tolerability and efficacy of epidermal growth factor (EGF) in the topical treatment of herpetic corneal ulcers in addition to topical acyclovir have been evaluated in a double-blind, placebo-controlled, randomized study in two groups of patients. The time required for complete reepithelialization of the cornea was recorded, and the data obtained were analyzed statistically. In the EGF group, the reepithelialization was significantly faster than in the control group. Tolerability of EGF was always excellent. These results indicate that EGF is safe and effective in reducing the healing time of herpetic corneal ulcers.", "nan" ]

[ "558739", "6476868", "7767", "7234386", "16061595" ]

[ "Adequacy of expressed breast milk for early growth of preterm infants.", "Multicentre trial on feeding low birthweight infants: effects of diet on early growth.", "Milk protein quantity and quality in low-birthweight infants: I. Metabolic responses and effects on growth.", "The metabolic consequences of human milk and formula feeding in premature infants.", "Randomized trial of donor human milk versus preterm formula as substitutes for mothers' own milk in the feeding of extremely premature infants." ]

[ "Poor weight gain observed in preterm infants who were fed expressed breast milk compared with those fed a cows' milk formular prompted a detailed study of early postnatal growth in preterm infants fed these two milks. 68 infants were divided into two categories by gestational age at birth (i) 28-32 weeks (n=28), (ii) 33-36 weeks (n=40). They were randomly allocated to a feed of expressed breast milk or a milk formula (Ostermilk 1). Rates of weight gain, linear growth, and head circumference growth were evaluated over two periods: birth-1 month, 1-2 months. The younger group who were fed breast milk showed slower overall growth rates over the first month than those fed formula. In the second month, and for the older infants over both of the 2-monthly periods, growth rates were similar in the two feeding regimens. It is concluded that expressed breast milk is inadequate for the growth of very immature preterm infants during early postnatal life.", "A large multicentre study on the short and long term clinical and developmental outcome of infants randomised to different diets is being undertaken. This report represents an interim analysis of the early postnatal growth performance of an unselected population of 194 preterm infants (gestation, mean (SD) 31 . 0 (2 . 9) weeks; birthweight, mean (SD) 1364 (294) g), both ill and well, examined in two (of four) parallel trials. One trial compared banked breast milk with a new preterm formula (primary trial); the other compared these diets as supplements to maternal milk (supplement trial). A major dietary effect on the number of days taken to regain birthweight and subsequent gains in weight, length, and head circumference was observed in the primary trial. Infants fed banked breast milk and weighing less than 1200 g at birth took a calculated additional three weeks to reach 2000 g compared with those fed on the preterm formula. A significant influence of diet on body proportions was seen in the relation between body weight, head circumference, and length. Similar though smaller differences in growth patterns were seen in the supplement trial. By the time they reach 2000 g, infants of birthweights 1200 to 1849 g fed on banked breast milk and infants below 1200 g fed on either banked breast milk or maternal milk supplemented (as necessary) with banked breast milk, fulfilled stringent criteria for failure to thrive (weight less than 2 SD below the mean for age). Only infants fed the preterm formula as their sole diet had maintained their birth centile by discharge from hospital. The misleading nature of comparisons between extrauterine and intrauterine steady state weight gains is emphasised.", "The optimal quantity and quality of protein for low-birthweight infants is undefined. In this study, 106 well, appropriate-for-gestational age, low-birthweight infants weighing 2,100 gm or less were grouped in three gestational age categories: T1 = 28 to 30 weeks; T2 = 31 to 33 weeks; T3 = 34 to 36 weeks. Each group was assigned randomly to either banked human milk (BM) or to one of four isocaloric formulas varying in quantity and quality of protein but not in mineral content or in fat content: formula 1 = 1.5 gm of protein per 100 ml, 60 parts bovine whey proteins to 40 parts bovine caseins; formula 2 = 3.0 gm of protein per 100 ml, 60:40; formula 3 = 1.5 gm of protein per 100 ml, 18:82; formula 4 = 3.0 gm of protein per 100 ml, 18:82. Caloric intake was 117 kcal/150 ml/kg/day for the formulas. Human milk was fed at 170 ml/kg/day in order to attain a caloric intake approximately equal to that of the formulas. No significant differences were found in the rate of growth in crown-rump length, in femoral length, in head circumference, or in rate of gain in weight from time of regaining birthweight to time of discharge at 2,400 gm. Blood urea nitrogen, urine osmolarity, total serum protein, serum albumin, and serum globulin varied directly with the quantity of protein in the diet: F2, F4 greater than F1, F3 greater than BM. Blood ammonia concentration varied with both quantity and quality of protein in the diet: F2, F3, F4 greater than F1, BM. Metabolic acidosis was more frequent, more severe, and more prolonged in the infants fed the casein-predominant formulas (F3,F4) than in those fed the whey protein-predominant formulas (F1, F2).", "Twenty premature low-birthweight infants were divided into two groups and assigned randomly to either a pooled human milk or to a cow's milk based infant formula feeding regimen. The protein intake was 2.0 g/kg/day in the human milk fed group and 4.4 g/kg/day in the formula fed group of infants. The concentrations of different metabolites were estimated at weekly intervals, and plasma amino acid analysis was performed biweekly on blood samples in the two groups of infants during the four-week study period. Formula milk fed infants had significantly lower fasting blood glucose levels and developed azotaemia, hyperaminoacidemia and metabolic acidosis in the early weeks of postnatal life. Blood lactate and plasma free fatty acid concentrations did not change significantly in the two groups during the study. No significant differences were found in the rate of weight gain between the two groups of infants, although formula fed infants regained their birthweight more slowly than human milk fed infants. High protein formula feeding causes potentially unfavorable metabolic and amino acid imbalances in preterm infants in the early postnatal life.", "Compared with preterm formula (PF), mother's milk (MM) is associated with lower rates of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) among premature infants. Because not all mothers of premature infants produce sufficient milk to supply their infants throughout hospitalization, we reasoned that pasteurized donor human milk (DM) would be a suitable alternative.\n Extremely premature infants (<30 weeks of gestation) whose mothers intended to breastfeed were assigned randomly to receive either pasteurized DM or PF if the supply of their own MM became insufficient during the study (birth to 90 days of age or hospital discharge). Infection-related events (LOS, NEC, meningitis, presumed sepsis, or urinary tract infection) that occurred after the attainment of a milk intake of 50 mL/kg, dietary intake, growth, skin-to-skin contact, and duration of hospital stay were compared. The primary analysis compared groups DM and PF on an intent-to-treat basis. If no differences were noted, then these groups were combined and compared with the reference group, group MM. If differences were noted, then the subsequent analyses compared each group with group MM.\n Of 243 infants, 70 (29%) received only MM; group DM included 81 infants and group PF included 92 infants. Because of poor weight gain, 17 infants (21%), all in group DM, were switched to PF. There were no differences in birth weight, gestational age, multiple births, and age at attainment of feeding of 50 mL/kg among groups. There were no differences between group DM and group PF in LOS and/or NEC, other infection-related events, hospital stay, or number of deaths. Group DM received a greater intake of milk and more nutritional supplements but had a slower rate of weight gain, compared with group PF. Compared with groups DM and PF, group MM had fewer episodes of LOS and/or NEC and total infection-related events and a shorter duration of hospital stay. Group MM also had fewer Gram-negative organisms isolated from blood cultures than did the other groups.\n In this randomized, blinded trial of feeding of extremely premature infants, we found that, as a substitute for MM, DM offered little observed short-term advantage over PF for feeding extremely premature infants. Advantages to an exclusive diet of MM were observed in terms of fewer infection-related events and shorter hospital stays." ]

[ "18411239" ]

[ "Randomized efficacy trial of early preconception counseling for diabetic teens (READY-girls)." ]

[ "To develop and assess the feasibility of an early preconception counseling program for adolescents called READY-Girls (Reproductive-health Education and Awareness of Diabetes in Youth for Girls).\n A total of 53 adolescent females with type 1 diabetes between 16 and 19.9 years of age were randomized into groups receiving a CD-ROM, a book, or standard care (control) and given one comprehensive session. Outcomes were assessed at baseline, immediately after, and at 3 months.\n Teens who received the CD and those who received the book demonstrated significant (P < or = 0.05) sustained improvement (over 3 months) in knowledge, perceived benefits of both receiving preconception counseling and using effective family planning, and perceived more support with reproductive health issues.\n Clinical feasibility of the program was demonstrated. Both the CD and the book appeared to be efficacious formats for the short term. Future studies should examine repeated boosters of a CD and a book, which are not meant to replace but rather to reinforce and supplement health professional education." ]

[ "14681639", "17967712", "10986030", "16799184", "2403699", "1920650" ]

[ "Randomized trial and local biological effect of autologous platelets used as adjuvant therapy for chronic venous leg ulcers.", "Synergistic action of protease-modulating matrix and autologous growth factors in healing of diabetic foot ulcers. A prospective randomized trial.", "Randomised double-blind placebo controlled trial of topical autologous platelet lysate in venous ulcer healing.", "A prospective, randomized, controlled trial of autologous platelet-rich plasma gel for the treatment of diabetic foot ulcers.", "Stimulation of repair in chronic, nonhealing, cutaneous ulcers using platelet-derived wound healing formula.", "A prospective randomized trial of autologous platelet-derived wound healing factors for treatment of chronic nonhealing wounds: a preliminary report." ]

[ "Platelet products have been proposed as adjuvant therapy for wound healing. We undertook this study to determine the healing effect of topically applied frozen autologous platelets (FAP) on chronic venous ulcers, compared with effect of placebo, and whether use of topical FAP modifies local expression of vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF), interleukin 8 (IL-8), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in wound fluid.\n This randomized, placebo-controlled, double-blind trial was carried out in institutional practice, with ambulatory patients with proved chronic venous leg ulcers. In all patients, whole venous blood was drawn for preparation of FAP. FAP or normal saline solution was applied three times per week for up to 12 weeks, together with hydrocolloids and standardized compression bandages. Leg ulcer surface was assessed with numerical pictures. IL-8, VEGF, KGF, and TIMP-1 levels were determined (enzyme-linked immunosorbent assay) in wound fluid after each 4 weeks of treatment.\n Fifteen patients were randomized into two groups with comparable leg ulcer characteristics. Mean percent reduction in ulcer area was 26.2% in the FAP group versus 15.2% in the placebo group (P =.94). One ulcer in each group was completely healed at study end. Levels of TIMP-1 increased significantly during FAP treatment. IL-8 concentration was significantly lower in wound fluid of healing ulcers than in the fluid of nonhealing ulcers, in both FAP and placebo groups. Growth factor levels were not modified with FAP treatment.\n Topical autologous platelets have no significant adjuvant effect on healing of chronic venous leg ulcers and increased wound fluid TIMP-1 concentration. Ulcer healing is associated with a decrease in wound fluid IL-8.", "This study tests the hypothesis that addition of a protease-modulating matrix enhances the efficacy of autologous growth factors in diabetic ulcers. Fifty-one patients with chronic diabetic foot ulcers were managed as outpatients at the Democritus University Hospital of Alexandroupolis and followed up for 8 weeks. All target ulcers were > or = 2.5 cm in any one dimension and had been previously treated only with moist gauze. Patients were randomly allocated in three groups of 17 patients each: Group A was treated only with the oxidized regenerated cellulose/collagen biomaterial (Promogran, Johnson & Johnson, New Brunswick, NJ), Group B was treated only with autologous growth factors delivered by Gravitational Platelet Separation System (GPS, Biomet), and Group C was managed by a combination of both. All ulcers were digitally photographed at initiation of the study and then at change of dressings once weekly. Computerized planimetry (Texas Health Science Center ImageTool, Version 3.0) was used to assess ulcer dimensions that were analyzed for homogeneity and significance using the Statistical Package for Social Sciences, Version 13.0. Post hoc analysis revealed that there was significantly greater reduction of all three dimensions of the ulcers in Group C compared to Groups A and B (all P<.001). Although reduction of ulcer dimensions was greater in Group A than in Group B, these differences did not reach statistical significance. It is concluded that protease-modulating dressings act synergistically with autologous growth factors and enhance their efficacy in diabetic foot ulcers.", "to assess the effect of topical autologous platelet lysate on the healing of chronic venous ulcers. Design: a randomised placebo controlled double-blind trial.\n all patients had blood taken for preparation of autologous platelet lysate. Methods: patients with proven chronic venous ulceration were randomised to the trial. Autologous platelet lysate or placebo buffer solution were applied twice per week for up to 9 months in combination with standardised compression bandaging.\n a total of 86 patients (36 males and 50 females, median age 70 years) were entered into the study. The patient and treatment groups were equivalent for ulcer size, ulcer duration and other characteristics. Cox regression analysis of the time to ulcer healing did not show any difference in healing between platelet lysate and placebo application.\n platelet lysate prepared and delivered by the method used in this study had no influence on the healing of chronic venous ulceration.\n Copyright 2000 Harcourt Publishers Ltd.", "Nonhealing diabetic foot ulcers are a common cause of amputation. Emerging cellular therapies such as platelet-rich plasma gel provide ulcer management options to avoid loss of limb. The purpose of this prospective, randomized, controlled, blinded, multicenter clinical study was to evaluate the safety and efficacy of autologous platelet-rich plasma gel for the treatment of nonhealing diabetic foot ulcers. One hundred, twenty-nine (129) patients were screened; 72 completed a 7-day screening period and met the study inclusion criteria. Patients were randomized into two groups - the standard care with platelet-rich plasma gel or control (saline gel) dressing group - and evaluated biweekly for 12 weeks or until healing. Healing was confirmed 1 week following closure and monitored for another 11 weeks. An independent audit led to the exclusion of 32 patients from the final per-protocol analysis because of protocol violations and failure to complete treatment. In this group, 13 out of 19 (68.4%) of the platelet-rich plasma gel and nine out of 21 (42.9%) of the control wounds healed. After adjusting for wound size outliers (n = 5), significantly more platelet-rich plasma gel (13 out of 16, 81.3%) than control gel (eight out of 19, 42.1%) treated wounds healed (P = 0.036, Fisher's exact test). Kaplan-Meier time-to-healing also was significantly different between groups (log-rank, P = 0.0177). No treatment-related serious adverse events were reported and bovine thrombin used in the preparation of PRP did not cause Factor V inhibition. When used with good standards of care, the majority of nonhealing diabetic foot ulcers treated with autologous platelet-rich plasma gel can be expected to heal.", "Chronic, nonhealing, cutaneous ulcers are a serious clinical problem. The results of previous studies using platelet-derived wound healing formula (PDWHF), derived from autologous platelets, provided evidence that PDWHF actively stimulates repair of the wound. To test whether or not PDWHF accelerates repair, a prospectively randomized, blinded trial was conducted using a placebo control. A total of 32 patients with chronic, nonhealing, cutaneous wounds of the lower extremity were randomized and treated for eight weeks with PDWHF or placebo. Epithelialization of the wound was the end point of study. In the group who received treatment, 81 per cent of patients had epithelialization in eight weeks compared with 15 per cent in the control group (p less than 0.0001). After crossover to treatment with PDWHF, all of the patients in the control group had epithelialization in an average of 7.1 weeks. Regression analysis of the rates of epithelialization also showed significant differences during the initial eight week trial and showed no difference after crossover of the control group to therapy with PDWHF. Results from this study demonstrate a highly statistically significant effect of topically applied platelet-derived growth factors on the repair of chronic, nonhealing, cutaneous ulcers.", "Previous studies have suggested that topically applied platelet-derived wound healing factors (PDWHF) accelerate wound healing by stimulating angiogenesis, fibroblast proliferation, and collagen synthesis. To assess the ability of platelet factors to facilitate healing of chronic cutaneous ulcers we performed a randomized, prospective, double-blind, placebo-controlled study of topical PDWHF in 18 patients with 26 lower extremity wounds refractory to conventional therapy. Wounds were present for at least 8 weeks (mean, 5.5 +/- 4.3 months). They were extensively debrided initially and were measured and photographed at weekly intervals for 12 weeks. Eight patients with nine wounds were treated with placebo solution (controls), and 10 patients with 17 wounds were treated with PDWHF (treatment group). Seventy-eight percent of patients had diabetes mellitus, 72% had occlusive peripheral vascular disease, and 28% had venous disease; distribution of these disorders was equivalent in both groups. Ankle-brachial indexes, which were often spuriously elevated, averaged 0.93 +/- 0.54 in controls and 1.04 +/- 0.56 in patients treated with PDWHF (p greater than 0.5). Mean transcutaneous oxygen tension was 37.8 +/- 11.9 mmHg in controls and 37.1 +/- 9.1 mmHg in patients treated with PDWHF. Initial wound area was larger in controls than in the patients treated with PDWHF (28.9 +/- 45.2 cm2 vs 13.0 +/- 4.4 cm2), but this difference was not statistically significant (p = 0.19). Three (33%) wounds (in two patients) healed in controls, and four (24%) wounds (in three patients) healed in the PDWHF group (p greater than 0.5). The rate of healing in controls was 1.9 +/- 2.7 cm2/week.(ABSTRACT TRUNCATED AT 250 WORDS)" ]

[ "2352247", "15172862", "12414003", "10988044", "3965310", "14511875" ]

[ "Pain relief in hysterosalpingography. A comparison of analgesics.", "The use of intrauterine lidocaine to minimize pain during hysterosalpingography: a randomized trial.", "Transcervical intrauterine topical local anesthetic at hysterosalpingography: a prospective, randomized, double-blind, placebo-controlled trial.", "Paracetamol as a prophylactic analgesic for hysterosalpingography: a double blind randomized controlled trial.", "Reduction of pain following hysterosalpingogram by prior analgesic administration.", "Intrauterine lidocaine gel application for pain relief during and after hysterosalpingography." ]

[ "Hysterosalpingography provides important information in the evaluation of infertility but is generally considered an uncomfortable and painful procedure. We evaluated various analgesics for decreasing or eliminating the discomfort from this procedure. Two types of analgesia were required to give maximum pain relief during and after the examination in the 180 patients evaluated. The best results were achieved with a combination of naproxen sodium, 550 mg, given orally two hours before the examination, and 20% benzocaine, applied to the cervix.", "A hysterosalpingogram is an integral part of the evaluation of infertility but is often painful. Intrauterine anesthesia may help to alleviate the discomfort associated with this procedure.\n We conducted a randomized, double-blinded, placebo-controlled trial of intrauterine lidocaine in women undergoing hysterosalpingography (HSG). All women were instructed to take a nonsteroidal analgesic before the hysterosalpingogram. Patients received 3 mL of buffered 2% lidocaine solution or 0.9% normal saline instilled into the uterus before HSG. The primary outcome was the degree of pain experienced documented via 10-cm visual analogue pain scales. Systematic assessments of discomfort were also collected by the attending physician, radiology technician, and radiology physician.\n Sixty-four patients were randomly assigned to placebo and 63 women were randomly assigned to the lidocaine group. There were no differences in mean age, race, parity, or history of dysmenorrhea or chronic pelvic pain. There were no differences in the pain scores at baseline, during, or after the study procedure between the 2 groups. Peak pain scale scores associated with the procedure were 5.3 +/- 0.4 in both the placebo and study groups. In addition, assessments of patient discomfort revealed no significant differences between the 2 groups.\n We found no difference in pain between the intrauterine-lidocaine and placebo groups. Intrauterine lidocaine does not appear to be effective in decreasing pain in women undergoing HSG.\n I", "To assess whether transcervical intrauterine topical instillation of a local anesthetic agent reduces pain at hysterosalpingography.\n Prospective, randomized, double-blind, placebo-controlled study.\n Department of reproductive medicine at a university teaching hospital.\n One hundred ten women undergoing hysterosalpingography (HSG).\n Subjects were randomized to receive either 2 mL of 2% plain lignocaine or 2 mL of 0.9% sodium chloride solution (placebo) topically into the uterine cavity before the HSG was performed.\n The degree of lower abdominal pain experienced both during the injection of contrast media at HSG and 10 minutes after the procedure using a 20-cm visual analogue scale (VAS) and a four-point verbal descriptor scale (VDS).\n There was no difference in pain scores between lignocaine and placebo during the HSG. However, at 10 minutes after the HSG, subjects receiving lignocaine experienced more pain than those on placebo.\n Transcervical intrauterine topical instillation of 2 mL of 2% plain lignocaine does not reduce pain during HSG and may lead to increased pain immediately after the procedure.", "To evaluate the effectiveness of paracetamol as a prophylactic analgesic for hysterosalpingography (HSG).\n A prospective double blind randomized controlled trial comparing one 1 g of paracetamol (SmithKline Beecham, Brentford, U.K.) to placebo taken 30 min before HSG. One hundred consecutive out-patients were studied prospectively. The analgesic effectiveness during the procedure and at 24 h and 1 week post procedure was analysed by a postal pain score questionnaire. Additional data on the ethnicity of the patient, sex and level of experience of the radiologist performing the hysterosalpingogram, the parity of the patient, the ease of the procedure, and whether pathology was identified were also recorded.\n Eighty-eight patients (88%) replied, 39 (44%) received paracetamol and 49 placebo (56%). During the procedure 3/39 (7%) of women in the paracetamol group were pain-free compared to 9/49 (18%) in the placebo group, which was not significant (P = 0.11). At 24 h, 15/39 (38%) of women in the paracetamol group were pain-free compared to 20/49 (41%) in the placebo group, which was not significant (P = 0.82). At 1 week, 27/39 (69%) of women in the paracetamol group were pain-free compared to 29/49 (59%) in the placebo group, which was not significant (P = 0.33). No significant difference in mean pain scores was determined during the procedure (P = 0.91), or at 24 h post procedure (P = 0.94). Similarly, no difference in mean pain scores was identified with regard to the ethnicity of the patient, the sex of the radiologist performing the procedure, the level of experience of the radiologist performing the procedure, or whether pathology was present or not. Difficult cannulations were associated with higher mean pain scores, however, there was no difference in mean pain scores between the paracetamol or placebo groups for both easy and difficult cannulations.\n Paracetamol is not effective as a prophylactic analgesic for HSG. If a prophylactic analgesic is considered necessary for pain relief during HSG we recommend that a non-steroidal anti-inflammatory drug (NSAID) is used.", "nan", "nan" ]

[ "1098594", "2378830", "7018950", "4883649", "1101946", "3049266", "2037265", "3858547", "1187056", "4800555", "4928966", "1683403", "4817629", "7033847", "3172062", "7553254", "6996132", "453287", "4863299", "7047172", "391210", "3684122", "1209435", "355958", "6411113", "766555", "4582587", "3279351", "5949195", "4567863", "4928965", "788774", "341635", "394563", "1673628", "4557896", "15087045", "4896144", "15279347", "324946", "4896143", "127773", "4886952", "12774875", "370526", "4556543", "766822", "4868189", "3214386", "334356", "5688731", "53330", "14168254", "4883650", "959129", "11431615" ]

[ "Further evaluation of quinestrol in the inhibition of lactation: a double-blind comparison of two dose levels against placebo.", "Lactation inhibition by a single injection of a new depot-bromocriptine.", "Effects of lisuride and bromocriptine on inhibition of lactation and on serum prolactin levels: comparative double-blind study.", "Inhibition of lactation.", "Effect of bromocriptine and chlorotrianisene on inhibition of lactation and serum prolactin. A comparative double-blind study.", "Suppression of puerperal lactation by terguride. A double-blind study.", "Cabergoline versus bromocriptine in suppression of lactation after cesarean delivery.", "Effect of prostaglandin E2 on puerperal breast discomfort and prolactin secretion.", "[New method for inhibition of lactogenesis].", "A new approach to the inhibition of puerperal lactation.", "Inhibition of lactation.", "Oral cabergoline. Single-dose inhibition of puerperal lactation.", "Comparison between quinestrol and diethylstilbestrol for the inhibition of lactation.", "Lactation suppression with bromocriptine.", "Suppression of lactation. A comparison of bromocriptine and prostaglandin E2.", "[Puerperal inhibition of lactation with metergoline or bromocriptine].", "Inhibition of puerperal lactation: A comparative study of bromocriptine and pyridoxine.", "The effect of chlorotrianisene as postpartum lactation suppression on blood coagulation factors.", "A double-blind trial of chlorotrianisene in the suppression of lactation.", "Metergoline versus bromocriptine in the prevention of puerperal lactation. A double-blind clinical trial.", "Inhibition of puerperal lactation: evaluation of bromocriptine and placebo.", "Bromocriptine in an injectable retard form for puerperal lactation suppression: comparison with Estandron prolongatum.", "Suppression of lactation with high doses of pyridoxine.", "Effects of bromocriptine mesylate on the composition of the mammary secretion in non-breast-feeding women.", "Inhibition of lactation by cyclofenil and bromocriptine.", "Study of the suppression of lactation and the influence on blood clotting with bromocriptine (CB 154) (Parlodel): a double blind comparison with diethylstilboestrol.", "A clinical study of lactation suppression.", "Prevention of puerperal lactation by a single oral administration of the new prolactin-inhibiting drug, cabergoline.", "Testosterone enanthate (180 mg.) and estradiol valerate (8 mg.) for suppression of lactation: a double-blind evaluation.", "A combined/oestrogen/progestogen/testosterone agent for the inhibition of lactation.", "Lactation inhibition in the Outer Hebrides. A trial of a fat-stored oestrogen.", "Serum prolactin and the suppression of lactation.", "Inhibition of puerperal lactation. A double blind study of bromocriptine and placebo.", "Puerperal lactation suppression and prolactin.", "Lactation inhibition by the dopamine agonist CV 205-502.", "A comparative study of two fat-stored oestrogens in inhibiting lactation.", "[Cabergoline for inhibition of lactation].", "An assessment of quinestrol in the inhibition of lactation.", "The combined oral contraceptive pill versus bromocriptine to suppress lactation in puerperium: a randomized double blind study.", "The suppression of puerperal lactation with bromocriptine.", "'Instant' inhibition of lactation.", "Prevention of postpartum breast engorgement: double-blind comparison of chlorotrianisene 72 mg. and placebo.", "Evaluation of postpartum breast engorgement by thermography.", "Breast binding... is it all that it's wrapped up to be?", "Bromocriptine, methyl testosterone and placebo for inhibition of physiological lactation: a controlled study.", "Suppression of puerperal lactation with an ergot alkaloid: a double-blind study.", "The failure of pyridoxine in suppression of puerperal lactation.", "The effectiveness of stilboestrol in the suppression on postpartum lactation.", "Suppression of puerperal lactation using jasmine flowers (Jasminum sambac).", "Efficacy of bromocriptine and chlorotrianisene in preventing postpartum lactation.", "Inhibition of lactation with quinestrol.", "Controlled trial of bromocriptine, quinoestrol, and placebo in suppression of puerperal lactation.", "PREVENTION OF LACTATION.", "Stilboestrol inhibition of lactation.", "The treatment of puerperal lactation with bromocriptine.", "[Treatment of pain due to unwanted lactation with a homeopathic preparation given in the immediate post-partum period]." ]

[ "One hundred and ninetysix post-partum women, in whom lactation was to be prevented, were given under double-blind conditions either placebo or quinestrol 2 mg or 4 mg as a single oral dose within twentyfour hours of delivery. Early assessment of the results gave a failure rate of 58 per cent, 15 per cent and 5 per cent respectively, with statistically significant differences among the three groups of patients. At the follow-up evaluation, which could be made in only about one third of the women, breast troubles were recorded in 20 to 30 per cent, without significant differences among the groups. Post-partum amenorrhea showed a progressive prolongation from an average of 47.9 days in the controls to 64.6 and 72.6 days respectively in the 2 and 4 mg quinestrol groups. Adverse reactions, represented by delayed uterine involution during hospital stay and abnormal uterine bleeding in the late puerperium, were somewhat more frequent in the higher dose group than in the lower dose and control groups. On the basis of the prsent findings and of similar, though rare, experiences reported in the relevant literature, the question is therefore raised whether the 2 mg quinestrol dose would not be preferable to the 4 mg one for routine use in post-partum nonusing women.", "Recently, long-acting injectable forms of bromocriptine have become available for the prevention of lactation. The first developed depot-form was very effective, but had the disadvantage of a slowly metabolized carrier. we investigated the pharmacokinetics, efficacy, tolerance and safety of 40 and 50 mg of a new rapidly eliminated depot-form in 61 postpartum women. Bromocriptine rapidly increased after injection and prolactin was effectively suppressed during the study-period of 60 days. Overall efficacy was very good or good in 98% and no rebound lactation occurred. Sixteen women experienced side effects. Tolerance at the injection site was good and safety tests did not show abnormalities. There were no differences between the two dosages. We conclude that this new depot-bromocriptine is a safe, well tolerated and effective drug in the suppression of prolactin and the prevention of post-partum lactation.", "The effects of lisuride (Schering) and bromocriptine (Parlodel, Sandoz), two dopaminergic drugs, on the inhibition of puerperal lactation were compared in a double-blind study. At the dosages selected, lisuride was as effective as bromocriptine for the inhibition of lactation but bromocriptine was more effective in lowering serum prolactin levels.", "nan", "A double-blind study to compare the effect of 2-Br-alpha-ergocryptine (bromocriptine, CB 154, Sandoz) an ergot alkaloid with chlorotrianisene (Tace, Mer-National) on the inhibition of postpartum lactation was carried out in 38 women. At the dosages selected bromocriptine was more effective than chlorotrianisene in inhibiting lactation. Furthermore, bromocriptine significantly reduced serum prolactin levels to low normal values by the seventh day of treatment, whereas chlorotrianisene did not alter the normal progressive reduction in prolactin post-partum. Neither drug had significant toxic effects.", "Clinical efficacy, prolactin (PRL)-lowering effect and tolerance of terguride (an 8-alpha-ergoline derived from Lisuride which acts as a partial dopaminergic agonist) were investigated in a double-blind study on inhibition of puerperal lactation using three different daily doses of the drug (0.25, 0.5 and 1.0 mg). With 0.5 and 1.0 daily therapeutical regimens PRL levels were suppressed in a dose-dependent manner and lactation was prevented. Terguride was highly well tolerated.", "We evaluated the efficacy of cabergoline, a new ergoline derivative, in blocking puerperal lactation in a group of women delivered by cesarean section. In a single-blind controlled trial 36 women were randomly allocated to treatment with cabergoline 1 mg in a single dose p.o. (n = 18) or bromocriptine 5 mg/day p.o. for 14 days (n = 18). Treatment was started about 50 h after delivery. Clinical assessment of breast signs and determination of serum prolactin were performed just before treatment and at 3, 5, 7 and 14 days. In the cabergoline-treated group milk secretion was inhibited in 17 women (94.4%). Maximum decrease of serum prolactin was -89.7% at 5 days, and the prolactin-lowering effect of cabergoline was still present at 14 days. In the bromocriptine group milk secretion was inhibited in 16 women (88.9%). Maximum prolactin decrease (-86.9%) was reached at 3 days. Persistent side effects were comparable in the two groups. This study demonstrates that a single oral dose of 1 mg cabergoline is as effective in suppressing puerperal lactation as a full treatment with bromocriptine, even in women delivered by cesarean section.", "The effect of prostaglandin E2 (PGE2) (3 mg/day orally for four days) on puerperal breast discomfort and prolactin secretion was investigated in eight women in a double-blind, placebo-controlled study. Scoring systems were used for daily assessment of the degree of breast discomfort. PGE2 had no effect on breast lactation, breast swelling or pain. No difference was seen between serum prolactin in the placebo- and PGE2-treated women. Contrary to a previous report, in our experimental design PGE2 had no effect on puerperal breast lactation, swelling or pain or on serum prolactin.", "nan", "nan", "nan", "Cabergoline, a new dopaminergic drug with a long-lasting prolactin inhibitory effect, was investigated at different single oral doses administered to puerperas who wished to inhibit their lactation. The study was prospective, randomized and double blind and included 140 puerperas divided into three groups of 40 women each treated with cabergoline and one group of 20 women who received a placebo. The tested doses were 1.0, 0.75 and 0.5 mg, administered orally within 24 hours after delivery. Prolactin levels were measured immediately before drug administration and then after 6 and 12 hours as well as on days 2, 3, 4, 5 and 14 after delivery. At those times the subjects were examined for milk secretion, breast engorgement, pain and possible side effects. In cases of symptoms requiring treatment, an additional 1 mg of cabergoline was administered. Complete inhibition of lactation up to day 14 was obtained in 90.2% of the women given 1 mg, 62.5% of those given 0.75 mg, 45% of those given 0.5 mg and 20% of those given a placebo. Four subjects experienced mild and transient side effects.", "nan", "The efficacy and acceptability of bromocriptine in suppressing postpartum lactation was determined in a double blind study in which bromocriptine 2.5 mg twice daily for 14 days was compared with a placebo. Forty women who decide during the antenatal period not to breast feed entered the study. The bromocriptine treated group had significantly less mammary secretion and breast engorgement than the control group and also required less analgesia. The most noticeable side effects during the trial were dizziness, headache and abdominal pain. The only statistical difference between the two groups was a higher incidence of dizziness in the bromocriptine treated group.", "Women in the puerperium who requested lactation suppression were randomly allocated to receive bromocriptine from puerperal day 1 to 14 or prostaglandin E2 from day 3 or 4 for 24 hours. Subjectively, lactation suppression was satisfactory in all cases. Objective measurements showed a trend toward more-effective early suppression with bromocriptine. After discharge from the hospital, 3 of the 21 women who received prostaglandin E2 complained of mild breast tenderness, whereas 10 of the 22 who received bromocriptine reported severe \"rebound\" breast tenderness.", "In a controlled, randomised, prospective, clinical study, the effect of prolactin suppression and clinical course of the lactation suppressors Bromocriptine and Metergoline were investigated. During 7 months 150 patients were studied. 81 of those patients, who did not nurse, were treated by Bromocriptine (primary lactation suppression: n = 62, secondary suppression: n = 19) and 69 of the patients were treated by Metergoline (primary suppression: n = 54, secondary suppression: n = 15). The drugs were administrated orally to all subjects, dosed 2 x 2.5 mg/d of Bromocriptine for 14 days and 3 x 4 mg/d of Metergoline for 10 days, starting in average after 13 hours. Puerperal suppression of prolactine were compared with randomised breast feeding subjects (n = 30). In Bromocriptine treated women the average plasma prolactin level decreased from 78.4 +/- 22 ng/ml to 17.0 +/- 3.3 ng/ml during five days of treatment. In Metergoline treated women the plasma prolactin level decreased from 129.7 +/- 15.1 ng/ml to 56.9 +/- 10.0 ng/ml during the first days of treatment. Prolactin level of breast feeding subjects decreased from 233.6 +/- 21.4 ng/ml to 185.8 +/- 23.7 ng/ml during the same period (p < 0.05). There is no statistical significancy of clinical difference of both drugs, but a statistical trend was seen. With Bromocriptine treated women were suppressed efficiently in 71 of 81 cases, 10 refused. Refusals were divided in two quality levels, level I with subjects with moderate complaints and little puerperal lactation, level II with subjects with considerable complaints including strong puerperal lactation. With Metergoline suppressed women, treatment was efficiently in 51 of 69 cases, but refusals of level I were observed in 11 cases and refusals of level II were observed in 7 cases. The results show that Bromocriptine and Metergoline are effective on suppression of lactation. Under the current drug dose of Metergoline an advantage of Bromocriptine were observed. Only further studies could investigate, whether an adaptation of drug dose would improve the clinical efficiency of Metergoline.", "Ninety-seven patients requiring suppression of lactation in the postpartum period were treated on a double-blind basis with bromocriptine and pyridoxine--49 patients received bromocriptine and 48 pyridoxine. A statistically significant difference between the two groups was noted, beginning after 1 day of treatment. Bromocriptine was superior to pyridoxine in the parameters measured. At the end of therapy the clinician, the midwife and the patient assessed the therapeutic efficacy of the trial drug. There was a statistically significant difference in favour of bromocriptine. Two patients treated with bromocriptine reported mild side-effects, but medication was not discontinued. In 1 patient receiving pyridoxine side-effects were so severe that medication was discontinued--however, the patient was already receiving the inactive tablets at this stage.", "Coagulation changes and increased risk of thromboembolic disease may occur in association with estrogen administration. The puerperium is also a high-risk period for thromboembolism, and estrogen administration at this time may increase this risk. Patients with congenital deficiency of antithrombin III have recurrent venous thromboembolic disease, suggesting that low levels of this factor may be associated with \"hypercoagulability\" states. We studied 50 postpartum patients who received chlorotrianisene (Tace) or placebo for lactation suppression in a prospective, double-blind, randomized fashion. Antithrombin III values were significantly lower on the third day post partum in the treated group compared to the placebo group (p less than 0.05). In addition, our clinical data from a total of 99 patients support the previous evidence that estrogens delay rather than prevent breast engorgement. Thus, with questionable benefit and a possible increased thromboembolic risk, it would appear prudent to discontinue the practice of estrogen administration for lactation suppression.", "nan", "In a double blind study of the prevention of puerperal lactation, the clinical efficacy of two antiprolactin drugs was compared: metergoline 4 mg tid and bromocriptine 2.5 mg bid were both given for 7 days. An additional 7 days of treatment was administered to 16 patients in whom mammary activity was still present or appeared in the following 3 days. The first 7 day period of treatment was effective in 16/20 women receiving metergoline and in 7/20 on bromocriptine (p less than 0.02); the second period of treatment was effective in all remaining patients. These data indicate that metergoline acts rapidly to arrest puerperal lactation, possibly by a mechanism different from that of bromocriptine.", "Bromocriptine and placebo were randomly allocated to 50 patients who wished to suppress lactation. Patients on bromocriptine suffered no subjective symptoms such as breast pain and engorgement, and lactation was significantly reduced compared with patients on the placebo with or without breast binding. No side-effects were noted, and rebound lactation was seen in only 3 patients. In most patients contraceptives were commenced once the drug therapy ceased on the fourteenth day.", "Intramuscular injection of a single 50-mg dose of long-acting bromocriptine microspheres was compared with a single intramuscular dose of an estradiol/testosterone ester combination in a single-blind, randomized study of 54 subjects. Bromocriptine was significantly more effective than the steroid drug in preventing milk flow, and rebound lactation was not observed in any bromocriptine-treated patients. Neither group showed deleterious side effects or significant biologic changes in coagulation parameters. There were no blood pressure or electrocardiographic alterations. Postpartum prolactin suppression was more intense after bromocriptine administration than after steroid therapy.", "Administration of high doses of vitamins B6, B1 and B12 successfully inhibited lactation without any untoward side-effects or discomfort in 96% of patients who had not yet established lactation, compared with 76,5% of control patients who received placebo.", "A double-blind trial was performed on 26 women, who had elected not to breast-feed their infants, to determine the effect of bromocriptine mesylate (2.5 mg twice daily for 14 days postpartum) on the composition of the mammary secretion during lactogenesis. Mammary secretion (less than 5.0 ml) was collected from each breast of each woman at daily intervals during the 14-day treatment period and the progressive changes in the concentration of the milk constituents, lactose, alpha-lactalbumin, serum albumin, total protein, lactoferin, IgA, IgG, sodium and potassium were determined. The degree of milk leakage and breast engorgement were also assessed. Both the subjective assessments and the changes in the concentration of the milk constituents demonstrated that lactogenesis occurred between about Day 2 and Day 5 postpartum in the placebo group (in the absence of the suckling stimulus) but was suppressed in the bromocriptine-treated group.", "In a double blind controlled study of the inhibition of lactation 13 women received 300 mg of cyclofenil and 11 women 2.5 mg of bromocriptine twice daily for 14 days. Lactation was effectively inhibited by both drugs, but with bromocriptine there was a significantly higher frequency of relapse. The plasma concentration of prolactin, which decreased rapidly with bromocriptine, returned to the pretreatment level the day after drug treatment stopped, but with cyclofenil it remained low. Plasma oestradiol followed a similar pattern. Plasma FSH increased more rapidly with bromocriptine than with cyclofenil. There was no significant difference between the treatment groups at any stage for haematology, coagulation or liver function tests. The more sustained effect of cyclofenil on prolactin secretion with a reduced frequency of relapse, and the lower oestradiol level, which might indicate a reduced risk of thromboembolism, suggest that this drug has some advantage over bromocriptine in the inhibition of postpartum lactation.", "Inhibition of lactation was studied in 38 puerperal women in a double blind trial to assess the effect of bromocriptine in comparison with diethylstilboestrol (DS). Simultaneously the influence of both compounds on blood clotting was studied, along with a control group of 20 women not receiving any medication. Bromocriptine was given in a daily dose of 5 mg for 14 days and DS in a daily dose of 20 mg for 7 days followed by a placebo for a further 7 days. The first doses were not later than 8 hours after delivery. Both compounds showed an inhibitory effect on the onset of lactation and mammary congestion. This inhibitory effect on both parameters was significantly in favour of bromocriptine during the last days of the treatment due to rebound in the DS group. The bromocriptine doses used (5 mg daily for 2 weeks) caused no objective side effects and no subjective restraint. Treatment with bromocriptine caused no untoward effect on the blood clotting, while in the DS group a slower return to normal antithrombin III could be observed. Also in this group one case of thrombophlebitis occurred. Bromocriptine can be administered to puerperal women for the suppression of lactation.", "nan", "To evaluate the efficacy of a single oral administration of the new ergot derivative Cabergoline in the prevention of post-partum lactation, we compared the effects of three different doses of the drug with those of placebo in 32 puerperal women. In a controlled, double-blind trial, the subjects were randomly allocated to four treatment groups receiving either placebo or 400, 600, or 800 micrograms Cabergoline (N = 8 in each group) within 24 hours after delivery. Treatment efficacy was assessed clinically by physical examination before (day 0) and at one, two, three, four, and 14 days after treatment. Plasma prolactin (PRL) concentrations were measured in blood samples collected before and at one, two, three, and four days after treatment. Lactation was prevented in four of the eight subjects (50%) who received 400 micrograms Cabergoline and in all subjects who received 600 or 800 micrograms Cabergoline. By contrast, only one of the eight subjects (12.5%) receiving placebo showed no signs of spontaneous lactation within the 14 days after delivery. No effects of placebo administration on plasma PRL levels were observed. Plasma PRL concentrations were significantly reduced starting from one day after Cabergoline administration, however, and the amount of inhibition of PRL secretion induced by different doses of the drug was not statistically different. These preliminary data demonstrate that Cabergoline has a dose-related effect in the prevention of postpartum lactation, and milk secretion can be prevented completely by a single oral administration of 600 or 800 micrograms of the drug.", "nan", "nan", "nan", "Bromocriptine (2 bromo-alpha-ergocryptine), stilboestrol, clomiphene citrate, testosterone propionate and a placebo were given to 75 postpartum women for the suppression of puerperal lactation. An additional 15 women who breast-fed their babies served as a control group. Blood samples were taken for the determination of serum prolactin levels by a specific homologous double antibody radioimmunoassay. Concurrently, the clinical effectiveness of the various treatments was assessed. High levels of prolactin were found at the time of delivery. Bromocriptine effectively reduced serum prolactin and prevented lactation; stilboestrol increased serum prolactin and partially suppressed lactation; clomiphene citrate and testosterone propionate both lowered serum prolactin levels and partially suppressed lactation. The placebo showed almost no effect on serum prolactin. It appeared that bromocriptine was the drug of choice in the suppression of puerperal lactation.", "Bromocriptine and placebo were randomly allocated for three weeks to 52 postpartum patients requiring lactation suppression. Bromocriptine significantly lowered plasma prolactin levels and suppressed breast milk, breast pain and engorgement quicker than placebo. No side-effects were noted and rebound lactation did not occur. Menstruation appeared to re-start sooner when Bromocriptine was given.", "Five methods for puerperal lactation inhibition were assessed in a randomized fashion. The 90 women were divided into five groups. Four of these received a pharmacologic treatment: oral stilbestrol (15 mg dd for 5 days), a diuretic compound (bendroflumethazide 15 mg dd for 5 days) by mouth, oral bromocriptine (5 mg dd for 14 days), or an intramuscular injection containing estradiol (10 mg and testosterone (200 mg) esters administered immediately after delivery. To the women in the remaining group only physical methods were applied (breast support and local infra-red waves) and they served as controls. Prolactin plasma concentrations were determined daily for five consecutive days and showed a correlation with the clinical effectiveness of the various treatment schedules. While bromocriptine reduced and stilbestrol augmented prolactin levels, both types of treatment were equally effective in preventing lactation during the observation period. Treatment with a diuretic compound or with an injection of steroids, though less effective than the first two regimens, was nevertheless significantly more efficacious than physical treatment.", "In an open pilot study with a parallel group design 30 bottle feeding women were randomly assigned in a two to one ratio to receive either the new dopamine agonist CV 205-502 or bromocriptine for lactation inhibition. Ten women who intended to breast feed served as normal controls. All treated women reached prepregnant prolactin levels within 72 h with once-daily 0.075 mg of CV 205-502 or twice-daily 2.5 mg of bromocriptine, at starting doses of 0.05 mg and 2.5 mg respectively. Fifteen of the 20 women treated with CV 205-502 reported breast symptoms, 50% occurring on days 3 and 4 of treatment. Three of the 10 women treated with bromocriptine had breast symptoms between days 2 and 28. Overall efficacy and tolerance in the two groups was very good. Side effects did not differ between the groups, with the exception of pulse rate in the standing position, which was significantly higher in the bromocriptine treated group than in either the CV 205-502 group (P = 0.02) or the breast feeding group (P less than 0.01). The coagulation tests (fibrinogen, AT III, PTT and APTT) showed no significant differences between the three groups.", "nan", "Despite advances in prevention inhibition of lactation, only administration of estrogens or these combined with androgens show variable effectiveness and are indirectly associated with high percentage for lactation rebound, thrombosis, or pulmonary embolism or both of the later during puerperium; in addition, bromocriptine, also used indirectly for inhibition of lactation, is associated with lactation, rebound in 18-40%. Cabergolin is a new ergoline with efficient and durable prolactin reducer effect with fewer adverse effects.\n Which will the smallest cabergolin dosage be to inhibit lactation?\n To demonstrate clinical effectiveness with smallest cabergolina dosage in lactation inhibition.\n We carried on a the Service Clinical test on patients hospitalization with an indication to inhibit lactation as the Hospital of Gynecology and Obstetrics, Infantil Maternal Institute of the State of Mexico (IMIEM). The study was done 80 patients to who we administered oral 0.5 mg cabergoline to 40 patients and another group of 40 whom we administered 1.0 mg of cabergoline orally at random and blinded by means of out-patient consultation. We studied correlation between dose and inhibition of lactation as well as presence of adverse effects.\n In the group of patients to whom administered 0.5 mg, we found 65% (n = 26) with lactation inhibition; adverse effects in this group appeared in 32.5% (n = 13) the second group with a dose of 1.0 mg; 95% with adverse effects in 25% P < 0.001.\n Inhibition of lactation with unique dose of 1.0 has satisfactory clinical effectiveness, this being the smaller dose to inhibit lactation at a suitable percentage.", "nan", "A randomised double blind comparative study of 230 HIV infected mothers who had a normal delivery at 37-42 weeks' gestation were divided into two groups; 116 combined pill users and 114 bromocriptine users to suppress lactation. There were 33 cases (28.5%) of combined pills users and 29 cases (25.4%) of bromocriptine users who had breast engorgement without statistical difference. All of them had mild breast engorgement without any treatment except one case (0.9%) in the bromocriptine group had severe breast engorgement with puerperal fever and needed an analgesic drug. There were no side effects of the drugs. This study showed that combined pills were beneficial to suppress lactation in HIV infected mothers to prevent postnatal mother-to-child transmission because of low risk and low cost.", "nan", "nan", "nan", "nan", "To investigate the difference in breast symptoms between breast binding and support bra wearing in nonbreastfeeding postpartum mothers.\n A systematic replication of an earlier study by Bristol using a pre-experimental posttest design.\n A private, for-profit hospital in a city in the south-central region of the United States.\n Sixty nonbreastfeeding postpartum women who gave birth to viable newborns of singleton gestations, had an uncomplicated postpartum, and did not receive hormonal lactation suppressants.\n Postpartum breast engorgement, leakage, tenderness, and use of pain relief measures as measured by the Bristol Record of Symptoms.\n Analysis of the data revealed no significant difference relative to breast engorgement between the two groups during the first 10 postpartum days. However, the breast-binder group reported a greater degree of breast tenderness, breast leakage, and use of other pain relief measures.\n Breast binding should be discontinued as a method of lactation suppression and use of support bras encouraged. Future studies need to focus on comfort for nonbreastfeeding, postpartum mothers.", "Lactation occurs when the fully developed breast is released from the inhibitory influence which oestrogen and progesterone exert upon the action of prolactin. The use of oestrogens to suppress lactation depends on a continuation of the peripheral, that is, mammary, inhibition of prolactin. Androgens are also believed to act by inhibition of the action of prolactin on the mammary gland epithelium. Bromocriptine, when compared in a double-blind trial with orally administered methyl testosterone and placebo, gave almost complete relief of breast discomfort and congestion, though a small amount of milk production was seen. Methyl testosterone, in the dosage used in this study, was quite ineffective in suppressing lactation or breast symptoms.", "A double-blind trial was performed in 60 women to establish the effectiveness of an ergot alkaloid, 2-Br-alpha-ergocryptine (ergocryptine; CB 154), in suppressing puerperal lactation and to compare it with stilboestrol and a placebo. At the doses selected ergocryptine and stilboestrol were equally effective.", "The benefits of pyridoxine in the suppression of lactation were assessed in a double blind controlled trial on 175 puerperal women. No significant differences were demonstrated between pyridoxine and the placebo whether assessed by subjective discomfort or by the persistence of lactation.", "nan", "The efficacy of jasmine flowers (Jasminum Sambac) applied to the breasts to suppress puerperal lactation was compared that of Bromocriptine. Effectiveness of both regimens was monitored by serum prolactin levels, clinical evaluation of the degree of breast engorgement and milk production and the analgesic intake. While both bromocriptine and jasmine flowers brought about a significant reduction in serum prolactin, the decrease was significantly greater with bromocriptine. However, clinical parameters such as breast engorgement, milk production and analgesic intake showed the 2 modes of therapy to be equally effective. The failure rates of the 2 regimens to suppress lactation were similar; however, rebound lactation occurred in a small proportion of women treated with bromocriptine. Jasmine flowers seem to be an effective and inexpensive method of suppressing puerperal lactation and can be used as an alternative in situations where cost and nonavailability restrict the use of bromocriptine.", "nan", "nan", "2-bromo-alpha-ergocryptine (bromocriptine) in a dosage of 2-5 mg twice daily caused a rapid fall in plasma prolactin. It was more effective than either a single dose of 4 mg quinoestrol or a placebo in suppressing puerperal lactation, as judged by milk flow and the relief of breast pain and congestion. Patients who received quinoestrol were more comfortable than those who received placebo.", "nan", "nan", "nan", "Dopaminergic agonists, such as Parlodel((R)), are now widely used to inhibit lactation. However, some countries, such as the United States, no longer use these drugs in this indication because of their sometimes serious adverse effects. In this context, the authors tested a homeopathic treatment designed for parturients unable or not wanting to breastfeed. The APIS MELLIFICA 9 CH and BRYONIA 9 CH combination was chosen for its anti-inflammatory and analgesic effects. 71 patients were included in this double-blind placebo-controlled study. All received basic treatment comprising naproxen and fluid restriction. A significant improvement of lactation pain (main criterion of the study) was observed in parturients treated with homeopathy (p<0.02 on D2 and p<0.01 on D4). A similar effect (p<0.05 on D4) was observed for breast tension and spontaneous milk flow. No significant difference was observed for the other criteria of the study. The homeopathic combination studied was therefore effective on the pain of lactation and should be integrated into the therapeutic armamentarium." ]

[ "8158817", "7648636", "11798728", "12934183", "1335650", "1320740" ]

[ "Protection against hepatitis A by an inactivated vaccine.", "[A prospective epidemiological investigation on the effect of China-mode attenuated live vaccine against hepatitis A in the population of Liu Zhou].", "[Further survey on efficacy of attenuated live hepatitis A vaccines].", "Efficacy of virosome hepatitis A vaccine in young children in Nicaragua: randomized placebo-controlled trial.", "Placebo-controlled efficacy study of hepatitis A vaccine in Valdivia, Chile.", "A controlled trial of a formalin-inactivated hepatitis A vaccine in healthy children." ]

[ "To evaluate the safety and efficacy of a new inactivated hepatitis A vaccine.\n Double-blind randomized controlled trial stratified by community.\n Community-based in Thailand.\n A total of 40,119 children, aged 1 to 16 years, attending 148 primary schools: 38,157 (95%) entered surveillance a mean of 138 days after receiving vaccine dose 1; 33,586 (84%) completed the controlled trial of 532 days; and 31,075 (81%) received crossover vaccine and remained under surveillance until day 844.\n Participants received hepatitis A vaccine or control hepatitis B vaccine starting January 7, 1991 (doses in months 0, 1, and 12), and crossed over to the alternate vaccine 18 months later.\n Cases of hepatitis A (symptoms, alanine aminotransferase levels of 45 U/L or higher, and IgM to hepatitis A virus) were identified by evaluating school absences of 2 or more days.\n There were no serious adverse reactions despite administration of more than 109,000 doses of hepatitis A vaccine. Among initially seronegative recipients of two doses of hepatitis A vaccine, the proportion with 20 mIU/mL or more of antibody to hepatitis A virus before and 5 months after a 1-year booster was 94% and 99%, respectively. Of 6976 episodes of illness during the controlled trial, there were 40 cases of hepatitis A; 38 were in the control group. Of the 40 cases, six, all in controls, occurred after the 1-year booster dose. Following two doses of hepatitis A vaccine (days 138 through 386), protective efficacy was 94% (95% confidence interval, 79% to 99%); cumulative efficacy including the postbooster period (days 138 to 532) was 95% (95% confidence interval, 82% to 99%). The two hepatitis A vaccine recipients who had symptomatic infections (257 and 267 days after dose 1) appeared to have been partially protected since their illnesses were brief and associated with only slight increases in alanine aminotransferase.\n Inactivated hepatitis A vaccine is safe; when administered in two doses, it protects against hepatitis A for at least 1 year.", "An 24-month prospective epidemiological investigation on the results of China-mode Hepatitis A attenuated live vaccine against hepatitis A by random group sampling was carried out. The incidence of case group was 15.91/10(5) (5/31421), the incidence of control group was 95.92/10(5) (30/ 31277) which showed a significant difference. In case group 2081 persons who missed vaccination, there was one person developed hepatitis A, making the incidence 48.05/10(5). In control group 760 persons were vaccinated by mistake and there was no case developed in this sub-population. There were 644 cases of hepatitis A in the external control group, the incidence was 90.14/10(5). Data showed that there was no significant difference among external control group, control group and persons from case group who missed vaccination. Comparing the data from case group and from the above 3 groups, the protective rates were 82.35%, 83.41% and 66.89%. respectively. When conparing the data from persons who had been mistakenly vaccinated in control group, there was no significant difference being noticed.", "To further survey the protective efficacy of the standard attenuated live hepatitis A vaccines (H(2) strain).\n Randomized and controlled trials were performed in Fucheng county, Hebei province. A total of 12 036 children were assigned into vaccine group (5 551) and control group (6 485) by cluster sampling. The morbidity of hepatitis A was observed and the blood was collected once hepatitis A showed epidemic to detect anti-HAV IgG and IgM.\n During the period of the first 7 months after vaccination, hepatitis A was sporadic, the morbidity of hepatitis A was 0.55/100 000, and only 1 case occurred in the control group and no case in the vaccine group. From January to August 1998, hepatitis A showed epidemic in a township of this county. The morbidities were 0.37% and 6.69% for vaccine group and control group, respectively. The protective efficacy of the vaccine was 94.47%. The ratios of clinical cases to subclinical infections were 1 to 11 and 1 to 1 for vaccine and control groups, respectively (P < 0.05).\n The H(2) strain vaccine has a very good protective efficacy, and obviously decreases the attack rate, new infection rate and clinical cases by HAV infection.", "Immunization of young children could control hepatitis A virus (HAV) infection, but the efficacy of hepatitis A vaccines in early childhood is unknown. In a randomized, double-blind trial of a single dose of a virosome-formulated, aluminum-free inactivated HAV vaccine in Nicaragua, 274 children (age range, 1.5-6 years) received vaccine or placebo injections; 239 children seronegative for hepatitis A were included in the primary efficacy analysis. HAV infection documented by immunoglobulin M antibodies was the primary end point. Among children seronegative for hepatitis A, infection was diagnosed in 4 children in the vaccine group and 22 children in the placebo group (protective efficacy, 84.6%; 95% confidence interval, 54.7%-96.1%). All infections in children in the vaccine group occurred within 6 weeks. After 6 weeks, protective efficacy was 100% (79.8%-100%). In children in the placebo group, the incidence of HAV infection was 17.6 and that of icteric illness was 1.6 cases/100 person-years. Adverse effects were rare in both children in the vaccine group and children in the placebo group. A single dose of a hepatitis A virosome vaccine is safe and protects young children against HAV infection.", "A placebo-controlled, double-blind study on the efficacy of a hepatitis A vaccine (SmithKline Beecham Biologicals) was started in a region of Chile in September 1990, using hepatitis B vaccine as control. A total of 260 healthy children, 6-15 years of age, negative for antibody to hepatitis A virus (anti-HAV), antibody to HAV immunoglobulin M (IgM), hepatitis B surface antigen, and antibody to hepatitis B surface and core antigens by ELISA tests within 7 days before vaccination, were randomly assigned to two study groups: 128 children received the vaccine with a yellow label (group 1), and 132 children the vaccine with an orange label (group 2) at months 0, 1 and 6. Blood for serology and transaminase determination was drawn at months 1, 2, 6, 7 and 12. Both vaccines were tolerated equally well and no serious side effects were seen. In group 1 (presumed hepatitis A vaccine group), anti-HAV was detected (20% inhibition was used as the cut-off level) in 122 of 128 children (95.5%) tested at month 1, in 126 of 127 (99.2%) at month 2, in 126 of 127 (99.2%) at month 6 and in 126 of 126 (100%) at month 7. One anti-HAV seroconversion seen at month 1 was associated with presence of anti-HAV IgM and therefore probably represents HAV infection. Geometric mean anti-HAV concentration of the other children was 128, 342, 214 and 2301 mIU/ml at months 1, 2, 6 and 7, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)", "Although inactivated hepatitis A vaccine is known to be well tolerated and immunogenic in healthy children and adults, its efficacy has yet to be established.\n To evaluate the efficacy of the hepatitis A vaccine in protecting against clinically apparent disease, we conducted a double-blind, placebo-controlled trial in an Hasidic Jewish community in upstate New York that has had recurrent outbreaks of hepatitis A. At the beginning of a summer outbreak, 1037 healthy seronegative children 2 to 16 years of age were randomly assigned to receive one intramuscular injection of a highly purified, formalin-inactivated hepatitis A vaccine or placebo. A case was defined by the presence of typical signs and symptoms, a diagnostic increase in IgM antibody to hepatitis A, and a serum concentration of alanine aminotransferase at least twice the upper limit of normal. Cases occurring greater than or equal to 50 days after the injection were included in the evaluation of efficacy. The children were followed for a mean of 103 days.\n A total of 519 children received vaccine, and 518 received placebo. The vaccine was well tolerated, with no serious adverse reactions. From day 50 after the injection, 25 cases of clinically apparent hepatitis A occurred in the placebo group and none in the vaccine group (P less than 0.001), confirming that the vaccine had 100 percent protective efficacy. Before day 21, seven cases occurred in the vaccine group and three cases in the placebo group. After that time, there were no cases among vaccine recipients and 34 cases among placebo recipients.\n The inactivated purified hepatitis A vaccine that we tested is well tolerated, and a single dose is highly protective against clinically apparent hepatitis A." ]

[ "8382899", "2850326", "10492316", "2650578", "1847026" ]

[ "Clinical assessment of low molecular weight heparin effects in peripheral vascular disease.", "A new low molecular weight heparin in the treatment of peripheral arterial disease.", "Randomized trial of the effects of low-dose calcium-heparin in patients with peripheral arterial disease and claudication. Italian CAP Study Group.", "Acenocoumarol and pentoxifylline in intermittent claudication. A controlled clinical study. The APIC Study Group.", "Efficacy of low-molecular-weight heparin in the management of intermittent claudication." ]

[ "This study was carried out, using the double-blind method vs placebo, on 36 patients suffering from stage II peripheral vascular disease (PVD) according to Leriche, to check the clinical and hemorrheologic effects of the administration of a new low molecular weight heparin (LMWH). After a one-month washout period, the patients were randomly assigned either to the group treated with the LMWH (15,000 aXaU/day sc) or to the group treated with indistinguishable placebo. At the start of the study and after three and six months of treatment, clinical, instrumental, and laboratory tests were performed to assess local and systemic efficacy and tolerance. The LMWH under study caused a statistically significant increase in claudication time, with a parallel increase in the absolute claudication distance and in the interval free of pain. The drug also led to a significant increase in activated partial thromboplastin time, the values of which, however, remained within the normal limits, and to a marked reduction in blood viscosity. No significant variation was observed in the tolerability parameters in the two treatment groups, and no local or systemic adverse reactions occurred.", "A double blind study was conducted on patients afflicted with obstructive arteriopathy of the lower limbs in order to verify the efficacy and tolerability, in long term treatment, of a new low molecular weight heparin (Alfa LMW1). Of the 55 patients studied, 28 were treated with Alfa LMW1 given subcutaneously in doses of 8,000 I.U. AXa daily for 6 months; the remainder 27 were treated with Placebo. Efficacy of Alfa LMW1 was evaluated by monitoring the lower limb segmental pressures and some pressure ratios (thigh/arm, ankle/arm). Moreover, by means of the treadmill test, also checked were: time of claudication; ankle/arm pressure ratio before and after exercise and time required to return to initial pressure. By means of the strain gauge plethysmography, basal flow and peak flow after ischemia were also evaluated. The results obtained indicated a significant difference in efficacy between the two therapies, most notable after the third month. While in the Alfa LMW1 group a significant (p less than 0.01) and progressive improvement by the third month of treatment was seen, in the Placebo group a slight improvement was registered only at the end of the study and this was significantly inferior with respect to the comparison group.", "We performed a long-term, multicenter, randomized, double-blind trial to evaluate the efficacy and tolerability of low-dose, subcutaneous calcium-heparin (12,500 IU/day) in comparison with placebo in patients with stable peripheral arterial disease of the lower extremities.\n At the end of a 2-week washout period, during which aspirin placebo was given, 201 patients were randomly assigned to receive either subcutaneous calcium-heparin or placebo for two 3-month treatment periods, each of which was followed by a 6-month period of observation. All of the patients were given low-dose aspirin (50 mg/day) throughout the 18-month study. The main efficacy variables were pain-free and maximum walking time (by standard treadmill test). Patients answered a questionnaire about pain and the limitation of daily activities. Results were analyzed by intention-to-treat.\n At the end of the study, the estimated increase in pain-free walking time was 39% in the heparin group and 23% in the placebo group (P = 0.09). The estimated increase in maximum walking time was 40% in the heparin group and 16% in the placebo group (P = 0.05). Patients treated with heparin also reported that they had to stop walking because of leg pain, or had daily activities limited by leg pain, less frequently than the placebo group (P <0.01).\n Treatment with low-dose subcutaneous calcium-heparin is safe and effective in improving walking performance and reducing physical disability in patients with stable peripheral arterial disease and claudication.", "The efficacy and safety of pentoxifylline (400 mg tid orally) and acenocoumarol, administered singly or in combination, in the treatment of intermittent claudication associated with chronic occlusive arterial disease were evaluated in a multi-center, randomized, factorial, blind clinical trial involving 146 patients. The response to treatment was assessed by measuring pain-free walking time on the treadmill and by Doppler ankle/arm systolic pressure ratio at rest and after treadmill. Both pentoxifylline and acenocoumarol were significantly more effective than placebo in increasing the proportion of patients who improved their performance on the treadmill after one year of treatment. Benefit from active treatment was also apparent from the results of Doppler examinations performed after physical exercise. No significant differences were observed in comparing the effect of one active drug versus the other or versus the combined treatment. Five major hemorrhagic complications were registered in anticoagulated patients, two fatal cerebral hemorrhages and one gastrointestinal bleeding occurring in the group treated with both active drugs. The investigators conclude that (1) pentoxifylline is effective and safe in the treatment of patients with intermittent claudication (2) the benefits of oral anticoagulant therapy are outweighed by the risk of serious bleeding, and (3) the risk of bleeding is probably increased by the combined treatment with pentoxifylline.", "Treating chronic arterial occlusive disease with heparin is controversial because of the risks associated with long-term anticoagulant therapy. Low molecular weight (LMW) heparin (mw about 5000 Dalton), which selectively inhibits the Xa factor with minimal risk of hemorrhage, seems to offer new possibilities in the prevention and treatment of both venous and acute arterial thromboembolism. Therefore, 44 patients with intermittent claudication were recruited to a randomized, double-blind, controlled study. Twenty-two were treated for six months with a single daily subcutaneous dose (15,000 UaXa) of LMW heparin and 22 with placebo administered in the same way over the same period of time. After six months, LMW heparin treatment not only improved walking capacity (by lengthening the pain-free walking time by 25%) but also significantly modified the hemorrheologic pattern (by reducing fibrinogen concentrations and whole blood viscosity at low shear rates). LMW heparin also exerted an antithrombotic and profibrinolytic effect by significantly increasing both the anti-Xa factor and plasminogen activity without markedly modifying activated partial thromboplastin time (+20%). No LMW heparin-treated patient hemorrhaged or reported other noteworthy side effects. These results suggest LMW heparin might be a useful drug in the long-term treatment of chronic arterial occlusive disease of the limbs." ]

[ "20963843" ]

[ "Randomized trial of biofilm testing to select antibiotics for cystic fibrosis airway infection." ]

[ "In cystic fibrosis (CF), conventional antibiotic susceptibility results correlate poorly with clinical outcomes. We hypothesized that biofilm testing would more accurately reflect the susceptibilities of bacteria infecting CF airways.\n A multicenter randomized pilot trial was conducted to assess the efficacy and safety of using biofilm susceptibility testing of Pseudomonas aeruginosa sputum isolates to guide antibiotic regimens for chronic airway infections in clinically stable adolescent and adult CF patients. Thirty-nine participants were randomized to biofilm or conventional treatment groups; 14-day courses of two antibiotics were selected according to an activity-based algorithm using the corresponding susceptibility results.\n Of the agents tested, meropenem was most active against biofilm-grown bacteria, and was included in regimens for about half of each study group. For 19 of 39 randomized participants, randomization to the other study group would not have changed the antibiotic classes of the assigned regimen. Study groups were comparable at baseline, and had similar mean decreases in bacterial density, measured in log(10) colony forming units per gram of sputum (biofilm, -2.94 [SD 2.83] vs. conventional, -3.27 [SD 3.09]), and mean increases in forced expiratory volume in 1 sec, measured in liters (0.18 [SD 0.20] vs. 0.12 [SD 0.22]).\n In this pilot study, antibiotic regimens based on biofilm testing did not differ significantly from regimens based on conventional testing in terms of microbiological and clinical responses. The predictive value of biofilm testing may nonetheless warrant evaluation in an adequately powered clinical trial in younger CF patients or those experiencing acute pulmonary exacerbation.\n Copyright © 2011 Wiley-Liss, Inc." ]

[ "10500075", "1447500" ]

[ "Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double-blind trial.", "A controlled trial of prednisolone treatment in primary biliary cirrhosis. Three-year results." ]

[ "Ursodeoxycholic acid (UDCA) is used for treatment of primary biliary cirrhosis. Previous studies showed that, compared with UDCA monotherapy, bile salts plus prednisolone had no further effect on laboratory data but improved liver histology. Thirty percent of these patients had prednisolone-related side effects. Budesonide is a glucocorticoid with a high receptor affinity and a high first-pass metabolism. In this study we investigated whether budesonide and UDCA are superior to UDCA monotherapy.\n A 2-year prospective, controlled double-blind trial was performed. Twenty patients (mainly with early-stage disease) were treated with UDCA at a dose of 10-15 mg/kg daily in addition to 3 mg budesonide 3 times daily (group A), and 19 patients (1 dropped out for personal reasons) were treated with UDCA plus placebo (group B). Liver biopsy specimens were taken before, after 12 months, and at the end of study. Glucose tolerance tests, serum cortisol levels, and adrenocorticotropin-stimulated cortisol secretion were assessed at regular intervals. Bone mass density was measured by dual-energy photon absorptiometry.\n Compared with pretreatment values, liver enzyme and immunoglobulin M and G levels decreased significantly in both groups. Improvement in group A was significantly more pronounced (P < 0.05) than in group B. Titers of antimitochondrial antibodies did not change. In group A, the point score of liver histology improved by 30.3%; in group B, it deteriorated by 3.5% (P < 0.001). Changes in bone mineral density after 2 years were -1.747% in group A and -0.983% in group B (P = 0.43). Budesonide had little influence on the hypothalamic-pituitary-adrenal axis. One patient in group A had budesonide-related side effects; in 3 patients in group B, complications of liver disease developed.\n Combination therapy with UDCA and budesonide is superior to UDCA and placebo.", "The results of a 3-year, placebo-controlled trial of prednisolone treatment in primary biliary cirrhosis (PBC) are presented. The active (n = 19) and placebo (n = 17) arms were initially well matched for age, menopausal status and disease severity. At 3 years hepatic symptoms were relatively improved in the prednisolone group. Hepatic mortality was 3/19 (prednisolone), 5/17 (placebo) (p = n.s.). For all liver blood tests the trend favoured prednisolone treatment, though the differences were only significant for alkaline phosphatase and protein. All immunoglobulins fell significantly. Quantitative ELISA determination of antimitochondrial antibody showed a significant fall in the prednisolone group compared with placebo (p less than 0.001 at 1 year, p less than 0.05 at 3 years). Deterioration in histology (appearance of cirrhosis) was more common in the placebo group. Overall hepatic function (hepatic mortality, doubling in bilirubin, 6 milligrams fall in albumin, de novo appearance of cirrhosis or symptoms of portal hypertension) was significantly worse in the placebo group (p less than 0.01). After 3 years no significant differences could be detected in bone mineral content (single photon absorptiometry of radius and femur) between the two groups or in comparison with other PBC patients. Thus, after 3 years, prednisolone treatment was associated with a better overall hepatic outcome and little evidence of increased bone loss." ]

[ "8864674", "9054280", "8114833", "9855069", "12045777" ]

[ "Transdermal nicotine compared with oral prednisolone therapy for active ulcerative colitis.", "Transdermal nicotine for mildly to moderately active ulcerative colitis. A randomized, double-blind, placebo-controlled trial.", "Transdermal nicotine for active ulcerative colitis.", "Outcome of ulcerative colitis after treatment with transdermal nicotine.", "Distal ulcerative colitis refractory to rectal mesalamine: role of transdermal nicotine versus oral mesalamine." ]

[ "Ulcerative colitis is largely a disease of non-smokers. Previous controlled trials have shown benefit with transdermal nicotine when given with 5-aminosalicylic acid in active disease but not when given alone as maintenance therapy.\n To examine nicotine alone compared with prednisolone in active disease.\n Sixty-one patients with active ulcerative colitis were treated with either transdermal nicotine patches or 15 mg prednisolone for 6 weeks in a randomized, double-blind study. Incremental doses of nicotine were given for the first 9 days; patients tolerated between 15 and 25 mg daily. Most patients were taking mesalazine at entry which was discontinued at day 10; a few were taking topical steroids which were discontinued at the onset. Clinical, sigmoidoscopic and histological assessments were made at baseline and 6 weeks, or at premature withdrawal. Symptoms were recorded on a diary card, and the clinician made a global clinical assessment. Side effects and serum nicotine and cotinine concentrations were monitored throughout the study.\n Forty-three patients completed the 6-week trial; of these, 6 of 19 in the nicotine group achieved full sigmoidoscopic remission compared with 14 of 24 with prednisolone (P = 0.08). In those who completed the 6-week study, there was significant improvement within both the nicotine and prednisolone group for the St Mark's score (P < 0.05 and P < 0.01, respectively), Global Clinical Grade (P < 0.01 for both), blood in the stool (P < 0.05 and P < 0.01), abdominal pain (P < 0.05 and P < 0.01) and sigmoidoscopic score (P < 0.01 and P < 0.001); differences between groups tend to favour prednisolone, but none reach statistical significance. However, on intention-to-treat analyses there is little clear evidence of improvement in either group apart from sigmoidoscopic score in which prednisolone was associated with a significantly greater improvement than nicotine (P < or = 0.05). The nicotine group had more withdrawals than the prednisolone group, 11 versus 7, respectively (P = 0.23), both for deterioration (6 vs. 5) and side effects (5 vs. 2, P = 0.15). Side effects were more frequently reported in the nicotine group (average 1.47 episodes per person) than the prednisolone group (average 0.61; P = 0.03), the most common of which were nausea, light-headedness and tremor.\n In those who managed to complete the 6-week study, nicotine alone appeared to be of only very modest benefit in acute colitis and was not as effective as 15 mg of prednisolone daily.", "Ulcerative colitis is predominantly a disease of nonsmokers. Transdermal nicotine may help control clinical manifestations of this condition.\n To determine the efficacy of transdermal nicotine for controlling clinical disease activity in active ulcerative colitis.\n Randomized, double-blind, placebo-controlled, single-center clinical trial.\n Multispecialty group serving as an academic tertiary referral center.\n 64 nonsmoking patients with mildly to moderately active ulcerative colitis despite the use of medication.\n Patients were stratified on the basis of smoking history, extent of disease, and concomitant medical therapy. After stratification, patients were randomly assigned to daily treatment with transdermal nicotine (n = 31) at the highest tolerated dose (11 mg for 1 week and then < or = 22 mg for 3 weeks) or placebo (n = 33).\n Clinical features were assessed at baseline and 4 weeks by endoscopy, physician assessment, and a patient diary of daily symptoms. Serum concentrations of nicotine were determined by using gas chromatography and mass spectrometry, and plasma concentrations of cotinine were measured by using high-performance liquid chromatography.\n At 4 weeks, 12 of 31 patients (39%) who received nicotine showed clinical improvement compared with 3 of 33 patients (9%) who received placebo (P = 0.007). Four patients receiving nicotine discontinued therapy because of side effects (contact dermatitis [n = 2], nausea [n = 1], and acute pancreatitis [n = 1]). At week 4, the nicotine group had a mean (+/-SD) trough serum nicotine concentration of 11.3 +/- 8.4 ng/mL and a mean trough plasma cotinine concentration of 192 +/- 95 ng/mL.\n Transdermal nicotine administered at the highest tolerated dosage (< or = 22 mg/d) for 4 weeks is efficacious for controlling clinical manifestations of mildly to moderately active ulcerative colitis.", "Ulcerative colitis is largely a disease of nonsmokers. Because anecdotal reports suggest that smoking and nicotine may improve the symptoms of the disease, we examined the effect of nicotine as a supplemental treatment for ulcerative colitis.\n We treated 72 patients with active ulcerative colitis with either transdermal nicotine patches or placebo patches for six weeks in a randomized, double-blind study. Incremental doses of nicotine were given; most patients tolerated doses of 15 to 25 mg per 24 hours. All the patients had been taking mesalamine, and 12 were receiving low doses of glucocorticoids; these medications were continued without change during the study. Clinical, sigmoidoscopic, and histologic assessments were made at base line and at the end of the study; symptoms were recorded daily on a diary card, and the clinician made a global assessment. Side effects and plasma nicotine and cotinine concentrations were monitored throughout the study.\n Seventeen of the 35 patients in the nicotine group had complete remissions, as compared with 9 of the 37 patients in the placebo group (P = 0.03). The patients in the nicotine group had greater improvement in the global clinical grade of colitis (P < 0.001) and the histologic grade (P = 0.03), lower stool frequency (a difference of 1.6 stools daily; P = 0.008), less abdominal pain (P = 0.05), and less fecal urgency (P = 0.009). More patients in the nicotine group had side effects (23, vs. 11 in the placebo group; P = 0.002), the most common of which were nausea, lightheadedness, headache, and sleep disturbance. Withdrawals due to ineffective therapy were more common in the placebo group (3 vs. 8, P = 0.12).\n The addition of transdermal nicotine to conventional maintenance therapy improves symptoms in patients with ulcerative colitis.", "Transdermal nicotine appears to be of benefit in the short-term treatment of patients with ulcerative colitis. The aim of this study was to determine its long-term effects.\n A randomized, comparative study.\n Patients with mild to moderate clinical relapses of left-sided ulcerative colitis during maintenance treatment with mesalamine 1 g b.i.d. were allocated to an additional treatment with either transdermal nicotine or prednisone for 5 weeks. The first consecutive 15 patients per group, with clinical and endoscopic signs of remission, were followed up for 6 months, while continuing mesalamine maintenance treatment.\n Relapses of active colitis were observed in 20% of patients formerly treated with nicotine and in 60% of patients in the prednisone group (P = 0.027). Relapses occurred earlier in the latter group.\n Our results confirm that nicotine is useful in cases of ulcerative colitis with mild or moderate activity and suggest that remissions induced by nicotine may last longer than those obtained with oral corticosteroids.", "Distal ulcerative colitis usually responds to treatment with rectal mesalamine, but the management of refractory cases is poorly defined.\n To evaluate the possible therapeutic benefit of transdermal nicotine versus oral mesalamine.\n Thirty patients with left-sided ulcerative colitis unresponsive to treatment with a mesalamine 4 g enema at bedtime were randomly allocated to additional therapy with either transdermal nicotine 15 mg daily or oral mesalamine 800 mg tid for four weeks. Clinical remission was evaluated by Rachmilewitz's activity index and confirmed by sigmoidoscopy.\n Remission was observed in 12 of 15 patients receiving additional treatment with nicotine and in five of 15 patients receiving additional treatment with oral mesalamine (P=0.027).\n The addition of transdermal nicotine to treatment with mesalamine enemas is significantly superior to combined therapy with oral and rectal mesalamine in patients with distal ulcerative colitis refractory to rectal mesalamine alone." ]

[ "14709941", "9690979", "9517912", "9421348", "2569214", "15200743", "7846195", "1821700", "11354236", "12204314" ]

[ "Associations between baseline plasma MHPG (3-methoxy-4-hydroxyphenylglycol) levels and clinical responses with respect to milnacipran versus paroxetine treatment.", "A double-blind comparison of the efficacy and safety of milnacipran and fluoxetine in depressed inpatients.", "Double-blind study of the efficacy and safety of milnacipran and imipramine in elderly patients with major depressive episode.", "Long-term efficacy and safety of milnacipran compared to clomipramine in patients with major depression.", "Controlled comparison of two doses of milnacipran (F 2207) and amitriptyline in major depressive inpatients.", "A comparative study of milnacipran and imipramine in the treatment of major depressive disorder.", "Controlled comparison of milnacipran and fluoxetine in major depression.", "Interest of a loading dose of milnacipran in endogenous depressive inpatients. Comparison with the standard regimen and with fluvoxamine.", "Antidepressant efficacy and tolerability of milnacipran, a dual serotonin and noradrenaline reuptake inhibitor: a comparison with fluvoxamine.", "A randomised, double-blind comparison of milnacipran and imipramine in the treatment of depression." ]

[ "The purpose of this study was to investigate the effects of milnacipran and paroxetine on plasma levels of catecholamine metabolites, and we attempted to elucidate the differences between the mechanisms of these drugs in catecholaminergic neurons. In depressed patients, we investigated the relationships among pretreatment levels of catecholamine metabolites, the changes in plasma catecholamine metabolite levels before and after administration of milnacipran or paroxetine, and clinical response to these drugs. Responders to milnacipran showed lower pretreatment levels of plasma 3-methoxy-4-hydroxyphenylglycol (pMHPG) than did nonresponders to milnacipran; there was also a positive correlation between changes in pMHPG levels and percent improvement of the score on the 17-item Hamilton Rating Scale for Depression (HRSD). On the other hand, responders to paroxetine showed higher pretreatment levels of pMHPG than did nonresponders to paroxetine, and a negative correlation was observed between changes in pMHPG levels and percent improvement of the HRSD score. However, a significant difference was not observed in the pretreatment plasma level of homovanillic acid between responders and nonresponders to treatment with milnacipran or paroxetine. These results suggest that there is an association between baseline pMHPG levels and clinical responses with respect to milnacipran versus paroxetine treatment.", "This double-blind, randomised, multicentre study compared the antidepressant efficacy and safety of two doses of milnacipran (100 mg/day and 200 mg/day) and fluoxetine (20 mg/day) in 289 inpatients with endogenous depression. After a placebo washout period of 4-7 days, assessments were performed weekly during the first 4 weeks, and then after 6, 8 and 12 weeks, using the 17-item Hamilton Depression Rating Scale (HDRS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI). HDRS total score was reduced by a mean of 14.8 in the milnacipran 100 mg/day group, 12.9 in the milnacipran 200 mg/day group and 12.1 in the fluoxetine 20 mg/day group. MADRS total score decreased by 17.4, 15.8 and 14.6, respectively. No significant difference could be shown between the three treatment groups for either the HDRS or MADRS total scores. However, the time-by-time change showed a trend in favour of milnacipran 100 mg/day, which was found significantly superior to fluoxetine at day 28 for several converging parameters (MADRS, CGI-3). Overall, efficacy ratings for all parameters were highest for milnacipran 100 mg/day, followed by milnacipran 200 mg/day and fluoxetine 20 mg/day. Side-effect profiles were not significantly different between groups except for a significantly greater frequency of dose-related increase in heart rate > or = 100 bpm in milnacipran recipients and a significantly greater weight loss in fluoxetine recipients.", "The novel antidepressant agent milnacipran is a dual and equipotent serotonin and noradrenaline reuptake inhibitor. The aim of this double-blind study was to compare the efficacy and safety of milnacipran (50 mg twice daily) with that of imipramine (50 mg twice daily) in elderly patients with major depressive episode. A total of 219 patients were randomly assigned to 8 weeks of double-blind treatment with either milnacipran or imipramine; 72 patients withdrew from the study. At the end of treatment no significant differences were found between milnacipran and imipramine in antidepressant efficacy. A significantly greater number of side-effects, particularly anticholinergic effects, was observed in the imipramine group. Milnacipran may be preferable to imipramine in elderly depressed patients, as it provides the same antidepressant activity as imipramine with a lower incidence of side-effects, and does not impair cognitive ability.", "Milnacipran is a new antidepressive drug, a combined noradrenaline/serotonin (NA/5-HT) reuptake inhibitor, which has been suggested to be as effective as and better tolerated than tricyclic antidepressants. Since long-term studies are lacking, we compared the efficacy, safety and tolerability of milnacipran and clomipramine in a double-blind, randomized, parallel-group study setting during 26 weeks of treatment in patients with major depression. A total of 107 patients were treated with either milnacipran (n=52) or clomipramine (n=55). Due to active treatment of duration less than 12 days in four patients and protocol deviation in one patient, in total 47 milnacipran-treated patients were eligible for efficacy analysis. Nine patients in the clomipramine group continued on active treatment for less than 12 days. Thus 46 clomipramine-treated patients were finally included in the efficacy analysis. After 1 week of dose escalation, there was a fixed dosage regimen of either milnacipran (200 mg daily) or clomipramine (150 mg daily) during weeks 2 to 10, followed by flexible dosing of milnacipran (100, 150 or 200 mg daily) or clomipramine (75, 100 or 150 mg daily) during weeks 11 to 26. A total of 53 patients (49%) completed the 26-week study period; 21% (11/52) of the patients in the milnacipran group and 38% (21/55) of the patients in the clomipramine group discontinued their medication prematurely due to adverse events, whereas 19% (10/52) of those on milnacipran and 7% (4/55) of those on clomipramine treatment withdrew due to either lack of efficacy or clinical deterioration. The mean change (+/-SD) in the Hamilton Depression Rating Scale (HAMD) score between the baseline and the last rating ranged from 23.7+/-3.1 to 12.0+/-9.5 in the milnacipran-treated patients and from 23.1+/-3.5 to 8.0+/-8.5 in the clomipramine-treated patients, revealing a significant difference in favour of clomipramine. In total 58% of the milnacipran-treated patients vs. 72% of the clomipramine-treated patients showed a > or = 50% reduction in their baseline HAMD scores and 45% vs. 63% had an HAMD score of < or = 7 at the last rating, respectively. Moreover, the time to the onset of the antidepressant action (defined as > or = 50% reduction of the baseline HAMD score) showed a significant difference in favour of clomipramine. In addition, clomipramine was significantly more efficacious in patients with a baseline HAMD score of > or = 24 as evidenced by the analysis of the HAMD score at week 6 and at the last rating. The Montgomery Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI) scale did not show significant differences between the treatment groups. The safety analysis did not reveal any differences of clinical significance in cardiovascular variables between the study drugs. Dry mouth was significantly less frequently reported by the milnacipran-treated patients during the early and later phases (weeks 6 to 26) of the study, while insomnia was more common in the milnacipran group during weeks 1 to 6. In conclusion, milnacipran appeared to be less effective than clomipramine in the long-term treatment of depression. The side-effects of the drugs differed to a certain extent, and milnacipran tended to be somewhat better tolerated than clomipramine.", "A multicenter study compared the antidepressant efficacy and the tolerance of two doses of milnacipran (50 mg and 100 mg/day) and amitriptyline (150 mg/day) in three parallel groups of 45 major depressive inpatients defined by Research Diagnostic Criteria. After a wash-out period of 4-7 days on placebo with lorazepam and/or nitrazepam if necessary, patients were randomly assigned to a daily dose of milnacipran 50 mg, milnacipran 100 mg or amitriptyline 150 mg reached on the 5th day and then stable over a 4-week period, with weekly assessments by means of the Montgomery and Asberg depression scale, the Hamilton depression scale, the Clinical Global Impressions (CGI) and the Target Emergent Signs and Symptoms. Results showed significant superiority of both milnacipran 100 mg/day and amitriptyline over milnacipran 50 mg/day at the end of the treatment period. However, amitriptyline induced a nonsignificant trend toward more rapid improvement after 2 weeks of treatment, mainly based on items related to insomnia, supporting more sedative properties of amitriptyline as compared to milnacipran. Anticholinergic side-effects were significantly lower with milnacipran than with amitriptyline, explaining why milnacipran 100 mg exhibited at the end of the treatment period, a nonsignificantly better efficacy index on the CGI. Moreover, in contrast to milnacipran, amitriptyline was responsible for a significant decrease in blood pressure and a significant weight gain.", "The antidepressant efficacy and safety of milnacipran, a dual action antidepressant drug which inhibits the reuptake of serotonin and noradrenaline, was compared with that of the tricyclic antidepressant, imipramine, in a multi-centre, double-blind, randomised, parallel group, comparative trial in 5 hospital centres in Spain. One hundred patients hospitalised with a diagnosis of major depressive disorder according to the Diagnostic and Statistical Manual of the American Psychiatry Association (third revision), with a minimum score of 25 on the Montgomery and Asberg Depression Rating Scale were treated for 6 weeks with milnacipran (100 mg/day) or imipramine (150 mg/day). Both treatments showed similar efficacy in reducing depressive symptoms. The frequency of most adverse events in the milnacipran-treated patients was lower than that observed in the imipramine group, particularly those related to anticholinergic symptoms. Dysuria and shivering, however, were more common with milnacipran. The results of this study support others which have demonstrated that milnacipran has equivalent efficacy but superior tolerability to a tricyclic antidepressant such as imipramine.", "The efficacy and the tolerance of milnacipran (100 mg/day), a second generation antidepressant which equipotently inhibits both noradrenaline and serotonin reuptake, was compared to fluoxetine (20 mg/day), a selective serotonin reuptake inhibitor, in two parallel groups of, respectively, 97 and 93 major depressive outpatients. The duration of the study was 6 weeks, with assessments every 2 weeks by means of the Montgomery and Asberg depression scale (MADRS), the Hamilton depression scale, the clinical global impressions (CGI), and a checklist of symptoms and side-effects. Results showed significant superiority of fluoxetine over milnacipran on most rating instruments: MADRS (P = 0.01) including five individual items, Hamilton depression scale (P = 0.002) including ten individual items, CGI of severity (P = 0.01) and therapeutical index (P = 0.002). On visual analogue scales assessing the clinical profile of the compounds, fluoxetine was rated as exhibiting more psychostimulating activity than milnacipran (P = 0.0008). The tolerance of the two antidepressants was very similar, with the exception of symptoms of dizziness which were more frequently reported with milnacipran (P = 0.01). These differences in efficacy favoring fluoxetine could result from the selection of a dose of milnacipran below the optimal therapeutic dose for this type of psychiatric patients or to the administration of the compounds in single daily intakes, whereas milnacipran possesses a plasma elimination half-life of only 7 h.", "A multicenter controlled study was designed to test the hypothesis that a loading dose of an antidepressant could shorten the latency of its clinical efficacy. Three parallel groups of about 40 endogenous depressive inpatients received either a loading dose of milnacipran (300 mg daily for 2 weeks and 150 mg daily during the 2 following weeks), the standard regimen of milnacipran in severe depression (200 mg daily for 4 weeks), or fluvoxamine (200 mg daily for 4 weeks). The duration of the study was 4 weeks, with assessments at baseline and after 4, 9, 14, 21, and 28 days of therapy by means of Montgomery and Asberg depression scale (MADS), the Hamilton depression scale, the Clinical Global Impressions (CGI), and a checklist of symptoms and side-effects. Results showed very similar evolution in the 3 treatment groups. In addition, the level of side-effects did not exhibit significant differences among the treatment groups, except for excitement-nervousness and akathisia which were more frequently reported with fluvoxamine. These results do not support the usefulness of a loading dose of an antidepressant such as milnacipran. They demonstrate however that milnacipran can be given at a 300 mg daily dose from the very first day of treatment with an excellent tolerance.", "The antidepressant efficacy and tolerability of milnacipran, a dual action serotonin-noradrenaline reuptake inhibitor, were compared with those of the selective serotonin reuptake inhibitor, fluvoxamine, in 113 patients with moderate to severe major depression. Treatment with milnacipran, 50 mg b.d. for 6 weeks, produced a significantly greater reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores than fluvoxamine, 100 mg b.d. (P = 0.007; 65.4% versus 49.9%, respectively); significantly greater decreases were also seen on days 7 (P = 0.04) and 28 (P = 0.03). The response rate (the proportion of patients showing a decrease in MADRS scores of at least 50%) was 78.9% in patients receiving milnacipran, compared with 60.7% in fluvoxamine-treated patients (P = 0.04). Milnacipran also produced greater improvements in 24-item Hamilton Depression Rating Scale scores (P = 0.05). On the Clinical Global Impression Improvement scale, 77.2% of milnacipran-treated patients were rated as considerably or markedly improved, compared with 60.7% of patients receiving fluvoxamine (P = 0.06 chi-squared). Both treatments were well tolerated; the only significant difference between the two groups was a higher incidence of tremor and drowsiness in patients treated with fluvoxamine. It is concluded that milnacipran may offer some advantages over selective serotonin reuptake inhibitors, such as fluvoxamine, in the treatment of moderate to severe major depression.", "This multicentre, double-blind, randomised trial in 109 patients compared the efficacy and tolerance of the novel selective serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressant milnacipran (50 mg twice daily, n=53) with the established tricyclic agent imipramine (75 mg twice daily, n=56) over a period of 6 weeks, in patients with major depression (Montgomery-Asberg depression rating score (MADRS) > or =25). Initiation of antidepressant medication was conducted during a 2-week period of hospitalisation, after a 3- to 7-day washout period. Concomitant psychiatric medication was limited to lorazepam, cyamemazine, chloral hydrate and long-term uncomplicated lithium therapy. Assessment for efficacy using the MADRS and Hamilton rating scales of depression, a visual analogue scale and global evaluation revealed both agents to be highly effective (P=0.0001) in this group of patients. Milnacipran was found to be of similar efficacy to imipramine. Tolerance, assessed by physiological and biochemical examinations with routine inventory and spontaneous report of adverse events, revealed a clear advantage for milnacipran. The incidence of anticholinergic events with milnacipran was about half that with imipramine and the overall incidence of adverse events by either reporting method was markedly lower with milnacipran than with imipramine. Furthermore, the patient drop-out rate with imipramine was double that experienced with milnacipran. Milnacipran appears to possess equal antidepressant efficacy to imipramine but with markedly superior tolerance. Therefore, milnacipran constitutes an important new treatment option in major depression." ]

[ "7088606", "3547298", "3670972", "1735830" ]

[ "Granulocyte transfusions in neonates with bacterial infection, neutropenia, and depletion of mature marrow neutrophils.", "Buffy coat transfusions in neonates with sepsis and neutrophil storage pool depletion.", "Buffy coat transfusions in neutropenic neonates with presumed sepsis: a prospective, randomized trial.", "Randomized trial of granulocyte transfusions versus intravenous immune globulin therapy for neonatal neutropenia and sepsis." ]

[ "During a three-year period, 26 neonates with bacterial infection and neutropenia were studied. In order to assess the marrow neutrophil reserves, bone marrow aspirates were obtained from each of these patients. The neutrophil storage pool (percent polymorphonuclear + band neutrophils + metamyelocytes in 1,000 nucleated marrow cells) was significantly greater in those who survived their infection (mean = 20.1%, range 3.2% to 60.8%) than in those who died (mean = 1.9%, range 0.4% to 5.2%, P less than .002). In an attempt to improve survival in this group, seven neutrophil-depleted patients with sepsis were given granulocyte transfusions and all survived. In contrast only one of nine nontransfused and all survived. In contrast only one of nine nontransfused, neutrophil-depleted infants with sepsis survived (P less than .01). The seven granulocyte recipients were examined for possible adverse effects of the transfusions and none were detected. It is suggested that infected, neutropenic neonates with depletion of mature marrow neutrophils are at high risk for death from sepsis, and that these infants may benefit from granulocyte transfusion therapy.", "A randomized study was initiated in neonates with neutropenia (absolute peripheral neutrophil count less than 1,500/microL) and suspected bacterial infection. Twenty infants with proven infection were enrolled, nine of whom had depletion of bone marrow stores of maturing neutrophils (less than or equal to 7% metamyelocyte, band and mature forms per 100 nucleated cells). These nine were randomized to receive 15 mL/kg of either buffy coat transfusions (group 2) or plasma and blood products (group 3). The remaining 11 (group 1) were observed. Peripheral neutrophil counts were monitored to determine the neutrophil response to transfusions. There were ten of 11 patients in group 1, two of four in group 2, and two of five in group 3 who lived at least seven days. No complications of transfusion were noted. No difference in the rate of peripheral neutrophil increase was found among the three groups. The study was stopped when it became clear that sufficient numbers of patients could not be entered into the study, in a reasonable period of time, to prove or disprove a clinically significant improvement in outcome. Although in vitro testing of the buffy coat preparations showed normal function in three of four cases, the clinical quality of the buffy coats may have been inadequate because of poor availability of whole fresh blood less than 24 hours old. The role of neutrophil transfusions in these patients remains unclear.", "Neonatal sepsis, accompanied by neutropenia, is associated with a high mortality. To determine whether granulocyte transfusions improve the survival of critically ill neutropenic infants, we prospectively randomized 25 infants to transfusion and nontransfusion groups, matching for birth weight (less than or equal to 1,500 g or greater than 1,500 g). Infants with necrotizing enterocolitis were randomized separately. Neutropenia was established by two successive absolute neutrophil counts less than or equal to 1,500 cells prior to randomization. The transfusion (n = 12) and nontransfusion (n = 13) groups did not differ with respect to clinical or hematologic characteristics. In 23 of 25, bone marrow aspirations were performed to determine the percentage of neutrophil storage pool. Granulocyte transfusions of buffy coats from single units of whole blood (0.1 to 0.9 X 10(9) polymorphonuclear leukocytes per kilogram) were given daily until the absolute neutrophil count increased to more than 1,500/microL. Only five infants, mostly those with necrotizing enterocolitis, required more than one transfusion. A circulating immature to total neutrophil ratio (I:T) greater than or equal to 0.80 was not predictive of an infant with a neutrophil storage pool less than or equal to 7%, and neither an I:T less than 0.80 nor a neutrophil storage pool greater than 7% were predictive of survival. Granulocyte transfusions did not improve survival when either comparing the whole group, those 17 infants with cultures positive for bacteria or viruses, the 19 infants with a circulating I:T greater than or equal to 0.80, or the nine infants with a neutrophil storage pool less than or equal to 7%.(ABSTRACT TRUNCATED AT 250 WORDS)", "We prospectively studied newborn infants with sepsis and neutropenia who were randomly selected to receive standard supportive care and either adjuvant granulocyte transfusions or intravenous immune globulin (IVIG) infusions; 21 infants received granulocyte transfusions and 14 received IVIG infusions. Half of the patients were premature (gestational age less than or equal to 32 weeks); the average postnatal age was 5 days (range 3 to 8 days). All infants had neutropenia by the criteria of Manroe et al., and the mean average bone marrow neutrophil storage pool ranged between 35% and 37%. There were no significant differences with respect to serum IgG, IgA, IgM, and total hemolytic complement values between treatment groups or between survivors and nonsurvivors. Clinical severity as defined by hypoxia, acidosis, and hypotension was similar between treatment groups. Group B streptococcus was the most common organism identified and accounted for almost 33% of all bacterial isolates. There was a significantly different survival rate in the group receiving polymorphonuclear leukocyte transfusions (100%, 21/21) compared with the group receiving IVIG infusions (64%, 9/14; p = less than 0.03). There were no significant complications in either treatment group with respect to fluid overload, secondary infection, blood group sensitization, pulmonary complications, or graft-versus-host disease. This pilot study suggests a possible benefit of granulocyte transfusions compared with 'IVIG therapy in the adjuvant treatment of neonatal neutropenia and overwhelming bacterial sepsis." ]

[ "11094034" ]

[ "Endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal angioplasty : results of a prospective randomized study." ]

[ "Inasmuch as endovascular brachytherapy (BT) has gained recent interest because of its inhibitory effect on mechanisms leading to restenosis after percutaneous transluminal angioplasty (PTA), we performed this randomized study to determine its efficacy for prophylaxis of restenosis after femoropopliteal PTA.\n One hundred thirteen patients (63 men, 50 women; mean age 71 years) with de novo or recurrent femoropopliteal lesions were included in this randomized trial comparing the restenosis rate after PTA plus BT (57 patients, PTA+BT group) versus PTA (56 patients, PTA group) without stent implantation. The mean treated length was 16.7 cm (PTA+BT group) versus 14.8 cm (PTA group). In patients randomized to PTA plus BT, a dose of 12 Gy was applied by an (192)Ir source 3 mm from the source axis. Follow-up examinations included measurement of the ankle-brachial index, color-flow duplex sonography, and angiography. The primary end point of the study was patency after 6 months. The overall recurrence rate after 6 months was 15 (28.3%) of 53 in the PTA+BT group versus 29 (53.7%) of 54 in the PTA group (chi(2) test, P<0.05). The cumulative patency rates at 12 months of follow-up were 63.6% in the PTA+BT group and 35.3% in the PTA group (log-rank test, P<0.005).\n This is the first randomized study to demonstrate the efficacy of endovascular BT for prophylaxis of restenosis after femoropopliteal PTA. The value of this approach should now be improved by modification of the BT procedure and by combination with stent implantation." ]

[ "3924221", "11213665", "9112303", "355879", "10217908" ]

[ "Chest physiotherapy in primary pneumonia.", "Benefits of osteopathic manipulative treatment for hospitalized elderly patients with pneumonia.", "Bottle-blowing in hospital-treated patients with community-acquired pneumonia.", "Efficacy of chest physiotherapy and intermittent positive-pressure breathing in the resolution of pneumonia.", "Adjunctive osteopathic manipulative treatment in the elderly hospitalized with pneumonia: a pilot study." ]

[ "One hundred and seventy one patients with primary pneumonia entered a single blind, placebo controlled trial of physiotherapy. Treatment was allocated at random, physiotherapy consisting of postural drainage, external help with breathing, percussion, and vibration and the controls receiving advice on expectoration, deep breathing, and how to exercise to avoid thrombosis. Principles of pharmaceutical management were the same in the two groups. There was no objective evidence that daily physiotherapy helped during the acute phase of the disease. On the contrary, in younger patients, smokers, and patients with interstitial pneumonia physiotherapy appeared to prolong the duration of fever as well as the hospital stay. It is concluded that chest physiotherapy is at best useless in patients with primary infectious pneumonia.", "While osteopathic manipulative treatment (OMT) is thought to be beneficial for patients with pneumonia, there have been few clinical trials--especially in the elderly. The authors' pilot study suggested that duration of intravenous antibiotic use and length of hospital stay were promising measures of outcome. Therefore, a larger randomized controlled study was conducted. Elderly patients hospitalized with acute pneumonia were recruited and randomly placed into two groups: 28 in the treatment group and 30 in the control group. The treatment group received a standardized OMT protocol, while the control group received a light touch protocol. There was no statistical difference between groups for age, sex, or simplified acute physiology scores. The treatment group had a significantly shorter duration of intravenous antibiotic treatment and a shorter hospital stay.", "A study was carried out to determine whether bottle-blowing has any positive effects in patients with pneumonia. In a prospective open study 145 adults with untreated community-acquired pneumonia requiring hospitalization were randomized to early mobilization (group A), to sit up and take 20 deep breaths on 10 occasions daily (group B), or to sit up and to blow bubbles in a bottle containing 10 cm water through a plastic tube 20 times on 10 occasions daily (group C). Peak expiratory flow (PEF), vital capacity (VC), forced expiratory volume in 1 sec (FEV1) and serum concentration of C-reactive protein (CRP) were determined on admission, and on days 4 and 42. Fever duration and hospital stay were recorded. In a subset of 16 patients, single breath diffusion capacity of carbon monoxide was measured on 3 occasions. The patients in group A were hospitalized for a mean of 5.3 days, group B for 4.6 days and group C for 3.9 days. Treatment was a significant factor (p = 0.037) in a Cox regression model, with group C significantly better than group A (p = 0.01). The number of days with fever was 2.3, 1.7 and 1.6 in groups A, B and C respectively. These differences were not significant (p = 0.28). No significant differences were found between the groups regarding CRP, PEF, VC, FEV1, or diffusion capacity. Intensive bottle-blowing shortens the hospital stay in patients with pneumonia. The underlying mechanism is not clear.", "We undertook a randomized clinical trial to evaluate the efficacy of chest physiotherapy and intermittent positive-pressure breathing in the treatment of pneumonia. The diagnosis of pneumonia required a compatible clinical history and x-ray confirmation. A total of 54 patients were assigned to treatment and control groups and were similar in age, smoking history, underlying lung disease and prior antibiotic treatment. Antibiotic therapy, guided by Gram stain and sputum and blood cultures, was similar in both groups. Chest physiotherapy, consisting of postural drainage, percussion and vibration, was given concurrently with intermittent positive-pressure breathing with use of racemic epinephrine every four hours. There was no statistically significant difference in duration of fever, extent of radiographic clearing, duration of hospital stay and mortality between the control and treated groups. Chest physiotherapy and intermittent positive-pressure breathing do not hasten the resolution of pneumonia.", "To evaluate the benefit of osteopathic manipulative treatment in the elderly with pneumonia, the authors recruited 21 individuals older than 60 years who were hospitalized with acute pneumonia. Eleven patients were randomly assigned to the treatment group and ten to the control group. The treatment group received specific osteopathic manipulative treatment for somatic dysfunction and a standardized treatment protocol. Both groups received conventional therapy, and the attending physician was blind to group assignments. No significant difference existed between groups for age, sex, or severity of illness. Although the mean duration of leukocytosis, intravenous antibiotic treatment, and length of stay were shorter for the treatment group, these measures did not reach statistical significance. However, the mean duration of oral antibiotic use did reach statistical significance at 3.1 days for the treatment group and 0.8 day for the control group. Osteopathic manipulative treatment may reduce antibiotic use and length of stay; however, a larger study is needed to clarify this outcome." ]

[ "8601552", "1350428", "1969247", "12892048", "8988802", "9627740", "8185007", "9727725", "7914238" ]

[ "A double-blind placebo-controlled study of vitamin E treatment of tardive dyskinesia.", "Treatment of tardive dyskinesia with vitamin E.", "Vitamin E in the treatment of tardive dyskinesia.", "Vitamin E treatment for tardive dyskinesia. Veterans Affairs Cooperative Study #394 Study Group.", "Treatment of long-term tardive dyskinesia with vitamin E.", "Long-term treatment effects of vitamin E for tardive dyskinesia.", "Effectiveness of vitamin E for treatment of long-term tardive dyskinesia.", "Vitamin E in the treatment of tardive dyskinesia: a preliminary study over 7 months at different doses.", "Vitamin E in the treatment of tardive dyskinesia." ]

[ "This study was designed to determine if vitamin E is effective in reducing the severity of abnormal movements in patients with tardive dyskinesia (TD).\n Thirty-five patients completed a double-blind placebo-controlled parallel-group study of vitamin E. Seventeen of the patients were randomly assigned to receive 800 IU b.i.d. of vitamin E and 18 were assigned to placebo for 2 months. Twenty-nine patients had a diagnosis of schizophrenia and 6 of mood disorder. Patients were assessed using modified versions of the Abnormal Involuntary Movement Scale (mAIMS), Simpson-Angus Scale for extrapyramidal side effects, and Brief Psychiatric Rating Scale. Additionally, a subgroup of 23 patients were assessed using instrumental measurements of dyskinesia.\n There was a significant reduction of dyskinesia in the vitamin E group, but not the placebo group, on both the mAIMS and the instrumental assessments. The overall reduction in mAIMS in the active group was 24%, with 5 (29%) of 17 patients demonstrating greater than 33% reduction in score. There was a greater reduction in mean mAIMS score (35%) with vitamin E in the subgroup of patients with TD for 5 years or less compared with the reduction (11%) in patients with TD for greater than 5 years. No change was observed in parkinsonism. In the patients with schizophrenia, there was a reduction in positive symptoms after vitamin E.\n Vitamin E appears to be effective in reducing the severity of TD, especially in patients who have had TD for 5 years or less.", "Vitamin E (alpha-tocopherol), a free-radical scavenger, has been reported to improve symptoms of tardive dyskinesia. The authors attempted to replicate this finding under more controlled conditions in a larger study group.\n Fifteen inpatients and six outpatients with tardive dyskinesia received up to 1600 IU/day of vitamin E for 6 weeks in a double-blind, placebo-controlled crossover study. Abnormal Involuntary Movement Scale (AIMS) examinations of these patients were videotaped and rated independently by two trained raters. Levels of neuroleptic medication and vitamin E were measured during both treatment periods. Eighteen patients who demonstrated high blood levels of vitamin E were included in the data analysis.\n Vitamin E levels were significantly higher while the patients were receiving vitamin E than while they were receiving placebo. For all 18 patients, there were no significant differences between AIMS scores after receiving vitamin E and AIMS scores after receiving placebo. In agreement with previous studies, however, the nine patients who had had tardive dyskinesia for 5 years or less had significantly lower AIMS scores after receiving vitamin E than after receiving placebo. There were no changes in neuroleptic levels during vitamin E treatment.\n Vitamin E had a minor beneficial effect on tardive dyskinesia ratings in a selected group of patients who had had tardive dyskinesia for 5 years or less. This effect was not due to an increase in blood levels of neuroleptic medications.", "Eight subjects with persistent tardive dyskinesia were treated with vitamin E and placebo in a randomized, double-blind crossover study. Their mean score on the Abnormal Involuntary Movement Scale (AIMS) was significantly lower after treatment with vitamin E than after placebo administration.", "Several short-term, controlled trials have documented the efficacy of vitamin E in treating tardive dyskinesia. However, the persistent nature of the disease prompted us to perform a multicenter, longer-term trial of vitamin E.\n The study was a prospective, randomized, 9-site trial of up to 2 years of treatment with d-vitamin E (1600 IU/d) vs matching placebo. One hundred fifty-eight subjects with tardive dyskinesia who were receiving neuroleptic medications were enrolled. The blinded assessments performed were clinical (Abnormal Involuntary Movements Scale, Barnes Akathisia Scale, and Modified Simpson-Angus [for Extrapyramidal Symptoms] Scale) and electromechanical assessments of movement disorders, psychiatric status (Brief Psychiatric Rating Scale), and functioning (Global Assessment of Functioning). There were no significant differences in baseline demographic characteristics or in study assessments between the group that received vitamin E and the group that received placebo.\n Vitamin E was well tolerated and subject compliance with medication was good and similar between treatment groups. One hundred seven subjects (70% of those receiving vitamin E and 66% of subjects receiving placebo) completed at least 1 year of treatment. There were no significant effects of vitamin E on total scores or subscale scores for the AIMS, electromechanical measures of dyskinesia, or scores from the other 4 scales.\n This long-term, randomized trial of vitamin E vs placebo found no evidence for efficacy of vitamin E in the treatment of tardive dyskinesia.", "nan", "Several studies have found that alpha-tocopherol (vitamin E) can effectively treat tardive dyskinesia (TD). A limitation of these trials is their short treatment durations (maximum of 12 weeks), which do not allow us to address the effects of long-term treatment.\n To participate, patients had to have TD and be on stable oral medications. The study enrolled 40 patients who received up to 36 weeks of treatment with d-vitamin E (1600 IU per day) or placebo.\n Using the Abnormal Involuntary Movements Scale (AIMS) score (sum of items #1-7) to measure TD severity, the study found a significant difference (3 points) in mean AIMS scores, in favor of vitamin E, starting at 10 weeks of treatment and continuing through the full 36 weeks. We used linear mixed-effects regression to quantify the impact of several covariates, and found that treatment assignment. TD duration, and chlorpromazine equivalents had significant effects on decreasing the AIMS score.\n The study's finding that vitamin E is effective in treating TD agrees with results from prior studies and provides evidence that the effect may extend to treatment of up to 36 weeks. These findings are in direct contrast to those of VA Cooperative Study #394, a much larger, long-term, multi-site study, conducted by many of the same investigators, in which Vitamin E was not superior to placebo.", "Eleven patients with tardive dyskinesia were treated in a double-blind study of vitamin E or placebo for 12 weeks. Abnormal Involuntary Movement Scale (AIMS) ratings were performed before and after treatment. Patients receiving vitamin E showed a significant reduction in their AIMS scale score, but patients receiving placebo showed no significant change. Vitamin E had a helpful effect even for patients whose tardive dyskinesia was mild and long-term.", "Vitamin E has been suggested to be a promising new treatment for tardive dyskinesia. However, little is known about the optimum dose. Twenty patients with tardive dyskinesia whose medication had been unchanged for at least 1 month were selected and randomly divided into a treatment group with 11 patients and a control group with nine patients. The treatment group was started on 600 mg of vitamin E per day, and this dose was increased over the 7 months of the trial to 1600 mg per day. The medication for the control group was unchanged. Severity of tardive dyskinesia was rated on the Abnormal Involuntary Movement Scale. Patients in the treatment group initially showed a significant response to the lower dose of 600 mg per day. However, this improvement was not maintained and differences between the two groups reached significant levels only after the dose of vitamin E was increased to 1600 mg per day. At this dose, there was a significant and sustained reduction in the severity of tardive dyskinesia. The results suggest that vitamin E is of value in the treatment of tardive dyskinesia and that the optimum dose for treating tardive dyskinesia is 1600 mg per day. In addition, there may be a dose related therapeutic effect of Vitamin E in tardive dyskinesia.", "In a double-blind placebo controlled trial, the efficacy of Vitamin E in the treatment of tardive dyskinesia (TD) was studied in 32 patients. After a two week wash-out phase a baseline (0 week) TD rating was assessed on the tardive dyskinesia rating scale (TDRS). Subsequently, the patients entered a four week treatment phase during which 17 patients received capsules of vitamin E (600 mg) and 15 patients received identical placebo capsules. In the first week the patients received 1 capsule daily which was then increased to two capsules per day from the second to the fourth week. All patients were rated on the TDRS at the end of each week. The baseline TDRS score in the vitamin E group was significantly higher than the placebo group. This was hence adjusted and the results were then subjected to analysis of co- variance. The TDRS score after four weeks treatment was significantly lower in the vitamin E group as compared to the placebo group (p = 0.03)." ]

[ "2407957", "6276746", "8135445", "7599447", "6455048", "9652994", "8695970", "1790403", "3111669", "6253303", "9692071" ]

[ "Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis.", "Effect of the fluoride/calcium regimen on vertebral fracture occurrence in postmenopausal osteoporosis. Comparison with conventional therapy.", "Slow-release sodium fluoride in the management of postmenopausal osteoporosis. A randomized controlled trial.", "Monofluorophosphate increases lumbar bone density in osteopenic patients: a double-masked randomized study.", "Relief of osteoporotic backache with fluoride, calcium, and calciferol.", "The effect of sodium monofluorophosphate plus calcium on vertebral fracture rate in postmenopausal women with moderate osteoporosis. A randomized, controlled trial.", "Treatment of postmenopausal vertebral osteopenia with monofluorophospate: a long-term calcium-controlled study.", "A randomized trial of sodium fluoride as a treatment for postmenopausal osteoporosis.", "The effect of fluoride and calcium on spinal bone mineral content: a controlled, prospective (3 years) study.", "Prevention of early postmenopausal bone loss: controlled 2-year study in 315 normal females.", "Fluoride salts are no better at preventing new vertebral fractures than calcium-vitamin D in postmenopausal osteoporosis: the FAVOStudy." ]

[ "Although fluoride increases bone mass, the newly formed bone may have reduced strength. To assess the effect of fluoride treatment on the fracture rate in osteoporosis, we conducted a four-year prospective clinical trial in 202 postmenopausal women with osteoporosis and vertebral fractures who were randomly assigned to receive sodium fluoride (75 mg per day) or placebo. All received a calcium supplement (1500 mg per day). Sixty-six women in the fluoride group and 69 women in the placebo group completed the trial. As compared with the placebo group, the treatment group had increases in median bone mineral density of 35 percent (P less than 0.0001) in the lumbar spine (predominantly cancellous bone), 12 percent (P less than 0.0001) in the femoral neck, and 10 percent (P less than 0.0001) in the femoral trochanter (sites of mixed cortical and cancellous bone), but the bone mineral density decreased by 4 percent (P less than 0.02) in the shaft of the radius (predominantly cortical bone). The number of new vertebral fractures was similar in the treatment and placebo groups (163 and 136, respectively; P not significant), but the number of nonvertebral fractures was higher in the treatment group (72 vs. 24; P less than 0.01). Fifty-four women in the fluoride group and 24 in the placebo group had side effects sufficiently severe to warrant dose reduction; the major side effects were gastrointestinal symptoms and lower-extremity pain. We conclude that fluoride therapy increases cancellous but decreases cortical bone mineral density and increases skeletal fragility. Thus, under the conditions of this study, the fluoride-calcium regimen was not effective treatment for postmenopausal osteoporosis.", "We assessed the rates of vertebral fracture in patients with postmenopausal osteoporosis. Forty-five patients were not treated (91 person-years of observation); 59 were treated conventionally, with calcium (alone or combined with estrogen) or vitamin D or both (218 years); and 61 were treated with sodium fluoride combined with conventional therapy (251 years). The fracture rate (per thousand person-years) was 834 in untreated patients, 419 in those given calcium with or without vitamin D, 304 in those given fluoride and calcium with or without vitamin D, 181 in those given estrogen and calcium with or without vitamin D, and 53 in those given fluoride, estrogen, and calcium with or without vitamin D. It was reduced in all treatment groups (P less than 0.001 for calcium and P less than 1 x 10(-6) for other combinations); fluoride (one years of treatment) and estrogen (but not vitamin D) independently reduced the rate from that observed with calcium alone (P less than 0.001). The combination of calcium fluoride, and estrogen was more effective than any other combination (P less than 0.001). These results provide grounds for optimism about the efficacy of combinations of available agents with sodium fluoride for fracture in postmenopausal osteoporosis.", "To test whether intermittent treatment with slow-release sodium fluoride and continuous calcium citrate supplementation inhibits vertebral fractures without causing fluoride complications.\n A placebo-controlled, randomized trial.\n Outpatient setting of specialty clinics in Dallas and Temple, Texas.\n Slow-release sodium fluoride (25 mg twice daily) in repeated 14-month cycles (12 months on treatment followed by 2 months off treatment) compared with placebo. Both groups took calcium citrate (400 mg calcium twice daily) continuously.\n 110 patients with postmenopausal osteoporosis were randomly assigned to two groups. In the slow-release sodium fluoride group, 48 of 54 patients completed more than 1 cycle of treatment (mean, 2.44 cycles/patient), whereas 51 of 56 patients in the placebo group completed at least 1 cycle (mean, 2.14 cycles/patient) in this interim analysis.\n Vertebral fracture rate and lumbar bone mineral content. Vertebral fractures were quantified from yearly radiographs. Bone mass was determined annually by densitometry.\n In the sodium fluoride group, the mean L2 to L4 bone mineral content increased by 4% to 6% in each cycle and the mean femoral neck bone density increased by 4.1% and 2.1% during the first two cycles, but the radial bone density did not change. The placebo group showed no statistical change in bone mass at any site. Compared with the placebo group, the sodium fluoride group had a lower individual new vertebral fracture rate (0.057/patient cycle compared with 0.204/patient cycle, P = 0.017), a higher fracture-free rate (83.3% compared with 64.7%, P = 0.042), and a lower group fracture rate (0.085/patient cycle compared with 0.239/patient cycle, P = 0.006). The side-effect profile was similar for the two groups; no patient developed microfractures, hip fractures, or blood loss anemia.\n Intermittent slow-release sodium fluoride plus continuous calcium citrate, administered for about 2.5 years, inhibits new vertebral fractures, increases the mean spinal bone mass without decreasing the radial shaft bone density, and is safe to use.", "To assess the efficacy of combined sodium monofluorophosphate and calcium therapy (FC) in increasing lumbar bone mineral density (BMD) in patients with low bone mass, we conducted a prospective double-masked randomized study in 94 patients aged 50-70 years. Patients were selected on the basis of a lumbar BMD at least 2 standard deviations (SD) below the young adult mean (T-score) but without evidence of previous vertebral fracture (severe osteopenia). They were randomly assigned to receive for 2 years, twice a day, either FC (13.2 mg F-, i.e. 100 mg sodium monofluorophosphate, and 500 mg Ca2+) or C (500 mg Ca2+). Vertebral BMD was measured by dual photon absorptiometry from L2 to L4. Comparison at final assessment in the 76 eligible patients (Student's t-test) showed a statistically significant difference between the two groups in the mean BMD increase in favour of FC. Furthermore, Student's t-test showed a significantly greater increase in lumbar BMD in FC-treated patients at 1 year, at 18 months and after 2 years (mean increase of 7.1%/year). These results were confirmed by ANOVA at 1 year, at 18 months and after 2 years of treatment. Of the FC-treated patients, 71.4% were considered to have responded (i.e. they showed an increase in lumbar BMD of more than 0.034 g/cm2). The dosage of 26.4 mg fluoride ion/day (i.e. 200 mg monofluorophosphate/day) therefore appears to be safe and to increase the BMD effectively in patients with low bone mass prior to vertebral fracture.", "In a prospective randomized clinical trial comprising 22 postmenopausal women with backache and a halisteretic spine with crush fracture(s), 12 women completed a 12-week therapy with sodium fluoride, calcium and calciferol and 10 with placebo. A statistically significant improvement (p less than 0.05), evaluated by a four-stage scale on pains, infirmity, and consumption of analgesics, was observed in the actively treated patients.", "Fluoride is effective in increasing trabecular bone mineral density (BMD) in the spine, but its efficacy in reducing vertebral fracture rates and its effect on BMD at cortical sites are controversial.\n To study the effect of low-dose fluoride (sodium monofluorophosphate [MFP]) plus a calcium supplement over 4 years on vertebral fractures and BMD at the lumbar spine and total hip in postmenopausal women with moderately low BMD of the spine.\n Randomized, double-blind, controlled clinical trial.\n Outpatient clinic for osteoporosis at a university medical center.\n 200 postmenopausal women with osteoporosis (according to the World Health Organization definition) and a T-score less than -2.5 for BMD of the spine.\n Women were randomly assigned (100 patients per group) to continuous daily treatment for 4 years with 1) oral MFP (20 mg of equivalent fluoride) plus 1000 mg of calcium (as calcium carbonate) or 2) calcium only.\n Lateral spine radiographs were taken at enrollment and at each year of follow-up for detection of new vertebral fractures (defined as a reduction > or =20% and > or =4 mm from baseline in any of the heights of a vertebral body). Nonvertebral fractures were also recorded. All analyses were done with the intention-to-treat approach.\n Radiologic follow-up was possible for 164 of 200 patients (82%). The rate of new vertebral fractures during the 4 years of the study was lower in the MFP-plus-calcium group (2 of 84 patients; 2.4% [95% CI, 0.3% to 8.3%]) than in the calcium-only group (8 of 80 patients; 10% [CI, 4.4% to 18.8%]). The difference between the groups was 7.6 percentage points (CI, 0.3 to 15 percentage points) (P = 0.05). A moderate but progressive increase in BMD of the spine (10.0% +/- 1.5% at 4 years) was found for MFP plus calcium compared with calcium only (P < 0.001), whereas the more modest increase in BMD of the total hip seen with MFP plus calcium (1.8% +/- 0.6%) did not differ from the increase seen with calcium only.\n Low-dose fluoride (20 mg/d) given continuously with calcium for prolonged periods can decrease vertebral fracture rates compared with calcium alone in patients with mild to moderate osteoporosis.", "The aim of the present study was to assess the effects of the new fluorine pro-drug monofluorophosphate (MFP) in postmenopausal women with vertebral osteopenia and high bone turnover. We enrolled postmenopausal women (PMW, 43-59 years) who had had a natural menopause 2-5 years before the study, had vertebral bone mineral density (BMD) < 1 SD from the premenopausal mean, and had at least one of the biochemical markers of bone remodeling > 1 SD over the mean for premenopausal women. Patients were randomly divided into two treatment groups (group 1, 500 mg/day of oral calcium; group 2, MFP at the dose of 20 mg F-equivalents + 600 mg calcium/day) for 2 years (n = 21 in each group). The lumbar vertebral (L2-4) BMD and total body bone mineral (TBBM) were measured by dual-energy X-ray absorptiometry (Lunar DPX, Lunar Corporation, USA). Urinary hydroxyproline excretion (OH-P/Cr), plasma bone Gla protein (BGP) and serum alkaline phosphatase (AP) were assayed. In group 1 the markers of bone turnover and vertebral BMD did not show any significant modification, while TBBM showed a significant (p < 0.05) decrease after 24 months. In group 2 a significant (p < 0.05) decrease in OH-P/Cr (-23.9 +/- 2.0%), and an increase in both BGP (+19.4 +/- 2.6%) and AP (+10.3 +/- 2.6%) levels were observed after 24 months of MFP administration. In this group, both vertebral BMD (+5.01 +/- 0.9%, p < 0.01) and TBBM (+4.0 +/- 0.6%, p < 0.05) showed a significant increase after 24 months. Present results suggest that, in osteopenic PMW, MFP administration induces a significant increase in vertebral BMD without impairment of cortical bone, with a reduction in bone resorption and an increase in bone formation rate.", "The anti-fracture efficacy of sodium fluoride (NaF) was evaluated in 84 postmenopausal white women with spinal osteoporosis. The dose of NaF used was 75 mg/day and all patients in this prospective, randomized, double-blind, placebo-controlled clinical trial received calcium supplements (carbonate salt) 1500 mg/day in addition to participating in a structured physical therapy program. For each of the outcome measures (change in stature, change in cortical bone mass in the forearm and development of new vertebral fractures determined by change in vertebral morphometry and by scintigraphy) there was no significant difference between the fluoride or placebo treated groups. Side effects, predominantly gastrointestinal symptoms and the development of the painful lower extremity syndrome, occurred significantly more frequently in the fluoride group (P less than 0.05). Peripheral fractures were not more frequent in the fluoride group. We conclude that, in the dose and manner used in this study, NaF is no more effective than placebo in retarding the progression of spinal osteoporosis. There is no role for NaF in the treatment of osteoporosis outside the confines of clinical research.", "Daily treatment with 30 mg of sodium fluoride (NaF) and 1 g of calcium over a 3-year period increased the bone mineral content (BMC) in the spines of women (n = 25) with osteoporosis. Determination of the BMC was followed with dual photon absorptiometry (137Cs-241Am) in the third lumbar vertebra. No increase in BMC was found with only 10 mg sodium fluoride in combination with calcium (n = 25), with calcium alone (n = 25), or with placebo (n = 25). No serious side effects were registered. There was, however, minor gastrointestinal distress in one-fifth of the patients taking 30 mg NaF daily.", "With the aim of preventing postmenopausal bone loss, a placebo-controlled double-blind trial of 2 years duration was performed. We randomized 315 healthy volunteers in their early natural menopause to seven treatment and three placebo groups: 17 beta-oestradiol, oestriol and sequential norethisteron (hormones); bendroflumethiazide 5 mg/day (thiazide); hormones and thiazide; sodium fluoride 20 mg/day; vitamin D3 2000 IU/day (D3); fluoride and D3; and 1 alpha (OH) vitamin D3 0.25 microgram/day (1 alpha D3). All participants were given daily calcium supplement of 500 mg. Every 3 months we measured the bone mineral content (BMC) of both forearms by photon absorptiometry and chemical quantities in blood and 48 h urinary collections. The study was completed by 264 (84%). The combined placebo groups showed a linear fall in BMC reaching 3.3% after 2 years (P < 0.001). Hormones and hormones and thiazide led to a 2.5% gain in BMC (P < 0.01). Thiazide alone postponed the BMC fall for 6 months. After 2 years the thiazide group showed a BMC fall of 1.5% (P < 0.05), less than that of the placebo group (P < 0.05). BMC declined by 3.6%, 4.5%, 3.7% and 3.7% during the respective use of fluoride, D3, fluoride and D3 and 1 alpha D3. Nevertheless, the urinary calcium excretion during 1 alpha D3 and D3 treatment was 1--1.5 mmol/day higher than in the placebo groups. Apparently, there is no real alternative to oestrogen/gestagen in the prevention of postmenopausal osteoporosis.", "Although fluoride salts have been shown to be capable of linearly increasing spinal bone mineral density (BMD) in postmenopausal osteoporosis, the effects of this gain in density on the vertebral fracture rate remain controversial. We conducted a 2-year multicenter, prospective, randomized, double-masked clinical trial in 354 osteoporotic women with vertebral fractures (mean age 65.7 years). They received either fluoride (208 patients), given as sodium fluoride (50 mg/day) or as monofluorophosphate (200 mg/day or 150 mg/day), or a placebo (146 patients). All patients received daily supplements of 1 g of calcium (Ca) and 800 IU of vitamin D2 (D). A 1-year open follow-up on Ca-D was obtained in 124 patients. After 2 years the fluoride group and the Ca-D group had increased their lumbar BMD by 10.8% and 2.4% respectively (p = 0.0001). However, the rate of patients with at least one new vertebral fracture, defined by semiquantitative assessment and evaluable on an intention-to-treat basis in 89% of patients, was similar in the fluoride groups and the Ca-D group. No difference between the three fluoride regimens was found. The percentage of patients with nonvertebral fractures was not different in the fluoride and Ca-D groups (1.9% and 1.4% respectively for hip fractures). A lower limb pain syndrome occurred more frequently in the fluoride groups. In the 124 patients followed for 1 year after cessation of fluoride therapy, the percentage of patients with at least one new vertebral fracture after 36 months was identical to the percentages in the previous fluoride group and the Ca-D group. We conclude that fluoride-Ca-D regimen was no more effective that Ca-D supplements for the prevention of new vertebral fractures in women with postmenopausal osteoporosis." ]

[ "11458140", "11224865", "10957696", "10515020", "9414052", "9415501", "8727142", "8929263" ]

[ "Radiofrequency facet joint denervation in the treatment of low back pain: a placebo-controlled clinical trial to assess efficacy.", "Randomized controlled trial of percutaneous intradiscal radiofrequency thermocoagulation for chronic discogenic back pain: lack of effect from a 90-second 70 C lesion.", "Psychological predictors of the effectiveness of radiofrequency lesioning of the cervical spinal dorsal ganglion (RF-DRG).", "Randomized trial of radiofrequency lumbar facet denervation for chronic low back pain.", "Resolution of psychological distress of whiplash patients following treatment by radiofrequency neurotomy: a randomised, double-blind, placebo-controlled trial.", "The efficacy of radiofrequency lesioning of the cervical spinal dorsal root ganglion in a double blinded randomized study: no difference between 40 degrees C and 67 degrees C treatments.", "Radiofrequency lesion adjacent to the dorsal root ganglion for cervicobrachial pain: a prospective double blind randomized study.", "Percutaneous radio-frequency neurotomy for chronic cervical zygapophyseal-joint pain." ]

[ "A prospective double-blind randomized controlled trial was performed.\n To assess the efficacy of percutaneous radiofrequency articular facet denervation for low back pain.\n Uncontrolled observational studies in patients with low back pain have reported some benefits from the use of facet joint radiofrequency denervation. Because the efficacy of percutaneous radiofrequency had not been clearly shown in previous studies, a randomized controlled trial was conducted to assess the efficacy of the technique for improving functional disabilities and reduce pain.\n For this study, 70 patients with low back pain lasting of more than 3 months duration and a good response after intraarticular facet injections under fluoroscopy were assigned randomly to receive percutaneous radiofrequency articular facet denervation under fluoroscopic guidance or the same procedure without effective denervation (sham therapy). The primary outcomes were functional disabilities, as assessed by the Oswestry and Roland-Morris scales, and pain indicated on a visual analog scale. Secondary outcomes included spinal mobility and strength.\n At 4 weeks, the Roland-Morris score had improved by a mean of 8.4% in the neurotomy group and 2.2% in the placebo group, showing a treatment effect of 6.2% (P = 0.05). At 4 weeks, no significant treatment effect was reflected in the Oswestry score (0.6% change) or the visual analog pain score (4.2% change). At 12 weeks, neither functional disability, as assessed by the Roland-Morris scale (2.6% change) and Oswestry scale (1.9% change), nor the pain level, as assessed by the visual analog scale (-7.6% change), showed any treatment effect.\n Although radiofrequency facet joint denervation may provide some short-term improvement in functional disability among patients with chronic low back pain, the efficacy of this treatment has not been established.", "A prospective double-blind randomized trial in 28 patients.\n To assess the clinical effect of percutaneous intradiscal radiofrequency thermocoagulation for reducing pain, functional disability, and physical impairment in patients with chronic discogenic low back pain.\n Chronic discogenic low back pain is a challenging problem in western countries. A treatment option is radiofrequency heating of the affected disc. Its clinical efficacy has never been formally tested in a controlled trial.\n Twenty-eight patients with a history of at least 1 year of chronic low back pain were selected on the basis of a diagnostic anesthetization of the lower intervertebral discs. Only patients with one putative painful level were selected and randomly assigned to one of two treatment groups. Each patient in the radiofrequency treatment group (n = 13) received a 90-second 70 C lesion of the intervertebral disc. Patients in the control group (n = 15) underwent the same procedure, but without use of radiofrequency current. Both the treating physician and the patients were blinded to the group assignment. Before treatment, physical impairment, rating of pain, the degree of disability, and quality of life were assessed by a blinded investigator.\n Eight weeks after treatment, there was one success in the radiofrequency group (n = 13) and two in the control group (n = 15). The adjusted and unadjusted odds ratio was 0.5 and 1.1, respectively (not significant). Also, visual analog scores for pain, global perceived effect, and the Oswestry disability scale showed no differences between the two groups.\n Percutaneous intradiscal radiofrequency thermocoagulation (90 seconds, 70 C) is not effective in reducing chronic discogenic low back pain.", "In this study, 54 patients suffering from chronic cervicobrachialgia (mean pain duration 7 years) were treated with radiofrequency lesioning of the cervical spinal dorsal root ganglion (RF-DRG). The aim of the study was to investigate whether psychological variables would be predictive for the changes in pain intensity after medical treatment. The following psychological aspects were measured: pain cognitions, negative self-efficacy and catastrophizing, physical and psychosocial dysfunction, and overall distress. The level of catastrophizing before treatment appeared to predict 10% of the changes in pain intensity after treatment. Changes in pain intensity after RF-DRG were positively correlated with changes in psychosocial dysfunction and negative self-efficacy.\n Copyright 2000 European Federation of Chapters of the International Association for the Study of Pain.", "A prospective double-blind randomized trial in 31 patients.\n To assess the clinical efficacy of percutaneous radiofrequency denervation of the lumbar zygapophysial joints in reducing pain, functional disability, and physical impairment in patients with back pain originating from the lumbar zygapophysial joints.\n Chronic low back pain is a major health problem in the industrialized world. A treatment option is percutaneous radiofrequency denervation of the lumbar zygapophysial joints. Its clinical efficacy has never been formally tested in a controlled trial.\n Thirty-one patients with a history of at least 1 year of chronic low back pain were selected on the basis of a positive response to a diagnostic nerve blockade and subsequently randomly assigned to one of two treatment groups. Each patient in the radiofrequency treatment group (15 patients) received an 80 C radiofrequency lesion of the dorsal ramus of the segmental nerve roots L3, L4, and L5. Patients in the control group (n = 16) underwent an the same procedure but without use of a radiofrequency current. Both the treating physician and the patients were blinded to the group assignment. Before treatment, physical impairment, rating of pain, the degree of disability, and quality of life were assessed by a blinded investigator.\n Eight weeks after treatment, there were 10 success patients in the radiofrequency group (n = 15) and 6 in the sham group (n = 16). The unadjusted odds ratio was 3.3 (P = 0.05, not significant), and the adjusted odds ratio was 4.8 (P < 0.05, significant). The differences in effect on the visual analog scale scores, global perceived effect, and the Oswestry disability scale were statistically significant. Three, 6, and 12 months after treatment, there were significantly more success patients in the radiofrequency group compared with the sham group.\n Radiofrequency lumbar zygapophysial joint denervation results in a significant alleviation of pain and functional disability in a select group of patients with chronic low back pain, both on a short-term and a long-term basis.", "It is well recognised that patients with chronic pain, in particular, chronic whiplash-associated neck pain, exhibit psychological distress. However, debate continues as to whether the psychological distress precedes and causes the chronic pain or, conversely, the psychological distress is a consequence of chronic pain. Using cervical zygapophysial joint pain as a model for chronic pain, the effect of a definitive neurosurgical treatment on the associated psychological distress was studied. Seventeen patients with a single painful cervical zygapophysial joint participated in a randomised, double-blind, placebo-controlled trial of percutaneous radiofrequency neurotomy. Their pain and psychological status were evaluated pre-operatively and 3 months post-operatively by medical interview and examination, a visual analogue pain scale, the McGill Pain Questionnaire, and the SCL-90-R psychological questionnaire. All patients who obtained complete pain relief exhibited resolution of their pre-operative psychological distress. In contrast, all but one of the patients whose pain remained unrelieved continued to suffer psychological distress. Because psychological distress resolved following a neurosurgical treatment which completely relieved pain, without psychological co-therapy, it is concluded that the psychological distress exhibited by these patients was a consequence of the chronic somatic pain.", "The efficacy of radiofrequency lesion treatment of the cervical dorsal root ganglion (RF-DRG) in cervicobrachialgia was investigated in 61 patients by a randomized prospective double blinded study. Before lesion treatment the putative pain provoking spinal root was identified by diagnostic blocks with a local anesthetic agent. One group of patients (n = 32, group I) was treated with a radiofrequency lesion of 67 degrees C and in a control group (n = 29, group II) a temperature of 40 degrees C was applied. Three months after treatment a significant reduction in VAS scores was demonstrated in both groups. The outcome of the treatments was identical (VAS reduction: group I, 1.7; group II, 1.9; P = 0.001). In group I a VAS reduction of 3 or more occurred in 11/31 (34%) and in group II in 11/29 (38%) of patients. A VAS reduction of 2 or more occurred in group I in 15/31 (47%) and in group II in 15/29 (51%) of patients. This study suggests that treatment with 40 degrees C radiofrequency application of the dorsal root ganglion is equally effective as treatment at 67 degrees C. Further appraisal of this treatment is required.", "Each of 20 consecutive patients with a history of at least 1 year of intractable chronic cervicobrachial pain was randomly assigned to one of two treatment groups. The pretreatment investigation included at least three diagnostic segmental nerve blocks in each patient. Each patient in Group 1 received a 67 degrees C radiofrequency lesion adjacent to the dorsal root ganglion. The patients in Group II were treated in an identical manner as those in Group I, except that no actual radiofrequency lesion was made. Neither the therapist nor the patients were aware of the treatment group assignment. All patients were questioned about their pain experience 1 week before and 8 weeks after the procedure. The following tests were used in evaluating patient response: Visual Analogue Scale (VAS); McGill Pain Questionnaire, Dutch Language Version (MPQ-DLV); and Multidimensional Pain Inventory, Dutch Language Version (MPI-DLV). These tests showed that 8 weeks after the procedure, there was a significant number of \"successful\" patients in Group I compared to Group II (P = 0.0027); there was a significant reduction in VAS score (P < 0.01) and also in parameters measured with MPQ-DLV and MPI-DLV in Group I. This study indicates that a 67 degrees C radiofrequency lesion adjacent to the dorsal root ganglion can result in a significant alleviation of pain in chronic cervicobrachial pain.", "Chronic pain in the cervical zygapohyseal joints is a common problem after whiplash injury, but treatment is difficult. Percutaneous radiofrequency neurotomy can relieve the pain by denaturing the nerves innervating the painful joint, but the efficacy of this treatment has not been established.\n In a randomized, double-blind trial, we compared percutaneous radio-frequency neurotomy in which multiple lesions were made and the temperature of the electrode making the lesions was raised to 80 degrees C with a control treatment using an identical procedure except that the radio-frequency current was not turned on. We studied 24 patients (9 men and 15 women; mean age, 43 years) who had pain in one or more cervical zygapophyseal joints after an automobile accident (median duration of pain, 34 months). The source of their pain had been identified with the use of double-blind, placebo-controlled local anesthesia. Twelve patients received each treatment. The patients were followed by telephone interviews and clinic visits until they reported that their pain had returned to 50 percent of the preoperative level.\n The median time that elapsed before the pain returned to at least 50 percent of the preoperative level was 263 days in the active-treatment group and 8 days in the control group (P=0.04). At 27 weeks, seven patients in the active-treatment group and one patient in the control group were free of pain. Five patients in the active-treatment group had numbness in the territory of the treated nerves, but none considered it troubling.\n In patients with chronic cervical zygapophyseal-joint pain confirmed with double-blind, placebo-controlled local anesthesia, percutaneous radio-frequency neurotomy with multiple lesions of target nerves can provide lasting relief." ]

[ "7936231", "1909241", "6705752", "2731087", "2731086", "1957968", "3042126", "1547765", "2496577", "3301560" ]

[ "Flunarizine for treatment of partial seizures: results of a concentration-controlled trial.", "Nimodipine in refractory epilepsy: a placebo-controlled, add-on study.", "Double-blind placebo-controlled trial of flunarizine as add-on therapy in epilepsy.", "Flunarizine as a supplementary medication in refractory childhood epilepsy: a double-blind crossover study.", "Double-blind cross-over placebo controlled study of flunarizine in patients with therapy resistant epilepsy.", "Double-blind placebo-controlled trial of flunarizine as add-on therapy in refractory childhood epilepsy.", "Double-blind placebo-controlled trial with flunarizine in therapy-resistant epileptic patients.", "Nifedipine for epilepsy? A double-blind, placebo-controlled trial.", "Double-blind placebo-controlled evaluation of flunarizine as adjunct therapy in epilepsy with complex partial seizures.", "Flunarizine as add-on therapy in epilepsy. Crossover study vs placebo." ]

[ "The National Institutes of Health sponsored a randomized, double-blind, multicenter, placebo-controlled trial of flunarizine (FNR) in epileptic patients receiving concomitant phenytoin (PHT) or carbamazepine (CBZ). Because of FNR's long half-life (up to 7 weeks), a parallel rather than crossover design was used. Each patient received an individualized loading dose and maintenance dosage targeted at a 60-ng/ml plasma FNR concentration. Of 93 patients randomized, 92 provided seizure data for the full 25-week treatment period; one placebo-treated patient dropped out for personal reasons. Fifty-four patients received CBZ only, nine received PHT only, and 30 received both CBZ and PHT. Eighty-seven patients had a history of complex partial seizures, and 60 had secondarily generalized seizures. Eight patients discontinued FNR prematurely, all because of adverse neurologic or psychiatric signs or symptoms; depression was the specific cause in three cases. Calculated maintenance dosages, based on single-dose pharmacokinetic profiles, ranged from 7 to 138 mg/day (mean, 40 mg/day). Plasma FNR concentrations generally exceeded the target, with the highest concentrations observed immediately after loading; excluding the first three treatment weeks and all concentrations after a FNR dosage change, the median plasma FNR concentration was 71.7 ng/ml. The percent reduction from baseline seizure rate was statistically greater (p = 0.002) in the FNR-treated group (mean, 24.4%) than in the placebo-treated group (mean, 5.7%).", "Twenty-two patients (8 male, 14 female) with refractory epilepsy entered a balanced, double-blind, placebo-controlled crossover trial of nimodipine as adjunctive therapy. Treatment periods of 12 weeks (nimodipine 30 mg tds, 60 mg tds, 90 mg tds each for 4 weeks and matched placebo) were followed by wash-out intervals of 4 weeks. Five patients withdrew (2 side-effects, 1 intercurrent illness, 2 non-compliance). Median values (placebo vs. nimodipine) did not vary for total (17 vs. 18), partial (14 vs. 18) and generalised tonic-clonic seizures (2 vs. 5) or seizure days (13 vs. 13). Monthly analysis also failed to uncover any benefit for nimodipine. Side-effects were reported no more frequently with nimodipine than with placebo and pulse and blood pressure did not alter significantly. Antiepileptic drug levels were not affected by nimodipine treatment but circulating nimodipine concentrations were low. In this trial, nimodipine did not fulfil the promise of its success in animal models of epilepsy. Enzyme induction by concurrent antiepileptic therapy may provide an explanation.", "In a therapy-resistant epileptic population with partial complex seizures with or without secondary generalization, addition of flunarizine to existing therapy was accompanied by a significant reduction in complex partial and tonic-clonic seizures. This result did not appear to be due to serial effects or changes in the plasma levels of the co-medication. Side effects were rare. The serum flunarizine levels (13.8 ng/ml; range, 3-32.5 ng/ml) were lower than previously reported on a daily dose of 10 mg. This may reflect increased metabolism due to induction of liver enzymes by the co-medication. Given this finding, together with the low incidence of side effects, a further study is required to determine whether higher blood levels would give an improved degree and incidence of seizure reduction.", "We report a double blinded cross-over study involving Flunarizine versus placebo in the treatment of refractory childhood epilepsy. The patients studied were between the ages of 2 and 18; and were having more than 4 seizures per month not responsive to regular anticonvulsant medications. Of the 34 patients treated, 8 had a 50% decrease in their seizures during the placebo phase, 5 had a 50% decrease during the Flunarizine phase, and 1 patient had a 50% increase in seizures while taking Flunarizine. The remaining 25 patients showed no change in seizure activity in either phase. Patients having partial seizures with secondary generalization tended to do better on Flunarizine than those with other seizure types. Monitoring serum Flunarizine levels showed no significant difference between patients having improved seizure control and those who were unimproved. No significant side effects were noted with this medication, nor were any significant drug interactions noted.", "Twenty-five patients with long-standing therapy resistant epilepsy were studied in an eight-month double-blind cross-over add-on trial with a daily dose of 15 mg flunarizine. In five patients the seizure frequency decreased 50% or more. The mean seizure frequency reduction in the patients on flunarizine was 35%. Particularly the control of secondary generalized seizures improved. Flunarizine did not significantly alter the plasma levels of the regular anticonvulsant drugs. Minimal adverse side effects were reported equally in the flunarizine and the placebo group. In three patients depressive symptoms improved and two patients became free of postictal headaches. Flunarizine appears to be a safe adjuvant anticonvulsant.", "Flunarizine (FLN) has been suggested as an add-on treatment in drug-resistant epilepsy patients. In view of the discordant experiences and of the paucity of controlled trials in children, we studied its effectiveness in 20 patients aged 6 to 18 years (10 males and 10 females), affected by drug-resistant epilepsy. 14 had symptomatic generalized epilepsy (the Lennox-Gastaut syndrome in 10; other forms in 4); 3 had cryptogenic generalized epilepsy (the Lennox-Gastaut syndrome in 2; myoclonic absences epilepsy in 1); 3 had symptomatic partial epilepsy (temporal lobe epilepsy). 7 of them were withdrawn: only 1 because of side effects. An initial four-month baseline pretrial period was followed by two four-month periods of administration of FLN or a placebo, under double blind conditions, in a randomized sequence. Preexisting antiepileptic (AEDs) medication was maintained at a constant dose throughout the study. FLN was administered as drops in a single evening dose of 5 mg (patients less than 10 years) or 10 mg. (patients greater than 10 years). During the pretrial phase, after phase 1 and phase 2, a waking EEG was recorded and blood samples were taken for hematology, hepatic-function tests, and AED serum levels. The evaluation of the activity of FLN was based on the total number of seizures. A 30-60% reduction in seizure frequency was found in 5 out of the 13 patients completing the trial (no changes occurred in the remainders). This result did not appear to be due to changes in the plasma levels of the AEDs. No significant differences were seen in the EEG paroxysmal activity in the three phases of the study. Side effects were rare. The serum FLN levels ranged between 16.4 and 109 ng/ml. It seems that the antiepileptic properties of FLN need further validation, particularly in childhood.", "The anticonvulsant efficacy and side-effect liability of flunarizine (15 mg/day) was investigated in a randomized, double-blind, placebo-controlled, crossover design in 30 outpatients with drug-resistant complex partial seizures. Flunarizine or placebo was added to the preexisting medication and each patient was followed up for 10 months. At the end of the study data from 22 patients were available for evaluation. In patients taking first flunarizine and then placebo, plasma levels of flunarizine were still detectable at the end of the 4 months' placebo phase. In the group of 13 patients starting therapy with placebo, a significant seizure frequency reduction was observed during the flunarizine period in 11 patients, whereas one patient showed no change and seizure frequency increased in another patient. Two patients had a 50% reduction in seizure frequency. Flunarizine was well tolerated and few side effects were noted.", "The movement of calcium into neurons may be the common denominator for the triggering and propagation of seizure activity. We report results of the first double-blind, placebo-controlled, crossover trial with the dihidropyridine calcium antagonist nifedipine (NFD) as adjuvant therapy in refractory epilepsy. Twenty-two students (12 male, 10 female, age 17-22 years) attending Lingfield Hospital School received NFD retard and matched placebo for 8 weeks in 2 doses (20 and 40 mg b.i.d. each for 4 weeks) with a washout period of 8 weeks between treatment phases. In the 20 students who completed the trial, fewer partial seizures (p less than 0.05) were documented during the first 2 weeks of NFD administration. Similarly, fewer seizure days (p less than 0.05) were reported in the first month of active treatment. This response was not sustained into the second month of the trial. Blind scoring of EEGs suggested a small improvement with NFD (p less than 0.05). More patients reported headache when receiving NFD (p less than 0.02) than placebo, but heart rate and erect and supine blood pressure remained unaffected. Mean maximum NFD concentrations were 13.1 +/- 10.4 ng/ml. A weak correlation was noted between total (p less than 0.05) and partial (p = 0.025) seizure numbers and NFD concentrations following 8 weeks of treatment. This study does not support important anticonvulsant efficacy for NFD as adjuvant therapy for refractory epilepsy at doses appropriate for the treatment of angina or hypertension. Further trials are recommended using higher doses of NFD in less severely affected patients.", "Flunarizine was compared to placebo in a double-blind cross-over trial of 2 16-week treatment periods separated by a 4-week wash-out period. The patients had epilepsy with complex partial seizures with or without secondary generalised seizures. Twenty-nine patients entered the trial, but 7 dropped out. Of the 22 patients completing the trial, 13 were women; the median was 39 years (range 15-58) and the median duration of epilepsy 23 years (range 4-55). There was no statistically significant difference between flunarizine 15 mg daily and placebo as adjunct therapy in total seizure frequency, neuropsychological tests, and patient's preferences. No interactions with concomitant antiepileptic drugs and no laboratory abnormalities were registered.", "The anticonvulsive effect of flunarizine was studied in a multicenter trial, by means of a randomized, double-blind, single crossover design. The subjects who entered the study were 51 males and 39 females, aged 15 to 73 years. They were epileptic patients who suffered from at least two generalized seizures per month or more than 4 partial seizures per month. The patients were already being treated with major antiepileptic drugs. Flunarizine was administered in a single evening dose of 10 mg/die in patients who weighed less than 70 kg and of 15 mg/die in patients who weighed more 70 kg. Our results show that flunarizine, given as add-on therapy, produced a slight but significant decrease in the number of monthly seizures at the end of a 3-month period, while placebo did not significantly change the seizures frequency." ]

[ "6988265", "15197140", "17174222", "2527134", "19705345", "1748145", "12749508", "15334791", "21205128", "16114544", "11230779", "9589648", "17485893", "3891264", "20194881", "8082525", "1490692", "15860237", "16207627", "15375799", "10369424", "16506273", "9135927", "14693413", "11268714", "16026361", "10421233", "9742976", "9742977", "12401757", "2534084", "17145742", "14693964", "10406828", "15220012", "3935376", "17907113", "12746761", "7733122", "16864814", "15270789", "8077888", "3124685", "7843470", "8112188", "10097930", "7821128", "7556806", "15787663", "14768770", "16999648", "21409314", "11472451", "992232", "12870162", "15735185" ]

[ "Glipizide versus tolbutamide, an open trial. Effects on insulin secretory patterns and glucose concentrations.", "Regression of carotid atherosclerosis by control of postprandial hyperglycemia in type 2 diabetes mellitus.", "A one-year study comparing the efficacy and safety of rosiglitazone and glibenclamide in the treatment of type 2 diabetes.", "A randomized crossover study of sulphonylurea and insulin treatment in patients with type 2 diabetes poorly controlled on dietary therapy.", "Efficacy and safety comparison between the DPP-4 inhibitor vildagliptin and the sulfonylurea gliclazide after two years of monotherapy in drug-naïve patients with type 2 diabetes.", "Prospective comparative study in NIDDM patients of metformin and glibenclamide with special reference to lipid profiles.", "Comparison between repaglinide and glimepiride in patients with type 2 diabetes mellitus: a one-year, randomized, double-blind assessment of metabolic parameters and cardiovascular risk factors.", "Metabolic variations with oral antidiabetic drugs in patients with Type 2 diabetes: comparison between glimepiride and metformin.", "Liraglutide, a once-daily human glucagon-like peptide 1 analogue, provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetes.", "[Effects of glimepiride and metformin on free fatty acid in patients with Type 2 diabetes mellitus].", "Concentration of the complement activation product, acylation-stimulating protein, is related to C-reactive protein in patients with type 2 diabetes.", "Advantages of alpha-glucosidase inhibition as monotherapy in elderly type 2 diabetic patients.", "Effects of pioglitazone hydrochloride on Japanese patients with type 2 diabetes mellitus.", "Medication compliance in non-insulin-dependent diabetes: a randomized comparison of chlorpropamide and insulin.", "Effect of rosiglitazone on progression of coronary atherosclerosis in patients with type 2 diabetes mellitus and coronary artery disease: the assessment on the prevention of progression by rosiglitazone on atherosclerosis in diabetes patients with cardiovascular history trial.", "Efficacy of 24-week monotherapy with acarbose, glibenclamide, or placebo in NIDDM patients. The Essen Study.", "Efficacy of 6 months monotherapy with glucosidase inhibitor Acarbose versus sulphonylurea glibenclamide on metabolic control of dietary treated type II diabetics (NIDDM).", "Effect of pioglitazone on arteriosclerosis in comparison with that of glibenclamide.", "Influence of glucose control and improvement of insulin resistance on microvascular blood flow and endothelial function in patients with diabetes mellitus type 2.", "Effect of pioglitazone on carotid intima-media thickness and arterial stiffness in type 2 diabetic nephropathy patients.", "Repaglinide versus glyburide: a one-year comparison trial.", "Effect of pioglitazone on urinary liver-type fatty acid-binding protein concentrations in diabetes patients with microalbuminuria.", "The efficacy and safety of miglitol therapy compared with glibenclamide in patients with NIDDM inadequately controlled by diet alone.", "Is acarbose equivalent to tolbutamide as first treatment for newly diagnosed type 2 diabetes in general practice? A randomised controlled trial.", "Comparison of acarbose and gliclazide as first-line agents in patients with type 2 diabetes.", "Comparison of metabolic effects of pioglitazone, metformin, and glimepiride over 1 year in Japanese patients with newly diagnosed Type 2 diabetes.", "Effects of gliclazide versus metformin on the clinical profile and lipid peroxidation markers in type 2 diabetes.", "Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group.", "Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group.", "A comparison of the effects of rosiglitazone and glyburide on cardiovascular function and glycemic control in patients with type 2 diabetes.", "Effect of glycaemic control, metformin and gliclazide on platelet density and aggregability in recently diagnosed type 2 (non-insulin-dependent) diabetic patients.", "Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy.", "Favorable effects of pioglitazone and metformin compared with gliclazide on lipoprotein subfractions in overweight patients with early type 2 diabetes.", "Vasodilatory effects of troglitazone improve blood pressure at rest and during mental stress in type 2 diabetes mellitus.", "Effects of pioglitazone and glimepiride on glycemic control and insulin sensitivity in Mexican patients with type 2 diabetes mellitus: A multicenter, randomized, double-blind, parallel-group trial.", "Comparison of diabetic control in type 2 (non-insulin dependent) diabetic patients treated with different sulphonylureas.", "Long-term effects of pioglitazone versus gliclazide on hepatic and humoral coagulation factors in patients with type 2 diabetes.", "Metabolic effects of mealtime insulin lispro in comparison to glibenclamide in early type 2 diabetes.", "Multicenter, placebo-controlled trial comparing acarbose (BAY g 5421) with placebo, tolbutamide, and tolbutamide-plus-acarbose in non-insulin-dependent diabetes mellitus.", "Postprandial plasma glucose excursions and cognitive functioning in aged type 2 diabetics.", "Sustained effects of pioglitazone vs. glibenclamide on insulin sensitivity, glycaemic control, and lipid profiles in patients with Type 2 diabetes.", "A long-term, randomized, comparative study of insulin versus sulfonylurea therapy in type 2 diabetes.", "Glyburide or insulin for metabolic control in non-insulin-dependent diabetes mellitus. A randomized, double-blind study.", "One year comparative trial of metformin and glipizide in type 2 diabetes mellitus.", "Long-term randomized placebo-controlled double-blind therapeutic comparison of glipizide and glyburide. Glycemic control and insulin secretion during 15 months.", "A 1-year multicenter randomized double-blind comparison of repaglinide and glyburide for the treatment of type 2 diabetes. Dutch and German Repaglinide Study Group.", "Therapeutic comparison of metformin and sulfonylurea, alone and in various combinations. A double-blind controlled study.", "Comparison of miglitol and glibenclamide in diet-treated type 2 diabetic patients.", "A long-term comparison of pioglitazone and gliclazide in patients with Type 2 diabetes mellitus: a randomized, double-blind, parallel-group comparison trial.", "Prospective multicentre trial comparing the efficacy of, and compliance with, glimepiride or acarbose treatment in patients with type 2 diabetes not controlled with diet alone.", "Long-term safety of pioglitazone versus glyburide in patients with recently diagnosed type 2 diabetes mellitus.", "Effects of insulin versus sulphonylurea on beta-cell secretion in recently diagnosed type 2 diabetes patients: a 6-year follow-up study.", "Comparison between repaglinide and glipizide in Type 2 diabetes mellitus: a 1-year multicentre study.", "A study of the effects of hypoglycemia agents on vascular complications in patients with adult-onset diabetes. VI. Supplementary report on nonfatal events in patients treated with tolbutamide.", "Combination treatment with metformin and glibenclamide versus single-drug therapies in type 2 diabetes mellitus: a randomized, double-blind, comparative study.", "Comparison of pioglitazone and gliclazide in sustaining glycemic control over 2 years in patients with type 2 diabetes." ]

[ "An open parallel trial with glipizide or tolbutamide was carried out in a cohort of 29 comparable maturity-onset diabetic patients. Eighteen of these individuals were studied in detail. During six months of active drug therapy the mean decrease in fasting serum glucose levels on glipizide was 25 +/- 2% versus 17 +/- 2% on tolbutamide (p less than 0.025). Decreases in post prandial glucose levels were 12.2 and 10.4%. Glucose disappearance rates (Kg) during the sixth month of treatment with both drugs increased significantly: on glipizide from 0.47 +/- 0.04%/min to 0.85 +/- 0.08%/min(p less than 0.005), and on tolbutamide from 0.47 +/- 0.08%/min to 0.70 +/- 0.11%/min (p less than 0.01). Early and late insulin release (summed increases over basal for 2--10 min and 10--60 min) during intravenous glucose tolerance testing increased during glipizide, but not during tolbutamide therapy. Post prandial insulin increments over basal during an oral glucose tolerance test also increased during glipizide, but not tolbutamide therapy. Both drugs were comparable with regard to efficacy and safety; however, only glipizide had chronic effects upon insulin secretion.", "Postprandial hyperglycemia may be a risk factor for cardiovascular disease. We compared the effects of two insulin secretagogues, repaglinide and glyburide, known to have different efficacy on postprandial hyperglycemia, on carotid intima-media thickness (CIMT) and markers of systemic vascular inflammation in type 2 diabetic patients.\n We performed a randomized, single-blind trial on 175 drug-naive patients with type 2 diabetes mellitus (93 men and 82 women), 35 to 70 years of age, selected from a population of 401 patients who participated in an epidemiological analysis assessing the relation of postprandial hyperglycemia to surrogate measures of atherosclerosis. Eighty-eight patients were randomly assigned to receive repaglinide and 87 patients to glyburide, with a titration period of 6 to 8 weeks for optimization of drug dosage and a subsequent 12-month treatment period. The effects of repaglinide (1.5 to 12 mg/d) and glyburide (5 to 20 mg/d) on CIMT were compared by using blinded, serial assessments of the far wall. After 12 months, postprandial glucose peak was 148+/-28 mg/dL in the repaglinide group and 180+/-32 mg/dL in the glyburide group (P<0.01). HbA(1c) showed a similar decrease in both groups (-0.9%). CIMT regression, defined as a decrease of >0.020 mm, was observed in 52% of diabetics receiving repaglinide and in 18% of those receiving glyburide (P<0.01). Interleukin-6 (P=0.04) and C-reactive protein (P=0.02) decreased more in the repaglinide group than in the glyburide group. The reduction in CIMT was associated with changes in postprandial but not fasting hyperglycemia.\n Reduction of postprandial hyperglycemia in type 2 diabetic patients is associated with CIMT regression.", "This study was designed to compare the efficacy of rosiglitazone and glibenclamide in individuals with type 2 diabetes over a 12-month period.\n A total of 598 patients were randomized to double-blind treatment for 52 weeks with rosiglitazone 4 mg/d (n=200), rosiglitazone 8 mg/d (n=191) or glibenclamide (n=207; dose adjusted up to 15 mg/d over the first 12 weeks according to clinical response). Changes in fasting plasma glucose (FPG), haemoglobin A1c (HbA1c), fasting insulin and its precursor peptides, and lipids were measured and safety was evaluated. Significant reductions in HbA1c levels at 52 weeks compared with baseline were seen in all treatment groups (rosiglitazone 4 mg/d=-0.3%, P=0.0003; rosiglitazone 8 mg/d=-0.5%, P<0.0001; glibenclamide=-0.7%, P<0.0001). Mean FPG levels were also significantly reduced in all treatment groups (rosiglitazone 4 mg/d=-1.4 mmol/l; rosiglitazone 8 mg/d=-2.3 mmol/l; glibenclamide=-1.7 mmol/l; P<0.0001 vs. baseline for all treatments). Rosiglitazone therapy reduced plasma insulin, proinsulin, split proinsulin and free fatty acid levels compared with glibenclamide. Rosiglitazone improved insulin resistance while a worsening was seen with glibenclamide. Total:high-density lipoprotein cholesterol ratios were reduced with glibenclamide and unchanged with rosiglitazone. All treatments were generally well tolerated.\n The efficacy of rosiglitazone 8 mg/d in improving glycaemic control in patients with type 2 diabetes is comparable to that of glibenclamide. However, rosiglitazone reduced insulin resistance and proinsulin levels whereas glibenclamide use was associated with an increase in fasting insulin and proinsulin. This suggests that in the long term, rosiglitazone may protect the beta-cell whereas glibenclamide is likely to increase the burden.", "In 13 non-obese patients with Type 2 diabetes mellitus who failed to achieve adequate blood glucose control on dietary treatment (fasting blood glucose 13.4 +/- 2.7 (+/- SD) mmol l-1, glycosylated haemoglobin 13.0 +/- 1.7%), the effects of 6 months insulin or sulphonylurea therapy on blood glucose control and lipid metabolism were compared in a randomized crossover study. Three patients, who showed a clear improvement on insulin (median glycosylated haemoglobin fell from 14.7 to 8.6%), withdrew from the study prematurely because of subjective and objective signs of hyperglycaemia after crossover from insulin to sulphonylurea. Daily dose after 6 months was 2000 mg tolbutamide (n = 3), 18 +/- 1 mg glibenclamide (n = 7), or 34 +/- 3 U insulin. On insulin, fasting (8.0 +/- 1.9 mmol l-1) and postprandial blood glucose (10.4 +/- 2.7 mmol l-1), and glycosylated haemoglobin (9.5 +/- 1.1%) were lower than on sulphonylurea (11.0 +/- 3.4 mmol l-1, 14.4 +/- 4.8 mmol l-1 and 11.0 +/- 2.5%, respectively, p less than 0.05 in each case). Median increase in body weight was greater on insulin (4.2 vs 1.1 kg, p less than 0.05). Six patients experienced improved well-being on insulin compared with sulphonylurea. Median plasma non-esterified fatty acids decreased from 825 mumol l-1 to 476 mumol l-1 (sulphonylurea) and 642 mumol l-1 (insulin, both p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)", "This report is part of the overall evaluation of using vildagliptin in the treatment of type 2 diabetes. Here the results of a multi-center, double-blind, randomized, active-controlled study designed to compare the efficacy and safety of two years of monotherapy with vildagliptin 50 mg bid and gliclazide up to 320 mg/day in drug-naïve patients with type 2 diabetes are reported. A total of 546 patients were randomized and approximately 74% of patients completed the study in each group. HbA (1c) values were slightly higher in the gliclazide group (HbA (1c) of 8.7+/-0.1% vs. 8.5+/-0.1% in the vildagliptin group). The mean reduction in HbA (1c) from baseline to Week 104 was -0.5% in the vildagliptin group and -0.6% in the gliclazide group. The associated 95% confidence interval (CI) for the between-group difference (0.13%) in mean change was (-0.06%, 0.33%). Thus, noninferiority based on an upper limit of the CI of 0.3% was not met. In the vildagliptin group, weight increased by 0.8+/-0.2 kg compared to 1.6+/-0.2 kg in the gliclazide group (p<0.01). Mild hypoglycemia was recorded in 0.7% of patients in the vildagliptin group and in 1.7% in the gliclazide group. Both drugs were well tolerated. In summary, vildagliptin monotherapy resulted in improved glycemic control in drug-naïve patients with type 2 diabetes. Although the hypothesis of noninferiority to gliclazide was not borne out statistically, the reductions in HbA (1c) were similar over a two year period and vildagliptin had significant benefits in terms of less weight gain and less hypoglycemia.\n Georg Thieme Verlag KG Stuttgart. New York.", "Twenty-two NIDDM patients completed an open randomized cross-over study comparing metformin and glibenclamide over 1 year. The drugs had an equivalent effect on glycaemic control, but, in contrast to glibenclamide, metformin reduced body weight. Neither drug affected triglycerides, total- and LDL-cholesterol or C-peptide. Metformin caused a slight elevation of HDL-cholesterol (P less than 0.05). No serious adverse effects were observed. The results show that oral hypoglycaemic agents are not associated with undesirable effects on lipids and lipoproteins.", "Repaglinide and glimepiride are relatively new oral hypoglycemic agents. Few data are available concerning their effects on metabolic parameters other than measures of glycemic control.\n In addition to assessing the effects of repaglinide and glimepiride on glycemic control in patients with type 2 diabetes mellitus, this study also examined the effects of these agents on 3 metabolic parameters known to be cardiovascular risk factors--lipoprotein(a) (Lp[a]), plasminogen activator inhibitor-1 (PAI-1), and homocysteine (Hcy).\n This randomized, placebo-controlled, double-blind trial was conducted at a single center in Italy. Eligible patients were nonsmokers; had no hypertension or coronary heart disease; were taking no hypolipidemic drugs, diuretics, beta-blockers, or thyroxin; and had normal renal function. After an initial 4-week placebo washout period, patients were randomized to receive repaglinide 1 mg/d or glimepiride 1 mg/d. The dose of study drug was optimized over an 8-week titration period, which was followed by a 12-month treatment period. Measures of glycemic control (glycated hemoglobin [HbA1c], fasting plasma glucose [FPG], postprandial plasma glucose [PPG], fasting plasma insulin [FPI], postprandial plasma insulin [PPI]) and the other metabolic parameters of interest were assessed after 6 and 12 months of treatment.\n One hundred twenty-four patients (63 women, 61 men) completed the study, 62 in each treatment group. There were no significant differences in demographic characteristics between groups. After 6 and 12 months of treatment, FPG levels and HbA1c values were significantly reduced from baseline in both groups (6 months, P < 0.05; 12 months, P < 0.01). After 6 months, PPG levels were significantly decreased only in the repaglinide group (P < 0.05 vs baseline); at 12 months, however, PPG levels were significantly reduced from baseline in both groups (P < 0.01 repaglinide, P < 0.05 glimepiride). No significant changes from baseline in FPI or PPI levels were seen in either group at 6 months, although FPI levels were significantly increased in the repaglinide group at 12 months (P < 0.05). Repaglinide significantly lowered levels of Lp(a), PAI-1, and Hcy after 12 months (all, P < 0.05 vs baseline). Glimepiride significantly lowered levels of Lp(a) and Hcy after 6 months (both, P < 0.05 vs baseline) and levels of Lp(a) (P < 0.01 vs baseline), Hcy (P < 0.01 vs baseline), and PAI-1 (P < 0.05 vs baseline) after 12 months.\n Repaglinide and glimepiride improved glycemic control and reduced levels of other metabolic parameters of interest in this population of patients with type 2 diabetes. It is possible that the reductions in Lp(a), PAI-1, and Hcy were the result of improved glucose metabolism; however, the possibility that repaglinide and glimepiride may have a direct effect on these parameters should not be excluded.", "Patients with Type 2 diabetes (T2DM) are at high risk of morbidity and mortality from cardiovascular complications, and hypoglycaemia increases this risk. Furthermore, other metabolic parameters exacerbate cardiovascular risk in these patients. The aim of the study was to compare the metabolic effects of glimepiride and metformin in patients with T2DM. We evaluated 164 patients with T2DM (80 males, 84 females) in a multicentre, randomised, controlled, open, parallel group study comparing glimepiride with metformin. Eighty-one patients (aged 56+/-10 yr) received glimepiride (3+/-1 mg/d); 83 patients (aged 58+/-9 yr) received metformin (2500+/-500 mg/d). Patients had been diagnosed for < or = 6 months; they were non-smokers; had no hypertension or coronary heart disease; were not taking hypolipidaemic drugs, diuretics, beta-blockers or thyroxin; and had normal renal function. Metabolic parameters were measured after 6 and 12 months of treatment. Glimepiride significantly lowered lipoprotein(a) [Lp(a)] and homocysteine levels (HCT) at 6 and 12 months. Both glimepiride and metformin lowered plasminogen activator inhibitor Type 1 (PAI-1) at 12 months and significantly improved levels of glycosylated haemoglobin, fasting plasma glucose and post-prandial plasma glucose after 6 and 12 months. Metformin significantly lowered fasting plasma insulin and postprandial plasma insulin. Glimepiride and metformin also reduced levels of other metabolic parameters in patients with T2DM. In particular, glimepiride significantly reduced HCT, Lp(a), and PAI-1 levels, important metabolic risk factors for atherosclerotic vascular disease. These reductions may be owing to improved glucose metabolism, but it cannot be excluded that these drugs have a direct effect on additional metabolic parameters.", "Most treatments for type 2 diabetes fail over time, necessitating combination therapy. We investigated the safety, tolerability and efficacy of liraglutide monotherapy compared with glimepiride monotherapy over 2 years.\n Participants were randomized to receive once-daily liraglutide 1.2 mg, liraglutide 1.8 mg or glimepiride 8 mg. Participants completing the 1-year randomized, double-blind, double-dummy period could continue open-label treatment for an additional year. Safety data were evaluated for the full population exposed to treatment, and efficacy data were evaluated for the full intention-to-treat (ITT) and 2-year completer populations. Outcome measures included change in glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight and frequency of nausea and hypoglycaemia.\n For patients completing 2 years of therapy, HbA1c reductions were -0.6% with glimepiride versus -0.9% with liraglutide 1.2 mg (difference: -0.37, 95% CI: -0.71 to -0.02; p = 0.0376) and -1.1% with liraglutide 1.8 mg (difference: -0.55, 95% CI: -0.88 to -0.21; p = 0.0016). In the ITT population, HbA1c reductions were -0.3% with glimepiride versus -0.6% with liraglutide 1.2 mg (difference: -0.31, 95% CI: -0.54 to -0.08; p = 0.0076) and -0.9% with liraglutide 1.8 mg (difference: -0.60, 95% CI: -0.83 to -0.38; p < 0.0001). For both ITT and completer populations, liraglutide was more effective in reducing HbA1c, FPG and weight. Over 2 years, rates of minor hypoglycaemia [self-treated plasma glucose <3.1 mmol/l (<56 mg/dl)] were significantly lower with liraglutide 1.2 mg and 1.8 mg compared with glimepiride (p < 0.0001).\n Liraglutide monotherapy for 2 years provides significant and sustained improvements in glycaemic control and body weight compared with glimepiride monotherapy, at a lower risk of hypoglycaemia.\n © 2011 Blackwell Publishing Ltd.", "To investigate the effect of glimepiride and metformin on free fatty acid (FFA) in patients with Type 2 diabetes mellitus and to further study the relationship between free fatty acid and insulin resistance in patients with Type 2 diabetes mellitus.\n A prospective and case-control study was conducted. Ninty-four patients with Type 2 diabetes mellitus (35-70 year-old) were divided into 3 groups: glimepiride treated group (n=33), metformin treated group (n=29) and glimepiride plus metformin treated group (n=32). These patients were followed up for 6 months. Free fatty acids were measured by using an enzymatic colorimetry.\n The concentration of FFA didn't significantly change in the glimepiride treated group at the end of treatment, but it obviously decreased in the metformin treated group and in the glimepiride plus metformin treated group (P < 0.05 and P < 0.001, respectively). The decrease of FFA in the glimepiride plus metformin treated group was more obvious than that in the glimepiride treated group (P < 0.05). The fasting serum FFA concentration is positively related to HOMA-IR( homeostasis model assessment-insulin resistance) and the choice of drugs by stepwise regression analysis.\n Metformin alone or metformin plus glimepiride can decrease FFA levels, body weight index, blood glucose and insulin resistance. FFA level can reflect the index of insulin resistance to some degree.", "Type 2 diabetes is characterized by increased acute phase serum proteins. We wanted to study how these proteins are related to complement activation in type 2 diabetes and how improvement of glycemic control affects them or complement activation. A total of 29 type 2 diabetic patients (age, 55.2 +/- 1.8 years, glycosylated hemoglobin [HbA(1c)] 8.9% +/- 0.2%, body mass index [BMI] 30.9 +/- 0.8 kg/m(2), duration 5.9 +/- 1.3 years) participated in the study. They were previously treated either with diet alone or in combination with 1 oral antihyperglycemic medication. After a period of at least 4 weeks run-in on diet only, the patients were randomized to pioglitazone, glibenclamide, or placebo. Blood samples were taken before the treatments and at the end of the 6-month therapy. Basal C-reactive protein (CRP) level was related to acylation-stimulating protein (ASP) concentration (r =.55, P <.01), and many acute phase serum protein concentrations were associated with each other. The treatment reduced HbA(1c) level in the pioglitazone (from 9.1 +/- 0.3% to 8.0 +/- 0.5%, P <.05) and glibenclamide (from 8.9 % +/- 0.3% to 7.7% +/- 0.2%, P <.05) groups. Glibenclamide treatment was associated with a reduction in alpha-1-antitrypsin (P <.05), ceruloplasmin (P <.01), and complement C3 protein (C3) (P <.05). Although ASP did not change significantly in any of the treatment subgroups, in the whole patient population, the change in HbA(1c) during the treatments correlated positively with the change in ASP, (r =.43, P <.05). The changes in many acute phase serum proteins and ASP were related to each other. In conclusion, (1) inflammatory factors and complement activation are associated in patients with type 2 diabetes, and (2) changes in hyperglycemia are related to changes in the concentration of the complement activation product, ASP.\n Copyright 2001 by W.B. Saunders Company", "The objective of this study was to determine the safety, efficacy, and tolerability of the alpha-glucosidase inhibitor miglitol vs. the sulfonylurea glyburide in the treatment of elderly patients with type 2 diabetes mellitus, inadequately controlled by diet alone. This was a double-blind, randomized, placebo-controlled, 1-yr trial of miglitol 25 mg TID and 50 mg TID compared with placebo and a titrated dose of glyburide in a parallel group comparison study conducted in 30 out-patient sites across the United States. Four hundred eleven (411) diet-treated patients age 60 yr or greater were randomized to receive either placebo TID (n = 101), miglitol 25 mg TID (n = 104), miglitol 50 mg TID (n = 102), or a once-daily dose of glyburide titrated based on fasting plasma glucose (FPG) (n = 104), for a period of 56 weeks. Efficacy was assessed by glycated hemoglobin (HbA1c), fasting and post-meal glucose, insulin, and lipid levels, and by 24-h urinary excretion of glucose and albumin. Safety and tolerability were assessed by tabulation of adverse events, periodic laboratory determinations, and home blood glucose monitoring. HbA1c treatment effects (placebo-subtracted change in HbA1c from baseline) at the 1-yr endpoint were -0.49%, -0.40%, and -0.92% in the miglitol 25 mg TID, miglitol 50 mg TID, and glyburide groups, respectively (P < 0.05- 0.01 vs. placebo). Postprandial insulin levels were significantly greater than placebo and miglitol in the glyburide group (P < 0.01). Hypoglycemia, weight gain, and both routine and serious cardiovascular events were more frequent in the glyburide group (P < 0.05-0.01 vs. placebo or miglitol groups). Diarrhea (or soft stools) and flatulence were more common in both miglitol groups than in the other two groups in a dose-dependent manner, but resulted in relatively few study dropouts. Treatment with miglitol offers the elderly type 2 diabetic patient significant reductions in daylong glycemia as measured by HbA1c. The greater HbA1c reductions seen with once-a-day glyburide occurred at a cost of significant increases in weight, insulin levels, and the incidences of clinical and subclinical hypoglycemia, which did not occur in the miglitol groups. alpha-glucosidase inhibitors are a useful and relatively safe therapeutic option in the elderly patient with type 2 diabetes.", "The effects of pioglitazone hydrochloride monotherapy on abnormal lipid control were evaluated in Japanese patients with type 2 diabetes mellitus, comparing with glibenclamide monotherapy.\n Patients were randomly assigned to receive, once daily, pioglitazone hydrochloride, at 15 mg or 30 mg (n=46), or glibenclamide, at 1.25 mg or 2.5 mg (n=46). The 24-week study included patients with type 2 diabetes having high levels of triglyceride (TG).\n Pioglitazone hydrochloride produced beneficial effects on dyslipidemia in patients with type 2 diabetes, compared with the baseline and the glibenclamide group, as demonstrated by increases in high-density lipoprotein cholesterol (HDL-C) levels and low-density lipoprotein cholesterol (LDL) particle size, a fall in TG levels, and an increased ratio of visceral to subcutaneous fat volumes (V/S). Pioglitazone hydrochloride reduced fasting serum insulin levels, with low fasting plasma glucose (FPG) and glycohemoglobin levels, compared to the baseline, suggesting an improvement of insulin resistance.\n As expected, glibenclamide reduced FPG levels through increased insulin secretion. Pioglitazone hydrochloride and glibenclamide were well tolerated. Pioglitazone hydrochloride improved dyslipidemia related to insulin resistance, whereas glibenclamide enhanced insulin secretion, with only a minor effect on lipid control, in Japanese patients with type 2 diabetes.", "Medication compliance may be a problem in the management of patients with diabetes. Some physicians initially treat patients having non-insulin-dependent diabetes with oral sulfonylureas because they fear greater compliance problems with insulin therapy. We compared compliance with insulin and chlorpropamide in patients newly beginning medication for NIDDM. Seventy-seven adults with hyperglycemia despite diet therapy were randomly assigned to chlorpropamide or insulin. Compliance was measured four times over 24 wk. Patients then crossed over to the other medication and were followed for 24 additional weeks. Overall, there were no differences in compliance with the two medications in terms of percent of prescription used, proportion taking at least 80% of prescribed medication, self-report of medication or diet compliance, or protocol dropout rates. However, treatment satisfaction was higher with chlorpropamide, and most patients preferred chlorpropamide to insulin (P less than 0.0001). While such differences in satisfaction may affect long-term compliance, physicians should not assume that their patients will be less compliant with insulin than with oral sulfonylureas.", "Rosiglitazone has several properties that may affect progression of atherosclerosis. The Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in Diabetes Patients With Cardiovascular History (APPROACH) study was undertaken to determine the effect of the thiazolidinedione rosiglitazone on coronary atherosclerosis as assessed by intravascular ultrasound compared with the sulfonylurea glipizide.\n This was a randomized, double-blind, controlled 18-month study in 672 patients aged 30 to 80 years with established type 2 diabetes mellitus treated by lifestyle, 1 oral agent, or submaximal doses of 2 oral agents who had at least 1 atherosclerotic plaque with 10% to 50% luminal narrowing in a coronary artery that had not undergone intervention during a clinically indicated coronary angiography or percutaneous coronary intervention. The primary outcome was change in percent atheroma volume in the longest and least angulated epicardial coronary artery that had not undergone intervention. Secondary outcomes included change in normalized total atheroma volume and change in total atheroma volume in the most diseased baseline 10-mm segment. Rosiglitazone did not significantly reduce the primary outcome of percent atheroma volume compared with glipizide (-0.64%; 95% confidence interval, -1.46 to 0.17; P=0.12). The secondary outcome of normalized total atheroma volume was significantly reduced by rosiglitazone compared with glipizide (-5.1 mm(3); 95% confidence interval, -10.0 to -0.3; P=0.04); however, no significant difference between groups was observed for the change in total atheroma volume within the most diseased baseline 10-mm segment (-1.7 mm(3); 95% confidence interval, -3.9 to 0.5; P=0.13).\n Rosiglitazone did not significantly decrease the primary end point of progression of coronary atherosclerosis more than glipizide in patients with type 2 diabetes mellitus and coronary atherosclerosis. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique Identifier: NCT00116831.", "To compare the different therapeutic principles of alpha-glucosidase inhibitors and sulphonylureas as first-line treatment in non-insulin-dependent diabetes mellitus (NIDDM) patients with dietary failure.\n Ninety-six NIDDM patients (35-70 years of age, body mass index [BMI] < or = 35), insufficiently treated with diet alone (HbA1c 7-9%) were randomized into three groups and treated for 24 weeks with acarbose, glibenclamide, or placebo. Efficacy, based on fasting blood glucose (BG), BG 1 h after ingestion of standard breakfast (postprandial), serum insulin, postprandial insulin increase, and HbA1c; and tolerability, based on subjective symptoms and laboratory values, were investigated every 6 weeks. Efficacy evaluation was valid for 85 patients.\n The test drugs were dosed as follows: 100 mg acarbose (A) three times a day, 1 placebo tablet three times a day, 3.5 mg glibenclamide tablets dosed 1-0-0 or 1-0-1, mean dose 4.3 mg/day. Compared with the placebo, both drugs showed the same mean efficacy on fasting BG (-1.4 mM with acarbose, -1.6 mM with glibenclamide), 1-h postprandial BG (-2.2 mM with acarbose, -1.9 mM with glibenclamide), and HbA1c (-1.1% with acarbose, -0.9% with glibenclamide); but they showed a marked difference in 1-h postprandial insulin values (-80.7 pM with acarbose, 96.7 pM with glibenclamide). The mean relative insulin increase (1-h postprandial) was 1.5 in the placebo group, 1.1 in the acarbose group, and 2.5 in the glibenclamide group. No changes in body weight could be observed. No adverse events were seen under placebo. Acarbose led to mild or moderate intestinal symptoms in 38% of patients. Glibenclamide led to hypoglycemia, which could be solved by dose reduction, in 6% of patients. No dropouts occurred in any of the treatment groups.\n Acarbose and glibenclamide are effective drugs for the monotherapy of NIDDM patients when diet alone fails. Because postprandial insulin increase has been shown to be associated with increased risk for cardiovascular disease, acarbose, which lowers pp increase, may be superior to glibenclamide, which elevates postprandial insulin increase.", "Six months monotherapy with Acarbose vs. glibenclamide led to a marked improvement of BG and HbA1 in NIDDM, insufficiently controlled with diet. Beneficial effects of these distinct principles of action were statistically not different.", "Pioglitazone is an insulin-sensitizing agent that has been reported to have anti-arteriosclerotic effects.\n To investigate the anti-arteriosclerotic effects of pioglitazone in patients with diabetes mellitus using pulse wave velocity (PWV) as an index of efficacy.\n Twenty-seven patients with type 2 diabetes mellitus were randomly assigned to two groups, and pioglitazone (n=13) or glibenclamide (n=14) was administered for 6 months. The TG, TC, LDL-C, and HDL-C, FPG, HbA1c, IRI levels, HOMA-IR, and ba-PWV data were examined before and after administration of each agent.\n FPG and HbA1c were significantly improved in both the groups after treatment, but IRI, HOMA-IR and were improved only in the PIO group. The percent change of ba-PWV from the baseline after treatment in the PIO group improved significantly than that in the GC group (-6.3 +/- 5.6% versus 0.8 +/- 5.7%).\n The findings in this study suggested that pioglitazone has anti-arteriosclerotic effects. We concluded that drugs for the treatment of diabetes mellitus should be selected taking into consideration such endpoints as blood sugar control, and also the risk of complications such as cardiovascular events in the future.", "The study was performed to investigate the effect of improving metabolic control with pioglitazone in comparison to glimepiride on microvascular function in patients with diabetes mellitus type 2.\n A total of 179 patients were recruited and randomly assigned to one treatment group. Metabolic control (HbA1c), insulin resistance (HOMA index), and microvascular function (laser Doppler fluxmetry) were observed at baseline and after 3 and 6 months.\n HbA1c improved in both treatment arms (pioglitazone: 7.52 +/- 0.85% to 6.71 +/- 0.89%, p < .0001; glimepiride: 7.44 +/- 0.89% to 6.83 +/- 0.85%, p < .0001). Insulin-resistance decreased significantly in the pioglitazone group (6.15 +/- 4.05 to 3.85 +/- 1.92, p < .0001) and remained unchanged in the glimepiride group. The microvascular response to heat significantly improved in both treatment groups (pioglitazone 48.5 [15.2; 91.8] to 88.8 [57.6; 124.1] arbitrary units [AU], p < .0001; glimepiride 53.7 [14.1; 91.9] to 87.9 [52.9, 131.0] AU, p < .0001, median [lower and upper quartile]). Endothelial function as measured with the acetylcholine response improved in the pioglitazone group (38.5 [22.2; 68.0] to 60.2 [36.9; 82.8], p = .0427) and remained unchanged in the glimepiride group.\n Improving metabolic control has beneficial effects in microvascular function in type 2 diabetic patients. Treatment of type 2 diabetic patients with pioglitazone exerts additional effects on endothelial function beyond metabolic control.", "Atherosclerosis is the major cause of morbidity and mortality in patients with type 2 diabetes, and pioglitazone has been reported to have anti-inflammatory and potential antiatherogenic effects. The aim of the present study was to determine whether pioglitazone, glibenclamide, or voglibose affects carotid intima-media thickness (IMT), pulse wave velocity (PWV), and urinary albumin excretion (UAE) in normotensive type 2 diabetic nephropathy patients. Forty-five normotensive type 2 diabetes patients with microalbuminuria were randomized to 12-month treatment with pioglitazone (30 mg/d, n = 15), glibenclamide (5 mg/d, n = 15), or voglibose (0.6 mg/d, n = 15). Pre- and posttreatment UAE, PWV, and IMT values were compared between treatment groups and a group of age-matched healthy control subjects (n = 30). Pretreatment PWV, IMT, and UAE values differed little between the 3 groups, but UAE was greater in the 45 type 2 diabetes patients (132.5 +/- 36.4 microg/min) than in the control subjects (6.2 +/- 1.8 microg/min, P < .001). IMT (0.76 +/- 0.12 mm) was significantly greater in the diabetics than in the controls (0.60 +/- 0.08 mm, P < .01). PWV (1,840 +/- 320 cm/s) was also significantly greater in the diabetics than in the controls (1,350 +/- 225 cm/s, P < .01). After 6 and 12 months, UAE, IMT, and PWV in the pioglitazone treatment group were significantly lower than those in the glibenclamide treatment group and voglibose treatment group (UAE: 6 months, P < .05 and 12 months, P < .01; IMT and PWV: 6 months, P < .05 and 12 months, P < .05). Pioglitazone, but not glibenclamide or voglibose, appears to be effective in reducing UAE, IMT, and PWV in normotensive type 2 diabetes patients with microalbuminuria.", "This prospective, 1-year, multicenter, double-blind, randomized, parallel-group study was designed to show that repaglinide was at least equivalent to glyburide in patients with type 2 diabetes. Five hundred and seventy-six patients with type 2 diabetes of at least 6 months' duration were randomized to receive monotherapy with repaglinide (n = 383) or glyburide (n = 193). During weeks 1-8, doses were gradually increased to achieve a target fasting plasma glucose (FPG) range of 80-140 mg/dl. The final adjusted dose was maintained for 12 months. Repaglinide patients received a starting dose of 0.5 mg three times/day preprandially, adjusted as necessary to 1, 2 or 4 mg before breakfast, lunch and dinner. Glyburide patients received a starting dose of 2.5 mg before breakfast and placebo before lunch and dinner. Glyburide was increased as necessary to 5 or 10 mg before breakfast (placebo before lunch and dinner) or to 15 mg (10 mg before breakfast, placebo before lunch, and 5 mg before dinner). After study drug was stopped, patients were transferred to an appropriate therapy, as recommended by the investigator. Efficacy was assessed by changes from baseline in glycemic control parameters and in C-peptide, insulin, and lipid profiles. Repaglinide provided glycemic control that was at least as effective and potentially safer than that provided by glyburide. The glucose-lowering effect of repaglinide was most pronounced in pharmacotherapy-naive patients, who showed rapid and marked decreases in mean glycosylated hemoglobin levels from baseline (9.4%) to month 3 (7.6%) and month 12 (7.9%). Mean FPG levels also decreased overall in this group, from 222 mg/dl at baseline, to 175 mg/dl at month 3, to 188 mg/dl at month 12. At endpoint, morning C-peptide levels had increased significantly in glyburide-treated patients compared with those treated with repaglinide, but morning fasting insulin levels did not differ significantly between the two groups. Repaglinide efficacy was sustained over 1 year and was not influenced by age or sex. Overall safety and changes in lipid profile and body weight were similar with both agents, with no significant change after extended pharmacotherapy. Weight gain data for the subset of pharmacotherapy-naïve patients suggest that patients given repaglinide may gain less weight than those given glyburide. Repaglinide, at doses of 0.5-4.0 mg administered three times preprandially, was well tolerated and provided safe and consistently effectiveglycemic control during this 1-year study. Patients using repaglinide received the same therapeutic benefits as those using glyburide, and may have received additional benefits.", "Urinary liver-type fatty acid-binding protein (L-FABP) is a useful marker for renal tubulointerstitial injury. Pioglitazone is reported to be effective in early diabetic nephropathy. The aim of the present study was to determine whether pioglitazone affects urinary L-FABP levels in diabetic nephropathy patients with microalbuminuria.\n Sixty-eight patients with type 2 diabetes and microalbuminuria were randomized to a 12-month treatment with pioglitazone (30 mg/d, n = 17), glibenclamide (5 mg/d, n = 18), voglibose (0.6 mg/d, n = 17), or nateglinide (270 mg/d, n = 16). Pre- and posttreatment urinary albumin excretion (UAE) and urinary L-FABP concentrations were compared between the four treatment groups and 40 age-matched healthy subjects.\n Pretreatment UAE and urinary L-FABP levels differed little between the four groups. UAE and urinary L-FABP levels were significantly greater in the diabetes patients than in the healthy subjects (UAE: p < 0.001; L-FABP: p < 0.01). After 6 and 12 months, UAE and urinary L-FABP were significantly lower in the pioglitazone treatment group than in the other treatment groups (UAE: 6 months, p < 0.01 and 12 months, p < 0.001; L-FABP: 6 months, p < 0.05 and 12 months, p < 0.01).\n Pioglitazone, but not glibenclamide, voglibose, or nateglinide, appears to be effective in reducing UAE and the urinary L-FABP level, suggesting that pioglitazone has a specific role in ameliorating both glomerular and tubulointerstitial lesions associated with early diabetic nephropathy.", "To compare the therapeutic effects of the alpha-glucosidase inhibitor miglitol (BAY m 1099), the sulfonylurea glibenclamide, and placebo on parameters of metabolic control and safety in patients with NIDDM that is inadequately controlled by diet alone.\n After a 4-week placebo run-in period, 201 patients in 18 centers in 4 countries were randomized in a double-blind manner to miglitol (50 mg t.i.d., followed by 100 mg t.i.d.), glibenclamide (3.5 mg q.d/b.i.d.), or placebo for 24 weeks. Efficacy criteria were changes from baseline of HbA1c, fasting and postprandial blood glucose and insulin levels, body weight, and serum triglycerides.\n Efficacy was assessed in 119 patients who completed the full protocol, and the results were similar to those obtained in 186 patients who fulfilled the validity criteria for analysis. Compared with placebo, mean baseline-adjusted HbA1c decreased by 0.75% (P = 0.0021) and 1.01% (P = 0.0001) in the miglitol and glibenclamide treatment groups, respectively. Blood glucose decreased slightly in the fasting state and considerably in the postprandial state in both treatment groups but not in the placebo group. Fasting insulin levels increased slightly (NS) in all treatment groups; however, postprandial insulin levels decreased with miglitol, while increasing markedly with glibenclamide (P = 0.0001 between all treatment groups). Gastrointestinal side effects (flatulence and diarrhea) occurred mostly in the miglitol-treated patients, while some glibenclamide-treated patients had symptoms suggestive of hypoglycemia.\n Miglitol monotherapy is effective and safe in NIDDM patients. Compared with glibenclamide, it reduced HbA1c less effectively and caused more gastrointestinal side effects. On the other hand, glibenclamide, unlike miglitol, tended to cause hypoglycemia, hyperinsulinemia, and weight gain, which are not desirable in patients with NIDDM.", "We performed a double blind randomised controlled trial in general practice to assess equivalence between tolbutamide and acarbose with respect to the effect on mean HbA(1c) in newly diagnosed patients with type 2 diabetes. Secondary objectives were to compare the effects of both treatments on fasting and post-load blood glucose and insulin levels, lipids, and adverse events. Patients were randomised to receive acarbose, titrated step-wise to a maximum of 100mg three times daily (n=48) or tolbutamide, similarly titrated to a maximum of 2000 mg in three doses (n=48). The two treatments were considered equivalent if the two-sided 90% confidence interval (CI) for the difference in mean HbA(1c) levels was within the range -0.4 to 0.4%. Results were analysed on an intention-to-treat, per-protocol and on worst-case basis. Both agents reduced the HbA(1c) percentage and fasting blood glucose levels. The difference in mean decrease of HbA(1c) was 0.6% in favour of tolbutamide (90% CI 0.3, 0.9; 95% CI 0.2, 1.0). A worst-case analysis, assuming no change in HbA(1c) for dropouts, yielded a difference in mean decrease of 0.9% (90% CI 0.6, 1.2) in favour of tolbutamide. The difference in mean decrease of fasting blood glucose was 1.0 mmol/l in favour of tolbutamide (95% CI 0.3, 1.7). There were no significant differences in post-load blood glucose, fasting and post-load insulin levels, or lipids. In the acarbose group significantly more patients (15 versus 3) discontinued therapy because of adverse effects, mostly of gastrointestinal origin. We conclude that the results of this study favour tolbutamide over acarbose as first treatment for patients with newly diagnosed type 2 diabetes.", "To compare the effect of acarbose and gliclazide on clinical findings, biochemical parameters and safety in type 2 diabetic patients insufficiently controlled with medical nutrition therapy (MNT).\n Seventy-two patients (age 35-70 years, BMI < or = 35 kg/m2), who had not taken any oral antidiabetic drug previously, were randomised into two groups after a four-week placebo period, and treated for 24 weeks with acarbose (100 mg two to three times daily) and gliclazide (40-80 mg twice daily). The study was open and 57 patients (33 males and 24 females) completed it. MNT was provided for each patient based on personal requirements as defined by a dietitian. The effect of treatment was evaluated by fasting and postprandial (PP) metabolic parameters (blood glucose, insulin and C peptide levels), HbA1c and plasma lipid levels. In addition, side-effects were recorded and clinical examinations performed.\n Both drugs were effective in reducing of HbA1c, fasting and PP blood glucose levels. However, PP serum insulin levels in the gliclazide group increased more than those in the group treated with acarbose (p = 0.007). Moreover, a small weight reduction was obtained with acarbose treatment but not with gliclazide. Lipid levels were favourably affected by both drugs. Total cholesterol levels decreased in both groups, the decrease only reaching significance in the acarbose group (p = 0.013). However, serum levels of LDL cholesterol decreased in both groups (acarbose and gliclazide, p = 0.033 and p = 0.023, respectively), but the ratio of HDL to LDL cholesterol increased in the acarbose group only (p = 0.045). Both treatments were generally well tolerated. Common complaints in the acarbose group were flatulence and meteorism (29.6%). However, 10.0% of the patients in the gliclazide group reported at least one mild hypoglycaemic episode.\n The results of the study demonstrate that acarbose and gliclazide were reasonably effective in improving metabolic control in patients insufficiently controlled with diet alone, and both treatments were well tolerated. Because of its effects on weight reduction and PP hyperinsulinaemia, acarbose may be preferred as a first-line drug, particularly in the treatment of overweight type 2 diabetic patients.", "To compare the metabolic effects of pioglitazone, metformin, and glimepiride in the treatment of Japanese patients with newly diagnosed Type 2 diabetes.\n A total of 114 patients with Type 2 diabetes who had never used oral hypoglycaemic drugs were studied for 12 months. Patients were randomly assigned to pioglitazone (30-45 mg/day, n = 38), metformin (750 mg/day, n = 39), or glimepiride (1.0-2.0 mg/day, n = 37). The effect of treatment on fasting plasma glucose (FPG), glycated haemoglobin (HbA(1c)), 1,5-anhydroglucitol (1,5AG), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, free fatty acids (FFA), and fasting plasma insulin levels was monitored monthly. Body weight and safety data were also collected.\n Eight patients withdrew from the study (three in the pioglitazone group, two in the metformin group, and three in the glimepiride group). The rate of reduction of HbA(1c) was fastest in patients receiving glimepiride and slowest in patients receiving pioglitazone. Although there were no significant differences among the three groups in HbA(1c) levels at the end of the study, patients taking pioglitazone had relatively lower FPG and 1,5AG levels than patients taking the other two drugs. These results suggest that pioglitazone acts predominantly on nocturnal metabolism rather than at mealtimes. FFA were reduced significantly in those taking pioglitazone (542.2 microEq/l vs. 237.3 microEq/l; P < 0.01) before a decrease in HbA(1c) was apparent. The change in FFA levels correlated with the change in HbA(1c) (r = 0.409, P < 0.01). There were no significant differences in other lipid parameters among the groups.\n Pioglitazone, metformin, and glimepiride are equally effective in reducing blood glucose in patients with newly diagnosed Type 2 diabetes. However, their specific characteristics, such as the rapid action on blood glucose levels of glimepiride and the favourable action on FPG and FFA of pioglitazone, should be considered when choosing an appropriate agent.", "The sulfonylurea gliclazide and the biguanide metformin have different mechanisms to reduce glycemia. We performed a randomized study to compare these two agents with respect to glycemic control and effects on lipid peroxidation markers in 36 adult patients with type 2 diabetes. Both agents significantly decreased glycosylated hemoglobin ([HbA1c] P < .05), fructosamine (P < .05), and the glucose-excursion curve during the oral glucose tolerance test ([OGTT] P < .01). With regard to the insulin curve during this test, no significant change was observed with metformin and a significant increase was measured with gliclazide (P < .05). Considering the small number of events, no significant difference was detected in the number of hypoglycemic episodes between the two agents. More upper-gastrointestinal (GI) symptoms were observed with metformin compared with gliclazide (P < .05). Even with no change in the standard lipid profile, both agents increased serum vitamin E (P < .01 for gliclazide and P < .05 for metformin) and decreased the level of lipid peroxidation markers in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles (P < .05). Despite different mechanisms of action, gliclazide and metformin demonstrated comparable levels of efficacy and complementary effects on lipid peroxidation markers.", "Improved blood-glucose control decreases the progression of diabetic microvascular disease, but the effect on macrovascular complications is unknown. There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation. We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial.\n 3867 newly diagnosed patients with type 2 diabetes, median age 54 years (IQR 48-60 years), who after 3 months' diet treatment had a mean of two fasting plasma glucose (FPG) concentrations of 6.1-15.0 mmol/L were randomly assigned intensive policy with a sulphonylurea (chlorpropamide, glibenclamide, or glipizide) or with insulin, or conventional policy with diet. The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group, the aim was the best achievable FPG with diet alone; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment: any diabetes-related endpoint (sudden death, death from hyperglycaemia or hypoglycaemia, fatal or non-fatal myocardial infarction, angina, heart failure, stroke, renal failure, amputation [of at least one digit], vitreous haemorrhage, retinopathy requiring photocoagulation, blindness in one eye, or cataract extraction); diabetes-related death (death from myocardial infarction, stroke, peripheral vascular disease, renal disease, hyperglycaemia or hypoglycaemia, and sudden death); all-cause mortality. Single clinical endpoints and surrogate subclinical endpoints were also assessed. All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy.\n Over 10 years, haemoglobin A1c (HbA1c) was 7.0% (6.2-8.2) in the intensive group compared with 7.9% (6.9-8.8) in the conventional group--an 11% reduction. There was no difference in HbA1c among agents in the intensive group. Compared with the conventional group, the risk in the intensive group was 12% lower (95% CI 1-21, p=0.029) for any diabetes-related endpoint; 10% lower (-11 to 27, p=0.34) for any diabetes-related death; and 6% lower (-10 to 20, p=0.44) for all-cause mortality. Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25% risk reduction (7-40, p=0.0099) in microvascular endpoints, including the need for retinal photocoagulation. There was no difference for any of the three aggregate endpoints between the three intensive agents (chlorpropamide, glibenclamide, or insulin). Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis (both p<0.0001). The rates of major hypoglycaemic episodes per year were 0.7% with conventional treatment, 1.0% with chlorpropamide, 1.4% with glibenclamide, and 1.8% with insulin. Weight gain was significantly higher in the intensive group (mean 2.9 kg) than in the conventional group (p<0.001), and patients assigned insulin had a greater gain in weight (4.0 kg) than those assigned chlorpropamide (2.6 kg) or glibenclamide (1.7 kg).\n Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications, but not macrovascular disease, in patients with type 2 diabetes.(ABSTRACT TRUNCATED)", "In patients with type 2 diabetes, intensive blood-glucose control with insulin or sulphonylurea therapy decreases progression of microvascular disease and may also reduce the risk of heart attacks. This study investigated whether intensive glucose control with metformin has any specific advantage or disadvantage.\n Of 4075 patients recruited to UKPDS in 15 centres, 1704 overweight (>120% ideal bodyweight) patients with newly diagnosed type 2 diabetes, mean age 53 years, had raised fasting plasma glucose (FPG; 6.1-15.0 mmol/L) without hyperglycaemic symptoms after 3 months' initial diet. 753 were included in a randomised controlled trial, median duration 10.7 years, of conventional policy, primarily with diet alone (n=411) versus intensive blood-glucose control policy with metformin, aiming for FPG below 6 mmol/L (n=342). A secondary analysis compared the 342 patients allocated metformin with 951 overweight patients allocated intensive blood-glucose control with chlorpropamide (n=265), glibenclamide (n=277), or insulin (n=409). The primary outcome measures were aggregates of any diabetes-related clinical endpoint, diabetes-related death, and all-cause mortality. In a supplementary randomised controlled trial, 537 non-overweight and overweight patients, mean age 59 years, who were already on maximum sulphonylurea therapy but had raised FPG (6.1-15.0 mmol/L) were allocated continuing sulphonylurea therapy alone (n=269) or addition of metformin (n=268).\n Median glycated haemoglobin (HbA1c) was 7.4% in the metformin group compared with 8.0% in the conventional group. Patients allocated metformin, compared with the conventional group, had risk reductions of 32% (95% CI 13-47, p=0.002) for any diabetes-related endpoint, 42% for diabetes-related death (9-63, p=0.017), and 36% for all-cause mortality (9-55, p=0.011). Among patients allocated intensive blood-glucose control, metformin showed a greater effect than chlorpropamide, glibenclamide, or insulin for any diabetes-related endpoint (p=0.0034), all-cause mortality (p=0.021), and stroke (p=0.032). Early addition of metformin in sulphonylurea-treated patients was associated with an increased risk of diabetes-related death (96% increased risk [95% CI 2-275], p=0.039) compared with continued sulphonylurea alone. A combined analysis of the main and supplementary studies showed fewer metformin-allocated patients having diabetes-related endpoints (risk reduction 19% [2-33], p=0.033). Epidemiological assessment of the possible association of death from diabetes-related causes with the concurrent therapy of diabetes in 4416 patients did not show an increased risk in diabetes-related death in patients treated with a combination of sulphonylurea and metformin (risk reduction 5% [-33 to 32], p=0.78).\n Since intensive glucose control with metformin appears to decrease the risk of diabetes-related endpoints in overweight diabetic patients, and is associated with less weight gain and fewer hypoglycaemic attacks than are insulin and sulphonylureas, it may be the first-line pharmacological therapy of choice in these patients.", "This open-label, active-controlled study investigated the cardiac safety and antihyperglycemic effect of rosiglitazone (RSG) in patients with type 2 diabetes.\n Of the 203 patients randomly assigned to RSG (4 mg b.i.d.) or glyburide (GLB) (titrated to achieve optimal glycemic control for the first 8 weeks only to limit the risk of hypoglycemia; mean 10.5 mg/day), 118 had an echocardiogram performed at week 52. Left ventricular (LV) mass index, ejection fraction, and left ventricular end-diastolic volume were assessed by M-mode echocardiography at baseline and weeks 12, 28, and 52; 24-h ambulatory blood pressure was assessed at baseline and at weeks 28 and 52. Glycemic control was assessed by measuring fasting plasma glucose (FPG) and HbA(1c).\n Neither treatment produced an increase in LV mass index that exceeded 1 SD. Ejection fraction did not change in either group. Both groups had clinically insignificant increases in LV end-diastolic volume. RSG, but not GLB, caused a statistically significant reduction in ambulatory diastolic blood pressure. Both treatments reduced HbA(1c) and FPG.\n A total of 52 weeks of therapy with RSG (4 mg b.i.d.) did not adversely affect cardiac structure or function in patients with type 2 diabetes and produced significant and sustained reductions in hyperglycemia. Decreases in ambulatory diastolic blood pressure with RSG were superior to those with GLB.", "Platelet density profiles, intraplatelet nucleotides, intraplatelet beta thromboglobulin (beta TG), plasma beta TG levels, intraplatelet cyclic AMP (cAMP) levels, platelet release reaction, platelet thromboxane (TX)B2 production and plasma fibrinogen levels were investigated in 24 newly diagnosed, non-insulin-dependent diabetic patients and 12 comparable controls. These variables were measured at diagnosis, after a 3-6 week dietary run-in period, and again after 6 months on treatment with either metformin or gliclazide therapy. With dietary restriction of refined carbohydrate and oral hypoglycaemic therapy, there was a reduction in platelet density (p less than 0.05), intraplatelet nucleotides (p less than 0.001), intraplatelet beta TG (p less than 0.001), plasma beta TG (p less than 0.001) and there was an increase in intraplatelet cAMP levels (p less than 0.05). Although these platelet variables returned towards normal, only the platelet density mean returned to within the normal range. There was no significant change in the platelet TXB2 production and plasma fibrinogen levels with treatment. Metformin and gliclazide were equally effective in the glycaemic control of non-insulin-dependent diabetes, and there was no difference between the platelet variables measured in the two groups. We would therefore suggest that improvement of glycaemic control, rather than any specific effect of the oral hypoglycaemic agent employed, is the most important factor in returning these parameters towards normality.", "The efficacy of thiazolidinediones, as compared with other oral glucose-lowering medications, in maintaining long-term glycemic control in type 2 diabetes is not known.\n We evaluated rosiglitazone, metformin, and glyburide as initial treatment for recently diagnosed type 2 diabetes in a double-blind, randomized, controlled clinical trial involving 4360 patients. The patients were treated for a median of 4.0 years. The primary outcome was the time to monotherapy failure, which was defined as a confirmed level of fasting plasma glucose of more than 180 mg per deciliter (10.0 mmol per liter), for rosiglitazone, as compared with metformin or glyburide. Prespecified secondary outcomes were levels of fasting plasma glucose and glycated hemoglobin, insulin sensitivity, and beta-cell function.\n Kaplan-Meier analysis showed a cumulative incidence of monotherapy failure at 5 years of 15% with rosiglitazone, 21% with metformin, and 34% with glyburide. This represents a risk reduction of 32% for rosiglitazone, as compared with metformin, and 63%, as compared with glyburide (P<0.001 for both comparisons). The difference in the durability of the treatment effect was greater between rosiglitazone and glyburide than between rosiglitazone and metformin. Glyburide was associated with a lower risk of cardiovascular events (including congestive heart failure) than was rosiglitazone (P<0.05), and the risk associated with metformin was similar to that with rosiglitazone. Rosiglitazone was associated with more weight gain and edema than either metformin or glyburide but with fewer gastrointestinal events than metformin and with less hypoglycemia than glyburide (P<0.001 for all comparisons).\n The potential risks and benefits, the profile of adverse events, and the costs of these three drugs should all be considered to help inform the choice of pharmacotherapy for patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00279045 [ClinicalTrials.gov].).\n Copyright 2006 Massachusetts Medical Society.", "To compare effects of different oral hypoglycemic drugs as first-line therapy on lipoprotein subfractions in type 2 diabetes.\n Sixty overweight type 2 diabetic patients not on lipid-lowering therapy were randomized to metformin, pioglitazone, or gliclazide after a 3-month dietary run-in. Drug doses were uptitrated for 3 months to optimize glycemia and were kept fixed for a further 3 months. LDL subfractions (LDL(1), LDL(2), and LDL(3)) were prepared by density gradient ultracentrifugation at randomization and study end. Triglycerides, cholesterol, total protein, and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. The primary end point was change in proportion of LDL as LDL(3).\n HbA(1c), triglycerides, glucose, and cholesterol were comparable across groups at baseline and over time. LDL(3) mass and the LDL(3)-to-LDL ratio fell with pioglitazone (LDL(3) mass 36.2 to 28.0 mg/dl, P < 0.01; LDL(3)-to-LDL 19.2:13.3%, P < 0.01) and metformin (42.7 to 31.5 mg/dl, P < 0.01; 21.3:16.2%, P < 0.01, respectively) with no change on gliclazide. LDL(3) reductions were associated with reciprocal LDL(1) increases. Changes were independent of BMI, glycemic control, and triglycerides. Total HDL cholesterol increased on pioglitazone (1.28 to 1.36 mmol/l, P = 0.02) but not gliclazide (1.39 to 1.37 mmol/l, P = NS) or metformin (1.26 to 1.18 mmol/l, P = NS), largely due to an HDL(2) increase (0.3 to 0.4 mmol/l, P < 0.05). HDL(3) cholesterol fell on metformin (0.9 to 0.85 mmol/l, P < 0.01). On pioglitazone and metformin, the HDL(2)-to-HDL(3) ratio increased compared with no change on gliclazide.\n For the same improvement in glycemic control, pioglitazone and metformin produce favorable changes in HDL and LDL subfractions compared with gliclazide in overweight type 2 diabetic patients. Such changes may be associated with reduced atherosclerosis risk and may inform the choice of initial oral hypoglycemic agent.", "The present study examined the hemodynamic mechanisms of blood pressure (BP) lowering by troglitazone in patients with type 2 diabetes mellitus (DM) at rest and during a mental arithmetic test (MAT). Twenty-two patients with DM with normal to high-normal BP and 12 controls matched for age, gender, glucose tolerance, and BP were studied. DM subjects showed significantly higher systolic BP response during MAT than controls (157 versus 139 mm Hg; P<0.01). All 22 DM patients and 5 of 12 controls had systolic BP >140 mm Hg during MAT. Heart rate and diastolic BP were not significantly different between the 2 groups. The DM group was then randomized to receive troglitazone (n=10; 400 mg/d) or glyburide (n=12; 20 mg/d). MAT was repeated after 6 months of treatment. Both treatments reduced glucose equally (-1.7 mmol/L for troglitazone and -1.5 mmol/L for glyburide), but only troglitazone reduced insulin (-15 microU/mL; P<0.001) and C-peptide (-0.9 ng/mL; P<0.02) levels. Troglitazone significantly reduced BP at baseline (P<0.05) and systolic BP response to MAT (P<0.01), whereas glyburide did not affect BP at baseline or during MAT. Stroke volume and cardiac output did not change with either drug, but troglitazone decreased peripheral vascular resistance (-112 dyne. s. cm(-5); P<0.05). Improved insulin resistance rather than an improved glycemic control is associated with lower resting and stress BP values in patients with DM. A reduction in vascular resistance may be a primary hemodynamic mechanism of the manner in which troglitazone lowers BP. Insulin sensitizers may offer potential therapeutic advantage in subjects with DM with elevated BP.", "Pioglitazone and glimepiride improve glycemic control in patients with type 2 diabetes mellitus by different mechanisms. Pioglitazone is a thiazolidinedione that reduces insulin resistance, and glimepiride is a sulfonylurea insulin secretagogue.\n The goals of this study were to compare changes in measures of glycemic control and insulin sensitivity in Mexican patients with type 2 diabetes who received pioglitazone or glimepiride for 1 year.\n This was a multicenter, 52-week, double-blind, parallel-group trial. Patients were randomized to receive monotherapy with either glimepiride (2 mg QD initially) or pioglitazone (15 mg QD initially). Doses were titrated (maximal doses: pioglitazone 45 mg, glimepiride 8 mg) to achieve glycemic targets (fasting blood glucose < or =7 mmol/L and 1-hour postprandial blood glucose < or =10 mmol/L). Insulin sensitivity (primary end point) was evaluated in terms of the Homeostasis Model Assessment for Insulin Sensitivity (HOMA-S), the Quantitative Insulin Sensitivity Check Index (QUICKI), and fasting serum insulin (FSI) concentrations. Glycemic control was evaluated in terms of glycosylated hemoglobin (HbA(1c)) values and fasting plasma glucose (FPG) concentrations. Patients were encouraged to maintain their individual diet and exercise regimens throughout the study.\n Two hundred forty-four patients (125 women, 119 men; all but 1 Hispanic) were randomized to receive pioglitazone (n = 121) or glimepiride (n = 123). In the intent-to-treat sample, pioglitazone and glimepirede produced comparable reductions in HbA(1c) from baseline to the end of the study (-0.78% and -0.68%, respectively). The pioglitazone group had significantly higher HbA(1c) values compared with the glimepiride group after 12 weeks of therapy (8.66% vs 7.80%; P = 0.007) but had significantly lower values after 52 weeks (7.46% vs 7.77%; P = 0.027). Pioglitazone significantly reduced FPG compared with glimepiride (-0.6 vs 0.6 mmol/L; P = 0.01). Pioglitazone therapy was associated with significant increases in insulin sensitivity (reduced insulin resistance), whereas glimepiride had no effect. HOMA-S values changed 18.0% for pioglitazone and -7.9% for glimepiride (P < 0.001), QUICKI values changed a respective 0.013 and -0.007 (P < 0.001), and FSI values were -21.1 and 15.1 pmol/L (P< 0.001). Both drugs were well tolerated, with pioglitazone associated with more peripheral edema (number of treatment-emergent cases: 35/121[28.9%] vs 17/123 [13.8%]; P = 0.005) and fewer hypoglycemic episodes (19 [15.7%] vs 38 [30.9%]; P = 0.024). The incidence of weight gain was not significantly different between treatment groups. Conclusions: These data suggest that long-term treatment with pioglitazone enhances insulin sensitivity relative to glimepiride in Mexican patients with type 2 diabetes and that pioglitazone may have a more sustained antihyperglycemic effect.", "Diabetic control was compared in groups of Type 2 (non-insulin dependent) diabetic patients treated concurrently for 1 year with five different sulphonylurea drugs: chlorpropamide (21), glipizide (24), gliquidone (22), gliclazide (22) and glibenclamide (23). Glycosylated haemoglobin (HbA1) levels decreased in all groups over the first 2 months, but tended to level off or increase thereafter. In a total of 96 patients assessed after 1 year, gliclazide produced normal HbA1 levels in a significantly greater number of patients than chlorpropamide (p = 0.01) and gliquidone (p = 0.038), and glibenclamide was also significantly better than chlorpropamide (p = 0.02). Significant improvements in HbA1 were produced overall in the gliquidone (p less than 0.01), gliclazide (p less than 0.01) and glibenclamide (p less than 0.02) groups and the gliquidone and gliclazide groups were significantly better than the glipizide group (p less than 0.01 in both cases). Only the glibenclamide group had a significant change in weight (p less than 0.05). There may be differences between different sulphonylureas which could be of clinical advantage in certain patients.", "This study compared the long-term effects of pioglitazone and gliclazide on the production of coagulation factors in patients with type 2 diabetes. Patients (n=283) with glycosylated haemoglobin > 7.5% were randomised to receive either pioglitazone (30-45 mg/day) or gliclazide (80-320 mg/day) for one year. Coagulation factors were measured at baseline and at six and 12 months. While both pioglitazone and gliclazide induced a comparable improvement in glycaemic control, only pioglitazone improved insulin sensitivity. Pioglitazone significantly (p < or = 0.001) decreased circulating levels of von Willebrand factor (-9.7%, -9.4%) and plasminogen activator inhibitor-1 (-16.8 ng/ml, -12.3 ng/ml), and increased levels of antithrombin-III (+1.3 mg/dL, +1.5 mg/dL) after six and 12 months, respectively. The beneficial effects of pioglitazone on glycaemic control, lipid homeostasis, and coagulation and thrombosis, may improve vascular outcomes in patients with type 2 diabetes.", "The efficacy and safety of the preprandial injection of insulin lispro was compared with the oral administration of glibenclamide in patients with early type 2 diabetes. In this open-label, multicenter study, 143 patients with a glucagon-stimulated increase in C-peptide of at least 0.4 nmol/L were randomized to receive preprandial insulin lispro (LP) or glibenclamide (GB) for 26 weeks. Seventy-five patients received LP (51 male/24 female; age 40 to 70 years, duration of diabetes 4.4 +/- 2.9 years) and 68 patients received GB (39 male/29 female; age 39 to 70 years; duration of diabetes 4.3 +/- 3.4 years). After 12 weeks, mean 90 minute blood glucose excursions were 0.9 +/- 1.0 mmol/L for LP and 1.8 +/- 1.2 mmol/L for GB (p < 0.0001). After 24 weeks, mean blood glucose excursions were 1.0 +/- 1.1 mmol/L for LP and 1.7 +/- 1.2 mmol/L for GB (p = 0.002). Body weight decreased slightly from 87.2 +/- 2.3 to 86.5 +/- 12.2 kg in the LP group and increased from 84.1 +/- 13.7 to 84.4 +/- 13.3 kg in the GB group. LP versus GB induced changes from baseline to endpoint in fasting C-peptide (nmol/L), proinsulin and insulin levels (pmol/L) were - 0.2 +/- 0.4 versus - 0.1 +/- 0.6 (p = 0.04), - 11.2 +/- 26.0 versus - 1.1 +/- 17.3 (p = 0.03), and - 27.8 +/- 147.4 versus + 32.6 +/- 286.2 (not significant), respectively. HbA 1c at baseline was 7.5 +/- 1.0 % for LP and 7.7 +/- 1.2 % for GB and did not change significantly in either group during the investigation. No significant difference was observed between the groups with respect to hypoglycemic episodes. Treatment with LP improved postprandial blood glucose control more than GB without increasing body weight or hypoglycemic episodes. In addition, use of LP was associated with a decrease in fasting C-peptide and proinsulin levels, suggesting a potential down regulation of endogenous insulin production and improved proinsulin processing efficiency.", "Acarbose delays release of glucose from complex carbohydrates and disaccharides by inhibiting intestinal alpha-glucosidases, thereby attenuating postprandial increments in blood glucose and insulin. This multicenter, double-blind, placebo-controlled study compared the efficacy and safety of diet alone, acarbose, tolbutamide, and acarbose-plus-tolbutamide in non-insulin-dependent diabetes mellitus (NIDDM) patients.\n A total of 290 patients with NIDDM and fasting plasma glucose levels of at least 140 mg/dL were randomized to receive treatment TID with acarbose 200 mg, tolbutamide 250 to 1,000 mg, a combination of both drugs, or placebo. A 6-week run-in period was followed by double-blind treatment for 24 weeks, then a 6-week follow-up period.\n All active treatments were superior (P < 0.05) to placebo in reducing postprandial hyperglycemia and HbA1c levels. The ranking in order of efficacy was: acarbose-plus-tolbutamide, tolbutamide, acarbose, and placebo. The postprandial reductions in glucose were approximately 85 mg/dL for acarbose-plus-tolbutamide, 71 mg/dL for tolbutamide, 56 mg/dL for acarbose, and 13 mg/dL for placebo. Tolbutamide was associated with increases in body weight and postprandial insulin levels when taken alone, but these were ameliorated when tolbutamide was taken in combination with acarbose. Acarbose alone or in combination with tolbutamide caused significantly more gastrointestinal adverse events (mainly flatulence and soft stools or diarrhea) than tolbutamide or placebo, but these were generally well tolerated. Clinically significant elevations in hepatic transaminase levels occurred in 3 patients in the acarbose group and 2 in the acarbose-plus-tolbutamide group. Transaminase levels returned to normal when therapy was discontinued.\n Acarbose was effective and well tolerated in the treatment of NIDDM. Control of glycemia was significantly better with acarbose compared with diet alone. Acarbose-plus-tolbutamide was superior to tolbutamide alone.", "Postprandial plasma glucose (PPG) excursion is a significant determinant of overall metabolic control as well as an increased risk for diabetic complications. Older persons with type 2 diabetes mellitus (DM2) are more likely to have moderate cognitive deficits and neurophysiologic and structural changes in brain tissue. Considering that poor metabolic control is considered a deranging factor for tissue/organ damage in diabetics, the authors hypothesized that PPG excursion is associated with a decline in cognitive functioning and that a tighter control of PPG may prevent cognitive decline.\n Two groups of aged diabetic patients were randomly selected to be treated with repaglinide (n = 77) or glibenclamide (n = 79).\n Coefficient of variation of PPG (CV-PPG) was associated with Mini-Mental State Examination (MMSE) scores (r = -0.3410; p < 0.001) and a composite score of executive and attention functioning (r = -0.3744; p < 0.001) after adjusting for multiple confounders. Both groups showed a significant decline in hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG), but only the repaglinide group demonstrated a significant decline of CV-PPG over time. In models investigating the change in cognitive functioning over time, adjusted for HbA1c and CV-FPG, a decline in cognitive functioning was observed only in the glibenclamide group (p < 0.001). After adjusting for CV-PPG, the authors no longer found a decline in executive and attention functioning composite score (p = 0.085) or the MMSE (p = 0.080) with glibenclamide.\n Exaggerated postprandial glucose (PPG) excursions are associated with a derangement of both global, executive, and attention functioning. A tighter control of PPG may prevent cognitive decline in older diabetic individuals.", "This study compared the effects of 52 weeks' treatment with pioglitazone, a thiazolidinedione that reduces insulin resistance, and glibenclamide, on insulin sensitivity, glycaemic control, and lipids in patients with Type 2 diabetes.\n Patients with Type 2 diabetes were randomized to receive either pioglitazone (initially 30 mg QD, n = 91) or micronized glibenclamide (initially 1.75 mg QD, n = 109) as monotherapy. Doses were titrated (to 45 mg for pioglitazone and 10.5 mg for glibenclamide) to achieve glycaemic targets during the next 12 weeks: fasting blood glucose of < or = 7 mmol/l and 1-h postprandial blood glucose of < or = 10 mmol/l. Patients were maintained on the titrated dose for 40 weeks.\n Pioglitazone significantly increased insulin sensitivity compared with glibenclamide, as assessed by homeostasis model assessment (17.0% vs. -13.0%; P < 0.001), quantitative insulin sensitivity check index (0.011 vs. -0.007; P < 0.001) and fasting serum insulin (-1.3 pmol/l vs. 23.8 pmol/l; P = 0.007). The glibenclamide group had significantly lower HbA1c than the pioglitazone group after 12 weeks of therapy (7.8% vs. 8.3%, P = 0.015), but significantly higher HbA1c after 52 weeks of therapy (7.8% vs. 7.2%, P = 0.001). Pioglitazone significantly (vs. glibenclamide) increased mean HDL-C (P < 0.001), decreased mean triglycerides (P = 0.019), and decreased mean atherogenic index of plasma (AIP; P = 0.001) and mean total cholesterol/HDL-C (P = 0.004), without significantly elevating mean total cholesterol or mean LDL-C compared with glibenclamide. CONCLUSIONS These data suggest that the effects of pioglitazone are more sustained than those of glibenclamide for improving insulin sensitivity in patients with Type 2 diabetes, and that 52 weeks' treatment with pioglitazone has favourable effects on glycaemic control and lipoprotein profile.\n Copyright 2004 Diabetes UK", "To study the effect of insulin and sulfonylurea (SU) therapy on glycaemic control, insulin resistance and cardiovascular risk factors in type 2 diabetic subjects.\n A prospective, parallel, randomized, controlled, long-term study.\n Outpatient clinic in tertiary referral centre.\n Thirty-six type 2 diabetic subjects treated with diet and SU, aged 44-69 years and a duration of diabetes of between 2 and 14 years.\n Individually adjusted doses of insulin and glibenclamide.\n Glycosylated haemoglobin (HbA1c), insulin resistance (euglycaemic glucose clamp), levels of lipids, lipoproteins and blood pressure.\n Glycaemic control improved during insulin treatment, but deteriorated on SU; HbA1c levels differed significantly between groups after 12 months of therapy (mean +/- SEM 7.9 +/- 0.3 vs. 9.5 +/- 0.4%, P = 0.004). Body mass index increased significantly during insulin treatment (26.4 +/- 0.7 to 27.8 +/- 0.7 kg/m2, P = 0.0001) and 30% of this increase was a result of an increase in lean body mass. The total glucose disposal rate showed a small increase in the insulin group. Levels of triglycerides and apolipoprotein B were significantly reduced during insulin treatment (1.8 +/- 0.2 to 1.5 +/- 0.2 mmol L-1, P = 0.03 and 1.58 +/- 0.1 to 1.40 +/- 0.08 g L-1, P = 0.003), and insulin prevented a reduction in the levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1 and an increase in Lp(a) lipoprotein observed in the SU group. Blood pressure levels did not change during therapy.\n Insulin therapy was superior to SU treatment in achieving good metabolic control. Despite a modest improvement in cardiovascular risk factors in the insulin-treated group, no significant differences were observed between the groups after 1 year's treatment.", "To compare the relative efficacy, risks, and benefits of insulin with glyburide in achieving normoglycemia in non-insulin-dependent diabetes mellitus.\n Randomized, double-blind, placebo-controlled trial with a 9-month treatment period.\n University hospital.\n Thirty-one patients with non-insulin-dependent diabetes mellitus who did not have normal glucose control with diet alone.\n Once-per-day NPH insulin and placebo glyburide, or glyburide and once-per-day placebo insulin injection. Active drug and placebo adjusted in parallel to achieve fasting plasma glucose level less than 6.4 mmol/L (115 mg/dL) without hypoglycemia. MEASUREMENTS and\n Insulin and glyburide produced similar improvement in fasting blood glucose levels and hemoglobin A1c concentrations, similar frequencies of mild symptomatic hypoglycemia, and similar weight gain despite dietary reinforcement. Triglyceride and cholesterol levels decreased and high-density lipoprotein cholesterol and ratios of high-density lipoprotein to total cholesterol increased in both groups, with a significantly greater improvement in high-density lipoprotein cholesterol and ratio of high-density lipoprotein total cholesterol in patients treated with insulin.\n Therapy with glyburide or once-per-day NPH insulin provides a similar degree of glucose control in patients with non-insulin-dependent diabetes mellitus. Insulin may have a relative advantage in that it is associated with higher levels of high-density lipoprotein cholesterol and a higher ratio of high-density lipoprotein to total cholesterol.", "Forty-eight diabetic subjects with diet-failed Type 2 mellitus, aged 40-69 years, were randomised to metformin (24 patients) or glipizide (24 patients) therapy, and followed prospectively for 12 months. Most subjects were obese. Metformin gave better fasting plasma glucose control compared to glipizide at 24 (p < 0.01), 36 (p < 0.05) and 52 weeks (p < 0.05) with a lower HbA1 concentration at 52 weeks (p < 0.05). Metformin treated patients lost weight whereas glipizide treated subjects gained weight. The weight change between the treatment groups reached significance at 4 weeks (p < 0.05) and was highly significant (p < 0.001) at 8, 12, 24, 36 and 52 weeks. There were no significant changes in either fasting plasma lipid or blood lactate levels in either the metformin or glipizide treated groups. Both drugs caused a similar reduction in albumin excretion rates. In conclusion, metformin gave better glycaemic control than glipizide, with weight loss rather than weight gain in obese Type 2 patients.", "To examine the long-term (15 months) effects on glycemic control and insulin secretion of glipizide and glyburide treatment in patients with non-insulin-dependent diabetes mellitus (NIDDM).\n Prospective, randomized, double-blind, placebo-controlled study on 46 NIDDM patients comparing fasting levels and test-meal responses of glucose and insulin during 15 months of follow-up.\n A comparable reduction in HbA1c levels by both agents versus placebo was observed throughout the study period, but after a marked initial reduction in both sulfonylurea groups, all three groups showed gradually increasing HbA1c levels. However, both glipizide and glyburide achieved and maintained lowered postprandial glucose levels and increased fasting and postprandial insulin levels compared with placebo.\n Both glipizide and glyburide may achieve and maintain glycemic reduction and stimulation of insulin secretion during long-term treatment. However, these agents do not prevent the gradual increase in overall glycemia that develops over time in NIDDM patients.", "Repaglinide is a newly developed oral blood glucose-lowering agent that exerts its effect by stimulating insulin secretion. This multicenter study was designed to compare the efficacy and safety of this drug with glyburide in a 1-year randomized double-blind study of outpatients with type 2 diabetes.\n A total of 424 subjects (154 women, 270 men) participated and had the following characteristics: age, 61 +/- 9 years; duration of diabetes. 8 years (range 0.5-35); BMI, 28.3 +/- 3.5 kg/m2; HbA1c, 7.1 +/- 1.4%; and fasting plasma glucose, 10.8 +/- 3.1 mmol/l. The majority of the subjects (91%) were previously treated with sulfonylurea, alone or in combination with metformin. The patients were randomized to a 2:1 ratio of repaglinide (0.5-4 mg t.i.d.) or glyburide (1.75-10.5 mg daily) treatment. The study protocol included a screening visit to assess patient eligibility; a titration period of 6-8 weeks, during which the dosages of repaglinide and glyburide were optimized; and a subsequent 12-month treatment period on fixed, optimal dosages.\n The trial was completed by 320 subjects, 211 (74%) in the repaglinide and 109 (78%) in the glyburide group. HbA1c initially decreased in both groups and then increased during the second half-year of the maintenance period to a similar extent in the repaglinide and glyburide subjects (0.58 and 0.45% vs. at screening, respectively). In the small group of subjects who previously controlled their condition with diet only (n = 37), a sustained improvement of metabolic control could be observed with both drugs, which was slightly better with glyburide than with repaglinide (theta HbA1c -2.4 vs. -1.0%; P < 0.05). The same trends were seen with fasting plasma glucose. There were no changes in serum lipids. Over the course of the study, 15% of the repaglinide-treated and 13% of glyburide-treated subjects withdrew due to adverse events, mostly hyperglycemia. No differences in adverse events between both drugs were reported. There were no differences in incidences of hypoglycemia.\n Repaglinide is a safe and efficacious oral blood glucose-lowering agent, with a potency similar to that of glyburide. Its rapid onset of action and hepatic clearance allows meal-related administration, including in subjects with impaired kidney function.", "To assess and compare the therapeutic efficacy and safety of metformin (M) and sulfonylurea (glyburide, G), alone and in various combinations, in patients with non-insulin-dependent diabetes mellitus (NIDDM).\n Of 165 patients (fasting blood glucose [FBG] > or = 6.7 mmol/l) initially treated with diet alone, 144 (FBG still > or = 6.7 mmol/l) were randomized to double-blind, double-dummy controlled treatment with M, G, or primary combination therapy (MG). The dose was titrated, with FBG < 6.7 mmol/l as target, using, at most, six dose levels. The first three dose levels comprised increasing single-drug therapy (M or G) or primary combination at increasing but low dosage (MGL), and the second three levels were composed of various high-dose combinations, i.e., add-on therapy (M/G or G/M) and primary combination escalated to high dosage (MGH). Medication was maintained for 6 months after completed dose titration.\n The FBG target was achieved in 9% of patients after diet alone. Single-drug therapy was insufficient in 36% and MGL in 25% (NS) of the randomized patients. There was further improvement in glucose control by the high-dose combinations. Mean FBG +/- SE was reduced (P = 0.001) from 9.1 +/- 0.4 to 7.0 +/- 0.2 mmol/l in those maintained on single-drug treatment or low-dose primary combination. Those treated with different high-dose combinations had a large mean FBG reduction, from 13.3 +/- 0.8 to 7.8 +/- 0.6 mmol/l. HbA1c levels showed corresponding reductions, and glycemic levels rose after drug discontinuation. Fasting C-peptide rose during treatment with G and MGL but not with M, while fasting insulin was not significantly changed. Meal-stimulated C-peptide and insulin levels were unchanged by M but increased by G and, to a lesser extent, by MGL. There were no significant insulin or C-peptide differences between the different high-dose combinations (M/G, G/M, and MGH). Body weight did not change following treatment with M or combination but increased by 2.8 +/- 0.7 kg following G alone. Blood pressure was unchanged. Overall effects on plasma lipids were small, with no significant differences between groups. Drug safety was satisfactory, even if the reporting of (usually modest) adverse events was high; the profile, but not the frequency, differed between groups.\n Dose-effect titrated treatment with either metformin or glyburide promotes equal degrees of glycemic control. The former, but not the latter, is able to achieve this control without increasing body weight or hyperinsulinemia. Near-normal glycemia can be obtained by a combination of metformin and sulfonylurea, even in advanced NIDDM.", "The efficacy of the new intestinal alpha-glucosidase inhibitor, miglitol, and glibenclamide were compared in a 6-month double-blind controlled protocol involving 100 non-insulin dependent diabetic patients under diet alone. HbA1c levels (initially between 7 and 11%) were reduced (p < 0.05): -0.78 +/- 0.21% after miglitol and -1.18 +/- 0.20% after glibenclamide. The difference between the two treatments was not significant, although glibenclamide appeared to be more active than miglitol at 8 (p = 0.002) and 16 weeks (p = 0.01) but not at 24 weeks. Fasting glycaemia decreased after miglitol (8.7 +/- 0.3 vs 9.6 +/- 0.3 mmol/l, p = 0.005) and after glibenclamide (8.0 +/- 0.3 vs 9.1 +/- 0.3, p = 0.007). After miglitol, a decrease was noted after breakfast (p < 0.001) and lunch (p < 0.001). The same was true for glibenclamide (p = 0.004 and p < 0.001 respectively). A significant reduction in glucose incremental area during a standard meal test was noted at the end of miglitol (p = 0.008) or glibenclamide treatment (p = 0.04). Subgroups of nonresponders to both treatments were identified (10/49 with miglitol, 9/47 with glibenclamide). Side effects were recorded in 10 patients treated with miglitol (flatulence and meteorism, diarrhoea, 1 discontinued therapy) and in 10 treated with glibenclamide (asthenia, sensation of hunger). This study indicates that miglitol is suitable for initial application in diet-resistant Type 2 diabetic patients, providing, a persistent effect and acceptable side effects.", "This study compared the effects of pioglitazone and gliclazide on metabolic control in drug-naive patients with Type 2 diabetes mellitus.\n A total of 1270 patients with Type 2 diabetes were randomized in a parallel-group, double-dummy, double-blind study. Patients with poorly controlled Type 2 diabetes (HbA1c 7.5-11%), despite dietary advice, received either pioglitazone up to 45 mg once daily or gliclazide up to 160 mg two times daily. Primary efficacy endpoint was change in HbA1c from baseline to the end of the study. Secondary efficacy endpoints included change in fasting plasma glucose, fasting plasma insulin and plasma lipids. At selected centres, oral glucose tolerance tests were performed and C-peptide and pro-insulin levels were measured.\n Mean HbA1c values decreased by the same amount in the two treatment groups from baseline to week 52 [pioglitazone: -1.4%; gliclazide: -1.4%; (90% CI: -0.18 to 0.02)]. A significantly greater mean reduction in fasting plasma glucose was observed in the pioglitazone group (2.4 mmol/l) than in the gliclazide group [2.0 mmol/l; treatment difference -0.4 mmol/l in favour of pioglitazone; P = 0.002; (95% CI: -0.7 to -0.1)]. Improvements in high-density lipoprotein cholesterol (HDL-C) and total cholesterol/HDL-C were greater with pioglitazone than with gliclazide (P < 0.001). The frequencies of adverse events were comparable between the two treatment groups, but more hypoglycaemic events were reported for gliclazide, whereas twice as many patients reported oedema with pioglitazone than with gliclazide.\n Pioglitazone monotherapy was equivalent to gliclazide in reducing HbA1c, with specific differences between treatments in terms of mechanism of action, plasma lipids and adverse events.", "To determine the efficacy of, and compliance with, glimepiride or acarbose in patients with Type 2 diabetes.\n Two hundred and nineteen patients with Type 2 diabetes uncontrolled by diet alone were randomized to receive either glimepiride (1, 2, 3, 4 or 6 mg once daily, n = 111) or acarbose (50, 100, 150 or 200 mg 3 times daily, n = 108). Both drugs were titrated in a 6-week dose-finding phase to achieve a fasting blood glucose (FBG) concentration < or = 7.8 mmol/ (140 mg/dl). Patients achieving this target entered a 20-week treatment period. Efficacy was assessed by responder rate, number of patients achieving a FBG of < or = 7.8 mmol/l, HbA1c, blood glucose concentrations in response to a standard breakfast, body weight and compliance.\n Glimepiride was associated with a significantly greater responder rate than acarbose (61 vs 34%, p < 0.001), significantly greater decreases in HbA1c (2.5 +/- 2.2% vs 1.8 +/- 2.2%, p = 0.014) and FBG (2.6 +/- 2.6 mmol/l vs 1.4 +/- 2.8 mmo/l, p = 0.004), a decreased glucose response to breakfast compared with acarbose [area under curve (AUC) end: 8.9 +/- 2.7 mmol/l vs 11.3 +/- 3.9 mmol/l, p = 0.0001], and was accompanied by significantly greater compliance (91 < or = 12% vs 66 +/- 26%, p = 0.0001). Weight loss during the study was observed in both the acarbose group (1.9 +/- 3.9 kg, p = 0.001) and glimepiride group [0.4 +/- 5.2 kg, p = 0.8 (NS)].\n Improved efficacy and greater compliance were observed in response to treatment with glimepiride compared with acarbose, in patients with Type 2 diabetes.", "To evaluate the long-term safety and efficacy of glyburide versus pioglitazone in patients with a recent diagnosis of type 2 diabetes mellitus.\n Prospective, randomized, multicenter, double-blind trial with a 16-week titration period and a 40-week maintenance period.\n Sixty-five investigative sites in the United States and Puerto Rico.\n Five hundred two subjects with a recent diagnosis of type 2 diabetes that was unsuccessfully treated with diet and exercise were randomly assigned to study treatment. Of the 251 patients in each treatment group, 128 (51.0%) glyburide-treated patients and 134 (53.4%) pioglitazone-treated patients completed the study.\n Dosages of randomly assigned glyburide and pioglitazone were titrated every 4 weeks for 16 weeks in 5-mg/day and 15-mg/day increments, respectively, until a fasting plasma glucose level between 69 and 141 mg/dl was achieved. The optimized regimen was maintained during the subsequent 40-week double-blind phase.\n At week 56, glyburide and pioglitazone improved glucose control comparably (change in hemoglobin A(1c) -2.02% and -2.07%, respectively, p=0.669). Withdrawal due to lack of efficacy or adverse events occurred more frequently with glyburide (20.8%) than pioglitazone (12.8%, p<0.032). Significantly higher percentages of glyburide- than pioglitazone-treated patients had a hypoglycemic (24.3% vs 4.4%, p=0.0001) or cardiac (8.8% vs 4.4%, p=0.0478) event. Edema (4.8% vs 7.9%, p=0.1443) and weight gain (4.4% vs 4.0%, p=0.8238) did not differ significantly between the glyburide and pioglitazone groups. Only a few patients discontinued study drug because of weight gain (one glyburide, one pioglitazone), edema (one pioglitazone), or a cardiac event (two glyburide).\n With long-term treatment, both glyburide and pioglitazone resulted in comparable glycemic control; however, pioglitazone was associated with less hypoglycemia and fewer withdrawals due to lack of efficacy or adverse events.", "Early insulin treatment is considered more beneficial than anti-diabetic medication with sulphonylureas, because the latter may exert negative effects on beta-cell function, while the former may help preserve it. In a previous study, we found that C-peptide response was increased in the insulin-treated group, whereas it was decreased in the glibenclamide group. However, it was not certain whether the advantage remained in the longer term.\n In this study, we tested whether early insulin treatment is more beneficial than glibenclamide against a 6-year follow-up perspective.\n We designed a randomized clinical trial in subjects with newly diagnosed type 2 diabetes. Glucagon stimulatory tests, measuring C-peptide and islet amyloid polypeptide (IAPP), were performed after 2, and 3, days of temporary insulin and glibenclamide withdrawal.\n 18 subjects initially randomized to glibenclamide, and 16 randomized to two daily injections of insulin, participated in end-of-study investigations. C-peptide response to glucagon deteriorated (p < 0.01 vs. baseline) in initially glibenclamide-treated patients (n = 18), but not in insulin-treated patients (p < 0.05 for difference between groups, after 2 days of treatment withdrawal). The IAPP response to glucagon declined in the glibenclamide group (p < 0.001), but not in insulin-treated subjects (p = 0.05 for difference between groups).\n Early insulin treatment preserves beta-cell secretory function better than glibenclamide even in a 6-year perspective.", "To evaluate the long-term effectiveness and safety of repaglinide, a novel prandial glucose regulator, in comparison with glipizide in the treatment of patients with Type 2 diabetes.\n Diet or tablet-treated patients with Type 2 diabetes (n = 256; age 40-75 years, body mass index (BMI) 20-35 kg/m2, HbA1c 4.2-12.8%), without signs of severe microvascular or macrovascular complications, were included in this double-blind, multicentre, parallel-group comparative trial. Patients were randomized at a 2:1 ratio to repaglinide, 1-4 mg at mealtimes, or glipizide, 5-15 mg daily.\n Changes in fasting blood glucose (FBG) and HbA1c during the 12 months of treatment showed a significant difference in favour of repaglinide. In oral hypoglycaemic agents (OHA)-naive patients, HbA1c decreased in the repaglinide and glipizide groups by 1.5% and 0.3%, respectively (P < 0.05 between groups). Fasting blood glucose decreased in the repaglinide group by 2.4 mmol/l and increased in the glipizide group by 1.0 mmol/l (P < 0.05 between groups). In the study population as a whole, repaglinide was able to maintain glycaemic control (HbA1c level) during the 1-year study period, whereas control deteriorated significantly with glipizide. Change in HbA1c from baseline was significantly better with repaglinide than with glipizide after 12 months (P < 0.05). In addition, FBG deteriorated significantly in the glipizide group compared with the repaglinide group (P < 0.05). No patients in either group experienced a major hypoglycaemic event; the number of patients experiencing minor hypoglycaemia was similar in the repaglinide and glipizide groups (15% and 19%, respectively).\n Repaglinide, given as a prandial glucose regulator, is shown to be an effective and safe treatment of patients with Type 2 diabetes, and is better than glipizide in controlling HbA1c and FBG levels, overall, and in OHA-naive patients.", "nan", "To compare efficacy and tolerability of combination treatment with metformin and sulfonylurea with each of these drugs alone in the treatment of type 2 diabetes, 88 type 2 diabetic subjects (hemoglobin A1c [HbA1c] levels, 8.0%+/-1.0%; age, 57.3+/-7.1 years; body mass index [BMI]. 27.0+/-2.6 kg/m2; diabetes duration, 9.8+/-8.2 years; means +/- SD) were randomly assigned to double-blind treatment with metformin (500 to 3,000 mg/d), glibenclamide (5 to 15 mg/d), or their combination (metformin 400 to 2,400 mg/d + glibenclamide 2.5 to 15 mg/d) for 6 months. Thereafter, groups were crossed over for the following 6 months. Thus, each patient received metformin or glibenclamide alone, and the combination treatment. Doses were titrated to obtain HbA1c levels < or = 6.0% and fasting plasma glucose levels less than 140 mg/dL. Eighty patients concluded both treatment periods and were included in the analysis of treatment efficacy. In patients receiving metformin or glibenclamide alone, the maximal dose was reached in 21 and 25 patients, respectively; 8 and 15 of these subjects, respectively, required the maximal dose when they were on the combination treatment. During the study, 4 (10.0%) subjects receiving metformin, 7 (17.1%) receiving glibenclamide, and 31 (39.2%) receiving the combination treatment reached HbA1c levels < or = 6.0%. Moreover, when efficacy of the combination treatment on glycemic control was compared with that of single-drug therapies in each individual patient, the combination was significantly more effective than either metformin or glibenclamide (HbA1c after treatment, 6.1%+/-1.1% v 7.3%+/-1.4%, and 6.5%+/-0.7% v 7.6%+/-1.5%, respectively, both P<.0001). In conclusion, combination treatment with metformin and sulfonylurea is more effective than these drugs alone in improving glycemic control in type 2 diabetes, while also allowing a reduction of the dosage of each drug.", "The hypothesis that pioglitazone treatment is superior to gliclazide treatment in sustaining glycemic control for up to 2 years in patients with type 2 diabetes was tested.\n This was a randomized, multicenter, double-blind, double-dummy, parallel-group, 2-year study. Approximately 600 patients from 98 centers participated. Eligible patients had completed a previous 12-month study and consented to continue treatment for a further year. To avoid selection bias, all patients from all centers were included in the primary analysis (a comparison of the time-to-failure distributions of the two groups by using a log-rank test) regardless of whether they continued treatment for a 2nd year. By using repeated-measures ANOVA, time course of least square means of HbA(1c) and homeostasis model of assessment (HOMA) indexes (HOMA-%S and HOMA-%B) were analyzed.\n A greater proportion of patients treated with pioglitazone maintained HbA(1c) <8% over the 2-year period than those treated with gliclazide. A difference between the Kaplan-Meier curves was apparent as early as week 32 and widened at each time point thereafter, becoming statistically significant from week 52 onward. At week 104, 129 (47.8%) of 270 pioglitazone-treated patients and 110 (37.0%) of 297 gliclazide-treated patients maintained HbA(1c) <8%. Compared with gliclazide treatment, pioglitazone treatment produced a larger decrease in HbA(1c), a larger increase in HOMA-%S, and a smaller increase in HOMA-%B during the 2nd year of treatment.\n Pioglitazone is superior to gliclazide in sustaining glycemic control in patients with type 2 diabetes during the 2nd year of treatment." ]

[ "2396618", "7921089", "2189428", "9264888", "7246494", "6075662", "13489318", "5581596" ]

[ "Gowning on a postpartum ward fails to decrease colonization in the newborn infant.", "Gowning does not affect colonization or infection rates in a neonatal intensive care unit.", "A randomized controlled trial of a nursery ritual: wearing cover gowns to care for healthy newborns.", "Does routine gowning reduce nosocomial infection and mortality rates in a neonatal nursery? A Singapore experience.", "Evaluation of modified gowning procedures in a neonatal intensive care unit.", "Evaluation of precautions before entering a neonatal unit.", "Masking and gowning in nurseries for the newborn infant; effect on staphylococcal carriage and infection.", "Bacteriologic and clinical evaluation of gowning in a premature nursery." ]

[ "We conducted a randomized study to evaluate the effect of gowning by visitors and hospital personnel on a postpartum ward on nose and umbilical colonization and disease in healthy newborn infants. Cultures were obtained in infants assigned to the gowning and nongowning groups within 6 hours of birth from the anterior part of the nares and the base of the umbilicus and at the time of discharge from the nursery. There were 102 infants in the gowning group and 100 infants in the nongowning group. No significant differences were noted between the two groups with respect to sex, length of stay, mode of delivery, weight, or status of nursery admission culture results. The use of gowns on a postpartum ward failed to decrease nose or umbilical colonization when compared with infants in the nongowning group. Seventy (68.6%) of 102 infants in the gowning group and 65 (65%) of 100 infants in the nongowning group had negative umbilical cord cultures on admission to the nursery that became positive at discharge. On follow-up, no differences were noted between the two groups with respect to their health. Only one infant in each group had an infection develop in the first 4 weeks of life. We conclude that the routine use of cover gowns on postpartum units in healthy full-term infants is ineffective and costly. It may discourage health care providers from examining patients and providing care.", "To study the effect of gowning in a neonatal intensive care unit on colonization patterns, necrotizing enterocolitis, respiratory syncytial virus and other infections, mortality, and traffic and handwashing patterns.\n Alternate 2-month gowning and no-gowning cycles were established in a 24-bed level III neonatal intensive care unit for 8 months, with respiratory site, umbilical, and stool surveillance cultures done weekly on all patients. Traffic flow and handwashing compliance were evaluated by direct observation.\n Demographic data did not differ between periods. There were no significant differences between the gowning and no-gowning periods in the rates of bacterial colonization, any type of infection, or mortality. There was no effect on traffic flow or handwashing compliance.\n Gowning in the neonatal intensive care unit is an unnecessary custom without benefit in neonatal colonization, infection rates, mortality, traffic patterns, and handwashing behavior.", "The routine wearing of individual cover gowns by nurses and visitors for direct care of healthy newborns was usual practice on the maternity ward of a regional referral center. We conducted a randomized trial in which cover gowns were not provided for care of infants in the experimental group (n = 222), but were maintained for control infants (n = 230). The principal outcome measured was Staphylococcus aureus colonization of the newborn nares or umbilicus on day 3 or day of discharge. Twenty percent (n = 51) of the experimental group (no gown) had a positive culture compared with 21 percent (n = 47) of the controls. Of the infants with positive cultures, two in each group exhibited symptoms of overt S. aureus infection. Experimental infants were similar to controls with respect to feeding method, route of delivery, amount of time spent rooming-in, and average number of visitors per day. In the group of positively cultured infants, the mothers experienced longer labor, and more vaginal examinations in labor, and the number of males undergoing circumcision was higher. We concluded that routine use of cover gowns was unwarranted, and we have altered the ward policy accordingly. This also has had a positive economic effect.", "A 1 year prospective study on routine gowning before entering a neonatal unit was conducted in a maternity hospital in Singapore. This study was done based on previous work by Donowitz, Haque and Chagla and Agbayani et al., as there have been no known studies done in Singapore. The aim of the study was to test the hypothesis that routine gowning before entering a neonatal nursery does not reduce nosocomial infection and mortality rate. A total of 212 neonates from the neonatal intensive care unit (NICU) and 1694 neonates from the neonatal special care unit (NSCU) were studied. Neonates admitted during the 1 year study were assigned to the gowning (control) and no routine gowning (trial) group on every alternate 2 months. The hospital infection control nurse provided data on nosocomial infection. The overall nosocomial infection rate in the NICU was 24% (25 of 104 admissions) during gowning periods compared to 16.6% (18 of 108 admissions) when plastic aprons were not worn before entry. In the NSCU, the overall infection rate was 1.5% (12 of 800 admissions) during gowning periods compared to 2.1% (19 of 894 admissions) when no gown was worn before entry. Results of the study found no significant differences in the incidences of nosocomial infection and mortality in the neonates. The cost of gowns used during the no routine gowning periods was S$2012.8 compared to S$3708 used during the routine gowning procedure. The investigators recommend that routine gowning before entering a neonatal unit is not essential and cost effective for the purpose of reducing infection. Rather the focus should be on adequate handwashing by all hospital personnel and visitors before handling neonates.", "The effect of modified gowning techniques in a neonatal intensive care unit was evaluated. During alternate two-month intervals, no gowns were worn over street clothes in patient care areas by staff or visitors. Mortality and infections rates during these \"modified\" gowning intervals were the same as during the gowning periods. However, the incidence of necrotizing enterocolitis was significantly greater in the modified gowning periods (7/353) than in the gowning periods (1/371). An expansion of this one-year study to include another year showed an even greater effect. The prevalence of bacteria at three anatomic sites (nares, umbilicus, and groin) on days 2, 4, 7, 10, 14, 21, and 28 of hospitalization was comparable between those studied during modified gowning and gowning intervals. Exceptions were the significantly increased prevalence of Staphylococcus epidermidis in the groin (days 21 and 28) during gowning and S aureus in the nares (day 28) during modified gowning periods.", "nan", "nan", "nan" ]

[ "14988972", "21287886", "18465176", "19398690", "18333706", "19737992", "19897690", "11945214", "9932067", "17365766", "17090223" ]

[ "Opportunistic electronic reminders. Improving performance of preventive care in general practice.", "A demonstration project for using the electronic health record to identify and treat tobacco users.", "A computerized aid to support smoking cessation treatment for hospital patients.", "An electronic health record-based intervention to improve tobacco treatment in primary care: a cluster-randomized controlled trial.", "Care coordination to increase referrals to smoking cessation telephone counseling: a demonstration project.", "A method for educating patients and documenting smoking status in an electronic medical record.", "Smoking as a vital sign: prompts to ask and assess increase cessation counseling.", "The feasibility of paper-based Tracking Codes and electronic medical record systems to monitor tobacco-use assessment and intervention in an Individual Practice Association (IPA) Model health maintenance organization (HMO).", "Tools to improve documentation of smoking status. Continuous quality improvement and electronic medical records.", "Provider feedback to improve 5A's tobacco cessation in primary care: a cluster randomized clinical trial.", "Effects of the tobacco use cessation automated clinical practice guideline." ]

[ "Preventive care is an important role for general practitioners, yet opportunities for prevention are often missed.\n We provided an automatic electronic record preventive care reminder system for 12 preventive care activities for one 10 doctor practice. All patients who attended were randomised by the terminal digit of their record number.\n The control uptake of opportunistic prevention was low; ranging from 1.5% (tetanus immunisation) to 27% (influenza immunisation). The reminders increased this by significant but small amounts for four out of 12 activities (immunisation for tetanus and pneumococcus and recording of allergies and weight), insignificant increases for four (mumps, measles and rubella immunisation, recording of smoking, and taking of cervical smears and of blood pressure), and insignificantly decreased influenza immunisation, and screening for diabetes and hyperlipidaemia.\n Opportunistic electronic reminders have the potential to increase preventive care in general practice.", "While the majority of smokers visit a primary care physician each year, only a small proportion of them receive evidence-based tobacco dependence treatment. The electronic health record (EHR) provides an opportunity to prompt clinicians to deliver tobacco dependence treatment in primary care.\n Over 1 year, Dean Health Systems worked with the University of Wisconsin School of Medicine and Public Health to modify the existing Dean EHR system (Epic Systems Corp, Verona, Wisconsin) to improve identification and treatment of adult smokers visiting primary care clinics. Modifications included evidence-based prompts that helped guide medical assistants to identify smokers and clinicians to deliver a brief tobacco cessation intervention (medication and Wisconsin Tobacco Quit Line referral). Eighteen primary care clinics provided data 1 year before and 1 year after implementing the EHR modifications.\n A higher percentage of adult patients had their tobacco use status identified after EHR modification compared to pre-implementation (71.6% versus 78.4%, P < .001). During the post-implementation year, 6.3% of adult smokers were prescribed tobacco cessation medication, 2.5% of adult smokers had documentation of counseling, and 1.5% of adult smokers had counseling billed (pre-implementation data not available).\n This demonstration project showed that a large health care system can increase the delivery of tobacco dependence treatment interventions (increased identification of smokers and relatively high rates of delivering specific tobacco dependence clinical interventions) building on an existing EHR platform. The project demonstrated that brief, evidence-based tobacco dependence interventions can be incorporated into primary care, especially when the EHR is used to improve clinic workflow.", "Hospital-based interventions promote smoking cessation after discharge. Strategies to deliver these interventions are needed, especially now that providing smoking cessation advice or treatment, or both, to inpatient smokers is a publicly reported quality-of-care measure for US hospitals.\n To assess the effect of adding a tobacco order set to an existing computerized order-entry system used to admit Medicine patients to 1 hospital.\n Pre-post study.\n Proportion of admitted patients who had smoking status identified, a smoking counselor consulted, or nicotine replacement therapy (NRT) ordered during 4 months before and after the change. In 4 months after implementation, the order set was used with 76% of Medicine admissions, and a known smoking status was recorded for 81% of these patients. The intervention increased the proportion of admitted patients who were referred for smoking counseling (0.8 to 2.1%) and had NRT ordered (1.6 to 2.5%) (p < .0001 for both). Concomitantly, the hospital's performance on the smoking cessation quality measure improved.\n Adding a brief tobacco order set to an existing computerized order-entry system increased a hospital's provision of evidence-based tobacco treatment and helped to improve its performance on a publicly reported quality measure. It provides a model for US hospitals seeking to improve their quality of care for inpatients.", "To improve the documentation and treatment of tobacco use in primary care, we developed and implemented a 3-part electronic health record enhancement: (1)smoking status icons, (2) tobacco treatment reminders, and (3) a Tobacco Smart Form that facilitated the ordering of medication and fax and e-mail counseling referrals.\n We performed a cluster-randomized controlled trial of the enhancement in 26 primary care practices between December 19, 2006, and September 30, 2007. The primary outcome was the proportion of documented smokers who made contact with a smoking cessation counselor. Secondary outcomes included coded smoking status documentation and medication prescribing.\n During the 9-month study period, 132 630 patients made 315 962 visits to study practices. Coded documentation of smoking status increased from 37% of patients to 54% (+17%) in intervention practices and from 35% of patients to 46% (+11%) in control practices (P < .001 for the difference in differences). Among the 9589 patients who were documented smokers at the start of the study, more patients in the intervention practices were recorded as nonsmokers by the end of the study (5.3% vs 1.9% in control practices; P < .001). Among 12 207 documented smokers, more patients in the intervention practices made contact with a cessation counselor (3.9% vs 0.3% in control practices; P < .001). Smokers in the intervention practices were no more likely to be prescribed smoking cessation medication (2% vs 2% in control practices; P = .40).\n This electronic health record-based intervention improved smoking status documentation and increased counseling assistance to smokers but not the prescription of cessation medication.", "To test the effectiveness of a care coordination program for telephone counseling in raising referral and treatment rates for smoking cessation.\n A demonstration project implementing a smoking cessation care coordination program offering telephone counseling and medication management to patients referred from primary care.\n The study was performed at 18 Veterans Health Administration (VA) sites in California. Participants were VA patients receiving primary care. We randomly allocated 10 of 18 sites to receive the Telephone Care Coordination Program, which included simple 2-click referral, proactive care coordination, medication management, and 5 follow-up telephone calls. Each patient received a 30- to 45-minute counseling session from the California Smokers' Helpline. Patients at control sites received usual care.\n During 10 months, we received 2965 referrals. We were unable to reach 1156 patients (39%), despite at least 3 attempts. We excluded 73 patients (3%), and 391 patients (13%) were not interested. We connected the remaining 1345 patients (45%) to the Helpline. At 6-month followup, 335 patients (11% of all referrals and 25% of participating patients) were abstinent. Providers at intervention sites reported referring many more patients to telephone counseling than providers at control sites (15.6 vs 0.7 in the prior month).\n The program generated a large number of referrals; almost half of the patients referred were connected with the Helpline. Long-term abstinence was excellent. These results suggest that managed care organizations may be able to improve tobacco control by implementing a similar system of care coordination.", "Published evidence demonstrates benefit from pharmacist smoking cessation interventions; however, there is limited research evaluating the impact of a template within an electronic medical record used at pharmacy disease state management visits.\n To determine the rates of smoking cessation and movement along the transtheoretical model of change after implementation of a template into existing pharmacy-related progress notes within the electronic medical record.\n Patients who were routinely followed by clinical pharmacists for anticoagulation and diabetes mellitus education at 3 clinics at the Medical University of South Carolina were included. At each visit, the pharmacist would document patient smoking information in a newly designed template within the existing progress note. In addition, pharmacists would educate patients on the benefits of smoking cessation and pharmacologic options that may be available to them. Data were collected between April 2007 and March 2008. Baseline demographic data and smoking cessation rates and products were compared using descriptive statistics. The McNemar chi(2) test was used to compare the groups of patients achieving smoking cessation pre- and postintervention.\n Of the 90 current smokers, 38 (42%) achieved smoking cessation postintervention. Movement along the transtheoretical model of change was also seen, with 52 (58%) patients progressing to at least the next stage. Thirty-four patients in the contemplation/preparation stage and 4 patients in the precontemplation stage moved to the action or maintenance stage by the end of the study period (p = 0.03). A variety of pharmacologic therapies were used in individuals who stopped smoking, although varenicline was most common. Thirty-nine percent of the patients used no medications to achieve cessation.\n Incorporating a smoking cessation template into existing progress notes and providing education during existing pharmacy referral visits is a simple and effective method to assist patients in achieving smoking cessation.", "Strategies to improve smoking cessation counseling in clinical settings are critical to supporting smokers' attempts to quit. This study evaluates the impact of adding 2 smoking-related vital sign questions in an electronic medical records system on identification, assessment, and counseling for patients who smoke: \"Current smoker?\" and \"Plan to quit?\"\n Baseline data and data after intervention were collected through record review of 899 randomly selected patient visits across 3 outpatient clinics.\n From before to after intervention, identification of smokers increased 18% (from 71% to 84%; P<.001), and assessment for a plan to quit increased 100% (from 25.5% to 51%; P<.005). Among all smokers, cessation counseling increased 26% (from 23.6% to 29.8%; P=.41). Significantly more smokers who received the assessment for a plan to quit received cessation counseling (46% vs. 14%, P<.001). Regression analysis showed that patients receiving an assessment for plan to quit were 80% more likely to receive cessation counseling (OR 0.209; 95% CI, 0.095-0.456).\n Physician-documented counseling rates are significantly higher when patients are asked about smoking and assessed for a plan to quit. Two questions that ask about smoking status and assess plans to quit may provide prompts to increase the likelihood that patients who smoke receive cessation counseling.", "Despite evidence of its effectiveness, tobacco cessation is not systematically addressed in routine healthcare settings. Its measurement is part of the problem. A pilot study was designed to develop and implement two different tobacco tracking systems in two independent primary care offices that participated in an IPA Model health maintenance organization in Portland, Oregon. The first clinic, which utilized a paper-based charting system, implemented CPT-like tracking codes to measure and report tobacco-cessation activities, which were eventually included in the managed-care organization's (MCO) claims database. The second clinic implemented an electronic tracking system based on its computerized electronic medical record (EMR) charting system. This paper describes the pilot study, including the processes involved in building provider acceptance for the new tracking systems in these two clinics, the barriers and successes encountered during implementation, and the resources expended by the clinics and by the MCO during the pilot. The findings from the 3-month implementation period were that documentation of tobacco-use status remained stable at 42-45% in the paper-based clinic and increased from 79% to 88% in the EMR clinic. This pilot study demonstrated that Tracking Codes are a feasible preventive-care tracking system in paper-based medical offices. However, high levels of effort and support are needed, and a critical mass of insurers and health plans would need to adopt Tracking Codes before widespread use could be expected. Results of the EMR-based tracking system are also reviewed and discussed.", "Despite the deleterious effects of smoking on the nation's health and evidence that smoking cessation advice by family practice physicians is cost-effective, self-sustaining office systems to identify smokers in primary care clinics have been difficult to establish. We worked on a continuous quality improvement project group, aided by an electronic medical record, to design a system to document and periodically update smoking status in a consistent place in the medical record.\n Using the continuous quality improvement plan-do-study-act cycle, a 7-member group worked with nursing staff to define roles, routines and responsibilities for medical assistants to screen for and document 1 of 4 categories of smoking status in the major problem list of the electronic medical record for at least 80% of patient appointments. Screening rate was tracked monthly by means of the electronic medical record and feedback was given to staff.\n The screening rate rose from 18.4% to 80.3% within 2 weeks after the system was implemented and was maintained for 19 months. An additional benefit was an increased rate of smoking cessation counseling documented by providers, from a baseline rate of 17.1% to 48.3%.\n A continuous quality improvement group process aided by an electronic medical record is useful to develop a self-sustaining office system to screen, document, and periodically update smoking status in a consistent place in the medical record. Although screening for and documenting smoking status are only the first step toward helping patients stop smoking, it is an important one.", "The electronic health record (EHR) may be an effective tool to help clinicians address tobacco use more consistently. To evaluate the impact of EHR-generated practice feedback on rates of referral to a state-level tobacco quitline, we conducted a cluster randomized clinical trial (feedback versus no feedback) within 19 primary care clinics in Oregon. Intervention clinics received provider-specific monthly feedback reports generated from EHR data. The reports rated provider performance in asking, advising, assessing, and assisting with tobacco cessation compared with a clinic average and an achievable benchmark of care. During 12 months of follow-up, EHR-documented rates of advising, assessing, and assisting were significantly improved in the intervention clinics compared with the control clinics (p<.001). A higher case-mix index and presence of a clinic champion were associated with higher rates of referral to a state-level quitline. EHR-generated provider feedback improved documentation of assistance with tobacco cessation. Connecting physician offices to a state-level quitline was feasible and well accepted.", "To evaluate the effects of the Tobacco Use Cessation (TUC) Automated Clinical Practice Guideline (ACPG) (a variation of the US Department of Health and Human Services Clinical Practice Guideline on Treating Tobacco Use and Dependence) on guideline adherence in a multisite health system.\n The study used a pre-post cross-sectional design. Paneled patients were enrolled from 6 clinics, including 2 control clinics (arm 1), 2 control clinics that received a check-in screen only (the check-in screen provided a simplified method for entering patient vital signs into the electronic medical record) (arm 2), and 2 clinics that received the TUC intervention (arm 3).\n Baseline data on physician compliance with the 5 As (ask, assess, advise, assist, and arrange) at the last office visit were collected via telephone surveys from patients in the 3 study arms. The TUC-ACPG was then introduced in the TUC intervention clinics as part of the existing electronic medical record. Approximately 2 weeks after the TUC intervention, postimplementation data were collected via telephone survey.\n In the TUC intervention arm, postimplementation adherence rates increased relative to baseline for all 5 points of the guideline, with the largest increases seen in the assess and arrange guideline points. Controlling for factors such as age, race, and relevant comorbidities, logistic regression analysis indicated that the time (preimplementation vs postimplementation)-x-TUC intervention arm interaction demonstrated a statistically significant increase in the assess guideline point.\n Although baseline adherence rates were already high, the introduction of the TUC-ACPG led to further increases in guideline adherence." ]

[ "21960187", "21281564", "18498923", "19811111", "19811110", "19900071", "12647196", "22435648", "21664100", "17020726", "21522037", "12173995", "17018467", "18928643", "20528390", "19258920", "20504841", "9738173", "9493805", "18990549", "21477089", "19490659", "20008423", "17192118", "21300647", "11117660", "21087075", "14571236", "10469764", "15574622", "19967425", "22286828" ]

[ "Cost-effectiveness of palivizumab for respiratory syncytial virus infection in high-risk children, based on long-term epidemiologic data from Austria.", "Palivizumab for immunoprophylaxis of respiratory syncytial virus (RSV) bronchiolitis in high-risk infants and young children: a systematic review and additional economic modelling of subgroup analyses.", "Cost-effectiveness of palivizumab against respiratory syncytial viral infection in high-risk children in Austria.", "Cost effectiveness of palivizumab for RSV prevention in high-risk children in the Netherlands.", "Cost effectiveness of palivizumab in children with congenital heart disease in Germany.", "The cost effectiveness of palivizumab in term Inuit infants in the Eastern Canadian Arctic.", "Economic evaluation of possible prevention of RSV-related hospitalizations in premature infants in Germany.", "Cost-effectiveness analysis of palivizumab among pre-term infant populations covered by Medicaid in the United States.", "Economic evaluation of palivizumab in children with congenital heart disease: a Canadian perspective.", "[The efficiency (cost-effectiveness) of palivizumab as prophylaxis against respiratory syncytial virus infection in premature infants with a gestational age of 32-35 weeks in Spain].", "A randomized controlled trial of motavizumab versus palivizumab for the prophylaxis of serious respiratory syncytial virus disease in children with hemodynamically significant congenital heart disease.", "Cost-effectiveness of palivizumab in New Zealand.", "Cost-effectiveness analysis of palivizumab in premature infants without chronic lung disease.", "The cost-effectiveness of palivizumab for respiratory syncytial virus prophylaxis in premature infants with a gestational age of 32-35 weeks: a Canadian-based analysis .", "Cost-effectiveness of palivizumab in infancy.", "Safety, tolerability, pharmacokinetics, and immunogenicity of motavizumab, a humanized, enhanced-potency monoclonal antibody for the prevention of respiratory syncytial virus infection in at-risk children.", "Passive immunisation against respiratory syncytial virus: a cost-effectiveness analysis.", "Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. The IMpact-RSV Study Group.", "Safety, tolerance and pharmacokinetics of a humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. MEDI-493 Study Group.", "[Methodological aspects of economic evaluation in pediatrics: illustration by RSV infection prophylaxis in the French setting].", "Cost-effectiveness analysis of palivizumab as respiratory syncytial virus prophylaxis in preterm infants in Sweden.", "Cost-utility analysis of palivizumab in Italy: results from a simulation model in the prophylaxis of respiratory syncytial virus infection (RSV) among high-risk preterm infants.", "Motavizumab for prophylaxis of respiratory syncytial virus in high-risk children: a noninferiority trial.", "Cost effectiveness of palivizumab for respiratory syncytial virus prophylaxis in high-risk children: a UK analysis.", "Cost-effectiveness of respiratory syncytial virus prophylaxis in various indications.", "Palivizumab for respiratory syncytial virus prophylaxis in high-risk infants: a cost-effectiveness analysis.", "Changing costs and the impact on RSV prophylaxis.", "Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease.", "Cost-effectiveness of respiratory syncytial virus prophylaxis among preterm infants.", "Economic analysis of palivizumab in infants with congenital heart disease.", "Cost effectiveness of palivizumab in Spain: an analysis using observational data.", "Cost-effectiveness analysis of the use of palivizumab in the prophylaxis of preterm patients in Mexico." ]

[ "To assess the cost-effectiveness of palivizumab, a monoclonal antibody against respiratory syncytial virus (RSV), in infants at high risk for severe RSV lower respiratory tract infection, such as premature infants, infants with bronchopulmonary dysplasia, and those with congenital heart disease, based on long-term epidemiologic data from Austria.\n A decision-tree model was used, and the analysis was based on a lifetime follow-up investigating cost-effectiveness of palivizumab versus no RSV infection prevention. The primary perspective of the study was that of the healthcare system, the second that of society. Cost and effects were discounted by 5%. The base case analysis included only direct medical costs, and a scenario analysis included various indirect costs.\n Analyses were based on epidemiologic data on a total of 1579 children hospitalized because of RSV lower respiratory tract infection during 16 seasons. The incremental cost-effectiveness ratio for the first outcome measure (life years gained) amounted to discounted costs of €34,956 (for all preterm infants), €35,056 (for < 33 weeks' gestational age [wGA] infants), €35,233 (for 33-35 wGA infants), €35,611 (for infants with bronchopulmonary dysplasia), and €8956 (for infants with congenital heart disease). Use of palivizumab compared with no prophylaxis had an incremental cost-utility ratio of €26,212, €26,292, €24,392, €24,654, and €8484, respectively, per quality-adjusted life years. Results from the society perspective were more cost-effective in all study populations. An additional scenario analysis with 7 injections for the 33 to 35 wGA group revealed cost-effectiveness as well.\n Our results based on nationwide long-term epidemiologic data suggest that palivizumab is cost-effective in prevention of RSV disease in high-risk infants.", "Respiratory syncytial virus (RSV) is a seasonal infectious disease, with epidemics occurring annually from October to March in the UK. It is a very common infection in infants and young children and can lead to hospitalisation, particularly in those who are premature or who have chronic lung disease (CLD) or congenital heart disease (CHD). Palivizumab (Synagis®, MedImmune) is a monoclonal antibody designed to provide passive immunity against RSV and thereby prevent or reduce the severity of RSV infection. It is licensed for the prevention of serious lower respiratory tract infection caused by RSV in children at high risk. While it is recognised that a policy of using palivizumab for all children who meet the licensed indication does not meet conventional UK standards of cost-effectiveness, most clinicians feel that its use is justified in some children.\n To use systematic review evidence to estimate the cost-effectiveness of immunoprophylaxis of RSV using palivizumab in different subgroups of children with or without CLD or CHD who are at high risk of serious morbidity from RSV infection.\n A systematic review of the literature and an economic evaluation was carried out. The bibliographic databases included the Cochrane Library [Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] and five other databases, from inception to 2009. Research registries of ongoing trials including Current Controlled Trials metaRegister, Clinical Trials.gov and the National Institute for Health Research Clinical Research Network Portfolio were also searched.\n Searches were conducted for prognostic and hospitalisation studies covering 1950-2009 (the original report searches conducted in 2007 covering the period 1950-2007 were rerun in August 2009 to cover the period 2007-9) and the database of all references from the original report was sifted to find any relevant studies that may have been missed. The risk factors identified from the systematic review of included studies were analysed and synthesised using stata. The base-case decision tree model developed in the original HTA journal publication [Health Technol Assess 2008;12(36)] was used to derive the cost-effectiveness of immunoprophylaxis of RSV using palivizumab in different subgroups of pre-term infants and young children who are at high risk of serious morbidity from RSV infection. Cost-effective spectra of prophylaxis with palivizumab compared with no prophylaxis for children without CLD/CHD, children with CLD, children with acyanotic CHD and children with cyanotic CHD were derived.\n Thirteen studies were included in this analysis. Analysis of 16,128 subgroups showed that prophylaxis with palivizumab may be cost-effective [at a willingness-to-pay threshold of £30,000/quality-adjusted life-year (QALY)] for some subgroups. For example, for children without CLD or CHD, the cost-effective subgroups included children under 6 weeks old at the start of the RSV season who had at least two other risk factors that were considered in this report and were born at 24 weeks gestational age (GA) or less, but did not include children who were > 9 months old at the start of the RSV season or had a GA of > 32 weeks. For children with CLD, the cost-effective subgroups included children < 6 months old at the start of the RSV season who were born at 28 weeks GA or less, but did not include children who were > 21 months old at the start of the RSV season. For children with acyanotic CHD, the cost-effective subgroups included children < 6 months old at the start of the RSV season who were born at 24 weeks GA or less, but did not include children who were > 21 months old at the start of the RSV season. For children with cyanotic CHD, the cost-effective subgroups included children < 6 weeks old at the start of the RSV season who were born at 24 weeks GA or less, but did not include children who were > 12 months old at the start of the RSV season.\n The poor quality of the studies feeding numerical results into this analysis means that the true cost-effectiveness may vary considerably from that estimated here. There is a risk that the relatively high mathematical precision of the point estimates of cost-effectiveness may be quite inaccurate because of poor-quality inputs.\n Prophylaxis with palivizumab does not represent good value for money based on the current UK incremental cost-effectiveness ratio threshold of £30,000/QALY when used unselectively in children without CLD/CHD or children with CLD or CHD. This subgroup analysis showed that prophylaxis with palivizumab may be cost-effective (at a willingness-to-pay threshold of £30,000/QALY) for some subgroups. In summary, the cost-effective subgroups for children who had no CLD or CHD must contain at least two other risk factors apart from GA and birth age. The cost-effective subgroups for children who had CLD or CHD do not necessarily need to have any other risk factors. Future research should be directed towards conducting much larger, better powered and better reported studies to derive better estimates of the risk factor effect sizes.\n This report was funded by the HTA programme of the National Institute for Health Research.", "The aim of this study was to estimate the cost-effectiveness of palivizumab, a monoclonal antibody against severe respiratory syncytial virus infection, in high-risk infants in Austria.\n A decision tree model was developed to determine cost-effectiveness in infants born prematurely (<or=35 weeks' gestational age), those with bronchopulmonary dysplasia (BPD), and children with congenital heart disease (CHD). The primary perspective of the analysis was that of the compulsory health insurance fund. The societal perspective was also considered.\n From the health insurance fund perspective, including the costs associated with asthma, the incremental cost-effectiveness ratio (cost per quality-adjusted life year [QALY] gained) without discounting was estimated to be euro 4484 (2006 euros) in preterm infants, euro 6719 in children with BPD, and euro 2668 in the CHD population. When discounted, these figures increased to euro 14,439, euro 21,672, and euro 9754, respectively. The results from the societal perspective were substantially more cost-effective in all populations. The undiscounted cost per QALY was euro 1435 in preterm infants, euro 4881 in children with BPD, and euro 251 in the CHD group. Discounted figures were euro 4623, euro 15,741, and euro 917, respectively. Sensitivity analyses confirmed the robustness of the model, and scenario analyses found that the inclusion of indirect costs led to further improvement in the cost-effectiveness outcomes for palivizumab.\n Use of palivizumab was cost-effective compared with no prophylaxis in high-risk infants and children in Austria.", "Respiratory syncytial virus (RSV) is a common pathogen that is the leading cause of lower respiratory tract infections in young children. High-risk children are at risk of severe infection, which may require hospitalisation. RSV is also associated with a high risk for respiratory morbidity and mortality, which may have long-term clinical and economic consequences.\n To assess the cost effectiveness of palivizumab, a humanised monoclonal antibody, used as prevention against severe respiratory syncytial virus (RSV) infection requiring hospitalisation, in the indication of preterm infants and infants with preterm/bronchopulmonary dysplasia and in the second indication of children with congenital heart disease in the Dutch healthcare setting.\n A decision-tree model was used to estimate the cost effectiveness of palivizumab, used as a preventative treatment against severe respiratory syncytial virus (RSV) infection, in high-risk groups of children in the Netherlands. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. Data sources included published literature, the palivizumab pivotal trials, official price/tariff lists and national population statistics. The study was conducted from the perspective of society in the Netherlands.\n The use of palivizumab results in undiscounted incremental cost-effectiveness ratios of €12,728/QALY and €4,256/QALY in preterm/bronchopulmonary dysplasia and congenital heart disease indications, respectively. Inclusion of indirect costs leads to even more favourable cost-effectiveness outcomes. The study is limited by a number of conservative assumptions. It was assumed that palivizumab only affects the occurrence of RSV hospitalisation and does not influence the severity of the RSV infection. Another assumption was that international clinical trial data and data on utilities could be applied to the Dutch healthcare setting.\n Palivizumab provides cost-effective prophylaxis against RSV in high-risk infants. The use of palivizumab in these children results in positive short- and long-term health-economic benefits.", "To assess the cost effectiveness of palivizumab, a humanised monoclonal antibody, used as prevention against severe respiratory syncytial virus (RSV) infection requiring hospitalisation, in infants with haemodynamically significant congenital heart disease (CHD) in the German healthcare setting.\n A decision-tree model was used to estimate the cost effectiveness of palivizumab for a hypothetical cohort of patients. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. Data sources included published literature, the palivizumab pivotal trials, official price/tariff lists and national population statistics. The study was conducted from the perspective of society (primary analysis) and the healthcare purchaser (secondary analysis).\n From the societal perspective, use of palivizumab results in an incremental cost-effectiveness ratio (ICER) of €2,615 per quality-adjusted life-year (QALY) without discounting, which increases to €9,529/QALY after discounting. From the perspective of the German healthcare purchaser, use of palivizumab results in an ICER of €4,576/QALY without discounting, which increases to €16,673/QALY after discounting. Probabilistic sensitivity analyses confirmed the robustness of the model. The study is limited by a number of conservative assumptions. It was assumed that palivizumab only affects the occurrence of RSV hospitalisation and does not influence the severity of the RSV infection. Another assumption was that international clinical trial data and data on utilities could be applied to the German healthcare setting.\n This analysis showed that palivizumab represents a cost-effective means of prophylaxis against severe RSV infection requiring hospitalisation in infants with haemodynamically significant CHD.", "Canadian, Inuit, full term infants have the highest rate of respiratory syncytial virus (RSV) infection globally, which results in substantial costs associated hospitalisation.\n Decision-analytical techniques were used to estimate the incremental cost-effectiveness ratio (ICER) for palivizumab compared to no prophylaxis for Inuit infants of all gestational age. The time horizon was that of life-time follow-up, and costs and effectiveness were discounted at 5% per year. Costs (2007 CAD$) for palivizumab, hospitalisation (including medical evacuation, intensive care unit [ICU]), physician visits, and transportation were calculated based on the Canadian payer's perspective. Benefits on decreasing RSV hospitalisation were expressed as quality-adjusted life-years (QALYs). One-way and probabilistic sensitivity analysis (PSA) were conducted, varying: mortality rates, utilities, length of stay in hospital and ICU.\n For all of Baffin Island infants (<1 year), the ICER was $39,435/QALY. However, when infants were grouped by age and area of residence, those residing in Iqaluit (<1 year) had an ICER of $152,145/QALY, while those residing in rural areas (outside of Iqaluit) had an ICER of $24,750/QALY. Prophylaxis was a dominant strategy (cost saving) for rural infants under 6 months of age, with the PSA demonstrating that it was dominant 98% of the time.\n The ICERs suggested that palivizumab is a cost-effective option for the prevention of RSV for Inuit infants on Baffin Island compared to no prophylaxis. Palivizumab is highly cost effective in Arctic infants <1 year of age specifically residing outside of Iqaluit and is a dominant strategy for those under 6 months of age in rural areas. However, palivizumab is not cost effective compared to no treatment for infants of all ages residing in Iqaluit.", "Palivizumab (Synagis, MedImmune Inc./Abbott Laboratories) has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations in premature infants. The cost-effectiveness ratio of this prophylaxis, however, has not been evaluated in the German health-care system to date. The aim of the study was to assess the costs and benefits of Palivizumab among premature infants </=35 weeks with different risk factors. Projecting a societal perspective, we used decision analysis to compare the strategies of a prophylaxis with and without Palivizumab. Probabilities and costs of hospitalization were derived from a retrospective, population-based cohort study on 1,103 prematurely born infants primarily admitted to nine neonatologic care units in southern Germany between November 1998 and October 1999. Costs of prophylaxis were based on hospital sources. Efficacy of prophylaxis and estimates of RSV mortality were derived from the literature. Effectiveness was defined as the number of averted hospitalizations. The cost-effectiveness ratio of Palivizumab varied strongly among the different risk groups. While demonstrating no net cost savings related to RSV prophylaxis for any of the risk groups analyzed, Palivizumab showed the best cost-effectiveness ratio among male infants with chronic lung disease, discharge from primary neonatal care between October and December, and the presence of siblings visiting a day-care group. One averted hospitalization in this high-risk group was associated with costs of Euro 6,639 (number needed to treat (NNT): 4). For infants in other risk groups, the ratios varied from Euro 25,288 (NNT: 8) to Euro 204,684 (NNT: 54) per hospitalization averted. The cost-effectiveness ratios were sensitive to varying assumptions about probabilities and costs of rehospitalization, efficacy, and costs of Palivizumab prophylaxis.\n The results of this cost-effectiveness analysis do not justify the widespread use of Palivizumab among preterm infants. Lowering the costs of prophylaxis would be the most direct way to improve the cost-effectiveness ratio of Palivizumab.", "Medicaid infants are at high risk of severe respiratory syncytial virus (RSV) disease. The study objective was to estimate the cost-effectiveness of palivizumab in a Medicaid population.\n A societal cost-utility analysis was conducted of prophylaxis with palivizumab vs no prophylaxis among four groups of premature infants: (1) <32 weeks gestational age (wGA) and ≤ 6 months chronologic age (CA); (2) 32-34 wGA, ≤ 3 months CA with 2009 American Academy of Pediatrics (AAP) risk factors (RF); (3) 32-35 wGA, ≤ 6 months CA with 2006 AAP RF; and (4) 32-35 wGA, ≤ 6 months CA with ≤ 1 RF. Full dosing of palivizumab was assumed throughout the RSV season (consistent with the FDA-approved label). All costs were in 2010 US dollars. The societal public payer spend for palivizumab was estimated using Medicaid reimbursement methodologies for the top 10 palivizumab-using states in 2010 minus mandatory manufacturer rebates. This study reports the incremental cost-effectiveness ratios (ICERs) in cost per quality-adjusted life-year (QALY) gained. Sensitivity and probabilistic analyses were also conducted.\n Palivizumab saved costs and improved QALYs among infants <32 wGA. Palivizumab was cost-effective in infants 32-34 wGA with 2009 AAP RF ($16,037 per QALY) and in infants 32-35 wGA with 2006 AAP RF ($38,244 per QALY). The ICER for infants 32-35 wGA with ≤ 1 RF was $281,892 per QALY. Influential variables in the sensitivity analysis included the background rate of RSV hospitalization, the cost of palivizumab, and the efficacy of palivizumab. KEY LIMITATIONS: These results are not generalizable to commercially insured infants or infants outside of the US.\n This is the first cost-utility analysis of palivizumab in a Medicaid population. Palivizumab, when dosed consistent with the FDA-approved labeling, was either cost-saving or cost-effective among current guideline-eligible infants in the Medicaid population. Palivizumab did not demonstrate cost-effectiveness in 32-35 wGA infants with ≤ 1 RF.", "Respiratory syncytial virus (RSV) is a common cause of bronchiolitis in infants. In children with congenital heart disease (CHD), it is associated with significant morbidity and mortality. Palivizumab is a monoclonal antibody that reduces the number of RSV-associated hospitalizations in children with CHD. We sought to assess cost savings and cost-effectiveness of palivizumab in children < 2 years old with hemodynamically significant CHD in a provincially administered RSV prophylaxis program.\n A cohort of children who received palivizumab (N = 292) from 2003-2007 was compared to a historical cohort of children (N = 412) from 1998-2003 who met the eligibility criteria for palivizumab prior to initiation of the prophylaxis program. Direct and indirect costs and benefits were determined.\n The direct and indirect costs in the historical cohort were $838 per patient season compared to $9130 per patient season in the palivizumab cohort. Risk of admission was reduced by 42%, and days in hospital were reduced by 83%. The incremental cost of the RSV prophylaxis program was $8292 per patient for 1 RSV season. The incremental cost to prevent 1 day of hospitalization was $15,514. The cost of palivizumab accounted for 87.9% of the cost of prophylaxis.\n Palivizumab is clinically effective; however, the cost was exceptionally high relative to the outcomes in this population. Given the financial constraints in a public health care setting, more strict criteria for patient selection or reduced drug costs would improve the cost-effectiveness of RSV prophylaxis.\n Copyright © 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.", "To evaluate the efficiency (cost-effectiveness) of palivizumab in preventing severe respiratory syncytial virus (RSV) infection in premature infants with a gestational age of 32-35 weeks (GA 32-35) and two or more risk factors (RF) in Spain.\n Design: decision tree model using data from the scientific literature and the FLIP I and FLIP II studies (cohort of 326 infants with GA 32-35 and two or more RF who received palivizumab) sponsored by the Spanish Society of Neonatology. Main effectiveness measure: quality-adjusted life years (QALY) gained. Perspectives: the national health service (NHS), which includes direct costs (administration of palivizumab and hospital admissions), and the societal perspective, which also includes indirect costs (the child's future lost productivity). Discount: 3 % annually for effectiveness and indirect costs. Sensitivity analysis: construction of 37 scenarios modifying variables related to effectiveness and costs.\n Prophylaxis with palivizumab in premature infants with GA 32-35 and two or more RF produced an incremental cost-effectiveness ratio (ICER) of 13,849 euro/QALY from the NHS perspective, and an ICER of 4,605 euro/QALY from the societal perspective. In the sensitivity analysis, from the NHS perspective the ICER ranged from 5,351 euro/QALY (most favorable scenario) to 23,276 euro/QALY (least favorable scenario).\n Palivizumab is a cost-effective therapy as prophylaxis against RSV in infants with GA 32-35 and two or more RF. Its use is efficient from the NHS perspective, since the cost of a QALY, even in the least favorable scenarios, is lower than the threshold of 30,000 Euro/QALY considered socially acceptable in Spain.", "Children with hemodynamically significant congenital heart disease (CHD) are at risk for serious respiratory syncytial virus (RSV) disease. This study was designed to assess the safety and tolerability of motavizumab versus palivizumab in children with CHD and was not powered for efficacy. Patients (n = 1236) aged ≤24 mo were randomized to receive five monthly doses (15 mg/kg) of motavizumab or palivizumab during the RSV season. Adverse events (AEs) and serious AEs (SAEs) were recorded through 30 d after the last dose. RSV hospitalizations and RSV outpatient medically attended lower respiratory tract infections (MALRI; season 2) were summarized. Approximately 93 and 50% of patients reported an AE or SAE, respectively. Skin events occurred in 19.3% of motavizumab recipients and 16.2% of palivizumab recipients. Rates of hospitalizations and RSV MALRI were similar between treatment groups [relative risk (RR): 0.75; 95% CI, 0.34-1.59 and RR: 0.49; 95% CI, 0.10-1.99, respectively; both p > 0.05]. Motavizumab and palivizumab had similar safety profiles in children with hemodynamically significantly CHD; with the exception of skin events which were increased in motavizumab recipients. Safety and efficacy were consistent with another study comparing motavizumab with palivizumab in premature infants without CHD.", "To establish the preterm infant hospitalization risks from respiratory syncytial virus (RSV) in New Zealand and the net cost per hospitalization averted by palivizumab.\n The 437 infants born < 32 weeks' gestation in 1997 and treated at five major neonatal units were identified. Subsequent admissions during the next 2 years for bronchiolitis, pneumonia and croup were tracked, and information collected on RSV tests performed. Data on the length of stay and hospital costs were used to calculate the potential net cost per hospitalization averted associated with the use of palivizumab and the number needed to treat (NNT) to prevent one hospitalization.\n Estimated RSV readmission risk before 1 year corrected age in infants < 32 weeks' gestation discharged home on oxygen, and those \" 28 weeks' gestation, or between 29 and 31 weeks' gestation with or without chronic lung disease was 42%, 23%, 19%, 10% and 8%, respectively. The NNT with palivizumab to prevent one hospitalization ranged from six to 26 across subgroups. Mean (range) net cost per hospitalization averted was 60,000 New Zealand dollars ($28,000-$166,700). In no subgroup would prophylaxis result in net cost saving. Prophylaxis for all NZ infants \" 28 weeks' gestation would cost approximately $1,090,000 net and prevent 29 hospitalizations annually, being equivalent to $37,000 net per hospitalization averted, with eight infants treated to prevent one hospitalization. Alternative assumptions about cost and efficacy failed to alter these findings.\n If value is placed on preventing morbidity, the priority groups for palivizumab prophylaxis are preterm infants discharged home on oxygen, followed by preterm infants of 28 weeks' gestation or less.", "To evaluate the cost-effectiveness of palivizumab as respiratory syncytial virus prophylaxis in premature infants without chronic lung disease and to evaluate the impact on cost-effectiveness of a potential reduction in risk of asthma following respiratory syncytial virus infection among infants receiving palivizumab.\n Two decision analytic models were designed, one with and the other without accounting for increased risk of asthma following respiratory syncytial virus infection.\n A hypothetical community or university hospital.\n Hypothetical cohorts of infants without chronic lung disease born at 26 to 32 weeks' gestation.\n Palivizumab prophylaxis vs no prophylaxis.\n Expected costs and incremental cost-effectiveness ratio expressed as cost per quality-adjusted life-year.\n The expected costs were higher for palivizumab prophylaxis as compared with no prophylaxis. The incremental cost-effectiveness ratios were high for all gestations and are not considered cost-effective by today's standards (<$200 000 per quality-adjusted life-year). Both models were sensitive to variation in the cost of palivizumab. The model that included asthma was sensitive to variation in quality of life for children with asthma. In instances where asthma was considered severe with profound worsening in quality of life compared with life without asthma, some infants had an incremental cost per quality-adjusted life-year that was less than $200 000.\n Our model supports implementing more restrictive guidelines for palivizumab prophylaxis. Palivizumab was cost-effective for some infants in an analysis that accounted for increased risk of severe asthma following respiratory syncytial virus infection.", "Prophylactic therapy with palivizumab, a humanized monoclonal antibody, has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations in preterm infants, including those in the 32-35 weeks' gestational age (GA) subgroup. The cost-effectiveness of this therapy in Canada is unknown.\n To evaluate the cost-effectiveness of palivizumab as respiratory syncytial virus prophylaxis in premature infants born at 32-35 weeks' GA. Design: A decision analytic model was designed to compare both direct and indirect medical costs and benefits of prophylaxis in this subgroup of premature infants. Sensitivity analyses were performed to ascertain the robustness of the model for five point estimates: mortality rate, discounting rates, health-utility values, degree of vial-sharing and administration costs. A probabilistic sensitivity analysis (PSA) was also conducted.\n Canadian publicly funded health-care system (Ministry of Health payer perspective) for base-case analysis. Societal perspective, accounting for future lost productivity, was adopted for a secondary analysis. Participants: Canadian infants born at 32-35 weeks' GA without chronic lung disease. Interventions: Palivizumab prophylaxis versus no prophylaxis. Main outcome measures: Expected costs and incremental cost-effectiveness ratio expressed as cost per life-year gained (LYG) and quality-adjusted life-year (QALY) using 2007 Canadian dollars. Results: The expected costs were higher for palivizumab prophylaxis as compared with no prophylaxis. The incremental cost-effectiveness ratio (ICER) for the base-case scenario was $20 924 per QALY after discounting, which is considered cost-effective in Canada. When the uncertainty of the input parameter assumptions was tested through sensitivity analyses assessing several data sources for five key parameters, no substantial differences were found from the base-case results. The PSA indicated a 0.99 probability that the ICER for palivizumab was less than $50 000/QALY. Sub-analyses that varied the number of risk factors found that for infants with two or more risk factors, or at least moderate risk, palivizumab had incremental costs per QALY that indicated moderate-to-strong evidence for adoption (range: $808-81 331, per QALY).\n Palivizumab was cost-effective and the authors' model supports prophylaxis for infants born at 32-35 weeks' GA, particularly those with more than two risk factors or at least a moderate level of risk according to a risk scoring tool.", "Respiratory syncytial virus is the most common cause of bronchiolitis, a lower respiratory tract infection occurring in infancy. It is responsible for several rehospitalizations, substantial morbidity and occasional deaths in the UK every year. Palivizumab is a recombinant monoclonal antibody that has been shown to reduce hospitalizations in infected infants. It is licensed for high-risk infants, primarily those born pre-term or with chronic pulmonary or cardiac conditions. Palivizumab is expensive, but several economic analyses have determined highly discrepant costs. This article reviews the limitations of the available efficacy and economic data, and highlights problems in interpretation and extrapolation. We also present the results of a cost-effectiveness analysis relevant to populations of high-risk infants in the UK.", ": Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children. Motavizumab is an investigational humanized monoclonal antibody for RSV prophylaxis.\n : A dose-escalation study was conducted followed by assessment of safety, tolerability, serum concentrations, and immunogenicity during a second consecutive RSV season. In season 1, premature infants aged < or =6 months or children < or =24 months with chronic lung disease of prematurity received monthly motavizumab (3 or 15 mg/kg). In season 2, children who received > or =3 motavizumab doses in season 1 were randomized to receive monthly motavizumab or palivizumab 15 mg/kg.\n : Of 217 children enrolled in season 1, 211 (97.2%) received motavizumab 15 mg/kg and 205 (94.5%) patients completed the study through 90 days after the final dose. In season 2, 136 children were randomized to receive motavizumab (n = 66) or palivizumab (n = 70). The most commonly reported related adverse event was transient injection site erythema. In season 1, mean trough motavizumab concentrations were 7.9 and 50.2 microg/mL after the 3- and 15-mg/kg doses, respectively. Trough concentrations increased with repeated motavizumab dosing; a similar pattern was seen in season 2. Antimotavizumab reactivity occurred infrequently (3.3%) in season 1. In season 2, no treatment group-specific antidrug antibody was detected through 90 to 120 days after dosing with either product.\n : The pharmacokinetic profile of motavizumab was similar to that of other IgG1 antibodies. Increased adverse reactions or immunogenicity were not observed during and after a second season of treatment with motavizumab. Safety findings from these studies supported the continued development of motavizumab.", "The cost-effectiveness of passive immunisation against respiratory syncytial virus (RSV) in the Netherlands was studied by assessing incremental costs to prevent one hospitalisation in high-risk children using a novel individualised monthly approach.\n Cost-effectiveness analysis was performed by combining estimates of individual hospitalisation costs and monthly hospitalisation risks, with immunisation costs, parental costs and efficacy of passive immunisation for a reference case with the highest hospitalisation risks and costs of hospitalisation during the RSV season (male, gestational age < or =28 weeks, birth weight < or =2500 g, having bronchopulmonary dysplasia (BPD), aged 0 months at the beginning of the season (October)). Various sensitivity analyses and a cost-neutrality analysis were performed.\n Cost-effectiveness of passive immunisation varied widely by child characteristics and seasonal month. For the reference case it was most cost effective in December at euro13,190 per hospitalisation averted. Cost-effectiveness was most sensitive to changes in hospitalisation risk. For the reference case, cost neutrality was reached in December, if acquisition costs of passive immunisation decreased from euro 930 to euro 375, monthly hospitalisation risk increased from 7.6% to 17%, or hospitalisation costs increased from euro 10 250 to euro 23 250 per hospitalisation. Even if passive immunisation prevented all hospitalisations, costs per hospitalisation averted in December would still exceed euro 2645.\n Although cost-effectiveness of passive immunisation varied strongly by child characteristics and seasonal month, incremental costs per hospitalisation averted were always high. A restrictive immunisation policy only immunising children with BPD in high-risk months is therefore recommended. The costs of passive immunisation would have to be considerably reduced to achieve cost-effectiveness.", "To determine the safety and efficacy of prophylaxis with palivizumab in reducing the incidence of hospitalization because of respiratory syncytial virus (RSV) infection in high-risk infants.\n A randomized, double-blind, placebo-controlled trial was conducted at 139 centers in the United States, the United Kingdom, and Canada. During the 1996 to 1997 RSV season, 1502 children with prematurity (less than or equal to 35 weeks) or bronchopulmonary dysplasia (BPD) were randomized to receive 5 injections of either palivizumab (15 mg/kg) or an equivalent volume of placebo by intramuscular injection every 30 days. The primary endpoint was hospitalization with confirmed RSV infection. Children were followed for 150 days (30 days from the last injection). Those with hospitalization as a result of RSV infection were evaluated for total number of days in the hospital, total days with increased supplemental oxygen, total days with moderate or severe lower respiratory tract illness, and incidence and total days of intensive care and mechanical ventilation. The incidence of hospitalization for respiratory illness not caused by RSV and the incidence of otitis media were also evaluated. The placebo and palivizumab groups were balanced at entry for demographics and RSV risk factors. Ninety-nine percent of children in both groups completed the protocol and approximately 93% received all five scheduled injections.\n Palivizumab prophylaxis resulted in a 55% reduction in hospitalization as a result of RSV (10.6% placebo vs 4.8% palivizumab). Children with prematurity but without BPD had a 78% reduction in RSV hospitalization (8.1% vs 1.8%); children with BPD had a 39% reduction (12.8% vs 7.9%). When gender, entry age, entry weight, BPD, and gestational age were included in a logistic regression model, the effect of prophylaxis with palivizumab remained statistically significant. The palivizumab group had proportionally fewer total RSV hospital days, fewer RSV hospital days with increased oxygen, fewer RSV hospital days with a moderate/severe lower respiratory tract illness, and a lower incidence of intensive care unit admission. Palivizumab was safe and well tolerated. No significant differences were observed in reported adverse events between the two groups. Few children discontinued injections for related adverse events (0.3%). Reactions at the site of injection were uncommon (1.8% placebo vs 2.7% palivizumab); the most frequent reaction was mild and transient erythema. Mild or moderate elevations of aspartate aminotransferase occurred in 1.6% of placebo recipients and 3.6% of palivizumab recipients; for alanine aminotransferase these percentages were 2.0% and 2.3%, respectively. Hepatic and renal adverse events related to the study drug were similar in the two groups.\n Monthly intramuscular administration of palivizumab is safe and effective for prevention of serious RSV illness in premature children and those with BPD.", "Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants. MEDI-493 (palivizumab) is a humanized monoclonal antibody to the fusion protein of RSV and is active in animal models for prevention of pulmonary RSV replication.\n To describe the safety, tolerance, immunogenicity and pharmacokinetics of repeat intravenous doses of MEDI-493 in premature infants or infants with bronchopulmonary dysplasia.\n Phase I/II multicenter, randomized, double blind, placebo-controlled, dose escalation trial.\n Infants born prematurely (< or = 35 weeks of gestation) who were < or = 6 months of age and infants with bronchopulmonary dysplasia who were < or = 24 months of age were eligible for study participation. STUDY AGENTS: Participants received 3, 10 or 15 mg/kg MEDI-493 or 0.9% saline intravenously every 30 days for up to five doses.\n MEDI-493 was safe and well-tolerated and did not induce a specific anti-MEDI-493 response. The mean half-life of 20 days was comparable with that of other immunoglobulin G preparations. Mean trough serum concentrations 30 days after Infusion 1 were 6.8, 36.1 and 60.6 microg/ml for the 3-, 10- and 15-mg/kg dose groups, respectively. After Infusion 2 the trough concentrations were 11.9, 45.2 and 70.7 microg/ml. After subsequent doses the mean trough values ranged from 14 to 18 microg/ml in those given 3 mg/kg and were > 40 microg/ml for patients who received 10 or 15 mg/kg MEDI-493 (46 to 72 microg/ml and 88 to 96 microg/ml, respectively).\n MEDI-493 was safe and well-tolerated in this high risk pediatric population. Mean serum concentrations of MEDI-493 that have been shown to produce a 2-log reduction in pulmonary RSV titer in cotton rats were maintained when 10 or 15 mg/kg MEDI-493 was given every 30 days to pediatric patients at high risk for serious RSV disease. Monthly doses of 15 mg/kg maintained concentrations of > 40 microg/ml for the majority of patients.", "The methodological approach of the economic evaluation of drugs in pediatrics is illustrated by the case study of the prophylaxis for RSV infections using palivizumab in the French setting. The indications for the reimbursement of this treatment have been restricted to premature children with bronchopulmonary dysplasia (BPD) or hemodynamically significant congenital-heart disease. A model was developed primarily using the results of the pivotal clinical studies on palivizumab. Unit costs were estimated (2006 values) in both societal and payer's perspectives. An assumption was made and discussed on the benefits of the prophylaxis on mortality. Based on the different data available and the estimated costs and benefits, different cost-effectiveness ratios (CERs) were estimated from both the society's and payer's points of view. A discount rate of 3% was applied to benefit. The CER obtained in the most unfavorable case is considered acceptable for the innovative-medical technologies in the French-healthcare system. Some of the parameters used by the model will be illustrated from the EPIPAGE study data from 2 of the 9 regions involved in this study: this evaluation suggests that the children not having an RSV infection during their 1st year of life will continue to require significantly fewer hospitalizations in the following years. These additional evaluations also suggest that the model overestimates the costs of the treatment with regard to the true medical situation. This could be explained by the model not using the children's exact weight or the real number of injections because the children had been discharged from the maternity ward based on their date of birth and the epidemic period. In spite of these factors, RSV prophylaxis using palivizumab in premature children with BPD or hemodynamically significant congenital-heart disease can be considered cost-effective in France.", "To investigate the cost-effectiveness of palivizumab vs. no prophylaxis for respiratory syncytial virus (RSV) infection in preterm infants in Sweden.\n A probabilistic Markov model was populated using a nationwide register linkage and data from the literature. Cost-effectiveness was investigated from a societal perspective over a lifetime for infants born at <29 weeks of gestation. Palivizumab was modelled using assumptions for its direct effect on RSV hospitalization risk and an indirect effect (via decreased RSV hospitalization) on subsequent asthma and mortality during the epidemic. Costs and effects were discounted by 3%.\n In the base case, prophylaxis resulted in an additional 0.102 quality-adjusted life-year (QALY) at a cost of 20,000 SEK relative to no prophylaxis (incremental cost-effectiveness ratio [ICER] 195,000 SEK/QALY). The probability of prophylaxis being cost-effective was 99% at a willingness-to-pay of 500,000 SEK/QALY. Assumptions about a causal association between RSV infection and subsequent asthma had a moderate impact, while exclusion of the indirect prophylaxis effect on mortality increased the ICER to 492,000 SEK/QALY. When excluding both of these, prophylaxis was not cost-effective.\n Based on a willingness-to-pay of 500,000 SEK/QALY, palivizumab was found to be cost-effective compared with no prophylaxis for infants born at <29 weeks if severe RSV infection was assumed to increase subsequent asthma or mortality risk.\n © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.", "The aim of this study was to assess the cost-utility of palivizumab versus no prophylaxis in the prevention of respiratory syncytial virus infection among high-risk preterm infants.\n We used and adapted a pre-existent model in which two cohorts of patients received palivizumab or no prophylaxis. The patients were followed for their expected lifetimes. The economic evaluation was conducted from the perspective of the Italian National Health Service. We considered Life-Years Gained (LYGs), Quality-Adjusted Life-Years (QALYs) and direct medical costs (pharmacological treatment, hospitalization, recurrences for wheezing, etc.). LYGs and QALYs were based on the results of a double blind cohort study with prospective follow-up and direct medical costs were based on Italian treatment patterns. Benefits and costs were discounted at 3%. Costs were assessed in 2007 Euros. Sensitivity and threshold analysis on key clinical and economic parameters were performed.\n For the two cohorts, the expected life-years (per patient) with palivizumab versus no prophylaxis were 29.842 and 29.754 years, respectively. Quality-adjusted life years (per patient) with palivizumab were 29.202, and for no prophylaxis were 29.043. The expected cost (per patient) was euro 6,244.20 with palivizumab and euro 4,867.70 with no prophylaxis. We calculated for palivizumab versus no prophylaxis the incremental cost per LYG and per QALY gained. It was euro 15,568.65 and euro 8,676.74, respectively.\n This study suggests that, compared with no prophylaxis, palivizumab is cost-effective in the prevention of respiratory syncytial virus infection among high risk preterm infants.", "Palivizumab reduces respiratory syncytial virus (RSV) hospitalization in children at high risk by approximately 50% compared with placebo. We compared the efficacy and safety of motavizumab, an investigational monoclonal antibody with enhanced anti-RSV activity in preclinical studies, with palivizumab.\n This randomized, double-blind, multinational, phase 3, noninferiority trial assessed safety and RSV hospitalization in 6635 preterm infants aged <or=6 months at enrollment or children aged <or=24 months with chronic lung disease of prematurity who received 15 mg/kg palivizumab or motavizumab monthly. Secondary end points included outpatient medically attended lower respiratory tract infections (MALRIs), RSV-specific LRIs, otitis media, antibiotic use, development of antimotavizumab antibodies, and motavizumab serum concentrations.\n Motavizumab recipients had a 26% relative reduction in RSV hospitalization compared with palivizumab recipients, achieving noninferiority. Motavizumab was superior to palivizumab for reduction of RSV-specific outpatient MALRIs (50% relative reduction). Overall, adverse events (AEs) were not significantly different between groups. Cutaneous events were reported in 2 percentage points more motavizumab recipients (7.2% vs 5.1%); most were mild, but 0.3% resulted in dosing discontinuation. Antidrug antibodies (ADA) were detected in 1.8% of motavizumab recipients. Patients with anti-drug antibody reported 6 RSV events and 17 cutaneous events.\n Children receiving prophylaxis with motavizumab or palivizumab had low rates of RSV hospitalization; motavizumab recipients experienced 50% fewer RSV MALRIs than palivizumab recipients. AEs were similar in both groups, although cutaneous AEs were higher for motavizumab recipients. Motavizumab may offer an improved alternative in prophylaxis for serious RSV disease in infants and children at high risk.", "To assess the cost effectiveness of palivizumab (a preventative treatment against severe respiratory syncytial virus [RSV] infection) in children at high risk of hospitalisation, i.e. preterm infants < or = 35 weeks gestation, children with bronchopulmonary dysplasia (BPD) and children with congenital heart disease (CHD).\n A decision tree model was developed employing data sources from the published literature, palivizumab clinical trials, official UK price/tariff lists and national population statistics. The comparator was no prophylaxis. The primary perspective of the study was that of the UK NHS. In a societal perspective scenario analysis, the future lost productivity of a child resulting from RSV-related mortality (indirect costs) was also included. The cost of administration of palivizumab, hospital care for RSV infections and the cost of asthma treatment were included. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. The primary efficacy outcome in the palivizumab clinical trials was the number of RSV hospitalisations avoided, which was extrapolated to effectiveness outcomes, i.e. number of life-years gained and number of QALYs. Costs and effects were discounted by 3.5%.\n In preterm infants and children with BPD, prophylaxis with palivizumab compared with no prophylaxis had an incremental cost-effectiveness ratio (ICER) of 7042 pounds/QALY without discounting outcomes, increasing to 16,720 pounds/QALY after discounting. In babies with CHD, the use of palivizumab resulted in an ICER of 2427 pounds/QALY without discounting outcomes and 6664 pounds/QALY after discounting. One-way sensitivity analyses and probabilistic sensitivity analyses confirmed the robustness of the model. A scenario analysis showed that the inclusion of indirect costs leads to further improvement in the cost-effectiveness outcomes for palivizumab.\n This study suggests that palivizumab prophylaxis against severe RSV infection in children at high risk may be cost effective from the NHS perspective (vs no prophylaxis), and that the positive clinical and economic benefits may persist beyond one RSV season.", "To evaluate the cost-effectiveness of immunoprophylaxis against respiratory syncytial virus (RSV) infections with palivizumab based on actual cost and observed incidence rates in various pediatric risk groups.\n Decision tree analysis comparing children with various combinations of the following indications: chronic lung disease, congenital heart disease, or prematurity (≤32 weeks gestation), and children with none of these indications. One-way sensitivity analyses and Monte Carlo simulations were used to quantify parameter uncertainty.\n Florida during the 2004-2005 RSV season.\n A total of 159,790 Medicaid-eligible children aged 0 to 2 years.\n Palivizumab prophylaxis compared with no prophylaxis. OUTCOMES MEASURE: Incremental cost (2010 US dollars) per hospitalization for RSV infection avoided.\n The mean cost of palivizumab per dose ranged from $1661 for infants younger than 6 months of age to $2584 for children in their second year of life. Among preterm infants younger than 6 months of age without other indications, immunoprophylaxis with palivizumab cost $302,103 (95% confidence interval, $141,850-$914,798) to prevent 1 RSV-related hospitalization. Given a mean cost of $8910 for 1 RSV-related hospitalization in this subgroup, palivizumab would be cost-neutral at a per-dose cost of $47. Incremental cost-effectiveness ratios for the other subgroups ranged from $361,727 to more than $1.3 million per RSV-related hospitalization avoided in children up to 2 years of age with chronic lung disease and no additional risk factors. Younger age and multiple indications were associated with improvements in the incremental cost-effectiveness ratio.\n The cost of immunoprophylaxis with palivizumab far exceeded the economic benefit of preventing hospitalizations, even in infants at highest risk for RSV infection.", "Prophylactic therapy with palivizumab, a humanized monoclonal antibody, has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations in preterm infants. The cost-effectiveness of this therapy has not been evaluated from the provider's perspective using cost data.\n The objectives of this study were to determine the cost per RSV infection episode avoided by using prophylactic palivizumab therapy in a high-risk infant population and to determine whether certain subgroups of infants derived greater benefit from prophylactic therapy.\n A decision-analytic model simulating an RSV infection episode was developed to evaluate the cost-effectiveness of palivizumab prophylaxis from the perspective of the health care system (provider). Data to populate the model were gathered from the medical literature (identified through a MEDLINE search of studies on the incidence of RSV infection) and the IMpact-RSV clinical trial. Data included incidence of RSV infection and the associated health care resource use and costs. Costs to the provider were determined using a university-affiliated hospital cost-accounting system. Cost-effectiveness ratios were calculated over a range of RSV infection incidence rates in a control population. Sensitivity analyses were performed for the cost of palivizumab therapy, the cost of RSV-related hospitalization, and the number of emergency department, physician office, and home health care visits. For the subgroup analysis, infants were classified by gestational age (<32 and > or = 32 weeks) and stratified by severity of chronic lung disease.\n The cost per additional RSV infection episode avoided ranged from dollars 0 (cost savings) to dollars 39,591 for palivizumab prophylaxis costs of dollars 2500 and from dollars 2702 to dollars 79,706 for palivizumab prophylaxis costs of dollars 4500. The model was insensitive to changes in the number of emergency department, physician office, and home health care visits. The difference in RSV incidence between the treatment and control groups was greater among infants > or = 32 weeks' gestational age than among infants <32 weeks' gestational age. onclusions: The incremental cost-effectiveness of palivizumab compared with no prophylactic therapy was sensitive to changes in the incidence of RSV infection in control infants, the average cost of RSV hospitalization, and the cost of palivizumab. Clinicians may use this information along with additional factors to determine whether palivizumab is cost-effective in their clinical setting and geographic area.", "Acquisition costs of palivizumab have increased in Canada since 2007. This analysis aims to re-evaluate the cost effectiveness of palivizumab in Canada for premature infants born between 32 and 35 weeks' gestational age using updated 2010 healthcare costs compared to those used in a 2007 decision analytic model.\n New costs (CAN$) were acquired from the same Health Canada and Ontario Ministry of Health sources that were utilized in the previously published 2007 model. Palivizumab prices were acquired from Abbott Laboratories Ltd., current as of August 2010.\n Incremental cost-effectiveness ratios (ICERs) rose by $742, going from $30,618/QALY to $31,360/QALY. ICER changes increased from a range of $801,297 to $820,701 for infants with zero risk factors to a decrease from $808 to $192 for infants with four or more risk factors.\n Palivizumab ICERs remained fairly stable from 2007 to 2010. The original recommendation stating that palivizumab is cost effective in infants born between 32 and 35 weeks' GA with two or more risk factors, or who are at moderate-to-high risk based on a risk assessment model, does not change. Analyses founded on evolving country-specific variables are needed in order to accurately reassess the cost effectiveness of interventions as costs change worldwide.\n There are a limited number of publications reporting mortality in premature Canadian infants with RSV as a primary outcome. In addition, conclusions drawn from this analysis are country-specific and limited to premature infants dwelling in Canada.", "To evaluate the safety, tolerance, and efficacy of palivizumab in children with hemodynamically significant congenital heart disease (CHD).\n A randomized, double-blind, placebo-controlled trial included 1287 children with CHD randomly assigned 1:1 to receive 5 monthly intramuscular injections of 15 mg/kg palivizumab or placebo. Children were followed for 150 days. The primary efficacy end point was antigen-confirmed respiratory syncytial virus (RSV) hospitalization.\n Palivizumab recipients had a 45% relative reduction in RSV hospitalizations (P=.003), a 56% reduction in total days of RSV hospitalization per 100 children (P=.003), and a 73% reduction in total RSV hospital days with increased supplemental oxygen per 100 children (P=.014). Adverse events were similar in the treatment groups; no child had drug discontinued for a related adverse event. Serious adverse events occurred in 55.4% of palivizumab recipients and 63.1% of placebo recipients (P<.005); none were related to palivizumab. Twenty-one children (3.3%) in the palivizumab group and 27 (4.2%) in the placebo group died; no deaths were attributed to palivizumab. The rates of cardiac surgeries performed earlier than planned were similar in the treatment groups.\n Monthly palivizumab (15 mg/kg IM) was safe, well-tolerated, and effective for prophylaxis of serious RSV disease in young children with hemodynamically significant CHD.", "To evaluate the costs and benefits of two new agents, respiratory syncytial virus immune globulin (RSVIG) and palivizumab, to prevent respiratory syncytial virus (RSV) infection among premature infants discharged from the neonatal intensive care unit (NICU) before the start of the RSV season. Method. Decision analysis was used to compare the projected societal cost-effectiveness of three strategies-RSVIG, palivizumab, and no prophylaxis-among a hypothetical cohort of premature infants. Probabilities and costs of hospitalization were derived from a cohort of 1721 premature infants discharged from six Kaiser Permanente-Northern California NICUs. Efficacies of prophylaxis were based on published trials. Costs of prophylaxis were derived from published sources. Mortality among infants hospitalized for RSV was assumed to be 1.2%. Future benefits were discounted at 3%.\n Palivizumab was both more effective and less costly than RSVIG. Cost-effectiveness varied widely by subgroup. Palivizumab appeared most cost-effective for infants whose gestational age was </=32 weeks, who required >/=28 days of oxygen in the NICU, and who were discharged from the NICU from September through November. In this subgroup, palivizumab was predicted to cost $12,000 per hospitalization averted (after taking into account savings from prevention of RSV admissions) or $33,000 per life-year saved, and the number needed to treat to avoid one hospitalization was estimated at 7.4. However, for all other subgroups, ratios ranged from $39,000 to $420,000 per hospitalization averted or $110,000 to $1,200,000 per life-year saved, and the number needed to treat extended from 15 to 152. The results were sensitive to varying assumptions about the cost and efficacy of prophylaxis, as well as the probability of hospitalization, but were less sensitive to the cost of hospitalization.\n In our model, the cost of prophylaxis against RSV for most subgroups of preterm infants was high relative to the benefits realized. Lower costs might permit the benefits of prophylaxis to be extended to additional groups of preterm infants.", "Palivizumab has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations by 45% in children with congenital heart disease (CHD). The American Academy of Pediatrics has recommended that infants with hemodynamically significant CHD be considered for palivizumab. However, the economic implications of palivizumab prophylaxis in the CHD population have not been evaluated. In the present study, we sought to examine the cost savings and cost utility of RSV prophylaxis with palivizumab in children with CHD.\n Probabilities of hospitalization and efficacy of prophylaxis were based on published results. Costs of hospitalization were derived from a published analysis of bronchiolitis hospitalization costs from a consortium of children's hospitals. A hypothetical cohort of 10,000 CHD patients (half of whom would receive palivizumab) was created to calculate cost-savings and cost-utility. To assess cost utility, we assumed that by reducing hospitalization, palivizumab would reduce RSV-related hospital mortality, generally reported to be 3% in CHD patients. Sensitivity analysis was performed.\n On the basis of a protocol of 5 monthly doses of palivizumab, the cost of prophylaxis for 1 RSV season was calculated as 6160 dollars per patient. After accounting for impact on direct and indirect costs of hospitalization, administration of palivizumab to 5000 CHD patients would result in a net loss of 20,415,753 dollars. If one assumes that palivizumab confers a survival benefit, then the cost of life-year saved is 100,338 dollars and cost of quality-adjusted life-year saved is 114,337 dollars.\n The cost of palivizumab prophylaxis was high relative to benefits realized. Given the large number of CHD patients who might be considered candidates for RSV prophylaxis (>6000 patients per year in United States) routine use of palivizumab in young children with hemodynamically significant CHD needs to be evaluated further.", "To assess the cost effectiveness of palivizumab for prevention of severe respiratory syncytial virus (RSV) disease in high-risk infants in Spain, incorporating country-specific observational hospitalisation data.\n An existing decision tree model, designed using data from a large international clinical trial of palivizumab versus no prophylaxis, was updated to include Spanish observational hospitalisation data. The analysis was performed for preterm children born at or before 32 weeks gestational age, who are at high risk of developing severe RSV disease requiring hospitalisation. Data sources included published literature, official price/tariff lists and national population statistics. The primary perspective of the study was that of the Spanish National Health Service in 2006.\n The base-case analysis included the direct medical costs associated with palivizumab prophylaxis and hospital care for RSV infections. Use of palivizumab produces an undiscounted incremental cost-effectiveness ratio (ICER) of euro6,142 per quality-adjusted life-year (QALY), and a discounted ICER of euro12,814/QALY.\n Palivizumab provides a cost-effective method of prophylaxis against severe RSV disease requiring hospitalisation among preterm infants in Spain.", "The study evaluated the incremental cost-effectiveness ratio (ICER) of the prophylaxis of palivizumab, for the reduction of complications associated to the respiratory syncytial virus in preterm patients in Mexico.\n A decision tree was developed in preterm groups [<29 and 29-32 weeks of gestational age (wGA)], by using epidemiological and cost local data; the effectiveness was obtained with a systematic review. Patients were evaluated according to their life expectancy. Mexican Health System perspective was used. Effectiveness measures employed were LYG and QALYs. The costs are reported in USD 2009.\n ICERs per LYG resulted on values of USD $25,029 and USD $29,637 for <29 wGA and 29-32 wGA respectively, whereas ICERs per QALYs obtained in the model accounted for USD $17,532 and USD $20,760.\n Palivizumab prophylaxis for preterm newborn patients ≤32 weeks of age resulted in a cost-effective alternative." ]

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[ "Rhythmic auditory stimulation in gait training for Parkinson's disease patients.", "Effectiveness of physiotherapy in Parkinson's disease: the feasibility of a randomised controlled trial.", "The effects of incremental speed-dependent treadmill training on postural instability and fear of falling in Parkinson's disease.", "Cued task-specific training is better than exercise in improving sit-to-stand in patients with Parkinson's disease: A randomized controlled trial.", "Cueing training in the home improves gait-related mobility in Parkinson's disease: the RESCUE trial.", "Qigong exercise for the symptoms of Parkinson's disease: a randomized, controlled pilot study.", "Health-related quality of life and alternative forms of exercise in Parkinson disease.", "Does treadmill training improve lower-extremity tasks in Parkinson disease? A randomized controlled trial.", "A randomised controlled trial of a home based exercise programme to reduce the risk of falling among people with Parkinson's disease.", "The effects of an exercise program on fall risk factors in people with Parkinson's disease: a randomized controlled trial.", "[The effect of the complex rehabilitation on posture and gait in Parkinson disease].", "Gait and step training to reduce falls in Parkinson's disease.", "Exercise to improve spinal flexibility and function for people with Parkinson's disease: a randomized, controlled trial.", "The effect of exercise training in improving motor performance and corticomotor excitability in people with early Parkinson's disease.", "Symptom and gait changes after sensory attention focused exercise vs aerobic training in Parkinson's disease.", "Efficacy of a physical therapy program in patients with Parkinson's disease: a randomized controlled trial.", "Training with verbal instructional cues results in near-term improvement of gait in people with Parkinson disease." ]

[ "Rhythmic auditory stimulation (RAS) was used as a pacemaker during a 3-week home-based gait-training program for Parkinson's disease (PD) patients (n = 15). Electromyogram (EMG) patterns and stride parameters were assessed before and after the test without RAS to evaluate changes in gait patterns. Data were compared with those of two control groups (n = 11), who either did not participate in any gait training or who participated in an internally self-paced training program. RAS consisted of audiotapes with metronome-pulse patterns embedded into the on/off beat structure of rhythmically accentuated instrumental music. Patients who trained with RAS significantly (p < 0.05) improved their gait velocity by 25%, stride length by 12%, and step cadence by 10% more than self-paced subjects who improved their velocity by 7% and no-training subjects whose velocity decreased by 7%. In the RAS-group, timing of EMG patterns changed significantly (p < 0.05) in the anterior tibialis and vastus lateralis muscles. Evidence for rhythmic entrainment of gait patterns was shown by the ability of the RAS group to reproduce the speed of the last training tape within a 2% margin of error without RAS.", "To study the feasibility of a large randomised controlled trial (RCT) evaluating the effectiveness of physiotherapy in Parkinson's disease (PD), 173 patients were asked to participate in a study with random allocation to best practice physiotherapy, or to no physiotherapy. The primary outcome measures were the Parkinson's disease questionnaire-39, the Parkinson activity scale, and a patient preference outcome scale (PPOS). Only 14% of the patients could be included in the study. The PPOS showed the largest effect size (0.74) with a significant group effect (p<0.05). Specific alterations to the study design to ensure successful RCTs in this field are recommended.", "To detect the effectiveness of incremental speed-dependent treadmill training on postural instability, dynamic balance and fear of falling in patients with idiopathic Parkinson's disease.\n Randomized controlled trial.\n Ankara Education and Research Hospital, 2nd PM&R Clinic, Cardiopulmonary Rehabilitation Unit.\n Fifty-four patients with idiopathic Parkinson's disease in stage 2 or 3 of the Hoehn Yahr staging entered, and 31 patients (21 training, 10 control) had outcome data.\n Postural instability of patients with Parkinson's disease was assessed using the motor component of the Unified Parkinson's Disease Rating Scale (UPDRS), Berg Balance Test, Dynamic Gait Index and Falls Efficacy Scale. Twenty-one patients with Parkinson's disease participated in an eight-week exercise programme using incremental speed-dependent treadmill training. Before and after the training programme, balance, gait, fear of falling and walking distance and speed on treadmill were assessed in both Parkinson's disease groups.\n Walking distance and speed on treadmill, UPDRS, Berg Balance Test, Dynamic Gait Index and Falls Efficacy Scale.\n Initial total walking distance of the training group on treadmill was 266.45 +/- 82.14 m and this was progressively increased to 726.36 +/- 93.1 m after 16 training session (P < 0.001). Tolerated maximum speed of the training group on treadmill at baseline was 1.9 +/- 0.75 km/h and improved to 2.61 +/- 0.77 km/h (P < 0.001). Berg Balance Test, Dynamic Gait Index and Falls Efficacy Scale scores of the training group were improved significantly after the training programme (P < 0.01). There was no significant improvement in any of the outcome measurements in the control group (P > 0.05).\n Specific exercise programmes using incremental speed-dependent treadmill training may improve mobility, reduce postural instability and fear of falling in patients with Parkinson's disease.", "We examined whether 4 weeks of audio-visual (AV) cued task-specific training could enhance sit-to-stand (STS) and whether the treatment effects could outlast the treatment period by 2 weeks. Fifty-two subjects with PD completed the study. They were randomly allocated to receive 4 weeks of AV cued task-specific training, conventional exercise (Ex), or no treatment (control). Each subject was assessed before, at the end of 2 and 4 weeks of treatment, and 2 weeks after treatment ended. After 2 weeks of training, the AV group significantly increased the peak horizontal velocity (by 13%, P<0.01) when compared with the Ex group. After 4 weeks of training, AV group increased both peak horizontal and vertical velocities, respectively by 18% and 51%, and reduced the time taken to complete STS by 25%. These improvements were greater than those of the Ex group, who showed 8% (nonsignificant between-group) and 20% (P<0.05 between-group) increases respectively for peak horizontal and vertical velocities, and 10% decrease in movement time (P<0.05). Worth-noting is the improvements in AV group could be carried over to 2 weeks after treatment ended. These findings provided concrete evidence for the use of AV cued task-specific training to reeducate STS in patients with PD.\n (c) 2007 Movement Disorder Society.", "Gait and mobility problems are difficult to treat in people with Parkinson's disease. The Rehabilitation in Parkinson's Disease: Strategies for Cueing (RESCUE) trial investigated the effects of a home physiotherapy programme based on rhythmical cueing on gait and gait-related activity.\n A single-blind randomised crossover trial was set up, including 153 patients with Parkinson's disease aged between 41 and 80 years and in Hoehn and Yahr stage II-IV. Subjects allocated to early intervention (n = 76) received a 3-week home cueing programme using a prototype cueing device, followed by 3 weeks without training. Patients allocated to late intervention (n = 77) underwent the same intervention and control period in reverse order. After the initial 6 weeks, both groups had a 6-week follow-up without training. Posture and gait scores (PG scores) measured at 3, 6 and 12 weeks by blinded testers were the primary outcome measure. Secondary outcomes included specific measures on gait, freezing and balance, functional activities, quality of life and carer strain.\n Small but significant improvements were found after intervention of 4.2% on the PG scores (p = 0.005). Severity of freezing was reduced by 5.5% in freezers only (p = 0.007). Gait speed (p = 0.005), step length (p<0.001) and timed balance tests (p = 0.003) improved in the full cohort. Other than a greater confidence to carry out functional activities (Falls Efficacy Scale, p = 0.04), no carry-over effects were observed in functional and quality of life domains. Effects of intervention had reduced considerably at 6-week follow-up.\n Cueing training in the home has specific effects on gait, freezing and balance. The decline in effectiveness of intervention effects underscores the need for permanent cueing devices and follow-up treatment. Cueing training may be a useful therapeutic adjunct to the overall management of gait disturbance in Parkinson's disease.", "Irrespective of limited evidence, not only traditional physiotherapy, but also a wide array of complementary methods are applied by patients with Parkinson's disease (PD). We evaluated the immediate and sustained effects of Qigong on motor and nonmotor symptoms of PD, using an add-on design. Fifty-six patients with different levels of disease severity (mean age/standard deviation [SD], 63.8/7.5 years; disease duration 5.8/4.2 years; 43 men [76%]) were recruited from the outpatient movement disorder clinic of the Department of Neurology, University of Bonn. We compared the progression of motor symptoms assessed by Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) in the Qigong treatment group (n = 32) and a control group receiving no additional intervention (n = 24). Qigong exercises were applied as 90-minute weekly group instructions for 2 months, followed by a 2 months pause and a second 2-month treatment period. Assessments were carried out at baseline, 3, 6, and 12 months. More patients improved in the Qigong group than in the control group at 3 and 6 months (P = 0.0080 at 3 months and P = 0.0503 at 6 months; Fisher's exact test). At 12 months, there was a sustained difference between groups only when changes in UPDRS-III were related to baseline. Depression scores decreased in both groups, whereas the incidence of several nonmotor symptoms decreased in the treatment group only.\n Copyright 2005 Movement Disorder Society.", "Parkinson disease (PD) reduces health-related quality of life (HRQoL), but exercise may improve HRQoL. This pilot study compared the effects of Tango, Waltz/Foxtrot, Tai Chi and No Intervention on HRQoL in individuals with PD. Seventy-five persons with PD (Hoehn and Yahr I-III) were assigned to 20 lessons of Tango, Waltz/Foxtrot, Tai Chi, or an untreated No Intervention group. Participants completed the PDQ-39 before and after participation in 20 classes or within 13 weeks in the case of the No Intervention group. Two-way repeated measures ANOVAs determined differences between interventions. Tango significantly improved on mobility (p=0.03), social support (p=0.05) and the PDQ-39 SI (p<0.01) at post-testing. No significant changes in HRQoL were noted in the Waltz/Foxtrot, Tai Chi or No Intervention. Tango may be helpful for improving HRQoL in PD because it addresses balance and gait deficits in the context of a social interaction that requires working closely with a partner.", "To investigate whether gait training with treadmill improves functional tasks of lower extremities in patients with Parkinson disease (PD).\n Randomized controlled trial including two groups, the treadmill training group and the nonintervention group.\n University hospital.\n Thirty consecutive patients diagnosed with idiopathic PD, who were on stable regimens of antiparkinsonian medication, able to walk independently, and had not participated in a rehabilitation program in the previous 3 months. Patients with severe cognitive impairments or severe musculoskeletal, cardiopulmonary, neurologic, or other systemic disorders were excluded. Twenty-four patients completed the study.\n Group I attended a training program on a treadmill for 6 weeks, and group II served as the control group. Both groups were instructed in home mobility exercises.\n The primary study outcome measures were timed functional lower-extremity tasks (walking at a corridor, U-turn, turning around a chair, stairs, standing on one foot, standing from a chair), and secondary outcome measures were exercise test and patient's global assessment. Assessments were performed at baseline and at the end of the study.\n There were significant improvements in functional lower-extremity tests, exercise test parameters, and patients' global assessment in group I, whereas no significant improvements were observed in group II.\n Even though long-term effects remain unknown and the study sample was small, it was concluded that treadmill training in PD patients led to improvements in lower-extremity tasks, thus improving patients' physical well-being in daily life.", "To evaluate the effectiveness of a personalised home programme of exercises and strategies for repeat fallers with Parkinson's disease (PD).\n Patients with a confirmed diagnosis of idiopathic PD, independently mobile, living at home in the community, experiencing more than one fall in the previous 12 months and with intact gross cognitive function were invited to participate in this randomised controlled trial. Usual care was compared with a personalised 6 week, home based exercise and strategy programme. The primary outcomes were rates of falling at 8 weeks and 6 months. Whether participants had repeat fallen, nearly fallen or experienced injurious falls were also examined. Functional Reach, the Berg Balance Test, PD Self-assessment Scale and the Euro Quol were rated by a blinded assessor.\n Participants were randomised to the exercise (n = 70) and control (n = 72) groups. There was a consistent trend towards lower fall rates in the exercise group at both 8 weeks and 6 months and lower rates of injurious falls needing medical attention at 6 months. Lower rates of repeat near falling were evident for the exercise group at 8 weeks (p = 0.004) and 6 months (p = 0.007). There was a positive effect of exercises at 6 months on Functional Reach (p = 0.009) and quality of life (p = 0.033). No significant differences were found on other secondary outcomes measures.\n There was a trend towards a reduction in fall events and injurious falls with a positive effect of exercises on near falls and quality of life.", "This randomized controlled trial with blinded assessment aimed to determine the effect of a 6-month minimally supervised exercise program on fall risk factors in people with Parkinson's disease (PD). Forty-eight participants with PD who had fallen or were at risk of falling were randomized into exercise or control groups. The exercise group attended a monthly exercise class and exercised at home three times weekly. The intervention targeted leg muscle strength, balance, and freezing. The primary outcome measure was a PD falls risk score. The exercise group had no major adverse events and showed a greater improvement than the control group in the falls risk score, which was not statistically significant (between group mean difference = -7%, 95% CI -20 to 5, P = 0.26). There were statistically significant improvements in the exercise group compared with the control group for two secondary outcomes: Freezing of Gait Questionnaire (P = 0.03) and timed sit-to-stand (P = 0.03). There were statistically nonsignificant trends toward greater improvements in the exercise group for measures of muscle strength, walking, and fear of falling, but not for the measures of standing balance. Further investigation of the impact of exercise on falls in people with PD is warranted.", "Rehabilitation plays an important role in treatment of Parkinson's disease (PD). The influence of rehabilitation on balance and gait in PD hasn't been widely investigated. There is general agreement about positive influence of rehabilitation on postural instability and prevention of falls, but therapeutic program prevention of falls hasn't been worked out. Ambiguous results of studies indicate necessity of further investigations.\n 61 patient were included (H&Y 1, 5-3) and randomly assigned to two groups with and without rehabilitation. The balance test battery included: Functional Reach Test, Balance Performance-Oriented Mobility Assessment (Tinetti), assessment on force platform of quiet standing and active standing with Rhythmic Weight Shifts Test and dynamic task (reaction time, number of hitted targets). Gait was assessed with: timed Up&Go test, 10 m walk, locomotion test and 360 degrees turn. Patients were assessed 3 times, at month intervals. Between 1 and 2 assessment, exercising group took part in 1 month complex rehabilitation, consist of the 28 therapeutic sessions.\n The group, which took part in rehabilitation significantly improved in quiet standing with closed eyes after rehabilitation in comparison with initial status. All of the rest variables significantly improved in exercising group after rehabilitation both in comparison between evaluations and in comparison with the nonexercising group.\n Rehabilitation significantly influences balance and gait of patients with PD.", "Frequent falls and risk of injury are evident in individuals with Parkinson's disease (PD) as the disease progresses. There have been no reports of any interventions that reduce the incidence of falls in idiopathic PD.\n Assess the benefit of gait and step perturbation training in individuals with PD.\n Randomized, controlled trial.\n Outpatient research, education and clinical center in a tertiary care Veterans Affairs Medical Center.\n Gait parameters, 5-step test, report of falls.\n Eighteen men with idiopathic PD in stage 2 or 3 of the Hoehn and Yahr staging.\n Subjects were randomly assigned to a trained or control group. They were asked about any falls 2 weeks prior to and after an 8 week period. Gait speed, cadence, and step length were tested on an instrumented walkway. Subjects were timed while stepping onto and back down from an 8.8 cm step for 5 consecutive steps. Gait training consisted of walking on a treadmill at a speed greater than over ground walking speed while walking in 4 directions and while supported in a harness for safety. Step training consisted of suddenly turning the treadmill on and off while the subject stood in the safety harness facing either forwards, backwards, or sideways. Training occurred 1 hour per day, three times per week for 8 weeks. A two-factor (time and group) analysis of variance with repeated measures was used to compare the groups.\n Substantial reduction occurred in falls in the trained group, but not in the control group. Gait speed increased in the trained group from 1.28+/-0.33 meters/sec to 1.45+/-0.37 meters/sec, but not in the control group (from 1.26 to 1.27 m/s). The cadence increased for both groups: from 112.8 to 120.3 steps/min for the trained group and 117.7 to 124.3 steps/min for the control group. Stride lengths increased for the trained group, but not the control group. The 5-step test speed increased in the trained group from 0.40+/-0.08 steps/sec to 0.51+/-0.12 steps/sec, and in the control group (0.36+/-0.11 steps/sec to 0.42+/-0.11 steps/sec).\n Gait and step perturbation training resulted in a reduction in falls and improvements in gait and dynamic balance. This is a promising approach to reduce falls for patients with PD.", "The effectiveness of an exercise intervention for people in early and midstage Parkinson's disease (stages 2 and 3 of Hoehn and Yahr) in improving spinal flexibility and physical performance in a sample of community-dwelling older people is described.\n Fifty-one men and women, aged 55-84 years, identified through advertisement, local support groups, and local neurologists were enrolled into a randomized, controlled trial. Subjects were assigned randomly to an intervention or a usual care arm (i.e., no specific exercise). Of the original 51 participants, 46 completed the randomized, controlled trial. Participants in the exercise arm (n = 23) received individual instruction three times per week for 10 weeks. Participants in the usual care arm (n = 23) were \"wait listed\" for intervention.\n Changes over 10 weeks in spinal flexibility (i.e., functional axial rotation) and physical performance (i.e., functional reach, timed supine to stand) were the primary outcome measures.\n MANOVA conducted for the three primary outcome variables demonstrated significant differences (P < or = .05) between the two groups. Further analysis using ANOVA demonstrated significant differences between groups in functional axial rotation and functional reach for the intervention compared with the control group. There was no significant difference in supine to sit time.\n Study results demonstrate that improvements in axial mobility and physical performance can be achieved with a 10-week exercise program for people in the early and midstages of PD.", "To obtain preliminary data on the effects of high-intensity exercise on functional performance in people with Parkinson's disease (PD) relative to exercise at low and no intensity and to determine whether improved performance is accompanied by alterations in corticomotor excitability as measured through transcranial magnetic stimulation (TMS).\n Cohort (prospective), randomized controlled trial.\n University-based clinical and research facilities.\n Thirty people with PD, within 3 years of diagnosis with Hoehn and Yahr stage 1 or 2.\n Subjects were randomized to high-intensity exercise using body weight-supported treadmill training, low-intensity exercise, or a zero-intensity education group. Subjects in the 2 exercise groups completed 24 exercise sessions over 8 weeks. Subjects in the zero-intensity group completed 6 education classes over 8 weeks.\n Unified Parkinson's Disease Rating Scales (UPDRS), biomechanic analysis of self-selected and fast walking and sit-to-stand tasks; corticomotor excitability was assessed with cortical silent period (CSP) durations in response to single-pulse TMS.\n A small improvement in total and motor UPDRS was observed in all groups. High-intensity group subjects showed postexercise increases in gait speed, step and stride length, and hip and ankle joint excursion during self-selected and fast gait and improved weight distribution during sit-to-stand tasks. Improvements in gait and sit-to-stand measures were not consistently observed in low- and zero-intensity groups. The high-intensity group showed lengthening in CSP.\n The findings suggest the dose-dependent benefits of exercise and that high-intensity exercise can normalize corticomotor excitability in early PD.", "The current study compared lower-limb aerobic training and sensory attention focused exercise (PD SAFEx) to a non-exercise control group with the overall objective of determining which strategy would have a greater benefit for Parkinson's disease (PD) symptoms and gait. PD SAFEx was developed to focus on sensorimotor deficits identified in PD with the aim of increasing sensory feedback and body awareness, while the lower-limb aerobic training utilized a specially designed semi-recumbent elliptical device. Intervention groups (PD SAFEx, n = 18; aerobic, n = 13) exercised three times/week for 10-12 weeks, while nonexercise control participants (n = 15) maintained their regular activity level for 12 weeks. Outcome measures included the Unified Parkinson's disease rating scale motor section (UPDRS) administered by a blinded clinician; a posture and gait (PG) score (total of UPDRS items 27-31); the Timed-Up-and-Go (TUG); and spatiotemporal aspects of self-paced gait. PD SAFEx resulted in an improved UPDRS, PG score, and TUG (reached significance when participants with poor attendance were excluded) but not self-paced gait. The lower-limb aerobic training led to increased step length and velocity but had no change to disease severity. Since gait improvements were not combined with symptomatic changes, lower-limb aerobic exercise may not be optimal for individuals with PD. Conversely, sensory-based exercise (PD SAFEx) was beneficial, and led to improvement in symptoms and functional movement control.\n (c) 2009 Movement Disorder Society.", "To investigate the effects of a physical therapy (PT) program in groups of people with Parkinson's disease (PD).\n Randomized controlled trial with a crossover design.\n Two outpatient rehabilitation clinics in Boston and Amsterdam, respectively.\n Sixty-eight subjects diagnosed with typical, idiopathic PD, Hoehn and Yahr stage II or III, and stable medication use.\n Group A received PT and medication therapy (MT) for the first 6 weeks, followed by MT only for the second 6 weeks. Group B received only MT for the first 6 weeks and PT and MT for the second 6 weeks.\n The Sickness Impact Profile (SIP-68), the mobility portion of the SIP-68, the Unified Parkinson's Disease Rating Scale (UPDRS), and comfortable walking speed (CWS) at baseline, 6-week, 12-week, and 3-month follow-up.\n At 6 weeks, differences between groups were significant for the SIP mobility ( P =.015; effect size [ES]=.55), for CWS ( P =.012; ES=.49), for the activities of daily living (ADL) section of the UPDRS ( P =.014; ES=.45), and for the total UPDRS ( P =.007; ES=.56). The total SIP and the mentation and motor sections of the UPDRS did not differ significantly between groups. Significant differences were found at 3 months compared with baseline for CWS, the UPDRS ADL, and total scores.\n People with PD derive benefits in the short term from PT group treatment, in addition to their MT, for quality of life related to mobility, CWS, and ADLs; long-term benefits were found in CWS, UPDRS ADL, and total scores but varied between groups.", "To assess immediate and near-term effects of an instructional set on select gait parameters in people living with Parkinson disease (PD).\n Five individuals with early stage PD participated in a within subject design in Part One. Eleven individuals with early stage PD were randomly assigned to a treatment group (n = 5) or a control group (n = 6) in Part Two.\n The treatment consisted of a 10-day training program of walking 1800 feet per day and with the instructions to take long steps. Testing occurred before treatment (baseline), immediately after treatment, one week after treatment, and one month after treatment. Measurements of step length, velocity, and cadence were taken without the use of the instructional set.\n There was a significant increase in step length and velocity and a significant decrease in cadence between baseline and all post-test measures for part one. For part 2, step length of the treatment group significantly increased between baseline and all 3 post-tests and there was a significant difference between the treatment group and control group at all posttests for step length.\n The instructional set was effective in improving parameters of gait for at least 4 weeks. These data support the concept that people with Parkinson disease have a potential for motor learning." ]

[ "9248875", "1348161", "6891818", "380367", "9316669", "4388249", "6117347", "13935033", "2574191", "9989567", "1971117", "4883430", "9217519", "4862446", "6127747", "1494594", "2371367", "4909632", "9892313", "13863555", "5331284", "2686478", "4629815" ]

[ "Efficacy of lorazepam and haloperidol for rapid tranquilization in a psychiatric emergency room setting.", "Alprazolam as a neuroleptic adjunct in the emergency treatment of schizophrenia.", "Diazepam in high doses is effective in schizophrenia.", "Acute high-dose parenteral haloperidol treatment of psychosis.", "A double-blind comparison of clonazepam and placebo in the treatment of neuroleptic-induced akathisia.", "Combined drug treatment of newly hospitalized, acutely ill psychiatric patients.", "Schizophrenics fully remitted on neuroleptics for 3-5 years--to stop or continue drugs?", "A double-blind comparison of diazepam, chlordiazepoxide and chlorpromazine in psychotic patients.", "Successful clonazepam treatment of neuroleptic-induced akathisia in older adolescents and young adults: a double-blind, placebo-controlled study.", "Diazepam treatment of early signs of exacerbation in schizophrenia.", "Double blind, controlled study of the efficacy and safety of alpidem in the treatment of anxiety in schizophrenic in-patients.", "Itil TM, Keskiner A, Fink M: Thioridazine and chlordiazepoxide, alone and combined, in the treatment of chronic schizophrenia.", "Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study.", "A double-blind outpatient study of diazepam (Valium) and placebo.", "Prophylactic effect of neuroleptics in symptom-free schizophrenics.", "Haloperidol and lorazepam combined: clinical effects and drug plasma levels in the treatment of acute schizophrenic psychosis.", "The use of midazolam in acutely agitated psychiatric patients.", "Comparative effects of fluphenazine, fluphenazine-chlordiazepoxide and fluphenazine-imipramine.", "Intramuscular flunitrazepam versus intramuscular haloperidol in the emergency treatment of aggressive psychotic behavior.", "The effects of chlordiazepoxide (librium) in anxiety states. A multi-blind study.", "Chlorpromazine-chlordiazepoxide and chlorpromazine-imipramine treatment: side effects and clinical laboratory findings.", "Efficacy of combinations of intramuscular antipsychotics and sedative-hypnotics for control of psychotic agitation.", "The therapeutic effects of lorazepam in psychotic patients treated with haloperidol: a double-blind study." ]

[ "The efficacy of a benzodiazepine was compared with that of a neuroleptic for the rapid tranquilization of patients presenting at a psychiatric emergency room service. Thirty-seven highly agitated patients exhibiting psychotic symptoms were randomly assigned to receive either 2 mg lorazepam or 5 mg haloperidol as needed every 30 min for 4 h. Administration route was either intramuscular injection or oral concentrate. Symptom ratings were conducted each hour using double-blind procedures. Both medications reduced symptom ratings on the Brief Psychiatric Rating Scale and Global Clinical Impression of Overall Symptom Severity Scale. Global Clinical Impression scores for the two medication groups did not differ significantly either at baseline or at 4 h after entry into the study. However, Global Clinical Impression scores of patients in the lorazepam group were less severe at intermittent ratings. The groups did not differ on the Brief Psychiatric Rating Scale at any rating time. No differences were found either in the number of doses administered or in the administration route selected. Given the potential for severe extrapyramidal symptoms developing hours or days after a single dose of haloperidol, lorazepam may provide an excellent alternative for the rapid tranquilization of the acutely agitated psychotic patient in the emergency room setting.", "While neuroleptics remain the mainstay of drug intervention in the emergency management of psychosis, a variety of agents have received study as alternatives or adjuncts to these drugs in an attempt to improve the safety and efficacy of acute treatment. The purposes of this study were to investigate the efficacy and safety of alprazolam as a neuroleptic adjunct for schizophrenic patients in psychotic relapse and to clarify the effects of combination treatment on specific aspects of the psychotic process.\n Twenty-eight acutely psychotic patients with schizophrenia who were admitted to an emergency psychiatric service were randomly assigned to treatment with either haloperidol and alprazolam or haloperidol with placebo under double-blind conditions. Drug administration lasted 72 hours.\n Both groups improved significantly. The combination-treated group required significantly less medication and had 56% fewer dystonic reactions. The addition of alprazolam was most effective for symptoms of excitement and uncooperativeness, particularly in the initial hours of treatment.\n The combination of alprazolam and haloperidol seems to be the most effective for agitated patients, particularly in the first 48 hours of treatment. It may also result in fewer dystonic reactions.", "1. Diazepam in high doses, up to 400 mg per day, was administered to paranoid schizophrenic patients in a double-blind placebo-controlled study. 2. The effects of treatment were assessed by the following: the Brief Psychiatric Rating Scale (BPRS); the Clinical Global Impressions Scale (CGI); the Schizophrenia Subscale of the Present State Examination (SS-PSE); the Simpson-Angus Rating Scale (SARS) for extrapyramidal symptoms; the Nurses' Observation Scale for Inpatient Evaluation (NOSIE); and a 90 item Self-Assessment Questionnaire (SCL-90). 3. Within a few hours to a few days from the onset of diazepam treatment both positive (such as auditory hallucinations and persecutory delusions) and negative (such as emotional withdrawal and blunted affect) schizophrenic symptoms were dramatically eliminated in 5 out of the 6 patients.", "After 2 days of drug-free observation, 20 newly admitted psychotic patients received 20-35 mg of haloperidol intravenously and 20 patients received 30-40 mg of diazepam intravenously. Posttreatment ratings at 4 and 24 hours with the Brief Psychiatric Rating Scale and the Clinical Global Impressions revealed significant improvement in both groups but no significant differences between the two treatments.", "The present study was designed to investigate the efficacy of clonazepam in neuroleptic-induced akathisia. Twelve patients were treated during 2 weeks with clonazepam or placebo in a double-blind randomized design. Akathisia was scored by an independent rater before and after treatment, as well as 1 week after medication withdrawal. Clonazepam (0.5-2.5 mg/day) induced a significantly higher reduction in the akathisia scores than placebo (p < 0.05). One week after stopping the drug, there was a partial but significant relapse in the treated group as compared with controls, in whom the symptoms remained stable. In addition, the clinical improvement was significantly correlated with the daily dose of clonazepam (rs = 0.827; p < 0.002). These results support the potential usefulness of clonazepam in the treatment of neuroleptic-induced akathisia and suggest an optimal daily dose in the range of 10-40 micrograms/kg.", "nan", "A double-blind comparison between benzodiazepines and neuroleptics was carried out for 1 1/2 years on 30 schizophrenics who had hitherto continuously received neuroleptics and remained apparently in full remission for at least 3-5 years. The benzodiazepine-group had a significantly higher relapse rate than the neuroleptic-group, meaning that we cannot stop neuroleptics for these patients yet. Three possible reasons for this are (1) demand of the natural course of the illness, (2) the fact that the patients agreed to stay in therapy for so long may signify a need for therapy, (3) some of the relapses on stopping neuroleptics may be 'withdrawal psychosis' after prolonged neuroleptic therapy. If withdrawal of neuroleptics is really needed, however, it may be considered for a subgroup of female patients whose illness started after the age of 40.", "nan", "In a double-blind, placebo-controlled trial of clonazepam in the treatment of neuroleptic-induced akathisia in older adolescents, clonazepam was significantly more effective at reducing akathisia scores at the end of the first treatment week than placebo (p less than 0.0001). Clonazepam may be a safe and effective treatment for neuroleptic-induced akathisia in this age group.", "Therapeutic intervention at the earliest phase of symptom exacerbation in schizophrenia is an important clinical need, but specific pharmacotherapeutic interventions for this phase of illness have not been established. This study examined diazepam efficacy for this phase of treatment.\n A double-blind, randomized clinical trial with 53 schizophrenic patients compared diazepam with placebo (with fluphenazine treatment for a comparison group). Treatment was initiated at the earliest signs of exacerbation, and symptom progression was the dependent measure used to evaluate efficacy.\n Diazepam was statistically superior to placebo in preventing symptom progression and was comparable to fluphenazine.\n Efficacy data support the use of diazepam in treating prodromal and early warning signs of symptom exacerbation in schizophrenia. This therapeutic strategy may be especially important for patients who refuse antipsychotic drugs or as a supplemental approach in a treatment plan that emphasizes low-dose antipsychotic therapy.", "In this double-blind study, alpidem, a new imidazo-pyridine anxiolytic drug, was compared with placebo in order to test its efficacy and safety in chronic schizophrenic in-patients suffering from anxiety not directly related to the schizophrenic process. Sixty-six patients aged from 18 to 65 entered the trial. They also scored at least 18 on the Hamilton Rating Scale for Anxiety (HRSA) after a seven-day placebo run-in. Improvement in symptoms was evaluated by means of the HRSA, the Brief Psychiatric Rating Scale (BPRS), a Visual Analogue Scale (VAS), and the Clinical Global Impression score (CGI). Thirty-three patients were randomly allocated to alpidem and 33 to placebo. Alpidem was significantly more effective (P less than 0.0001) than placebo in improving HRSA scores (total score and factorial scores for somatic and psychic anxiety), BPRS, and VAS. Considering the results of CGI at 21 day, more patients were moderately to markedly improved on alpidem (30/33) than on placebo (2/33) (P less than 0.0001). The efficacy index, according to CGI, was significantly better (P less than 0.001 at least) for alpidem than for placebo. Side-effects were negligible in both groups.", "nan", "Rapid tranquilization is a routinely practiced method of calming agitated psychotic patients by use of neuroleptics, benzodiazepines, or both in combination. Although several studies have examined the efficacy of the three approaches, none have compared these treatments in a prospective, randomized, double-blind, multicenter trial. Ninety-eight psychotic, agitated, and aggressive patients (73 men and 25 women) were prospectively enrolled during an 18-month period in emergency departments in five university or general hospitals. Patients were randomly assigned to receive intramuscular injections of lorazepam (2 mg), haloperidol (5 mg), or both in combination. Patients in each treatment group received 1 to 6 injections of the same study drug within 12 hours, based on clinical need. They were evaluated hourly after the first injection until at least 12 hours after the last. Efficacy was assessed on the Agitated Behavior Scale (ABS), a modified Brief Psychiatric Rating Scale (MBPRS), Clinical Global impressions (CGI) scale, and an Alertness Scale. Effective symptom reduction was achieved in each treatment group with significant (P < .01) mean decreases from baseline at every hourly ABS evaluation. Significant (P < .05) mean differences on the ABS (hour 1) and MBPRS (hours 2 and 3) suggest that tranquilization was most rapid in patients receiving the combination treatment. Study event incidence (side effects) did not differ significantly between treatment groups, although patients receiving haloperidol alone tended to have more extrapyramidal system symptoms. The superior results produced by the combination treatment support the use of lorazepam plus haloperidol as the treatment of choice for acute psychotic agitation.", "nan", "Prophylactic effects of psychotropic drugs on 55 schizophrenics in remission were evaluated for 3 years in a double-blind controlled study employing a cross-over design. Patients were randomly assigned to the following drugs orally administered twice a day: placebo; diazepam 15 mg; imipramine 50 mg; chlorpromazine 75 mg; and haloperidol 3 mg. The number of days of remission for each patient was recorded. Since only two patients received all five drug treatments, the data were analyzed using the number of days allocated to the \"first assigned drugs\" only and the cross-over aspect of the experimental design was disregarded. All patients treated with either the placebo, diazepam or imipramine relapsed within a year. On the other hand, four patients treated with chlorpromazine, or with haloperidol, were in remission for more than 1 year. Fifty percent of the patients relapsed within 16 days with placebo; 88 days with diazepam; 30 days with imipramine; 165 days with chlorpromazine; and 74 days with haloperidol. Within a year, only chlorpromazine significantly prolonged the remission state as compared to placebo and imipramine. At the end of the 3-year trial, both chlorpromazine and haloperidol significantly prolonged the remission state as compared to the other three drugs. These data suggest that neuroleptic treatment for a longer period is vitally important to prevent relapse even in schizophrenics in remission and that such a trial seems an efficient method for investigating the prophylactic effects of neuroleptics.", "In 61 acute schizophrenic patients the effects of haloperidol (HPL) and lorazepam combined vs. HPL alone and the interaction between these drugs were evaluated. Patients were assigned to groups randomly. The study design was open. Study duration was 28 days. Psychopathology was evaluated on the basis of BPRS scores. Extrapyramidal side-effects were rated according to Simpson and Angus (1970). Pharmacological parameters included serum levels of lorazepam, HPL, and reduced HPL. Mean daily lorazepam dosage was 0.05 mg/kg, mean HPL dosage 0.5 mg/kg. None of the patients treated with lorazepam and HPL achieved better BPRS total or subscores, nor did their condition improve faster than in patients treated with HPL alone. A significant linear relationship between lorazepam serum levels and oral dosage was found, but none between lorazepam serum levels and BPRS total score, subscore reduction, or extrapyramidal side-effects. The authors conclude that beneficial effects of lorazepam in the treatment of acute psychosis are scant and may not justify the risks incurred with routine comedication of lorazepam.", "Agents currently used for acutely agitated patients such as sodium amytal and haloperidol are disadvantageous because of their adverse effects on the respiratory and extrapyramidal systems. Because of this, a rapid, safe, well-absorbed agent such as midazolam would be useful. This study compares the effectiveness of midazolam, sodium amytal, and haloperidol in agitated schizophrenic patients. Five male patients between 28 and 59 years were randomly assigned to each group. They were administered intramuscularly either 10 mg of haloperidol, 250 mg of sodium amytal, or 5 mg of midazolam. Over a 2-hour period, patients were rated for motor agitation, hostility, auditory hallucinations, and flight of ideas. Both midazolam and sodium amytal were significantly more effective than haloperidol in controlling motor agitation. There were no treatment differences on any other symptom rated. These results indicate that further studies on the use of midazolam to achieve rapid tranquilization would be useful.", "nan", "The authors examined the efficacy of intramuscular flunitrazepam compared with intramuscular haloperidol for the immediate control of agitated or aggressive behavior in acutely psychotic patients.\n Twenty-eight actively psychotic inpatients, aged 20-60 years, who were under treatment with neuroleptic agents were selected for the study. Each was randomly assigned on a double-blind basis to receive either 5 mg i.m. of haloperidol (N=13) or 1 mg i.m. of flunitrazepam (N=15) during an aggressive event. Verbal and physical aggression was measured over time with the Overt Aggression Scale. Patients were also rated with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale.\n Both flunitrazepam and haloperidol exhibited acute antiaggressive activity. This beneficial effect, as assessed by the Overt Aggression Scale, was obtained within 30 minutes.\n Intramuscular flunitrazepam may serve as a convenient, rapid, safe, and effective adjunct to neuroleptics in reducing aggressive behavior in emergency psychiatric settings.", "nan", "nan", "The combination of haloperidol, 5 mg, and lorazepam, 4 mg, was both effective and safe for managing agitated behavior in an open trial with acutely psychotic patients. The combination also appeared to be superior to its individual components when studied in a randomized, nonblind trial. The principle of the combined use of antipsychotics and sedative-hypnotics was further tested by comparing two new combinations: thiothixene, 5 mg, and lorazepam, 4 mg, versus haloperidol, 5 mg, and phenobarbital sodium, 130 mg. These combinations had comparable efficacy and safety, and the level of transquilization approached that produced by the haloperidol-lorazepam combination in the preceding studies.", "nan" ]

[ "20058059", "20204689", "15679185", "20232240", "19015968" ]

[ "A randomized controlled study of parent-assisted Children's Friendship Training with children having autism spectrum disorders.", "Promoting social skill development in children with pervasive developmental disorders: a feasibility and efficacy study.", "A social adjustment enhancement intervention for high functioning autism, Asperger's syndrome, and pervasive developmental disorder NOS.", "RCT of a manualized social treatment for high-functioning autism spectrum disorders.", "Parent-assisted social skills training to improve friendships in teens with autism spectrum disorders." ]

[ "This study evaluated Children's Friendship Training (CFT), a manualized parent-assisted intervention to improve social skills among second to fifth grade children with autism spectrum disorders. Comparison was made with a delayed treatment control group (DTC). Targeted skills included conversational skills, peer entry skills, developing friendship networks, good sportsmanship, good host behavior during play dates, and handling teasing. At post-testing, the CFT group was superior to the DTC group on parent measures of social skill and play date behavior, and child measures of popularity and loneliness, At 3-month follow-up, parent measures showed significant improvement from baseline. Post-hoc analysis indicated more than 87% of children receiving CFT showed reliable change on at least one measure at post-test and 66.7% after 3 months follow-up.", "A randomized controlled design was employed to evaluate a social skills intervention for children with pervasive developmental disorders. Aims included evaluating the acceptability of the program and gathering preliminary evidence on efficacy. Forty-four children, ages 8-11 years, were randomly assigned to treatment or wait list. Treatment consisted of a 16-week group intervention designed to teach appropriate social behavior. Between group comparisons showed that children in treatment were rated as improved on the primary outcome measure, (unblinded parent report), but not on the secondary outcome measure, a parent questionnaire. Parents reported a high level of satisfaction with the intervention. The study supports the feasibility of this intervention to families and highlights challenges for future research in social skills intervention.", "This paper reports the findings of a 20-week social adjustment enhancement curriculum for boys aged 8-12. The curriculum was designed to address three areas hypothesized to be deficient in persons with HFA, AS, and PDDNOS: emotion recognition and understanding; theory of mind; and executive functions/real life type problem solving. Parents attended a semi-structured concurrent psychoeducational training meeting during children's sessions. Statistically significant improvements in facial expression recognition, and problem solving were reported for intervention group children compared to waiting list control group children. For the intervention group (the only group for whom data were available), older and less cognitively able boy's scores on a depression inventory decreased significantly more than younger children's. Mother's depression scores tended to decrease and there were significant reductions in child problem behaviors reported. Results are discussed in the context of individual differences in participant cognitive levels and profiles, symptom severity, and affect-related variables.", "This RCT examined the efficacy of a manualized social intervention for children with HFASDs. Participants were randomly assigned to treatment or wait-list conditions. Treatment included instruction and therapeutic activities targeting social skills, face-emotion recognition, interest expansion, and interpretation of non-literal language. A response-cost program was applied to reduce problem behaviors and foster skills acquisition. Significant treatment effects were found for five of seven primary outcome measures (parent ratings and direct child measures). Secondary measures based on staff ratings (treatment group only) corroborated gains reported by parents. High levels of parent, child and staff satisfaction were reported, along with high levels of treatment fidelity. Standardized effect size estimates were primarily in the medium and large ranges and favored the treatment group.", "This study examines the efficacy of a manualized parent-assisted social skills intervention in comparison with a matched Delayed Treatment Control group to improve friendship quality and social skills among teens 13-17 years of age with autism spectrum disorders. Targeted skills included conversational skills, peer entry and exiting skills, developing friendship networks, good sportsmanship, good host behavior during get-togethers, changing bad reputations, and handling teasing, bullying, and arguments. Results revealed, in comparison with the control group, that the treatment group significantly improved their knowledge of social skills, increased frequency of hosted get-togethers, and improved overall social skills as reported by parents. Possibly due to poor return rate of questionnaires, social skills improvement reported by teachers was not significant. Future research should provide follow-up data to test the durability of treatment." ]

[ "18155755", "15196861" ]

[ "Comparison of outcome measures in patients with advanced squamous cell carcinoma of the vulva treated with surgery or primary chemoradiation.", "Chemoradiation with 5-fluorouracil and mitomycin C in the treatment of vulvar squamous cell carcinoma." ]

[ "To review outcome measures including overall survival (OS), progression free survival (PFS), and patterns of recurrence in patients with advanced vulvar cancer managed by primary surgery (PS) or primary chemoradiation (PCRT) as well as population characteristics for the two groups.\n Patients diagnosed with stage III and IV squamous cell carcinoma of the vulva from 1990 to 2006 were identified for retrospective analysis at a single institution. Charts were abstracted for clinical and pathologic findings, treatment modalities, complications, recurrence, and follow-up. Kaplan-Meier method was used to determine PFS and OS.\n Sixty-three patients with stage III (n=47) and IV (n=16) carcinoma of the vulva were identified; 30 patients were treated with PS, and 33 patients had tumor that was unresectable by vulvectomy and underwent PCRT. Patients treated with PCRT were younger (61 vs. 72 years; p=0.09), had less metastasis to lymph nodes (54% vs. 83%, p=0.01), and larger tumors (6 vs. 3.5 cm, p=0.0001) compared to patients treated with PS. Despite these differences, OS for the PS and PCRT groups was 69% and 76% (NS), respectively, with median follow-up at 31 months. There were no differences in PFS or recurrence rates between the two groups. By multivariate analysis, age was the only significant predictor of OS or PFS.\n Patients with advanced vulvar cancer that are managed with PS tend to be older patients that have smaller lesions but positive lymph nodes, whereas patients requiring PCRT are younger and have larger volume disease but fewer lymph node metastases. Despite these differences, patients treated with PS and PCRT have no differences in OS, PFS, or recurrence rates. Age is the most powerful predictor of survival when size, lymph node status, stage and treatment are accounted for.", "To investigate the acute and late toxicities associated with the use of chemoradiation therapy (CRT) with 5-fluorouracil (5-FU) and mitomycin C or mitomycin C alone for primary, adjuvant, and salvage therapy for vulvar cancer.\n Medical charts of 17 patients who received CRT with this regimen were reviewed. Toxicity was scored by 1998 standardized common toxicity criteria, Version 2.0, for acute toxicity and the RTOG/EORT Late Radiation Morbidity Scoring Schema for late toxicity. Median follow-up was 20 months (range: 5-74 months).\n Six patients had grade 4 neutropenia. In three patients, life-threatening neutropenic sepsis developed after the second cycle of chemotherapy. Severe enterocolitis was a direct cause of death in two patients. In four patients, the second cycle of chemotherapy was cancelled because of severe toxicity associated with the first cycle. One patient had grade 4 skin toxicity in the vulvar-perineal area. Six patients had grade 3 and seven patients had grade 2 acute skin toxicity. Skin toxicity necessitated the interruption of CRT in nine patients at a median dose of 32.4 Gy (range: 16.2-48 Gy). One patient developed bowel perforation and colovaginal fistula 1.5 years after completion of CRT.\n Chemoradiation therapy utilizing 5-FU and mitomycin C or mitomycin C alone in the treatment of vulvar cancer can be associated with a high incidence of morbidity and mortality. Strict attention to indications for treatment interruptions or chemotherapy dose adjustments is obligatory for safe delivery of CRT to these patients." ]

[ "678328", "10514661", "6773022", "3748681", "7070890", "7359242", "11483805", "448495" ]

[ "Minimal oxygen consumption in infants cared for under overhead radiant warmers compared with conventional incubators.", "[Incubator care versus \"open care\" in the warming bed for very small premature infants].", "Oxygen consumption and insensible water loss in premature infants under radiant heaters.", "Energy metabolism and substrate utilization in low birth weight neonates under radiant warmers.", "Relative efficacy of an incubator and an open warmer in producing thermoneutrality for the small premature infant.", "Heat balance in premature infants: comparative effects of convectively heated incubator and radiant warmer, with without plastic heat shield.", "A clinical comparison of radiant warmer and incubator care for preterm infants from birth to 1800 grams.", "Combined effect of radiant warmer and phototherapy on insensible water loss in low-birth-weight infants." ]

[ "Infants under radiant warmers have large increases in insensible water loss compared with infants in single wall incubators. To answer the question of whether or not a minimal rate of oxygen consumption could be achieved under overhead radiant warmers, we measured oxygen consumption, carbon dioxide production, and abdominal skin, cheek, rectal, thigh, and environmental temperature in ten healthy newborn infants in incubators and radiant warmers, using each infant as his/her own control. The minimal VO2 ranged from 4.41 to 8.87 and from 4.35 to 9.06 cc/kg/minute in the incubator and radiant warmer, respectively. The differences were clearly not significant (paired Student t-test, P greater than 0.60). There were no significant differences between the respiratory quotients, VCO2, or abdominal skin, check, rectal or environmental temperatures. These data support the hypothesis that a thermoneutral environment can be provided with a radiant warmer and imply that large increases in insensible water loss can occur without affecting minimal oxygen consumption.", "nan", "Oxygen consumption ((Vo2), carbon dioxide production (Vco2), and insensible water loss (IWL) were measured simultaneously in nine nondistressed, appropriately grown, premature infants less than 2 weeks old, nursed in a conventional, blow-warmed incubator, and were compared with measurements made on the same infants under a radiant heater. The infants had a pronounced increase (148% on average) in IWL when under the radiant heater (P < .001) whereas Vo2 increased by only 4.6% (P = .073). Abdominal skin temperature (servocontrolled to maintain 36.5 C) and esophageal temperature were the same under both conditions, but ambient air temperature was 0.7 C higher in the incubator (P < 05). Although a positive correlation was found between the increase in IWL and the change in Vo2 (r = .75, P < .01), the large increase in IWL (and, therefore, evaporative heat loss) under the radiant heater is out of proportion to, and cannot be accounted for, by the change in metabolic heat production. The heat transfer processes involved in maintaining body temperature constant under these conditions require further study.", "We evaluated the metabolic response to the thermal demands of an open radiant warmer device, as distinct from convection incubator, in 13 healthy premature infants (1.395 +/- 169 g, 28 +/- 12 days of age, mean +/- SD). Metabolic rate was 10% higher for infants under the radiant warmer than in the incubator (2.60 +/- 0.4 v 2.36 +/- 0.3 kcal/kg/h; P less than .05). The radiant warmer also induced a small (4%), but significant, increase in nonprotein respiratory quotient (0.94 +/- 0.1 v 0.90 +/- 0.1; P less than .05) and a 13% increase in carbon dioxide production (8.26 +/- 1.1 v 7.31 +/- 1.1 mL/kg/min; P less than .05). Subcutaneous fat accumulation (estimated from 60-second skin-fold thickness measurements) was greater under the radiant warmer than in the incubator (0.08 +/- 0.05 v 0.04 +/- 0.04 mm/d; P less than .05). Under the warmer, the infant's mean skin temperatures and core temperatures were normal and similar to those found in the incubator, but the foot temperature was on average 0.6 degrees C cooler. The average rate of weight gain (18 g/kg/d) was the same in the radiant environment. The pattern of the elevated metabolic rate, shift of respiratory quotient coupled with the accumulation of subcutaneous fat, and cool extremities of infants under the radiant warmer may represent a physiologic adaptive response to thermal stress. However, the reasons for the elevated metabolic rate are unclear, because activation of the sympathetic nervous system with the release of catecholamines is not apparently involved.(ABSTRACT TRUNCATED AT 250 WORDS)", "To determine which warming system more closely approximates a neutral thermal environment, the oxygen consumption of 16 premature babies, weighing less than 1,500 gm each, was measured in a convectively heated incubator and under an open radiant warmer. Both systems were controlled to maintain a skin temperature of 36 C. The oxygen consumption of the infants was significantly higher under the radiant warmer. This result is in agreement with published data for this group of premature infants.", "Insensible water loss, oxygen consumption, and carbon dioxide production were measured in eight premature infants under four different conditions: in conventional single-walled incubator with and without plastic heat shield, and under radiant warmer with and without heat shield. IWL was greater under the radiant warmer (3.40 +/- 1.50 ml/kg/hour, mean +/- SD) than in the incubator (2.37 +/- 1.15 ml/kg/hour) when both were compared without heat shield. Addition of the heat shield reduced IWL in the incubator (2.13 +/- 0.76 ml/kg/hour) but not under the radiant warmer (3.37 +/- 0.94 ml/kg/hour). There were no significant differences in VO2 or respiratory quotient between any two of the four study conditions.", "The objective of this study was to compare radiant warmer and incubator care for preterm infants from birth with respect to temperature control and weight gain.\n Sixty preterm infants <33 weeks' gestation were randomized at birth to radiant warmer or incubator care. The initial goal was to maintain abdominal temperature at 36.8 degrees C in both groups and axillary temperature at 36.8 to 37.3 degrees C; air servocontrol was used for incubator infants. Infants in both groups received added humidity for 5 days if their weight was <1000 g and for 3 days if they weighed between 1000 and 1249 g. During a 3-hour period on days 1 to 7, recordings of abdominal, forehead, and foot temperatures were obtained. The percentage of the recording time during which the abdominal temperature was in the target range of between 36 degrees C and 37.5 degrees C was determined as an indicator of temperature control. Weight gain from birth to 1800 g was compared. Secondary outcomes included fluid balance and clinical events.\n There were 30 infants in each group; 48 were <1500 g (of whom 17 were <1000 g). There were no significant differences in birth weight, gestation, gender, or illness severity scores in the 2 groups. Significant differences in temperature control were noted on day 1. Although admission temperatures were similar, lower abdominal temperatures were noted in the first 2 hours of life in the incubator group (medians were 36.6 degrees C and 35.9 degrees C in the radiant warmer and incubator groups, respectively). Similarly, mean abdominal temperatures during the 3-hour recording on day 1 were lower in the incubator group, and infants in this group spent a significantly greater percentage of the recording time with temperatures outside the target range (17.3% compared with 0.88%). Other temperature recordings from the forehead and foot were not significantly different in the groups. Fluid intakes were higher for infants under radiant warmer on days 2, 3, and 4, and the difference amounted to a mean of 12.8 mL/kg/d. Maximum sodium levels in the first week were similar in the 2 groups. Mean weight gain was 17.4 g/kg/d for the radiant warmer group and 17.1 g/kg/d for the incubator group; days to regain birth weight and length of hospital stay were not significantly different. Greater numbers of infants in the radiant warmer group required phototherapy, and adverse events (which included death, necrotizing enterocolitis, chronic lung disease, grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, or retinopathy requiring laser treatment) were less frequent in the radiant warmer group (1 infant compared with 8 in the incubator group; relative risk 0.1; 95% confidence intervals: 0.01-0.82).\n This study has shown differences in abdominal temperatures on day 1 and outcome, although the latter finding should be viewed with caution because of the sample size. The results indicate benefits for the initial use of the radiant warmer after birth. Although fluid requirements were higher in the radiant warmer group for days 2 through 4, the increased fluid volumes were given without apparent adverse effect.", "nan" ]

[ "7502549", "6140202", "38175", "38177", "10029609", "38176" ]

[ "Comparison between high dose 5-aminosalicylic acid and 6-methylprednisolone in active Crohn's ileocolitis. A multicenter randomized double-blind study. German 5-ASA Study Group.", "European Cooperative Crohn's Disease Study (ECCDS): results of drug treatment.", "National Cooperative Crohn's Disease Study: study design and conduct of the study.", "National Cooperative Crohn's Disease Study: adverse reactions to study drugs.", "Mesalamine in the treatment of mild to moderate active Crohn's ileitis: results of a randomized, multicenter trial.", "National Cooperative Crohn's Disease Study: results of drug treatment." ]

[ "The value of 5-aminosalicylic acid (5-ASA) in Crohn's disease (CD) is still under discussion. In a previous study 2 g 5-ASA per day were inferior to a standard glucocorticoid treatment with 6-methylprednisolone (6-MPred) (Can J Gastroenterol 1990; 4: 446-51). In the present study we tested whether in active CD response rates to 4.5 g 5-ASA/day were not different from those to 6-MPred.\n Multicenter randomized double-blind double-dummy trial. 34 patients with active CD (CDAI > 150) were included. 17 patients were in the 5-ASA group (Salofalk, 4.5 g/day), 17 patients in the 6-MPred group (Urbason, initial dose 48 mg/day, weekly tapering). Duration of treatment was 8 weeks. Main outcome measure was remission of CD (CDAI < 150) and decrease of at least 60 points.\n Both groups were comparable with respect to demographic and clinical parameters. The median CDAI decrease in the 5-ASA group was 85, in the 6-MPred group 122 (p = 0.7437). The median AUC of the CDAI in the 5-ASA group was 1027, in the 6-MPred group 950 (p = 0.137). The median AUC of the CDAI per treatment day was 22.94 in the 5-ASA group, and 17.33 in the 6-MPred group (p = 0.0555). On an intention-to-treat basis remission rates after 8 weeks were 40.0% in the 5-ASA group and 56.3% in the 6-MPred group (p = 0.5867).\n Response rates to 5-ASA or 6-MPred were not significantly different although there was a trend towards a higher efficacy of 6-MPred. 5-ASA may be considered as alternative treatment in patients with activer CD who are intolerant to or refuse glucocorticoids.", "A multicenter double-blind study of the effectiveness of sulfasalazine and 6-methylprednisolone, alone and in combination, was conducted on 452 patients with Crohn's disease. One hundred sixty patients were previously untreated; 292 patients were previously treated. The Crohn's disease activity index (CDAI) was used to determine whether a patient had active (CDAI greater than or equal to 150, n = 215) or quiescent disease (CDAI less than 150, n = 237). Treatment of active disease consisted of high-dose 6-methylprednisolone, 6-methylprednisolone combined with 3 g of sulfasalazine, 3 g of sulfasalazine alone, or placebo, and lasted 6 wk. Patients in remission received maintenance doses of one of these drug regimens for periods of up to 2 yr. One hundred ninety-two patients completed the 2-yr study period. Results were evaluated using life-table analysis and outcome ranking. These methods showed 6-methylprednisolone to be the most effective drug in overall comparison of all patients (p less than 0.001); in previously treated patients (p less than 0.001); and in subgroups: active disease (p less than 0.001), only small bowel disease (p less than 0.05), and both small bowel and colon disease (p less than 0.05). Combination of 6-methylprednisolone and sulfasalazine was the most effective regimen in previously untreated patients (p less than 0.05) and when disease was localized in the colon (p less than 0.001). Sulfasalazine alone was least effective in overall comparison of all patients (p less than 0.05) and in all strata. Drug treatment was of no significant benefit to patients with quiescent disease. Continuous administration of low doses of 6-methylprednisolone, or the combination regimen, was beneficial in patients who responded initially to treatment of active disease. The addition of sulfasalazine, however, offered no advantage.", "The design and execution of the National Cooperative Crohn's Disease Study are described in this paper. The Study incorporated several noteworthy features developed to meet specific demands of the disease and its therapy. A standard clinical grading system, the Crohn's Disease Activity Index (CDAI) was developed to allow uniform decentralized clinical evaluation and decision-making throughout the 5 yr of the study. All three drugs in widespread clinical use in Crohn's disease were studied both for suppressive and prophylactic efficacy and for toxicity. The study employed a scheme for double-blind evaluation of patient progress which allowed adjustment of prednisone dose according to the degree of illness and ensured continuous monitoring for serious toxicity of any study drug. Results were analyzed primarily by ranking the clinical outcome of every patient according to a uniform and detailed scheme and applying Wilcoxon nonparametric statistics. Outcome was also analyzed by life-table methods. Eleven hundred nineteen patients were entered and 604 patients were randomized at 14 study centers during the 5-yr duration of the study. Twenty patients were eliminated from analysis as not meeting diagnostic criteria for Crohn's disease, and another 15 patients were eliminated as not meeting other preestablished criteria for analysis. Nine percent of randomized patients, equally distributed in the four treatment groups, withdrew as noncompliant. Ninety percent of patients completed all or all but one protocol-specified visits, and 95% completed the final radiologic and sigmoidoscopic evaluation.", "Adverse reactions to the drugs employed in the National Cooperative Crohn's Disease Study were sought prospectively at each patient visit and by retrospective review of all patient charts. Prednisone caused evident side effects in over 50% of patients on high-dose suppressive therapy and in approximately one-third of patients on prophylactic dose. Thirty-two percent of patients on high-dose, and 26% on prophylactic-dose prednisone required dose reduction or withdrawal because of side effects. Comparable figures for sulfasalazine were 14% and 12%, and for azathioprine 32% and 20%. The incidence of nausea, vomiting, or anorexia among patients taking sulfasalazine was 46% and 34%, on high and low dose respectively; however, this incidence was no different than that observed among patients taking placebo. These symptoms occasioned withdrawal from the study of only 4% and 3% of patients on high and low doses of sulfasalazine, respectively. Azathioprine produced leukopenia at a dose of 2.5 mg/kg body weight in 15% of patients and the mean white cell count, lymphocyte count, granulocyte count, and hematocrit all fell significantly in patients on this dose. Pancreatitis occurred in 5% of patients taking azathioprine but in no other patients. Sulfasalazine proved to be the safest effective suppressive drug for Crohn's disease. Prednisone toxicity, though substantial, is acceptable in view of its demonstrated suppressive efficacy. Azathioprine was approximately as toxic as prednisone but no more effective than placebo in suppressing active disease. None of the drugs was effective prophylactically, and all showed appreciable long-term toxicity.", "The efficacy of 5-aminosalicylic acid (mesalamine) in the treatment of flare-ups of Crohn's disease is controversial. In previous studies, different locations and pathological behavior of Crohn's disease could have obscured the efficacy of these drugs that deliver their substance in different intestinal sites. The present study tested two different mesalamine formulations with 6-methylprednisolone in mild to moderate active Crohn's ileitis.\n Ninety-four patients with Crohn's ileitis (Crohn's Disease Activity Index [CDAI], 180-350) were randomly assigned to receive for 12 weeks mesalamine tablets, 4 g (35 patients); mesalamine microgranular preparation, 4 g (28 patients); and 6-methylprednisolone, 40 mg (31 patients). Mesalamine microgranular preparation was a gelatin capsule containing 400 mg of mesalamine microgranules coated with Eudragit S, which has been shown to deliver the drug in the terminal ileum.\n Patients taking mesalamine tablets experienced a decrease of CDAI median score value of 113.5 (95% confidence interval [CI], 33-149) compared with 123 (95% CI, 77-155) in the mesalamine microgranular group and 154 (95% CI, 99-197) in the 6-methylprednisolone group (P = 0.07 [NS]). Remission at the final visit occurred in 19 of 31 (61%) patients taking steroids compared with 21 of 35 (60%) patients taking mesalamine tablets and 22 of 28 (79%) patients taking microgranular mesalamine (NS). Five patients on steroids were withdrawn because of side effects, and a case of pancreatitis was related to microgranular mesalamine.\n Mesalamine in microgranular formulation seems to be equally as effective as a standard dosage of steroids in the treatment of the mild to moderate form of Crohn's ileitis.", "The response of active and quiescent Crohn's disease to prednisone, sulfasalazine, or azathioprine has been studied in 569 patients in a placebo-controlled, randomized, multicenter cooperative trial. The response of active symptomatic disease to prednisone or sulfasalazine was significantly better than to placebo. Response to azathioprine was better than to placebo, but the difference did not reach conventional levels of statistical significance. Patients with colonic involvement were especially responsive to sulfasalazine, and those with small bowel involvement were especially responsive to prednisone. Patients' drug therapy immediately before entry to the study significantly affected subsequent response. For patients with quiescent disease, none of the drugs was superior to placebo in prophylaxis against flare-up or recurrence. There is less than a 5% risk that a clinically significant prophylactic effect of any of the drug regimens was missed." ]

[ "11937123", "15105387", "15608039", "16600225", "12832372", "16600220", "16679325", "16616748", "16600232" ]

[ "Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy.", "Pain relief during oocyte retrieval with a new short duration electro-acupuncture technique--an alternative to conventional analgesic methods.", "Electro-acupuncture versus conventional analgesia: a comparison of pain levels during oocyte aspiration and patients' experiences of well-being after surgery.", "Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer.", "Electro-acupuncture as a peroperative analgesic method and its effects on implantation rate and neuropeptide Y concentrations in follicular fluid.", "Acupuncture and infertility: we need to stick to good science.", "Auricular electro-acupuncture as an additional perioperative analgesic method during oocyte aspiration in IVF treatment.", "Effect of acupuncture on the outcome of in vitro fertilization and intracytoplasmic sperm injection: a randomized, prospective, controlled clinical study.", "Acupuncture on the day of embryo transfer significantly improves the reproductive outcome in infertile women: a prospective, randomized trial." ]

[ "To evaluate the effect of acupuncture on the pregnancy rate in assisted reproduction therapy (ART) by comparing a group of patients receiving acupuncture treatment shortly before and after embryo transfer with a control group receiving no acupuncture.\n Prospective randomized study.\n Fertility center.\n After giving informed consent, 160 patients who were undergoing ART and who had good quality embryos were divided into the following two groups through random selection: embryo transfer with acupuncture (n = 80) and embryo transfer without acupuncture (n = 80).\n Acupuncture was performed in 80 patients 25 minutes before and after embryo transfer. In the control group, embryos were transferred without any supportive therapy.\n Clinical pregnancy was defined as the presence of a fetal sac during an ultrasound examination 6 weeks after embryo transfer.\n Clinical pregnancies were documented in 34 of 80 patients (42.5%) in the acupuncture group, whereas pregnancy rate was only 26.3% (21 out of 80 patients) in the control group.\n Acupuncture seems to be a useful tool for improving pregnancy rate after ART.", "Acupuncture previously has proved its pain-relieving effect for ovum pick-up (OPU). The analgesic effect of electro-acupuncture (EA) was evaluated when EA was applied for only a few minutes prior to OPU in an attempt to make EA more attractive for clinical use.\n Two hundred patients undergoing OPU were randomized prospectively using sealed, unlabelled envelopes, to receive pain relief with either EA in combination with a paracervical block (PCB) (n = 100) or conventional medical analgesia (CMA) in combination with a PCB (n = 100). A visual analogue scale (VAS) was used to evaluate pain and anxiety before, during and after OPU. The primary outcome measure was pain relief; secondary end-points were costs, time to discharge and clinical outcome parameters.\n There were no differences in any VAS ratings before the procedure. Directly after OPU, the EA group reported significantly higher mean and maximum pain, and 'pain now' than the CMA group. At 30 min after OPU and thereafter, no significant differences were found between the groups regarding abdominal pain. Time to discharge and costs were significantly lower in the EA group compared with the CMA group. No differences in clinical outcome parameters were seen.\n A significant difference was found between the EA and the CMA groups regarding pain during the OPU, probably due to the fact that the CMA group was pre-medicated as part of the study design. Despite a per-operative difference in pain rating, EA, given a few minutes prior to OPU, is a good alternative to CMA. The procedure is well tolerated by the patients, with a shorter hospitalization time and lower costs.", "The primary aims were to compare the pain-relieving effect and post-operative well-being between electro-acupuncture analgesia (EA) and conventional analgesia (CA) comprising opiates. Further aims were to compare time for mobilization, and costs for time and drug consumption.\n In all, 160 women undergoing IVF were randomized, according to a computer-generated list, to EA or CA. Well-being was evaluated with the State Trait Anxiety Inventory (STAI). Pain and subjective expectations and experiences were recorded on a visual analogue scale (VAS). Time and drug consumption were recorded.\n Although VAS pain ratings were significantly higher at oocyte aspiration (P < 0.0001) and after retrieval (P < 0.01) in the EA than in the CA group, they were similar 60 min after surgery. Both groups had similar STAI well-being scores. The EA group was significantly less tired and confused than the CA group after oocyte aspiration. No significant differences in time and costs for drug consumption were noted.\n EA cannot generally be recommended as a pain-relieving method at oocyte aspiration but might be an alternative for women desiring a non-pharmacological method. An advantage of EA is less post-operative tiredness and confusion compared with CA.", "To evaluate the effects of acupuncture on clinical pregnancy rates for women undergoing ET.\n Single-blind, randomized controlled trial using a noninvasive sham acupuncture control.\n Repromed, The Reproductive Medicine Unit of The University of Adelaide.\n Women undergoing IVF.\n Women were randomly allocated to acupuncture or noninvasive sham acupuncture with the placebo needle. All women received three sessions, the first undertaken on day 9 of stimulating injections, the second before ET, and the third immediately after ET.\n The primary outcome was pregnancy. Secondary outcomes were implantation, ongoing pregnancy rate at 18 weeks, adverse events, and health status.\n Two hundred twenty-eight subjects were randomized. The pregnancy rate was 31% in the acupuncture group and 23% in the control group. For those subjects receiving acupuncture, the odds of achieving a pregnancy were 1.5 higher than for the control group, but the difference did not reach statistical significance. The ongoing pregnancy rate at 18 weeks was higher in the treatment group (28% vs. 18%), but the difference was not statistically significant.\n There was no significant difference in the pregnancy rate between groups; however, a smaller treatment effect can not be excluded. Our results suggest that acupuncture was safe for women undergoing ET.", "In a previous study on the effect of electro-acupuncture (EA) in combination with a paracervical block (PCB) as an analgesic method during oocyte aspiration in IVF treatment, EA appeared to increase the pregnancy rate. This study was designed to test the hypothesis that EA as an analgesic during oocyte aspiration would result in: (i) a better IVF pregnancy rate than with alfentanil; (ii) peroperative analgesia that was as good as that produced by alfentanil; (iii) less postoperative abdominal pain, nausea and stress; and (iv) a reduction in the use of additional analgesics. Neuropeptide Y (NPY) concentrations in follicular fluid (FF) were analysed when possible.\n In this prospective, randomized, multicentre clinical trial, 286 women undergoing oocyte aspiration were randomly allocated to the EA group (EA plus a PCB) or to the alfentanil group (alfentanil plus a PCB). No significant differences were found between the EA and alfentanil groups in any of the IVF variables. NPY concentrations in FF were significantly higher in the EA group compared with the alfentanil group. No correlation between pregnancy rate and NPY concentrations was found in either analgesic group. Both EA plus a PCB and alfentanil plus a PCB induced adequate peroperative analgesia during oocyte aspiration evaluated using the visual analogue scale. After 2 h, the EA group reported significantly less abdominal pain, other pain, nausea and stress than the alfentanil group. In addition, the EA group received significantly lower amounts of additional alfentanil than the alfentanil group.\n EA does not improve pregnancy rate in the present clinical situation. The observation that NPY concentrations in FF were higher in the EA group may be important for human ovarian steroidogenesis. The analgesic effects produced by EA are as good as those produced by conventional analgesics, and the use of opiate analgesics with EA is lower than when conventional analgesics alone are used.", "The research published to date does not show a definitive positive impact of acupuncture on IVF success rates. However, researchers seem to lack traditional scientific practices when interpreting the data.", "The aim of this study was to compare the pain-relieving effect and the subjective well-being between auricular electro-acupuncture (EA) analgesia, auricular acupuncture (A) and conventional analgesia with remifentanil (CO).\n A total of 94 women undergoing IVF were randomized to auricular acupuncture with (EA, n = 32) or without (A, n = 32) continuous 1 Hz auricular stimulation (using a battery-powered miniaturized stimulator, P-Stim) or with adhesive tapes instead of needles and no electrical stimulation (control group, CO, n = 30) at the auricular acupuncture points 29, 55 and 57. All patients received patient-controlled analgesia (PCA) with remifentanil. Pain intensity and psychological well-being were assessed by means of visual analogue scales (VAS); tiredness, nausea and vomiting and analgesic drug consumption were documented.\n Pain relief and subjective well-being were significantly greater in group EA during and after the procedure as compared with groups A and CO (P < 0.001). The patients were significantly more tired in group CO than in groups A and EA (P < 0.001). Consumption of the opioid remifentanil was significantly lower in group EA, comparable nausea (P < 0.001).\n Auricular EA significantly reduces pain intensity and analgesic consumption of the opioid remifentanil during oocyte aspiration in IVF treatment.", "To determine the effect of luteal-phase acupuncture on the outcome of IVF/intracytoplasmic sperm injection (ICSI).\n Randomized, prospective, controlled clinical study.\n University IVF center.\n Two hundred twenty-five infertile patients undergoing IVF/ICSI.\n In group I, 116 patients received luteal-phase acupuncture according to the principles of traditional Chinese medicine. In group II, 109 patients received placebo acupuncture.\n Clinical and ongoing pregnancy rates.\n In group I, the clinical pregnancy rate and ongoing pregnancy rate (33.6% and 28.4%, respectively) were significantly higher than in group II (15.6% and 13.8%).\n Luteal-phase acupuncture has a positive effect on the outcome of IVF/ICSI.", "To evaluate the effect of acupuncture on reproductive outcome in patients treated with IVF/intracytoplasmic sperm injection (ICSI). One group of patients received acupuncture on the day of ET, another group on ET day and again 2 days later (i.e., closer to implantation day), and both groups were compared with a control group that did not receive acupuncture.\n Prospective, randomized trial.\n Private fertility center.\n During the study period all patients receiving IVF or ICSI treatment were offered participation in the study. On the day of oocyte retrieval, patients were randomly allocated (with sealed envelopes) to receive acupuncture on the day of ET (ACU 1 group, n = 95), on that day and again 2 days later (ACU 2 group, n = 91), or no acupuncture (control group, n = 87).\n Acupuncture was performed immediately before and after ET (ACU 1 and 2 groups), with each session lasting 25 minutes; and one 25-minute session was performed 2 days later in the ACU 2 group.\n Clinical pregnancy and ongoing pregnancy rates in the three groups.\n Clinical and ongoing pregnancy rates were significantly higher in the ACU 1 group as compared with controls (37 of 95 [39%] vs. 21 of 87 [26%] and 34 of 95 [36%] vs. 19 of 87 [22%]). The clinical and ongoing pregnancy rates in the ACU 2 group (36% and 26%) were higher than in controls, but the difference did not reach statistical difference.\n Acupuncture on the day of ET significantly improves the reproductive outcome of IVF/ICSI, compared with no acupuncture. Repeating acupuncture on ET day +2 provided no additional beneficial effect." ]

[ "7490154", "2207419", "7920126" ]

[ "Combinations of potassium, calcium, and magnesium supplements in hypertension.", "Efficacy of potassium and magnesium in essential hypertension: a double-blind, placebo controlled, crossover study.", "Reduction in blood pressure with a low sodium, high potassium, high magnesium salt in older subjects with mild to moderate hypertension." ]

[ "Dietary intakes of potassium, calcium, and magnesium have each been reported to lower blood pressure, but the extent of blood pressure reduction in epidemiological studies and clinical trials has tended to be small and inconsistent. We hypothesized that combinations of these mineral supplements would lower blood pressure and that the reductions would be greater than that usually reported in studies of each cation alone. One hundred twenty-five patients 82 men and 43 women) with untreated mild or borderline hypertension were randomly assigned to daily treatment with one of the following four regimens: 60 mmol potassium and 25 mmol (1000 mg) calcium, 60 mmol potassium and 15 mmol (360 mg) magnesium, calcium and magnesium, or placebo. Standardized clinic blood pressure measurements were obtained on 3 days at baseline and after 3 and 6 months of treatment. At baseline, systolic and diastolic blood pressures (mean +/- SD) were 139 +/- 12 and 90 +/- 4 mm Hg, respectively, and dietary intakes of potassium, calcium, and magnesium were 77 +/- 32, 19 +/- 13, and 12 +/- 52 mmol/d, respectively. The mean differences (with 95% confidence intervals) of the changes in systolic and diastolic blood pressures between the treatment and placebo groups were not significant: -0.7 (-4.3 to +2.9) and -0.4 (-2.9 to +2.1) for potassium and calcium, -1.3 (-4.4 to +1.8) and 0.4 (-2.5 to +3.3) for potassium and magnesium, and +2.1 (-1.8 to +6.0) and +2.2 (-1.0 to +5.4) for calcium and magnesium. In conclusion, this trial provides little evidence of an important role of combinations of cation supplements in the treatment of mild or borderline hypertension.", "To evaluate the antihypertensive activity of potassium given alone or in combination with magnesium in patients with mild hypertension.\n A double blind, randomised, placebo controlled, crossover trial of 32 weeks' duration.\n Cardiology outpatient department, Sassoon General Hospitals, Pune, India.\n 37 Adults with mild hypertension (diastolic blood pressure less than 110 mm Hg).\n Patients received either placebo or potassium 60 mmol/day alone or in combination with magnesium 20 mmol/day in a crossover design. No other drug treatment was allowed.\n Blood pressure and heart rate assessed at weekly intervals and biochemical parameters at monthly intervals.\n Potassium alone or in combination with magnesium produced a significant reduction in systolic and diastolic blood pressures (p less than 0.001) and a significant reduction in serum cholesterol concentration (p less than 0.05); other biochemical variables did not change. Magnesium did not have an additional effect. Urinary potassium excretion increased significantly in the groups who received potassium alone or in combination with magnesium. The drug was well tolerated and compliance was satisfactory.\n Potassium 60 mmol/day lowers arterial blood pressure in patients with mild hypertension. Giving magnesium as well has no added advantage.", "To examine the effect of a reduced sodium and increased potassium and magnesium intake on blood pressure.\n Randomised double blind placebo controlled trial.\n General population of a suburb of Rotterdam.\n 100 men and women between 55 and 75 years of age with untreated mild to moderate hypertension.\n During 24 weeks the intervention group received a mineral salt (sodium: potassium: magnesium 8:6:1) and foods prepared with the mineral salt. Controls received common salt and foods.\n Change in blood pressure.\n Complete follow up was achieved for 97 of the 100 randomised subjects. Systolic blood pressure (mean of measurements at weeks 8, 16, and 24) fell by 7.6 mm Hg (95% confidence interval 4.0 to 11.2) and diastolic blood pressure by 3.3 mm Hg (0.8 to 5.8) in the mineral salt group compared with the controls, with a 28% decrease in urinary sodium excretion and a 22% increase in urinary potassium excretion. Twenty five weeks after the study the difference in blood pressure between the groups was no longer detectable.\n Replacing common sodium salt by a low sodium, high potassium, high magnesium mineral salt could offer a valuable non-pharmacological approach to lowering blood pressure in older people with mild to moderate hypertension." ]

[ "6152311", "3976992", "7389760", "3966272", "1682845", "1595097", "8789652", "3434347", "2783342", "19097907", "6743012", "7121779", "2728855", "2053057", "2865674", "1375987", "17461199", "17200864" ]

[ "Long-term follow-up in 257 ICA occlusion: comparison between EIAB-treated and untreated patients.", "Surgical and nonsurgical treatment of total carotid artery occlusion.", "Medical versus surgical treatment of patients with cerebrovascular insufficiency. A retrospective comparative study.", "Long-term assessment of cerebral perfusion following STA-MCA by-pass in patients.", "Comparison of the clinical results of STA-MCA anastomosis and the medical treatment in the cerebral low perfusion patients with viable brain tissue.", "Evaluation of vasomotor reactivity by transcranial Doppler and acetazolamide test before and after extracranial-intracranial bypass in patients with internal carotid artery occlusion.", "Superficial temporal artery--middle cerebral artery anastomosis for acute cerebral ischemia: the effect of small augmentation of blood flow.", "Measurements of regional cerebral blood flow in patients following superficial temporal artery-middle cerebral artery anastomosis.", "Clinical results of extracranial-intracranial bypass surgery in patients with hemodynamic cerebrovascular disease.", "STA-MCA bypass for symptomatic carotid occlusion and haemodynamic impairment.", "Treatment of the totally occluded carotid artery.", "Overall management of vascular lesions considered treatable with extracranial-intracranial bypass: part 1. Internal carotid occlusion.", "Long-term clinical and neurophysiological effects of reconstructive vascular surgery for cerebral ischemia.", "Evaluation of extracranial-to-intracranial bypass surgery using iodine 123 iodoamphetamine single-photon emission computed tomography.", "Failure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke. Results of an international randomized trial. The EC/IC Bypass Study Group.", "STA-MCA bypass surgery for internal carotid artery occlusion--comparative follow-up study.", "[JET study (Japanese EC-IC Bypass Trial)].", "Perfusion MRI before and after acetazolamide administration for assessment of cerebrovascular reserve capacity in patients with symptomatic internal carotid artery (ICA) occlusion: comparison with 99mTc-ECD SPECT." ]

[ "The purpose of this paper is to estimate the real value of the Extra-Intracranial Arterial Bypass (EIAB) in preventing or reducing further and more catastrophic ischaemic events in patients suffering from an Internal Carotid Artery (ICA) occlusion. 257 patients, suffering from ICA occlusion, are considered retrospectively: 122 of them submitted to EIAB and 135 medically treated or untreated. In both groups, homogeneous by sex, age, neurological grading distribution and length of follow-up, the following parameters were considered: the incidence of ischaemic recurrences during the follow-up period; the characters of the recurrences with particular reference to the fatal stroke; the rate of ischaemic events per year. The comparison between the outcome in surgically treated patients and in \"untreated\" ones indicates that the EIAB can be effective in preventing or reducing the ischaemic recurrences and the frequency of fatal stroke in TIA-, RIND, or stroke-patients suffering from ICA occlusion.", "The natural history of totally occluded internal and common carotid arteries was studied in 102 patients (109 arteries) with a 97 percent follow-up (mean 39.7 months.) Symptomatic occlusions occurred in 72.6 percent of the patients, the reconstructed group (46 patients) having a greater number of symptomatic vessels than the nonreconstructed group (63 patients) (p less than 0.05). Contralateral disease was encountered in 46 percent. Initial mortality was 5 percent. Twenty patients (19.6 percent) were dead at the time of follow-up. Half of these deaths were from strokes and three fourths from atherosclerotic causes. Persisting neurologic symptoms were present in 14 percent of the patients and new events occurred in 5 percent. Fifteen percent of initially asymptomatic vessels were symptomatic at last follow-up. Twenty-one percent of the symptomatic occluded vessels were symptomatic on follow-up, 16 percent being in the reconstructed group and 26 percent in the nonreconstructed group.", "Report on a series of patients suffering from cerebrovascular insufficiency caused by stenosis and/or occlusion of one or several major cerebral vessels. The patients were divided in two groups, one being medically treated with anticoagulants, the other operated on either a carotid artery thrombosis by thromboendarterectomy or occlusion treated with an extracranial-intracranial arterial bypass. Results after a follow-up period of 1-3 years are compared and discussed in view of the recent literature.", "A prospective study of mean hemispheric cerebral blood flow (CBF) correlated with clinical status has now been completed for the past 54 months. Thirty-eight patients underwent superficial temporal to middle cerebral artery (STA-MCA) by-pass. They were compared with 22 patients with similar arteriographic lesions and clinical symptoms, treated medically throughout the same interval of time. Assignment to either treatment group was not randomized but depended solely on choice of patient or treating physician. Both groups were matched for age, clinical symptoms, angiographic abnormalities, and CBF values. All patients had proximal occlusion of one internal carotid artery or intracranial occlusive disease of the internal carotid or middle cerebral arteries. CBF measurements and clinical evaluations were repeated at regular intervals up to 54 months following surgery or institution of medical treatment. Mean follow up interval after STA-MCA by-pass was 28.7 months and for medical treatment was 29.7 months. Mean hemispheric CBF values for STA-MCA patients became significantly increased 2 weeks after operation. After that, CBF flow values decreased. At 24 months after surgery, flow values for surgically treated patients were significantly higher than among those treated medically, although there were no differences in flow values between the two groups at 3, 6, 12, 36 and 48 months. Prospective clinical evaluations after STA-MCA by-pass were as follows: 12 (32%) improved with cessation of TIAs and/or neurological improvement, 16 (42%) remained unchanged, 7 (18%) deteriorated (due to new or recurrent strokes) and 3 (8%) expired. Clinical results were the same for medical treatment: 6 (27%) improved, 10 (46%) unchanged, 4 (18%) deteriorated due to new or recurrent stroke, and 2 (9%) expired.", "The long-term clinical results of STA-MCA anastomosis as well as the medical treatments were compared in cases that were confined as having a focal cerebral perfusion deficit with viable brain tissue, based on either the drug induced EEG and evoked potential test (DEE test) and/or by positron emission tomography (PET). The criteria for viable cerebral tissue was determined by the following four conditions: (1) functional reversibility could be confirmed by the DEE test; (2) a haemodynamic process could be found in the DEE test; (3) a haemodynamic compromise could be confirmed in the PET study; (4) misery perfusion could be confirmed in the PET study. From 1975 to 1989, 55 cases were confirmed as having viable brain tissue according to the DEE test and the PET study. Of the 55 cases, bypass surgery was performed on 35. Conservative treatment was given to the other 20 cases. There were 3 cases of perioperative neurological deterioration. One was permanent and the other 2 were transient. Results of the long-term follow up are as follows, Ipsilateral attack: 1 case (2.0%) received surgery, and 7 cases (35%) received conservative treatment. Re-attack in the contralateral or posterior circulation: 6 cases (17.2%) received surgery, and 1 case (5%) received conservative treatment. Seventy-seven per cent of the surgical cases improved or had no change in the final functional status, while only 55% of the conservative group either improved or showed no change. The incidence of ipsilateral cerebral ischaemia was significantly low in the surgical group. Contralateral and/or posterior circulation ischaemia tended to be high in this group, however.(ABSTRACT TRUNCATED AT 250 WORDS)", "The aim of this trial was to evaluate the effectiveness of extracranial-intracranial bypass with respect to vasomotor reactivity in patients with internal carotid artery occlusions and absent vasomotor reactivity, comparing them with a control group treated conservatively.\n To test vasomotor reactivity in 104 patients with unilateral occlusion of the internal carotid artery, we measured blood flow velocity in the middle cerebral artery by transcranial Doppler sonography both at rest and after injection of acetazolamide. Among the 39 patients who failed to show increased mean blood flow velocity after the acetazolamide test distal to an occluded internal carotid artery by greater than or equal to 10%, 14 subjects subsequently underwent extracranial-intracranial bypass surgery (group A) and 14 age- and sex-matched subjects in whom no such procedure was done composed the control group (group B). Follow-up examinations were performed 3-6 months postoperatively and in the control group 3-6 months after initial examination.\n Baseline values of the mean blood flow velocity at rest on the affected side were reduced in both groups compared with the contralateral healthy side (group A, 46.0 +/- 15.1 cm/sec; group B, 48.1 +/- 16.7 cm/sec) and revealed only a marginal increase after acetazolamide. The contralateral side showed a normal blood flow velocity at rest and an adequate response to acetazolamide in both groups. On the follow-up examination group A demonstrated a normalized vasodilatory capacity. Blood flow velocity increased significantly after acetazolamide from 41.9 +/- 13.1 cm/sec to 53.5 +/- 16.0 cm/sec (p less than 0.002). In group B, the compromised vasomotor reactivity remained unchanged.\n Our results demonstrate that transcranial Doppler sonography together with the acetazolamide test can identify subjects with reduced vasomotor reactivity distal to an occluded internal carotid artery, who may improve hemodynamically by an extracranial-intracranial bypass.", "In order to evaluate the effectiveness of acute cerebral revascularisation, we conducted a review of 70 patients with acute arterial occlusion or severe stenosis. Of these, 35 underwent emergency superficial temporal artery--middle cerebral artery (STA-MCA) anastomosis (surgical group) and the other 35 were treated conservatively (non-surgical group) at different times. Statistical analysis indicated that the two groups were homogeneous for the prognostic indicators. Seven days after admission, neurological symptoms and signs improved in 43% of patients in the surgical group and in 29% of the non-surgical group, however, this difference was not significant. The ratios of independent life at 3 months were 51% and 31%, respectively (not significant). Subgroup analyses indicated that final outcomes for patients with mild to moderate paresis on admission were significantly better in the surgical group than in the non-surgical group (94% vs. 53%, p < 0.01). The ratios of haemorrhagic infarction, neurological worsening, and mortality were comparable between the two groups. Time of ischaemia is a less important factor in the criteria for surgical selection. Acute revascularisation in selected patients does improve a natural course and could be a therapeutic option for acute cerebral ischaemia.", "Regional cerebral blood flow (rCBF) was measured using the inhalation xenon 133 technique in 25 patients undergoing superficial temporal artery-middle cerebral artery anastomotic surgery. rCBF was measured once before and 3 times after operation, up to one year. Data were compared to rCBF-measurement in 16 patients with similar diagnosis, age distribution and medical treatment except that they were not operated on. Mean rCBF increased in some patients 4-8 weeks after surgery on the ipsilateral side. Compared to the non-surgical patients mean rCBF at this time was higher over both hemipheres. However, taking a flow increase of at least 15% as being significant only one third of all patients presented with a significant flow increase. Regional flow data indicated that the amount of hypoaemic areas in the operated side decreased significantly. Areas with normal flow increased in number from CBF 1 to the 4-8th week. There were no significant changes in flow distribution over the contralateral side. It was concluded that extracranial-intracranial bypass improves flow in patients with TIA or PRIND respectively only in some cases. Also a return to normal flow distribution can be achieved in only a few cases.", "The importance of hemodynamic factors in the pathogenesis and treatment of cerebrovascular disease remains uncertain. The extracranial-intracranial (EC-IC) bypass trial has been criticized for failing to identify and separately analyze those patients with chronic reduction in regional cerebral perfusion pressure (rCPP) who might be most likely to benefit from surgery. Positron emission tomography (PET) measurements of regional cerebral blood flow (rCBF) and blood volume (rCBV) were performed on 29 patients with symptomatic occlusion or intracranial stenosis of the carotid arterial system prior to undergoing EC-IC bypass surgery. Twenty-four patients had evidence of reduced rCPP (increased rCBV/rCBF ratio) distal to the arterial lesion. Of 21 patients who survived surgery without stroke, three suffered ipsilateral ischemic strokes during the 1st postoperative year. A nonrandomized control group of 23 nonsurgical patients' with similar clinical, arteriographic, and PET characteristics experienced no ipsilateral ischemic strokes during the 1st year following PET. Based on these results in 44 patients, the probability that successful surgery reduces the occurrence of ipsilateral ischemic stroke 1 year later was calculated. This probability ranged from 0.045 for a 50% reduction to 0.168 for a 10% reduction. Thus, there was little evidence to suggest that measurements of cerebral hemodynamics can identify a group of patients who would benefit from EC-IC bypass surgery.", "Patients with carotid artery occlusion and haemodynamic insufficiency have a high risk of stroke. Cerebral revascularization surgery improves cerebral blood flow, but it remains unclear whether this reduces the risk of stroke. This study assesses the long-term outcome of patients undergoing superficial temporal artery to middle cerebral artery (STA-MCA) bypass for symptomatic carotid occlusion. The long-term clinical follow-up and haemodynamic reserve, measured by (99)Technetium single photon emission computed tomography (Tc99 SPECT) scan with acetazolamide challenge, were reviewed for 19 consecutive patients before and after STA-MCA bypass. The stroke rate after bypass surgery was 8% per year. In patients waiting for surgery, the stroke rate was 18% per year. Cerebral perfusion assessed with SPECT scan improved in 88% of patients. These results are consistent with the high risks of haemodynamic infarction in untreated patients and a benefit from revascularization surgery. The percentage annual stroke risk compares favourably with an 18% rate reported for patients with internal carotid artery occlusion and impaired cerebrovascular reserve.", "Thirty-four patients, each with a totally occluded common or internal carotid artery, were treated over a 15-year period. Seventeen patients were treated nonsurgically, 17 underwent surgery. There were four patients in the nonsurgical group and six patients in the surgical group who were followed up until death. The average time span from diagnosis of carotid occlusion until death was 4.75 years in the nonsurgical group and 4.52 years in the surgical group. In the nonsurgical group, recurrent symptoms of cerebrovascular accident (CVA) developed in 60% of the patients available for extended follow-up. In contrast, 14% of the patients operated on and available for follow-up had recurrent symptoms, and no CVAs occurred postoperatively. From our data, we concluded that the stroke-free interval is improved, whereas survival is unaffected in the surgically treated patient. Endarterectomy of a contralateral stenotic carotid artery is particularly successful in achieving this reduction in morbidity.", "From 1973 to 1979, 49 patients with internal carotid occlusion were evaluated and treated. Eighteen of 49 (37%) presented with transient ischemic attack/prolonged reversible ischemic neurological deficit, 14 of 49 (29%) presented with mild completed stroke, 13 of 49 (27%) presented with severe completed stroke, and 4 of 49 (8%) were asymptomatic. Surgical treatment consisting of extracranial-intracranial (EC-IC) bypass, internal carotid stump reconstruction and endarterectomy to open the occlusion, contralateral endarterectomy for carotid stenosis opposite the occlusion, and iatrogenic carotid occlusion with EC-IC bypass was carried out on 22 (45%) patients considered at risk for ischemia based on angiographic evidence of poor collateral circulation and potential sources of emboli. Medical treatment consisting of anticoagulants or anti-platelet aggregation agents was used in 27 (55%) patients with good collateral circulation. By 6 weeks after the initiation of treatment, 10 of 49 (20%) reached end points of new strokes and death. By an average of 3 years after treatment began, 30 of 49 (61%) reached the same end points. The results suggest that new ischemic events in the distribution of the occluded carotid artery occur infrequently if the angiographic study shows adequate collateral circulation to the ischemic territory at risk. Surgical revascularization should be reserved for patients with (a) recurrent ischemic events after the diagnosis of carotid occlusion or (b) poor collateral circulation.", "In a series of patients with unilateral supratentorial ischemia, clinical scores and parameters derived from computer analysis of the EEG and from measurement of the CBF were determined in the first several weeks after the stroke. Seventeen of these patients underwent a carotid-endarterectomy and 15 a STA-MCA bypass operation. Matched control patients were selected from the remaining cases. All patients, including the controls, were eligible for vascular surgery. The measurements were repeated respectively 3 months and 3 years after the first examination. Clinical improvement occurred in all groups. The degree of these clinical changes was similar for operated and non operated cases. EEG changes indicated more improvement in the cases without surgery. Finally, the CBF was remarkably stable in all patients. The overall effects of reconstructive vascular surgery on the recovery after cerebral ischemia appeared to be negligible.", "Eleven patients with occlusive cerebrovascular diseases were imaged with N-isopropyl-p-I-123 iodoamphetamine. Preoperative and postoperative single-photon emission computed tomography was performed in 10 patients undergoing extracranial-to-intracranial bypass procedures. New images were reconstructed from the two images obtained on the different days by superimposition and division in each pixel to get the ratio of cerebral perfusion change. All patients with bypass procedures had an increase in cerebral blood flow in the affected areas, and nine of 10 had an increase in cerebral blood flow in the contralateral cortex. There was no increase in cerebral blood flow in one case with no operation. Neither our procedure nor the results in this small series prove that recovery of function is due to an increase in blood flow, but we believe this is the case.", "To determine whether bypass surgery would benefit patients with symptomatic atherosclerotic disease of the internal carotid artery, we studied 1377 patients with recent hemisphere strokes, retinal infarction, or transient ischemic attacks who had atherosclerotic narrowing or occlusion of the ipsilateral internal carotid or middle cerebral artery. Of these, 714 were randomly assigned to the best medical care, and 663 to the same regimen with the addition of bypass surgery joining the superficial temporal artery and the middle cerebral artery. The patients were followed for an average of 55.8 months. Thirty-day surgical mortality and major stroke morbidity rates were 0.6 and 2.5 per cent, respectively. The postoperative bypass patency rate was 96 per cent. Nonfatal and fatal stroke occurred both more frequently and earlier in the patients operated on. Secondary survival analyses comparing the two groups for major strokes and all deaths, for all strokes and all deaths, and for ipsilateral ischemic strokes demonstrated a similar lack of benefit from surgery. Separate analyses in patients with different angiographic lesions did not identify a subgroup with any benefit from surgery. Two important subgroups of patients fared substantially worse in the surgical group: those with severe middle-cerebral-artery stenosis (n = 109, Mantel-Haenszel chi-square = 4.74), and those with persistence of ischemic symptoms after an internal-carotid-artery occlusion had been demonstrated (n = 287, chi-square = 4.04). This study thus failed to confirm the hypothesis that extracranial-intracranial anastomosis is effective in preventing cerebral ischemia in patients with atherosclerotic arterial disease in the carotid and middle cerebral arteries.", "Sixty-three patients with internal carotid artery occlusion manifesting as transient ischemic attack or minor stroke received superficial temporal artery-middle cerebral artery bypass surgery and medical treatment (n = 27) or medical treatment only (n = 36). Long-term follow-up showed that there was no significant difference in the outcomes. However, positron emission tomography studies suggested that patients with misery perfusion in the chronic stage benefited from extracranial-intracranial bypass surgery.", "nan", "Impaired cerebral vascular reserve (CVR) in patients with symptomatic internal carotid artery (ICA) occlusion is regarded as a possible indication for performing extra-/intracranial (EC/IC) bypass surgery. As perfusion MR imaging (MRI) can demonstrate cerebral haemodynamics at capillary level, our hypothesis was that perfusion MRI could be used in these patients for the evaluation of CVR following acetazolamide challenge in a similar way to single photon emission CT (SPECT) and might provide additional information.\n Enrolled in the study were 12 patients (mean age 61.3 years; 11 male, 1 female) with symptomatic unilateral ICA occlusion proven by angiography. Both perfusion MRI and 99m-technetium-ethyl-cysteinate dimer ((99m)Tc-ECD) SPECT were performed before and after injection of acetazolamide (Diamox ,1000 mg i.v.). CVR parameters including regional cerebral blood flow (rCBF) and volume (rCBV), and mean transit times (MTT) were measured by perfusion MRI.\n The patients with impaired CVR proven by SPECT (n = 9) had a negative mean rCBF increment (-46.52%), negative rCBV increment (-13.5%) and delayed MTT (mean +2.98 s), respectively, on the occluded side (Student's t-test all P < 0.05). The patients with sufficient CVR (n = 3) had a mean rCBF increment of 1.2%, a decrement of rCBV of 10.46%, and a mean MTT shortening of 0.27 s following the acetazolamide injection.\n Perfusion MRI before and after acetazolamide administration compares favourably with (99m)Tc-ECD SPECT for the detection of impaired CVR. The impact that perfusion MRI studies (before and after acetazolamide administration) might have on the treatment decision in patients with ICA occlusion has yet to be determined by a prospective study." ]

[ "17321310", "16231970", "17321311" ]

[ "Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial.", "Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial.", "Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial." ]

[ "Male circumcision could provide substantial protection against acquisition of HIV-1 infection. Our aim was to determine whether male circumcision had a protective effect against HIV infection, and to assess safety and changes in sexual behaviour related to this intervention.\n We did a randomised controlled trial of 2784 men aged 18-24 years in Kisumu, Kenya. Men were randomly assigned to an intervention group (circumcision; n=1391) or a control group (delayed circumcision, 1393), and assessed by HIV testing, medical examinations, and behavioural interviews during follow-ups at 1, 3, 6, 12, 18, and 24 months. HIV seroincidence was estimated in an intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, with the number NCT00059371.\n The trial was stopped early on December 12, 2006, after a third interim analysis reviewed by the data and safety monitoring board. The median length of follow-up was 24 months. Follow-up for HIV status was incomplete for 240 (8.6%) participants. 22 men in the intervention group and 47 in the control group had tested positive for HIV when the study was stopped. The 2-year HIV incidence was 2.1% (95% CI 1.2-3.0) in the circumcision group and 4.2% (3.0-5.4) in the control group (p=0.0065); the relative risk of HIV infection in circumcised men was 0.47 (0.28-0.78), which corresponds to a reduction in the risk of acquiring an HIV infection of 53% (22-72). Adjusting for non-adherence to treatment and excluding four men found to be seropositive at enrollment, the protective effect of circumcision was 60% (32-77). Adverse events related to the intervention (21 events in 1.5% of those circumcised) resolved quickly. No behavioural risk compensation after circumcision was observed.\n Male circumcision significantly reduces the risk of HIV acquisition in young men in Africa. Where appropriate, voluntary, safe, and affordable circumcision services should be integrated with other HIV preventive interventions and provided as expeditiously as possible.", "Observational studies suggest that male circumcision may provide protection against HIV-1 infection. A randomized, controlled intervention trial was conducted in a general population of South Africa to test this hypothesis.\n A total of 3,274 uncircumcised men, aged 18-24 y, were randomized to a control or an intervention group with follow-up visits at months 3, 12, and 21. Male circumcision was offered to the intervention group immediately after randomization and to the control group at the end of the follow-up. The grouped censored data were analyzed in intention-to-treat, univariate and multivariate, analyses, using piecewise exponential, proportional hazards models. Rate ratios (RR) of HIV incidence were determined with 95% CI. Protection against HIV infection was calculated as 1 - RR. The trial was stopped at the interim analysis, and the mean (interquartile range) follow-up was 18.1 mo (13.0-21.0) when the data were analyzed. There were 20 HIV infections (incidence rate = 0.85 per 100 person-years) in the intervention group and 49 (2.1 per 100 person-years) in the control group, corresponding to an RR of 0.40 (95% CI: 0.24%-0.68%; p < 0.001). This RR corresponds to a protection of 60% (95% CI: 32%-76%). When controlling for behavioural factors, including sexual behaviour that increased slightly in the intervention group, condom use, and health-seeking behaviour, the protection was of 61% (95% CI: 34%-77%).\n Male circumcision provides a degree of protection against acquiring HIV infection, equivalent to what a vaccine of high efficacy would have achieved. Male circumcision may provide an important way of reducing the spread of HIV infection in sub-Saharan Africa. (Preliminary and partial results were presented at the International AIDS Society 2005 Conference, on 26 July 2005, in Rio de Janeiro, Brazil.).", "Ecological and observational studies suggest that male circumcision reduces the risk of HIV acquisition in men. Our aim was to investigate the effect of male circumcision on HIV incidence in men.\n 4996 uncircumcised, HIV-negative men aged 15-49 years who agreed to HIV testing and counselling were enrolled in this randomised trial in rural Rakai district, Uganda. Men were randomly assigned to receive immediate circumcision (n=2474) or circumcision delayed for 24 months (2522). HIV testing, physical examination, and interviews were repeated at 6, 12, and 24 month follow-up visits. The primary outcome was HIV incidence. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, with the number NCT00425984.\n Baseline characteristics of the men in the intervention and control groups were much the same at enrollment. Retention rates were much the same in the two groups, with 90-92% of participants retained at all time points. In the modified intention-to-treat analysis, HIV incidence over 24 months was 0.66 cases per 100 person-years in the intervention group and 1.33 cases per 100 person-years in the control group (estimated efficacy of intervention 51%, 95% CI 16-72; p=0.006). The as-treated efficacy was 55% (95% CI 22-75; p=0.002); efficacy from the Kaplan-Meier time-to-HIV-detection as-treated analysis was 60% (30-77; p=0.003). HIV incidence was lower in the intervention group than it was in the control group in all sociodemographic, behavioural, and sexually transmitted disease symptom subgroups. Moderate or severe adverse events occurred in 84 (3.6%) circumcisions; all resolved with treatment. Behaviours were much the same in both groups during follow-up.\n Male circumcision reduced HIV incidence in men without behavioural disinhibition. Circumcision can be recommended for HIV prevention in men." ]

[ "10566566", "7555472", "7587604", "2890501", "1797509", "1595776", "3148787", "9653594", "3118579", "7859936", "8941458", "1906584", "2507265", "8745203", "2125014", "10230643", "1406860", "2959438", "3129273", "10068412" ]

[ "Insulin lispro in the treatment of patients with type 2 diabetes mellitus after oral agent failure.", "Comparison of insulin with or without continuation of oral hypoglycemic agents in the treatment of secondary failure in NIDDM patients.", "[The effectiveness of combined insulin and sulfonylurea in treating non-insulin dependent diabetic patients].", "Glyburide decreases insulin requirement, increases beta-cell response to mixed meal, and does not affect insulin sensitivity: effects of short- and long-term combined treatment in secondary failure to sulfonylurea.", "Effects of combination therapy with glyburide and insulin on serum lipid levels in NIDDM patients with secondary sulfonylurea failure.", "Combined therapy for obese type 2 diabetes: suppertime mixed insulin with daytime sulfonylurea.", "[Combination therapy with insulin/sulfonylurea in the long-term therapy of type II diabetes following \"secondary failure\"].", "Beginning insulin treatment of obese patients with evening 70/30 insulin plus glimepiride versus insulin alone. Glimepiride Combination Group.", "[Long-term effect of combination glibenclamide-insulin treatment in the secondary failure of sulfonylurea therapy--results of a one-year double blind study].", "Bedtime insulin/daytime glipizide. Effective therapy for sulfonylurea failures in NIDDM.", "Comparison of different insulin regimens in elderly patients with NIDDM.", "[The effects of insulin combined with glibenclamide on glucose and lipid metabolism in patients with Type II diabetes mellitus].", "Efficacy of bedtime NPH insulin with daytime sulfonylurea for subpopulation of type II diabetic subjects.", "Insulin versus a combination of insulin and sulfonylurea in the treatment of NIDDM patients with secondary oral failure.", "Combined therapy with glibenclamide and ultralente insulin in lean patients with NIDDM with secondary failure of sulfonylureas. Follow up at two years.", "Causes of weight gain during insulin therapy with and without metformin in patients with Type II diabetes mellitus.", "Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus.", "Sulphonylurea failure in type 2 diabetes: treatment with a basal insulin supplement.", "[Effectiveness of combined treatment with glibenclamide and insulin in secondary sulfonylurea failure. A controlled multicenter double-blind clinical trial].", "Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. A randomized, controlled trial." ]

[ "This study assessed the safety profile and efficacy of a new combination therapy (insulin lispro plus sulfonylurea) in patients with type 2 diabetes mellitus experiencing secondary oral agent failure. A total of 423 patients were randomly assigned to 3 treatment groups: preprandial insulin lispro plus sulfonylurea (L + S), bedtime neutral protamine Hagedorn (NPH) insulin plus sulfonylurea (N + S), and preprandial insulin lispro plus bedtime NPH insulin (L + N). Mean decreases in glycosylated hemoglobin from baseline were 1.60%+/-1.27% for patients receiving L + S, 1.21%+/-1.21% for those receiving N + S, and 1.40%+/-1.46% for those receiving L + N (within treatment, P<0.001; for L + S vs. N + S, P = 0.003). Fasting blood glucose level was higher in patients receiving L + S (171+/-46.5 mg/dL) or L + N (166+/-52.5 mg/dL) than in those receiving N + S (144+/-48.2 mg/dL) (P<0.001, for both comparisons). Conversely, postprandial blood glucose level was lower in patients receiving L + S (165+/-41.6 mg/dL) or L + N (165+/-46.3 mg/dL) than in those receiving N + S (213+/-58.3 mg/dL) (P<0.001, for both comparisons). The overall rate of hypoglycemia (episodes per 30 days) was not statistically significant when the L + S, N + S, and L + N therapies were compared (0.99+/-1.74 vs. 0.87+/-2.31 vs. 1.16+/-2.38, respectively). The rate of nocturnal hypoglycemia was lowest in the L + S group (0.00+/-0.00 vs. 0.10+/-0.37 for the N + S group vs. 0.15+/-0.54 for the L + N group; P = 0.004). L + S, which has a safety profile equal to those of N + S and L + N, is an effective treatment for patients with type 2 diabetes who experience oral sulfonylurea agent failure. L + S offers an alternative to these established combination therapies in patients whose type 2 diabetes cannot be controlled with a sulfonylurea alone.", "Optimal insulin regimens for non-insulin-dependent diabetes mellitus (NIDDM) patients with secondary failure are controversial. We evaluated the efficacy, side effects, and quality of life of patients receiving insulin either alone or in combination with their previous oral hypoglycemic agents (OHAs).\n Fifty-three Chinese patients with NIDDM (mean age 53.9 +/- 12.6 years, duration of diabetes 9.0 +/- 4.9 years, body wt 60.4 +/- 13.3 kg with corresponding body mass index 24.2 +/- 4.3 kg/m2, receiving the maximum dose of sulfonylurea and/or metformin) were confirmed to have OHA failure. Twenty-seven patients were randomized to continue OHAs and were given additional bedtime insulin (combination group); 26 patients were randomized to insulin therapy alone with twice-daily insulin (insulin group). Insulin doses were increased incrementally, aiming at fasting plasma glucose (FPG) < 7.8 mmol/l during a stabilization period of up to 8 weeks. Insulin dosage, body weight, glycemic control, and quality of life were assessed before and at 3 and 6 months after stabilization.\n Both groups showed similar improvement of glycemic control. For the combination group, FPG decreased from 13.5 +/- 2.7 to 8.9 +/- 3.0 mmol/l at 3 months (P < 0.0001) and to 8.6 +/- 2.5 mmol/l at 6 months (P < 0.0001). For the insulin group, FPG decreased from 13.5 +/- 3.6 to 7.5 +/-3.0 mmol/l at 3 months (P < 0.0001) and to 9.8 +/- 3.5 mmol/l at 6 months (P < 0.0001). No significant differences were observed between the groups. Similarly, both groups had significant improvement of fructosamine and glycosylated hemoglobin (HbA1c). Fructosamine fell from a mean of 458 to 365 mumol/l at 3 months (P < 0.0001) and to 371 mumol/l at 6 months (P < 0.0001) and from 484 to 325 mumol/l at 3 months (P < 0.0001) and to 350 mumol/l at 6 months (P < 0.0001) for the combination and insulin groups, respectively. HbA1c decreased from 10.2 to 8.4% at 3 months (P < 0.0001) and to 8.7% at 6 months (P < 0.0001) in the combination group and from 10.7 to 7.8% at 3 months (P < 0.0001) and to 8.4% at 6 months (P < 0.0001) in the insulin group. Despite similar improvement of glycemia, insulin requirements were very different. At 3 months, the combination group was receiving a mean of 14.4 U/day compared with 57.5 U/day in the insulin group (P < 0.0001). Similar findings were observed at 6 months (15.0 vs 57.2 U/day, P < 0>0001). Both groups gained weight. However, for the combination group, weight gain was 1.6 +/- 1.8 kg at 3 months and 2.1 +/- 2.5% kg at 6 months (both P < 0.0001 vs baseline), whereas for the insulin group, weight gain was 3.5 +/- 4.3 and 5.2 +/- 4.1 kg, respectively (both P < 0.0001 vs baseline). Weight gain was significantly greater in the insulin group (P < 0.05 at 3 months, and P < 0.005 at 6 months). Fasting plasma triglyceride decreased in the insulin group (1.8 +/- 1.0 to 1.4 +/- 0.8 mmol/l at 3 months [P < 0.005] and to 1.4 +/ 0.7 mmol/l at 6 months [P < 0.02] but not in the combination group. No changes were observed in total and high-density lipoprotein cholesterol. No severe hypoglycemic reactions were recorded in either group. Mild reactions occurred with similar frequency in both groups. Well-being and quality of life improved significantly in both groups. The majority of patients (82.7%) wanted to continue insulin beyond 6 months, irrespective of the treatment group.\n In NIDDM patients with secondary OHA failure, therapy with a combination of OHAs and insulin and with insulin alone was equally effective and well tolerated. However, combination therapy was associated with a lower insulin dose and less weight gain. Combination treatment may be considered when OHA failure occurs as a potential intermediate stage before full insulin replacement.", "The effectiveness of combined therapy with insulin and sulfonylurea in non-insulin dependent diabetes mellitus (NIDDM) patients has, for decades, been a debated issue. In order to probe this question, we studied 33 diabetes mellitus patients aged 40 years and over, having a history of this disease for more than 5 years, treated with one of the sulfonylureas at maximal dosage for three weeks but without effect. These 33 cases were divided into three groups randomly: group A: treated with glurenorm and insulin. B insulin and C glurenorm. The treatment lasted 4 months. During the course of the trial, estimation of the free-insulin, C-peptide, blood glucose etc. was carried out three times i.e. one before the trial and then 2, 4 months after the trial. The data were dealed with U-test and comparison was made before and after the trial and between the three groups. It is shown that combined therapy with sulfonylurea and insulin is effective in NIDDM patients, especially in those with secondary failure of beta-cell function and the combined therapy may be used in NIDDM patients during the transitional period from treatment with sulfonylurea alone to traditional insulin cure.", "In 20 patients with non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to sulfonylurea, a double-blind randomized study was performed comparing two regimes: insulin plus placebo (IP) and insulin plus glyburide (IG). The protocol included two hospitalization periods (days 1-18 and 78-85) and follow-up at the outpatient clinic for 325 days. The metabolic control was kept as tight as possible. The subjects underwent normoglycemic clamp studies and meal tests with determination of insulin, C-peptide, glucagon, somatostatin, and gastric inhibitory polypeptide in plasma. On IG, they demonstrated marked and long-lasting improvement of metabolic control: HbA1c decreased from 11.1 +/- 0.3% on day 3 to 8.3 +/- 0.4% (P less than .001) on day 78 and 9.1 +/- 0.5% (P less than .001) on day 325. In subjects on IP, the corresponding values were 10.3 +/- 0.5, 8.4 +/- 0.4 (P less than .001), and 8.9 +/- 0.5% (P less than .05). Body weight increased by 6.0 +/- 1.5 kg (P less than .005) on IG and 2.9 +/- 2.1 kg (NS) on IP. The daily insulin requirement decreased on IG from 62.5 +/- 12.9 U/day on day 7 to 33.5 +/- 8.8 U/day on day 83 and 34.6 +/- 8.9 U/day on day 325. On IP the insulin requirement was almost constant: 62.0 +/- 10.7 U/day on day 7, 55.5 +/- 7.7 U/day on day 83, and 54.7 +/- 7.9 U/day on day 325. Insulin sensitivity measured with the hyperinsulinemic clamp (plasma insulin approximately equal to 130 microU/ml) was similar on IP and IG at the initiation of the study and was unchanged on days 18 and 85. A key observation of this study, although the mechanism is unclear, is that isoglycemic-meal-related insulin requirement was diminished by insulin treatment, indicating improvement of meal-related insulin sensitivity. Glyburide increased basal and meal-but not glucagon-stimulated insulin and C-peptide levels, and also augmented the effect of meals on somatostatin release. We conclude that in NIDDM, IG regime promptly and continuously decreased insulin requirement and improved metabolic control. This effect is, at least during the first 3 mo, mainly due to enhanced insulin secretion. IG and IP treatment had no effect on insulin sensitivity during hyperinsulinemic-normoglycemic clamp, whereas meal-related insulin sensitivity was augmented.", "To compare the long-term effect of combined treatment with insulin and glyburide versus insulin alone on serum lipid levels in non-insulin-dependent diabetic (NIDDM) patients with secondary failure to sulfonylurea therapy.\n The study was a randomized double-blind placebo-controlled parallel trial with a duration of 325 days. The study was conducted at a referral-based endocrinology clinic. Subjects were a sequential sample of 20 patients with NIDDM with failure to respond to glyburide treatment after at least 1 yr of adequate glucose control with this therapy. The patients were randomized to treatment with insulin and glyburide (IG) or insulin and placebo (IP). Insulin was given twice daily to all patients as a mixture of NPH and regular insulins in dosages aiming at optimal glucose control. Glyburide or placebo was taken before breakfast (7 mg) and dinner (3.5 mg).\n Mean HbA1c decreased from 11.1% (range 9.8-12.9%) before insulin to 9.1% (range 6.8-11.4%) on day 325 (P less than 0.001) in IG patients and from 10.3% (range 8.4-13.3%) to 9.0% (range 6.3-11.8%) (P less than 0.05) in IP patients. In both groups, there was an increase in high-density lipoprotein cholesterol of approximately 20% lasting throughout the study (P less than 0.01). During the first 83 days of the study, there was a decrease in serum cholesterol (P less than 0.01) and serum triglycerides (P less than 0.05) in both groups. All changes in lipid variables were comparable in magnitude and duration in both treatment with insulin and glyburide in NIDDM patients with secondary sulfonylurea failure improves lipid metabolism to a similar degree as insulin therapy alone.", "Combined insulin and sulfonylurea therapy for type 2 diabetes may improve the effectiveness of a single injection of insulin, thereby postponing the need for multiple injections. This concept was tested in 21 obese subjects imperfectly controlled by 20 mg of glyburide daily in a double masked, placebo-controlled, parallel design, 16-week protocol. Premixed 70% NPH/30% Regular insulin was taken before supper, and the dosage was adjusted weekly by an algorithm seeking nearly normal fasting glycemia. Eleven subjects using insulin plus 10 mg glyburide before breakfast had lower mean fasting glucose at 10-16 weeks than 10 subjects using insulin with placebo (mean +/- SEM; 5.9 +/- 0.3 versus 7.5 +/- 0.7 mmol/L; p less than 0.05), and had a greater decrement of glycosylated hemoglobin from baseline values (1.3 +/- 0.1 versus 0.8 +/- 0.2% A1, p less than 0.05). After 16 weeks the combined therapy group used half as much insulin as the insulin-only group (50 +/- 5 versus 101 +/- 13 units/d; p less than 0.01). Fasting serum free insulin values increased 58% from baseline after insulin therapy in the insulin-only group (p less than 0.05) but did not increase with combined therapy. Weight gain was similar in the two groups. These data support this form of combined therapy as one option for treating obese persons with type 2 diabetes no longer responsive to oral therapy alone.", "In type 2 diabetes with \"secondary failure of sulfonylurea therapy\" good metabolic control can seldom be achieved by insulin therapy even with high insulin doses. Hyperinsulinemia however is a possible risk factor of cardiovascular disease in type 2 diabetes. Maintaining the effects of sulfonylurea action insulin should be added in as small amounts as possible to avoid hyperinsulinemia and to ameliorate hyperglycemia. 16 type 2 diabetics with \"secondary failure\" were treated either with insulin alone (group A; n = 8) or with 3.5 mg b.i.d. glibenclamide plus small amounts of intermediate insulin (group B; n = 8) in a randomised order. After the inpatient period outpatient control was performed monthly up to six months, later on four times a year up to two years. Both groups were comparable with regard to age, duration of diabetes, body weight and metabolic control. The daily insulin dose was 14 +/- 2 IU (means +/- SEM) after one month and 19 +/- 2 IU after two years in group B. In contrast 30 +/- 3 IU and 43 +/- 5 IU respectively were needed in group A (p less than 0.001). All patients B were treated with one daily injection, all patients A needed two injections. Resulting in nearly identical metabolic control in group A basal insulin levels exceeded those in group B after two years significantly (28.6 +/- 3.7 vs. 18.6 +/- 1.6 mcU/ml; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)", "This study tested a simple algorithm for beginning insulin for obese patients with type 2 diabetes after sulfonylurea failure, comparing suppertime 70/30 insulin plus continued glimepiride with insulin alone.\n This was a multicenter ambulatory randomized double-masked parallel comparison. There were 208 subjects with secondary failure to sulfonylureas who took glimepiride titrated to 8 mg b.i.d. for 8 weeks; 145 subjects with fasting plasma glucose (FPG) 180-300 mg/dl (10-16.7 mmol/l) on this treatment were randomized to placebo plus insulin (PI) or glimepiride plus insulin (GI) for 24 weeks. A dosage of 70/30 insulin before supper was titrated, seeking fasting capillary blood glucose (FBG) 120 mg/dl (6.7 mmol/l), equivalent to FPG 140 mg/dl (7.8 mmol/l). Outcome measures included FPG, HbA1c, insulin dosage, weight, serum insulin and lipids, and adverse events.\n FPG and HbA1c were equivalent at baseline: 261 vs. 250 mg/dl (14.5 vs. 13.9 mmol/l), and 9.9 vs. 9.7%. At 24 weeks, the FPG target was achieved in both groups (136 vs. 138 mg/dl, 7.6 vs. 7.6 mmol/l), and HbA1c values were equal (7.7 vs. 7.6%). However, with GI, control improved faster and fewer subjects dropped out (3 vs. 15%, P < 0.01), and less insulin was needed (49 vs. 78 U/d, P < 0.001). The outcomes were alike in other respects. No subject had severe hypoglycemia.\n Injection of 70/30 insulin before supper safely restored glycemic control of type 2 diabetes not controlled by glimepiride alone. Control was restored more rapidly and with less injected insulin when glimepiride was continued.", "The long-term efficacy of combined insulin-glibenclamide treatment was investigated in 79 secondary drug failure patients by means of a double-blind, randomized placebo-controlled study. During a one-year follow-up period the patients on insulin plus glibenclamide required significantly lower exogenous insulin doses. Coincidentally, C-peptide concentrations were significantly raised in the verum versus the placebo group. Additionally, the administration of glibenclamide resulted in a decreased level of hyperglycaemia during the first six months of the observation period. Glibenclamide withdrawal after six and again after twelve months of the combined therapy provoked a deterioration of glycaemic control, as well as a lowering of the C-peptide concentrations. The findings demonstrate a prolonged beneficial effect of the combined treatment, in contrast to the solely short-term effects predicted by numerous studies. The metabolic improvement must be ascribed in part to the beta-cytotropic effect of glibenclamide. Extrapancreatic pathways via receptor/postreceptor mechanisms cannot be excluded.", "Bedtime insulin (BI)/daytime sulfonylurea (DSU) therapy was studied double-blind in 30 non-insulin-dependent diabetes mellitus subjects in whom sulfonylurea (SU) therapy had failed. Subjects were switched to glipizide for 2 months (phase I) to confirm failure (fasting plasma glucose [FPG] 12.0 +/- 0.4 mmol/l) and then randomly assigned into three groups: BI-DSU; BI-no DSU; and DSU-no BI. During phase II (3 months), the BI dose was fixed (20 U/1.73 m2, low-dose). In phase III (3 months), BI was titrated up (high-dose) to achieve good control or until hypoglycemic symptoms prevented further dose increases. In phase IV (6 months), 25 of the 30 original subjects received open-labeled, high-dose BI-DSU. Low-dose BI-DSU markedly reduced FPG (13.6 +/- 0.8 to 8.0 +/- 0.6 mmol/l, P < 0.001), mean 24-h glucose (P < 0.001), HbA1c (8.9 +/- 0.7 to 7.6 +/- 0.3%, P = 0.07), and basal hepatic glucose production (HGP) (P < 0.005). A positive correlation (r = 0.69, P < 0.05) between the declines in FPG and HGP was observed. Neither low-dose BI alone nor DSU alone reduced FPG, mean 24-h glucose, HbA1c, or basal HGP. High-dose (40 +/- 5 U/day) BI plus DSU further reduced the FPG (6.3 +/- 0.6 mmol/l), HbA1c (7.1 +/- 0.3%), mean 24-h plasma glucose, and basal HGP (all P < 0.05 vs. phase II).(ABSTRACT TRUNCATED AT 250 WORDS)", "To compare the metabolic effects of three different frequently used regimens of insulin administration on blood glucose control and serum lipids, and the costs associated with this treatment, in subjects with NIDDM, who were poorly controlled with oral antihyperglycemic agents.\n We studied 95 elderly patients with NIDDM (age 68 +/- 9 years, BMI 26.0 +/- 4.6 kg/m2, and median time since diagnosis of diabetes 9 years [range 1-37]; 37 men, 58 women), who were poorly controlled, despite diet and maximal doses of oral antihyperglycemic agents. Three insulin administration regimens were compared during a 6-month period: patients were randomized for treatment with a two-injection scheme (regimen A) or a combination of glibenclamide with one injection of NPH insulin, administered either at bedtime (regimen B) or before breakfast (regimen C), and insulin treatment was mainly instituted in an outpatient setting.\n After 6 months of insulin treatment, fasting blood glucose of the total patient population had decreased from an average of 14.1 +/- 2.2 to 8.3 +/- 2.0 mmol/L (P < 0.001), and HbA1c fell from 11.0 +/- 1.3 to 8.3 +/- 1.2% (P < 0.001); 34 patients reached HbA1c levels below 8.0%, 25 of them even below 7.5%. With two insulin injections daily, HbA1c decreased from 11.2 +/- 1.3 to 8.2 +/- 1.2%, while during combined treatment, HbA1c fell from 10.5 +/- 1.2 to 8.1 +/- 1.1% (regimen B) and from 11.1 +/- 1.3 to 8.5 +/- 1.1% (regimen C). Comparable improvement of the other measures of glycemic control, lipids and lipoproteins, was observed in the different treatment regimens. Body weight increase was moderate (mean +/- 4.0 kg) and similar in all patient groups. One-third of patients starting with one insulin injection daily needed a second injection to control glycemia. One episode of severe hypoglycemia was observed. Combined insulin-sulfonylurea treatment was almost 20% more expensive than twice-daily administration of insulin alone.\n Insulin treatment can safely be instituted in elderly patients with NIDDM. However, it is difficult to obtain optimal glycemic control. Insulin has moderate beneficial effects on serum lipoproteins. Although on the basis of glycemic control and weight gain, no preference for any treatment regimen can be discerned, twice-daily insulin administration is the most simple and cost-effective regimen.", "We compared the effects of twice-daily insulin injections (n = 22) with combined insulin-glibenclamide therapy (n = 25) on glucose and lipid metabolism in 47 type II diabetic patients (age 69 (SD 9) years, BMI 25.5 (4.8) kg/m2, diabetes duration 9 (range 1-34) years) with secondary failure to sulphonylurea. After 6 months, weight gain averaged 4.2 kg (p less than 0.05), fasting blood glucose had decreased from 14.6 to 8.5 mmol/l (p less than 0.001), HbA1c from 10.9% to 8.1% (p less than 0.001). Twenty-one patients reached HbA1c levels less than 8.0%. Patients on insulin alone injected more insulin (42 vs 26 U daily, p less than 0.01). The decrease of fasting blood glucose and HbA1c was comparable in both groups (p less than 0.001). HDL-cholesterol increased (insulin: 1.10 to 1.24 mmol/l, combined therapy: 1.03 to 1.14 mmol/l, both p less than 0.01), while plasma triglycerides and NEFA decreased (p less than 0.01). Only in patients on insulin alone did total cholesterol decrease from 7.1 to 6.3 mmol/l (p less than 0.001), and LDL-cholesterol from 4.7 to 4.1 mmol/l (p less than 0.05). Apolipoproteins AI, AII and B did not show significant changes. Almost all patients reported improved wellbeing; no severe hypoglycaemias were observed.", "Although insulin and sulfonylureas often have additive clinical effects when used in combination for type II (non-insulin-dependent) diabetes, these results are variable and a clinical role for this approach is not yet established. This study tests the efficacy of a specific combined regimen for a subpopulation of patients with a randomized double-masked placebo-controlled crossover design and under conditions similar to those of clinical practice. Twenty subjects with limited duration (less than 15 yr) type II diabetes who were moderately obese (less than 160% ideal wt) and proved imperfectly controlled on 10 mg glyburide twice daily completed two 4-mo crossover protocols, comparing a single injection of NPH insulin in the evening plus 10 mg glyburide in the morning with insulin plus placebo. Insulin dose was adjusted by experienced endocrinologists seeking the best glycemic control consistent with safety. All subjects had glycosylated hemoglobin values less than or equal to 150% of the control mean on combined therapy, and combined therapy was superior to insulin alone (fasting plasma glucose 8.0 +/- 0.3 vs. 11.1 +/- 0.6 mM, P less than .01; glycosylated hemoglobin 9.8 +/- 0.1 vs. 10.6 +/- 0.2%, P less than .01). Despite greater weight gain on combined therapy, blood pressure and plasma lipid concentrations were the same on the two regimens. These results suggest this simple regimen offers another option, besides multiple injections of insulin, for patients of this kind who are unsuccessful with a sulfonylurea or a single injection of insulin alone.", "Comparison of the effectiveness of combined therapy vs. an insulin regimen in NIDDM patients with secondary failure of oral hypoglycemic agents. RESEARCH DESIGN, PATIENTS AND METHODS: 27 NIDDM patients were randomly allocated to Group A (n = 14, insulin) and Group B (n = 13, insulin and sulfonylurea) with crossover after 3 months. After the next 3 months a decision was made about the further treatment according to the metabolic control. The patients were then treated for another year with the more successful regimen. Metabolic control, residual beta-cell secretory capacity, degree of peripheral insulin resistance (clamp) and insulin dose were followed during the whole study.\n (median, interquartile range, in brackets; *, statistically significant difference at P < 0.05): the combined therapy was better than insulin alone in 2/3 of patients. Glycemic control was better (HbA1c at 3 months: Group A = 7.9(1.1)% vs. Group B = 7.0(0.5)%*; HbA1c at 6 months: Group A = 7.4(1.5)% vs. Group B = 8.1(1.5)%. Insulin dose was lower during the combined therapy in the first 3 months: Group A = 0.62(0.18) U/kg body weight vs. Group B = 0.39(0.16) U/kg body weight*. Combined treatment was associated with increased C-peptide excretion both fasting and postprandially. No significant differences in peripheral insulin resistance were noted between the two groups. The combined treatment remained successful even after one year. The two groups of patients with different effective treatment did not differ significantly in any of the observed parameters.\n the combined therapy was more effective than insulin alone. Its favourable effect persisted after treatment for a year. It seems better to start the treatment of the oral failure with combined therapy compared with insulin first and later followed by combined therapy. On the basis of the observed parameters it is impossible to determine in advance which kind of treatment is more suitable for the individual patient.", "Nine lean diabetic patients with secondary failure of oral hypoglycemic agents and with a poor residual insulin release under treatment with glibenclamide (15 mg/day) entered a cross-over study, in which ultralente insulin was administered alone or in combination with glibenclamide (15 mg/day). Combined therapy was accompanied by increased serum free-insulin levels and was more effective than glibenclamide alone on daily blood glucose profile, on glycosylated haemoglobin (HbA1C) and on Beta-OH butyrate; in 6 patients a near normalization of blood glucose control (daily blood glucose levels less than 180 mg/dl) occurred. C peptide release, evaluated as daily profile and as response to i.v. glucagon, did not significantly change. When patients received insulin alone, daily blood glucose profile and HbA1C worsened, and serum free-insulin levels and C peptide release decreased, while Beta-OH butyrate levels remained low. These data indicate that combined therapy is effective since it maintains insulin release and enhances free insulin levels in insulinopenic patients. Four responders continued combined therapy for 2 years: the treatment was still effective and was accompanied by an increased C peptide release, probably due to persistent euglycemia.", "To determine causes of weight gain during insulin therapy with and without metformin in Type II (non-insulin-dependent) diabetes mellitus.\n Twenty-six patients with Type II diabetes (body mass index 28+/-1 kg/m2) were treated with insulin alone (n = 13) or insulin and with metformin (n = 13). Components of energy balance (basal metabolic rate, energy intake, glucosuria) were measured at 0 and 12 months.\n Glycaemic control improved similarly in patients using (HbA1c 10.5+/-0.3 vs 7.6+/-0.2%, p<0.001) and not using (10.2+/-0.3 vs 7.8+/-0.3%, p < 0.001) metformin. The metformin group required 47 % less insulin than the group not using metformin (p < 0.001). Body weight increased by 3.8+/-0.8 and 7.5+/-1.6 kg (p < 0.05), respectively. Basal metabolic rate and glucosuria were similar at 0 and 12 months in both groups but the metformin group decreased energy intake by 1.12+/-0.46 MJ/day, whereas it remained unchanged in the other group (0.15+/-0.42 MJ/day). Changes in body weight and glycaemia were statistically significant independent determinants of basal metabolic rate. Their change in opposite directions explained why basal metabolic rate remained unchanged.\n Improved glycaemia promotes weight gain by decreasing both basal metabolic rate and glucosuria. Use of metformin decreases weight gain by reducing energy intake and is therefore a useful adjunct to insulin therapy in patients with Type II diabetes.", "Insulin is widely used to improve metabolic control in patients with non-insulin-dependent diabetes mellitus (NIDDM), but there is no consensus about the optimal regimen of insulin treatment.\n We treated 153 patients with NIDDM for three months with five regimens: (1) oral hypoglycemic drug therapy plus NPH insulin given at 7 a.m. (the morning-NPH group), (2) oral hypoglycemic drug therapy plus NPH insulin given at 9 p.m. (the evening-NPH group), (3) NPH and regular insulin (ratio, 70 units to 30 units) given before breakfast and dinner (the two-insulin-injection group), (4) NPH insulin at 9 p.m. and regular insulin before meals (the multiple-insulin-injection group), and (5) continued oral hypoglycemic drug therapy (the control group).\n The mean (+/- SE) value for glycosylated hemoglobin decreased similarly in all four insulin-treatment groups (1.7 +/- 0.3, 1.9 +/- 0.2, 1.8 +/- 0.3, and 1.6 +/- 0.3 percent, respectively). The decrease was significantly greater in these four groups than in the control group (0.5 +/- 0.2 percent; P < 0.001 vs. all insulin-treated groups). Weight gain was significantly less (1.2 +/- 0.5 kg) in the evening-NPH group than in the other insulin-treatment groups (2.2 +/- 0.5 kg in the morning-NPH group, 1.8 +/- 0.5 kg in the two-insulin-injection group, and 2.9 +/- 0.5 kg in the multiple-injection group; P < 0.05). In addition, the increment in the mean diurnal serum free insulin concentration was 50 to 65 percent smaller in the evening-NPH group than in the other insulin-treatment groups. Subjective well-being improved significantly more in the insulin-treatment groups than in the control group (P < 0.001).\n In patients with NIDDM who are receiving oral hypoglycemic drug therapy, the addition of NPH insulin in the evening improves glycemic control in a manner similar to combination therapy with NPH insulin in the morning, a two-insulin-injection regimen, or a multiple-insulin-injection regimen, but induces less weight gain and hyperinsulinemia. The data thus suggest that patients with NIDDM do not benefit from multiple insulin injections and that nocturnal insulin administration appears preferable to daytime administration.", "Many diabetic patients continue to have hyperglycaemia on maximal sulphonylurea therapy. Five different therapeutic options, with the prime aim of achieving normal fasting plasma glucose concentrations, have been compared in 15 asymptomatic, sulphonylurea-treated type 2 diabetic patients in a randomized crossover study of 8-week periods. In 24 h metabolic profiles the overnight mean (+/- 1SD) basal plasma glucose level on sulphonylurea therapy was 8.9 +/- 4.2 mmol/l. This was slightly improved with added metformin therapy (7.3 +/- 4.3 mmol/l, p = 0.013), but reduced to normal by added ultralente insulin (5.2 +/- 3.2 mmol/l, p less than 0.001), ultralente insulin alone (5.1 +/- 1.6 mmol/l, p = 0.005) or by ultralente and soluble insulin (4.7 +/- 1.4 mmol/l, p = 0.003). The mean glycosylated haemoglobin concentration was reduced significantly only by the treatments which included insulin. None of the patients had severe or incapacitating hypoglycaemia and only when on additional soluble insulin did patients show a significant gain in weight. Combining sulphonylurea therapy with ultralente insulin did not significantly improve overall glucose control over treatment with ultralente alone, although the insulin dose required to restore fasting normoglycaemia was significantly lower (median (interquartile range), 25 (12-41) versus 40 (27-80) U/day, p = 0.001). In type 2 diabetic patients who continue to have fasting hyperglycaemia on maximal sulphonylurea therapy, fasting normoglycaemia can be achieved easily, without minimal changes in diet or lifestyle, by means of a basal insulin supplement.", "The effectiveness of combined insulin and glibenclamide was compared with that of insulin alone in a multicenter double-blind trial of secondary sulphonylurea failures. Protocols of 176 patients at 26 centers were available, but only 68 could ultimately be included in the analysis. Combined insulin and glibenclamide (Euglucon N) had been taken by 37 patients, combined insulin and placebo by 31. The final criterion, postprandial one-hour blood sugar level of less than or equal to 220 mg/100 ml after 24 weeks, was attained by nearly 75% of patients in both groups. Fasting blood sugar and postprandial one-hour blood sugar as well as HbA1 did not differ during the entire test period of 24 weeks. Mean daily insulin dose was 20 IU in the insulin/glibenclamide group, 35 IU in the insulin/placebo group. This increased the number of second evening insulin injections by 50% in the insulin/placebo group compared with the insulin/glibenclamide group. The frequency of mild hypoglycemia was similar in the two groups. The results indicate that combined insulin/glibenclamide, given over a period of six months to patients with secondary sulphonylurea failure, provided metabolic results as good as those with insulin alone. The required insulin dosage was thus reduced by more than a third.", "Compared with other insulin regimens, combination therapy with oral hypoglycemic agents and bedtime insulin produces similar improvement in glycemic control but induces less weight gain.\n To determine whether bedtime insulin regimens differ with respect to their effects on weight gain in patients with type 2 diabetes.\n Randomized, controlled trial.\n Four outpatient clinics at central hospitals.\n 96 patients (mean age, 58 +/- 1 years; mean body mass index, 29 +/- 1 kg/m2) whose type 2 diabetes was poorly controlled with sulfonylurea therapy (mean glycosylated hemoglobin value, 9.9% +/- 0.2%; mean fasting plasma glucose level, 11.9 +/- 0.3 mmol/L [214 +/- 5 mg/dL]).\n Random assignment to 1 year of treatment with bedtime intermediate-acting insulin plus glyburide (10.5 mg) and placebo, metformin (2 g) and placebo, glyburide and metformin, or a second injection of intermediate-acting insulin in the morning. Patients were taught to adjust the bedtime insulin dose on the basis of fasting glucose measurements.\n Body weight, biochemical and symptomatic hypoglycemias, and indices of glycemic control.\n At 1 year, body weight remained unchanged in patients receiving bedtime insulin plus metformin (mean change, 0.9 +/- 1.2 kg; P < 0.001 compared with all other groups) but increased by 3.9 +/- 0.7 kg, 3.6 +/- 1.2 kg, and 4.6 +/- 1.0 kg in patients receiving bedtime insulin plus glyburide, those receiving bedtime insulin plus both oral drugs, and those receiving bedtime and morning insulin, respectively. The greatest decrease in the glycosylated hemoglobin value was observed in the bedtime insulin and metformin group (from 9.7% +/- 0.4% to 7.2% +/- 0.2% [difference, -2.5 +/- 0.4 percentage points] at 1 year; P < 0.001 compared with 0 months and P < 0.05 compared with other groups). This group also had significantly fewer symptomatic and biochemical cases of hypoglycemia (P < 0.05) than the other groups.\n Combination therapy with bedtime insulin plus metformin prevents weight gain. This regimen also seems superior to other bedtime insulin regimens with respect to improvement in glycemic control and frequency of hypoglycemia." ]

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[ "Once daily treatment of psoriasis with tacalcitol compared with twice daily treatment with calcipotriol. A double-blind trial.", "Effectiveness of kukui nut oil as a topical treatment for psoriasis.", "Improvement of psoriasis by a topical vitamin D3 analogue (MC 903) in a double-blind study.", "Limited benefit of combined use of tar-based shampoo with 50 microg/ml calcipotriol solution in scalp psoriasis.", "1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone in the treatment of intertriginous psoriasis: a double-blind, randomized controlled study.", "Highly purified omega-3-polyunsaturated fatty acids for topical treatment of psoriasis. Results of a double-blind, placebo-controlled multicentre study.", "Betamethasone valerate foam 0.12%: a novel vehicle with enhanced delivery and efficacy.", "A calcipotriene/betamethasone dipropionate two-compound scalp formulation in the treatment of scalp psoriasis in Hispanic/Latino and Black/African American patients: results of the randomized, 8-week, double-blind phase of a clinical trial.", "The efficacy and safety of topically applied indigo naturalis ointment in patients with plaque-type psoriasis.", "Clinical assessment of patients with recalcitrant psoriasis in a randomized, observer-blind, vehicle-controlled trial using indigo naturalis.", "Efficacy of topical 5% liquor carbonis detergens vs. its emollient base in the treatment of psoriasis.", "Evaluation of halobetasol propionate ointment in the treatment of plaque psoriasis: report on two double-blind, vehicle-controlled studies.", "Comparative study of calcipotriene (MC 903) ointment and fluocinonide ointment in the treatment of psoriasis.", "Efficacy of topical treatment in psoriasis with MC903, a new vitamin D analogue.", "Clobetasol propionate lotion in the treatment of moderate to severe plaque-type psoriasis.", "Treatment of psoriasis with topical sirolimus: preclinical development and a randomized, double-blind trial.", "Treatment of psoriasis with topical NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthesis.", "Clobetasol propionate shampoo 0.05% and calcipotriol solution 0.005%: a randomized comparison of efficacy and safety in subjects with scalp psoriasis.", "A new calcipotriol/betamethasone dipropionate formulation (Daivobet) is an effective once-daily treatment for psoriasis vulgaris.", "Pilot, multicenter, double-blind, randomized placebo-controlled bilateral comparative study of a combination of calcipotriene and nicotinamide for the treatment of psoriasis.", "Comparative effects of calcipotriol ointment (50 micrograms/g) and 5% coal tar/2% allantoin/0.5% hydrocortisone cream in treating plaque psoriasis.", "A double-blind comparison of 0.1% dithranol in a 17% urea base (\"Psoradrate\") and base alone in the treatment of active chronic psoriasis.", "Lack of efficacy of topical mycophenolic acid in psoriasis vulgaris.", "Once-daily treatment of psoriasis with topical glucocorticosteroid ointments.", "A randomized, double-blind, placebo-controlled study of clobetasol propionate 0.05% foam in the treatment of nonscalp psoriasis.", "Topical tacrolimus is not effective in chronic plaque psoriasis. A pilot study.", "Clobetasol propionate followed by calcipotriol is superior to calcipotriol alone in topical treatment of psoriasis.", "Calcitriol 3 microg/g ointment in the management of mild to moderate plaque type psoriasis: results from 2 placebo-controlled, multicenter, randomized double-blind, clinical studies.", "Tacrolimus ointment is effective for facial and intertriginous psoriasis.", "Comparative efficacy of calcipotriol (MC903) cream and betamethasone 17-valerate cream in the treatment of chronic plaque psoriasis. A randomized, double-blind, parallel group multicentre study. Calcipotriol Study Group.", "Efficacy, safety and quality of life of calcipotriol/betamethasone dipropionate (Dovobet) versus calcipotriol (Daivonex) in the treatment of psoriasis vulgaris: a randomized, multicentre, clinical trial.", "Efficacy and tolerance of topical calcitriol 3 microg g(-1) in psoriasis treatment: a review of our experience in Poland.", "Efficacy and safety of calcipotriol plus betamethasone dipropionate scalp formulation compared with calcipotriol scalp solution in the treatment of scalp psoriasis: a randomized controlled trial.", "Efficacy results of a 52-week, randomised, double-blind, safety study of a calcipotriol/betamethasone dipropionate two-compound product (Daivobet/Dovobet/Taclonex) in the treatment of psoriasis vulgaris.", "Efficacy of once-daily treatment regimens with calcipotriol/betamethasone dipropionate ointment and calcipotriol ointment in psoriasis vulgaris.", "A comparison of subjective and objective measures of reduction of psoriasis with the use of ultrasound, reflectance colorimetry, computerized video image analysis, and nitric oxide production.", "Double-blind, placebo-controlled, randomized, right-left study comparing calcipotriol monotherapy with a combined treatment of calcipotriol and diflucortolone valerate in chronic plaque psoriasis.", "Topical maxacalcitol for the treatment of psoriasis vulgaris: a placebo-controlled, double-blind, dose-finding study with active comparator.", "A comparison of tazarotene 0.1% gel once daily plus mometasone furoate 0.1% cream once daily versus calcipotriene 0.005% ointment twice daily in the treatment of plaque psoriasis.", "Betamethasone valerate foam for treatment of nonscalp psoriasis.", "Use of calcipotriene cream (Dovonex cream) following acute treatment of psoriasis vulgaris with the calcipotriene/betamethasone dipropionate two-compound product (Taclonex): a randomized, parallel-group clinical trial.", "Clinical trial of a potent non-halogenated topical steroid, Budesonide.", "A randomized double-blind comparison of the effects on systemic calcium homeostasis of topical calcitriol (3 micrograms/g) and calcipotriol (50 micrograms/g) in the treatment of chronic plaque psoriasis vulgaris.", "Betamethasone dipropionate in optimized vehicle. Intermittent pulse dosing for extended maintenance treatment of psoriasis.", "A comparative study of calcipotriol ointment and tar in chronic plaque psoriasis.", "A randomized, multicenter study of calcipotriene ointment and clobetasol propionate foam in the sequential treatment of localized plaque-type psoriasis: short- and long-term outcomes.", "Clobetasol propionate shampoo 0.05% is efficacious and safe for long-term control of scalp psoriasis.", "A new calcipotriol/betamethasone formulation with rapid onset of action was superior to monotherapy with betamethasone dipropionate or calcipotriol in psoriasis vulgaris.", "Tazarotene cream in the treatment of psoriasis: Two multicenter, double-blind, randomized, vehicle-controlled studies of the safety and efficacy of tazarotene creams 0.05% and 0.1% applied once daily for 12 weeks.", "A clinical study to determine the efficacy and safety of 1% methotrexate/Azone (MAZ) gel applied topically once daily in patients with psoriasis vulgaris.", "Topical calcitriol in the treatment of chronic plaque psoriasis: a double-blind study.", "Calcipotriol in psoriasis vulgaris: a controlled trial comparing betamethasone dipropionate + salicylic acid.", "Efficacy and safety of calcipotriene 0.005% foam for the treatment of plaque-type psoriasis: results of two multicenter, randomized, double-blind, vehicle-controlled, phase III clinical trials.", "Comparison of cutaneous tolerance and efficacy of calcitriol 3 microg g(-1) ointment and tacrolimus 0.3 mg g(-1) ointment in chronic plaque psoriasis involving facial or genitofemoral areas: a double-blind, randomized controlled trial.", "Clobetasol propionate shampoo 0.05%: a new option to treat patients with moderate to severe scalp psoriasis.", "Efficacy and safety of topical calcitriol (1,25-dihydroxyvitamin d3) for the treatment of psoriasis.", "Occlusion enhances the efficacy of topical calcipotriol in the treatment of psoriasis vulgaris.", "Double-blind comparison of halcinonide solution and placebo control in treatment of psoriasis of the scalp.", "A double-blind study of topical 1 alpha,25-dihydroxyvitamin D3 in psoriasis.", "Clobetasol propionate lotion, an efficient and safe alternative to clobetasol propionate emollient cream in subjects with moderate to severe plaque-type psoriasis.", "Calcipotriol plus betamethasone dipropionate gel compared with tacalcitol ointment and the gel vehicle alone in patients with psoriasis vulgaris: a randomized, controlled clinical trial.", "A double-blind, vehicle-controlled paired comparison of halobetasol propionate cream on patients with plaque psoriasis.", "Failure of topical polymyxin B to improve mild plaque psoriasis.", "Calcipotriol plus betamethasone dipropionate gel compared with its active components in the same vehicle and the vehicle alone in the treatment of psoriasis vulgaris: a randomised, parallel group, double-blind, exploratory study.", "Early onset of action and efficacy of a combination of calcipotriene and betamethasone dipropionate in the treatment of psoriasis.", "Calcitriol ointment and clobetasol propionate cream: a new regimen for the treatment of plaque psoriasis.", "Comparison of tazarotene 0.1% gel plus petrolatum once daily versus calcipotriol 0.005% ointment twice daily in the treatment of plaque psoriasis.", "Treatment of psoriasis vulgaris with topical calcipotriol has no short-term effect on calcium or bone metabolism. A randomized, double-blind, placebo-controlled study.", "Topical calcipotriol in childhood psoriasis.", "Management of psoriasis vulgaris with methotrexate 0.25% in a hydrophilic gel: a placebo-controlled, double-blind study.", "Clobetasol propionate foam 0.05%: a novel vehicle with enhanced delivery.", "Betamethasone dipropionate ointment in the treatment of psoriasis and atopic dermatitis: a double-blind study.", "Topical fish oil in psoriasis--a controlled and blind study.", "Intermittent corticosteroid maintenance treatment of psoriasis: a double-blind multicenter trial of augmented betamethasone dipropionate ointment in a pulse dose treatment regimen.", "Intra-individual comparison of the cutaneous safety and efficacy of calcitriol 3 microg g(-1) ointment and calcipotriol 50 microg g(-1) ointment on chronic plaque psoriasis localized in facial, hairline, retroauricular or flexural areas.", "Efficacy of treatment with calcipotriol/betamethasone dipropionate followed by calcipotriol alone compared with tacalcitol for the treatment of psoriasis vulgaris: a randomised, double-blind trial.", "0.3% Tacrolimus gel and 0.5% Tacrolimus cream show efficacy in mild to moderate plaque psoriasis: Results of a randomized, open-label, observer-blinded study.", "Comparative effects of calcipotriol solution (50 micrograms/ml) and betamethasone 17-valerate solution (1 mg/ml) in the treatment of scalp psoriasis.", "Effect of salicylic acid on the activity of betamethasone-17,21-dipropionate in the treatment of erythematous squamous dermatoses.", "A comparison of single and multiple applications of halcinonide cream.", "Calcipotriene-induced improvement in psoriasis is associated with reduced interleukin-8 and increased interleukin-10 levels within lesions.", "Calcipotriol cream with or without concurrent topical corticosteroid in psoriasis: tolerability and efficacy.", "Vitamin B(12) cream containing avocado oil in the therapy of plaque psoriasis.", "Tacalcitol ointment in the treatment of psoriasis vulgaris: a multicentre, placebo-controlled, double-blind study on efficacy and safety.", "Short-contact treatment at home with Micanol.", "Topical PTH (1-34) is a novel, safe and effective treatment for psoriasis: a randomized self-controlled trial and an open trial.", "A comparison of twice-daily calcipotriol ointment with once-daily short-contact dithranol cream therapy: a randomized controlled trial of supervised treatment of psoriasis vulgaris in a day-care setting.", "Fluocinolone acetonide topical oil for scalp psoriasis.", "A new scalp formulation of calcipotriol plus betamethasone dipropionate compared with each of its active ingredients in the same vehicle for the treatment of scalp psoriasis: a randomized, double-blind, controlled trial.", "Tazarotene gel, a new retinoid, for topical therapy of psoriasis: vehicle-controlled study of safety, efficacy, and duration of therapeutic effect.", "Efficacy and tolerability of a cosmetically acceptable coal tar solution in the treatment of moderate plaque psoriasis: a controlled comparison with calcipotriene (calcipotriol) cream.", "Treatment of mild to moderate psoriasis with Reliéva, a Mahonia aquifolium extract--a double-blind, placebo-controlled study.", "Calcipotriene ointment 0.005% for psoriasis: a safety and efficacy study. Calcipotriene Study Group.", "The safety and efficacy of tazarotene gel, a topical acetylenic retinoid, in the treatment of psoriasis.", "Calcipotriol plus betamethasone dipropionate scalp formulation is effective and well tolerated in the treatment of scalp psoriasis: a phase II study.", "Comparison of two different dose combinations of calcipotriol/hydrocortisone ointment used once daily for the treatment of psoriasis vulgaris on the face and body.", "Efficacy and safety of a new combination of calcipotriol and betamethasone dipropionate (once or twice daily) compared to calcipotriol (twice daily) in the treatment of psoriasis vulgaris: a randomized, double-blind, vehicle-controlled clinical trial.", "A double-blind, vehicle-controlled study of clobetasol propionate 0.05% (Temovate) scalp application in the treatment of moderate to severe scalp psoriasis.", "A new scalp formulation of calcipotriene plus betamethasone compared with its active ingredients and the vehicle in the treatment of scalp psoriasis: a randomized, double-blind, controlled trial.", "Pimecrolimus cream 1% in the treatment of intertriginous psoriasis: a double-blind, randomized study.", "Calcipotriol ointment under occlusion gives a fast onset of action.", "Topical becocalcidiol for the treatment of psoriasis vulgaris: a randomized, placebo-controlled, double-blind, multicentre study.", "Comparison of calcipotriol monotherapy and a combination of calcipotriol and betamethasone valerate after 2 weeks' treatment with calcipotriol in the topical therapy of psoriasis vulgaris: a multicentre, double-blind, randomized study.", "A study of the safety and efficacy of calcipotriol and betamethasone dipropionate scalp formulation in the long-term management of scalp psoriasis.", "Management of psoriasis with Aloe vera extract in a hydrophilic cream: a placebo-controlled, double-blind study.", "Comparing clobetasol propionate 0.05% spray to calcipotriene 0.005% betamethasone dipropionate 0.064% ointment for the treatment of moderate to severe plaque psoriasis.", "Scalp psoriasis: topical calcipotriol 50 micrograms/g/ml solution vs. betamethasone valerate 1% lotion.", "Comparative study of calcipotriol (MC 903) ointment and betamethasone 17-valerate ointment in patients with psoriasis vulgaris.", "Evaluation of the efficacy of topical caffeine in the treatment of psoriasis vulgaris.", "Calcitriol shows greater persistence of treatment effect than betamethasone dipropionate in topical psoriasis therapy.", "Calcipotriene ointment applied once a day for psoriasis: a double-blind, multicenter, placebo-controlled study.", "Efficacy and safety of calcipotriol (MC 903) ointment in psoriasis vulgaris. A randomized, double-blind, right/left comparative, vehicle-controlled study.", "Clobetasol propionate emollient 0.05 percent: hypothalamic-pituitary-adrenal-axis safety and four-week clinical efficacy results in plaque-type psoriasis.", "Efficacy of 2 weeks' application of theophylline ointment in psoriasis vulgaris.", "One-minute dithranol therapy in psoriasis: a placebo-controlled paired comparative study.", "Comparative effects of calcipotriol (MC903) solution and placebo (vehicle of MC903) in the treatment of psoriasis of the scalp.", "Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris.", "A double-blind study comparing oleum horwathiensis with placebo in the treatment of psoriasis.", "Calcipotriol: clinical trial versus betamethasone dipropionate + salicylic acid.", "A multicentre, parallel-group comparison of calcipotriol ointment and short-contact dithranol therapy in chronic plaque psoriasis.", "A comparison of treatment with dithranol and calcipotriol on the clinical severity and quality of life in patients with psoriasis.", "Efficacy and safety of fluticasone propionate 0.005% ointment in the treatment of psoriasis.", "Safety and efficacy of combined high-dose treatment with calcipotriol ointment and solution in patients with psoriasis.", "The efficacy, safety and tolerance of calcitriol 3 microg/g ointment in the treatment of plaque psoriasis: a comparison with short-contact dithranol.", "The efficacy and tolerability of clobetasol propionate foam 0.05% in the treatment of mild to moderate plaque-type psoriasis of nonscalp regions.", "Topical paricalcitol (19-nor-1 alpha,25-dihydroxyvitamin D2) is a novel, safe and effective treatment for plaque psoriasis: a pilot study.", "An intra-individual randomized safety and efficacy comparison of clobetasol propionate 0.05% spray and its vehicle in the treatment of plaque psoriasis.", "Rationale for use and clinical responsiveness of hexafluoro-1,25-dihydroxyvitamin D3 for the treatment of plaque psoriasis: a pilot study." ]

[ "Once daily topical treatment of psoriasis with tacalcitol ointment (4 micrograms/g) was compared with twice daily treatment with calcipotriol ointment (50 micrograms/g) in a double-blind, randomized study over a treatment period of 8 weeks. The severity of pruritus, erythema, infiltration and scaling was scored on a scale from 0 to 4. These features were scored at the initiation of treatment, after 2, 4, 6 and 8 weeks of treatment, and at 4 weeks after discontinuation of treatment. The sum score was the total score for erythema, infiltration and scaling. Serum levels of calcium, phosphate, ionized calcium and intact parathyroid hormone were used as safety parameters. Two hundred and eighty-seven adults with stable plaque psoriasis participated and were treated at least once. Both tacalcitol and calcipotriol ointments effectively reduced the severity of psoriasis. The mean reduction in the sum score in the intention-to-treat population of 287 patients was 4.03 in the group treated with tacalcitol compared with 5.05 in the group treated with calcipotriol. The mean baseline sum scores were 7.64 and 7.15, respectively. The acceptability of both ointments was excellent, and none of the patients had adverse effects in terms of increased serum calcium or other alterations in calcium metabolism. Although less effective than calcipotriol ointment used twice daily, tacalcitol ointment is an effective and useful once daily treatment of chronic plaque psoriasis.", "No cure for psoriasis exists for the 1-3% of the American population who suffer from it; however, anecdotal reports from patients with psoriasis visiting Hawaii who purchased kukui nut oil, claim it helped reduce the severity of their lesions.\n This pilot study was a double-blind, placebo-controlled clinical trial to determine the effectiveness of kukui nut oil as a topical treatment for psoriasis.\n Thirty adult subjects (18-78 year) were recruited from the community for a 12-week randomized, double-blind, placebo-controlled pilot study. Subjects were previously diagnosed with mild, stable plaque psoriasis (less than 15% of total body surface area [TBSA]) and agreed to abstain from other treatments during the course of the study. Following a 4-week washout period the subjects were randomized into a treatment group (15 subjects applying kukui nut oil) or a control group (15 applying the mineral oil placebo). Patients were seen every 2 weeks (seven visits at 0, 2, 4, 6, 8, 10, and 12 weeks) by a dermatological nurse practitioner under the general supervision of a board certified dermatologist. Measurable outcomes included evaluation of one targeted lesion and of the overall severity of their psoriasis using clinical evaluation, Psoriasis Area and Sensitivity Index (PASI), Global Severity of Psoriasis Scale, and photographs. Each patient also evaluated their own lesions daily using the Global Severity of Psoriasis Scale, and noted any side-effects or other treatments used.\n Although both groups improved, we found no significant difference between the treatment (kukui nut oil) and the placebo (mineral oil) among the 24 out of 30 subjects (80%) who completed the study. No side-effects or adverse events were reported.\n Kukui nut oil did not significantly reduce symptoms of psoriasis; however, this was a small pilot study, and the use of this oil cannot be dismissed without using a larger study population of patients with psoriasis.", "nan", "nan", "During the last decades, management of intertriginous psoriasis (IP) has been unsatisfactory because of the adverse effects associated with long-term corticosteroid application and the lack of alternatives. Recently, both pimecrolimus and tacrolimus have been investigated for this indication and shown to be safe and effective. So far, to our knowledge, a comparison of one of these drugs with standard regimens for IP has not been performed.\n A single-center, 4-week, double-blind, randomized, vehicle-controlled comparison study to assess the safety and efficacy of 1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone valerate in the treatment of IP.\n Dermatologic hospital at Ruhr University of Bochum.\n Eighty adults with IP.\n Treatment of IP with 1% pimecrolimus, 0.005% calcipotriol, 0.1% betamethasone, or the vehicle once daily for 28 days.\n Mean reduction of the Modified Psoriasis Area and Severity Index (M-PASI) score after 28 days of treatment was considered the primary outcome measure, which was analyzed on an intention-to-treat basis. The secondary outcome was a visual analog scale score for itching.\n After 4 weeks of treatment, the 3 active compounds and the vehicle resulted in a significant decrease in mean M-PASI score (86.4% for 0.1% betamethasone, 62.4% for 0.005% calcipotriol, 39.7% for 1% pimecrolimus, and 21.1% for vehicle). The 0.1% betamethasone was significantly more effective than 1% pimecrolimus during the study period (P<.05). No significant difference was found between 0.005% calcipotriol and 0.1% betamethasone and between 0.005% calcipotriol and 1% pimecrolimus. The visual analog scale score for pruritus decreased by 78% for 0.1% betamethasone, 57% for 0.005% calcipotriol, 35% for 1% pimecrolimus, and 43% for the vehicle, again demonstrating a clear advantage for the corticosteroid (P<.05).\n The 1% pimecrolimus was shown to be less potent than 0.1% betamethasone in the treatment of IP. Considering the adverse-effect profile of long-term application of corticosteroids, occasional or intermittent rescue therapy with short-term topical corticosteroids and maintenance with a less potent agent, such as 1% pimecrolimus or 0.005% calcipotriol, might be appropriate for patients with IP in general practice.", "We report the results of a multicentre, double-blind, placebo-controlled study of topical therapy with omega-3-polyunsaturated fatty acids (omega-3-PUFA) in 52 patients suffering from moderate plaque-type psoriasis. In each patient, two similar stable psoriatic plaques served as indicator lesions for the study. One indicator lesion was randomly assigned to treatment with topical preparations of highly purified omega-3-PUFA in one of two concentrations (1 or 10%), and the other was treated with placebo. Efficacy assessment was based on changes in local psoriasis severity index, area involved, erythema, desquamation, induration and pruritus. After 8 weeks of treatment, all indicator lesions had improved significantly, compared with baseline. However, no statistically or clinically relevant differences between the omega-3-PUFA-treated and the placebo-treated lesions were found. Therapy was well tolerated and, apart from one patient who developed perilesional eczema, no clinically relevant adverse events occurred. In conclusion, topical omega-3-PUFA were not effective in a randomized, placebo-controlled, double-blind setting. Results of non-blind trials should be (re-)considered with caution.", "A new topical formulation of betamethasone valerate (BMV) with enhanced dermal penetration has been developed.\n These studies were designed to evaluate: (1) the relative bioavailability of BMV foam, and (2) the safety and efficacy of BMV foam in the treatment of scalp psoriasis as compared to a lotion formulation of BMV and placebo.\n Safety and efficacy were evaluated in a randomized, multicenter, double-blind, active-and placebo-controlled trial in adult patients with moderate to severe scalp psoriasis. A separate study in 18 patients was conducted to evaluate the potential for suppression of the hypothalamic-pituitary-adrenal (HPA) axis. Relative bioavailability was measured using the human cadaver skin model.\n 72% of patients using BMV foam were clear or almost clear of disease at the end of 28-days of treatment as judged by the investigator's global assessment of response. Only 47% of BMV lotion patients and 21% of placebo showed a similar level of response. There was no evidence of increased toxicity or HPA-axis suppression for BMV foam, but assessment of relative bioavailability showed BMV penetration into the skin to be more than two-fold greater than from BMV lotion.\n A novel foam formulation with enhanced BMV bioavailability has been shown to be of increased efficacy in the treatment of scalp psoriasis without an associated increase in toxicity.", "The calcipotriene/betamethasone dipropionate two-compound scalp formulation has been shown to be safe and effective in the treatment of scalp psoriasis over 8 weeks, but the patients studied were mainly White and non-Hispanic. The aim of this study was to evaluate the efficacy and safety of the two-compound scalp formulation in the treatment of scalp psoriasis in Hispanic/Latino and Black/African American patients. A total of 99 Hispanic/Latino and 78 Black/African American patients were randomized double-blind in a 3:1 ratio to 8 weeks of once daily treatment of scalp psoriasis with either the two-compound scalp formulation (n=135) or its vehicle (n=42). In the two-compound group, 71.9% of patients had cleared or minimal disease at week 8 by the investigator's global assessment compared to 40.5% in the vehicle group (odds ratio 3.30; 95% CI 1.62-6.72; P<0.001). For the five secondary efficacy response criteria, three (total sign score, thickness of scalp psoriasis, patient's global assessment) showed that two-compound scalp formulation was statistically significantly more effective than its vehicle, and the other two (redness and scaliness of scalp psoriasis) approached statistical significance in favor of the two-compound scalp formulation. There was no statistically significant difference (P=1.00) between the percentage of patients with adverse reactions in the two-compound group (7.0%) and the vehicle group (7.9%). The two-compound scalp formulation is safe and effective in the treatment of scalp psoriasis over 8 weeks in Hispanic/Latino and Black/African American patients.\n © 2010 The International Society of Dermatology.", "It has been reported in the Chinese literature that indigo naturalis exhibits potential antipsoriatic effects in systemic therapy.\n To evaluate the efficacy and safety of topically applied indigo naturalis on treating plaque-type psoriasis and to analyze the histological change in skin tissues.\n Fourteen patients with chronic plaque psoriasis were enrolled. The patients were topically applied with either indigo naturalis ointment or vehicle ointment on contralateral skin lesions daily for 8 weeks. Efficacy was evaluated on the basis of the clinical scores, including induration, scaling, erythema and clearing percentage. At the end of treatment, skin punch biopsies were taken and prepared for the immunohistochemical analysis.\n A significant reduction in clinical scores was achieved with topically applied indigo naturalis ointment. Analysis of biopsies showed a marked improvement of skin histology. The expressions of proliferating marker Ki-67 and inflammatory marker CD3 were decreased, but the differentiation marker such as filaggrin was increased in the epidermis after indigo naturalis ointment treatment.\n The results suggest that topical application of indigo naturalis ointment may be a novel, safe and effective therapy for psoriasis that is mediated, at least in part, by modulating the proliferation and differentiation of keratinocytes in epidermis, as well as by inhibiting the infiltration of T lymphocytes and therefore the subsequent inflammatory reactions in psoriatic lesions.\n Copyright 2007 S. Karger AG, Basel.", "To evaluate the efficacy and safety of treatment with indigo naturalis in patients with recalcitrant plaque-type psoriasis.\n Randomized, observer-blind, vehicle-controlled, intrapatient comparison study.\n Ambulatory department of a hospital.\n Forty-two outpatients with chronic plaque psoriasis were enrolled in the study from May 1, 2004, to April 30, 2005.\n The patients applied either indigo naturalis ointment or vehicle ointment topically to each of 2 bilaterally symmetrical psoriatic plaque lesions for 12 weeks (depending on the date of enrollment in the study).\n The outcomes were assessed using the following criteria: the sum of erythema, scaling, and induration scores and the clearing percentage of the target plaque lesion assessed by 2 blinded observers.\n Significant reductions in the sum of scaling, erythema, and induration scores (P < .001) (mean score, 6.3 after indigo naturalis treatment vs 12.8 in control subjects) and plaque area percentage (P < .001) (mean percentage, 38.5% after indigo naturalis treatment vs 90% in controls) were achieved with topical application of indigo naturalis ointment. Approximately 31 of 42 patients (74%) experienced clearance or near clearance of their psoriasis in the indigo ointment-treated lesion.\n Topical indigo naturalis ointment was a novel, safe, and effective therapy for plaque-type psoriasis.", "Tar has been a mainstay in the treatment of psoriasis for centuries, but despite its widespread use, there is little evidence supporting its clinical efficacy without the combined use of ultraviolet radiation. The purpose of this study was to compare psoriasis improvement rates in patients using 5% liquor carbonis detergens (LCD) in an emollient base with the emollient base alone. Eighteen patients completed a randomized, bilaterally controlled, double-blind study. Emollient-treated plaques showed a mean improvement of 35.3% by 4 weeks of treatment, and LCD therapy produced a mean improvement of 48.7%, a difference which was statistically significant.", "The results of two studies are presented that reveal the efficacy and safety of 0.05% halobetasol ointment in the treatment of patients with plaque psoriasis of at least moderate severity. Both multicenter studies were randomized, double-blind, and vehicle controlled, and study medications were applied twice daily for 2 weeks. One study was a paired-comparison (PC); the other study was of parallel-group (PG) design. Both studies called for evaluations at entry (week 0) and after 1 and 2 weeks of treatment. The PC study enrolled 100 patients; the PG study enrolled 110 patients; 204 patients provided efficacy data over both studies. In the PC study, plaque elevation, erythema, and scaling, at least moderately severe at entry, showed at the end of treatment both statistical (p less than or equal to 0.0003) and clinical significance (all greater than 1-unit difference on the rating scale) favoring 0.05% halobetasol ointment over vehicle. Pruritus (initially mild) and total score also showed statistically significant treatment differences favoring halobetasol at the final evaluation. Patient global responses for \"effectiveness\" and \"overall rating\" favored 0.05% halobetasol ointment over vehicle. In the PG study, induration, erythema, and scaling, at least moderately severe at entry, showed at the end of treatment both statistically and clinically significant differences favoring 0.05% halobetasol ointment over vehicle. Physician's global evaluation favored 0.05% halobetasol ointment over vehicle after 2 weeks of use. No patients were released from either study because of adverse events. No systemic adverse events or findings of skin atrophy were reported in these studies. Reports of \"stings\" or \"burns\" were equally divided between halobetasol and its vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)", "The topical vitamin D analogue calcipotriene has been reported to be an effective treatment for patients with psoriasis. Comparative studies with topical steroids are informative in judging this new therapy.\n The purpose of this study was to evaluate the efficacy and safety of calcipotriene ointment 0.005% versus fluocinonide ointment 0.05% in the treatment of plaque psoriasis.\n This study was a randomized, double-blind, parallel-group, active-controlled trial in adults who had at least mild overall disease severity and plaque elevation of at least moderate severity. Treatments were applied twice daily for 6 weeks, and subjects were evaluated at weeks 0, 2, 4, and 6. Subjects were graded on a 9-point scale (0 to 8) for scaling, erythema, plaque elevation, and for overall disease severity. A physician's global assessment of improvement/worsening was performed at every visit.\n A total of 114 subjects were enrolled at six study sites. Ninety-nine subjects completed the trial. Mean scores for signs of scaling and plaque elevation in calcipotriene-treated subjects were significantly lower by week 2 than in the fluocinonide-treated subjects. These scores continued to be significantly lower than fluocinonide through week 6 (p < 0.05). Mean scores for erythema in calcipotriene-treated subjects were significantly lower than those in fluocinonide-treated subjects at weeks 4 and 6 (p < 0.05). Both the physician's global assessment and overall disease severity showed statistically significant treatment differences in favor of calcipotriene at week 4 (p < 0.05). This superior efficacy continued through week 6. Treatment-related adverse events were observed in 12 calcipotriene-treated subjects and 5 fluocinonide-treated subjects; all were considered minor.\n Calcipotriene was superior to fluocinonide in the treatment of plaque psoriasis.", "In 10 in-patients with chronic plaque psoriasis, the antipsoriatic effect of MC903, a new synthetic analogue of vitamin D was evaluated. In each patient two symmetrical located psoriatic plaques were selected for the study. Topical treatment with MC903 cream (containing 1.2 mg MC903 per g cream) was compared with placebo cream in a double-blind, controlled, left-right, randomized way during 6 weeks of therapy. Compared with baseline, the clinical (erythema, scaling and infiltration) improvement was significant after 1 week of therapy with MC903 cream, while lateral comparison showed MC903 cream significantly better than cream base after 4 weeks of therapy (p less than 0.05). Measurements of skin blood flow by the laser Doppler technique in evaluating the disease activity was not superior to the clinical assessments. In 3 patients the psoriatic lesions treated with MC903 cream cleared completely during 6 weeks of therapy. No essential adverse reactions were observed. MC903 has a potent effect on cell proliferation and cell differentiation, but has minimal effect on calcium metabolism. It is concluded that this synthetic vitamin D analogue is potentially useful in the treatment of psoriasis.", "Owing to its anti-inflammatory, antipruritic, vasoconstrictive, and immune-modulating properties, clobetasol propionate is used to treat psoriasis. This study was conducted to evaluate the efficacy, safety, and cosmetic acceptability of clobetasol propionate lotion compared with its vehicle and with clobetasol propionate cream in the treatment of moderate to severe plaque-type psoriasis. A total of 222 patients were treated. After 4 weeks of treatment, clobetasol propionate lotion was more efficient than vehicle lotion and of equivalent efficacy as clobetasol propionate cream. Cosmetic acceptability was significantly better with clobetasol propionate lotion than with clobetasol propionate cream. Clobetasol propionate lotion was efficient, safe, and well tolerated and offers a significantly higher cosmetic advantage in the treatment of moderate to severe plaque-type psoriasis compared with clobetasol propionate cream.", "Systemically administered sirolimus has demonstrated efficacy in psoriasis in a multicentre European study.\n To determine the efficacy and safety of topically applied sirolimus in treating psoriasis.\n In vitro studies were followed by a pilot study designed to determine if sirolimus penetrates human skin, and by a randomized, double-blind, left-right comparative, dose-ranging study consisting of treatment with 2.2% sirolimus for 6 weeks and 8% sirolimus for an additional 6 weeks in 24 patients with stable, chronic plaque psoriasis. The primary outcome measure was clinical score. Secondary measures were ultrasound plaque thickness, plaque erythema, and computerized image analysis of immunohistochemical stains for immunocytes and proliferating cells. Pharmacokinetics and blood chemistry monitoring for safety were also performed.\n A significant reduction in the clinical score (P = 0.03) (mean score 9.1 following sirolimus vs. 11.2 in control) was achieved with topical sirolimus. Measurements of plaque thickness and erythema did not show significant improvement with treatment. Computerized image analysis of biopsies showed a significant reduction in CD4+ cells (P = 0.0054) and proliferating cells (stained by Ki-67) in the epidermis (P = 0.0153) with sirolimus treatment compared with control.\n Topically applied sirolimus penetrates normal skin and may have some antipsoriatic and immunosuppressive activity.", "A double blind left, right comparative study was carried out in 17 psoriatic subjects to examine the influence of a topically applied inhibitor of nitric oxide (NO) synthesis on the pathogenic events of psoriasis. The inhibitor NG-monomethyl-L-arginine (L-NMMA) in aqueous cream BP was applied to one plaque while aqueous cream BP alone served as control. Compared with the control, the L-NMMA-treated side showed significant (77%) inhibition of NO production and a reduction in blood flow, confirming its bioavailability. L-NMMA significantly reduced staining for endothelial cells and intercellular adhesion molecule 1, while CD1a-positive Langerhans cells and CD8-positive suppressor cytotoxic T cells increased. CD4-positive lymphocytes and epidermal proliferation, as indicated by Ki-67 staining, were unaffected by this degree of inhibition of NO synthesis, and correspondingly significant clinical improvement was not found.", "Scalp involvement in psoriatic patients represents a common issue. Treatment of the hairy skin requires adequate pharmaceutical formulations; hence, a new specific shampoo formulation of clobetasol propionate 0.05% was developed by Galderma R&D, Inc.\n For this multicenter, randomized, investigator-masked, parallel group study, 151 subjects with moderate to severe scalp psoriasis were randomized to 4 weeks of treatment with clobetasol propionate shampoo or calcipotriol solution.\n Clobetasol propionate demonstrated significantly superior efficacy to calcipotriol solution (total severity score: mean difference 0.51, 95% CI 0.05-0.97, p = 0.028; global severity score: mean difference 0.43, 95% CI 0.08-0.78, p = 0.016). Adverse events were more common in the calcipotriol group than in the clobetasol propionate shampoo group. Telangiectasia and skin atrophy did not differ significantly between treatments; however, a burning sensation was significantly more common in the calcipotriol solution group.\n Short contact therapy of scalp psoriasis with this new shampoo formulation of clobetasol propionate was significantly more effective and better tolerated than calcipotriol solution for the treatment of scalp psoriasis.", "Topical corticosteroids and calcipotriol have been used separately for many years to treat psoriasis. A new combination ointment has been formulated, which contains both calcipotriol and the corticosteroid betamethasone dipropionate.\n To compare the combination ointment with betamethasone dipropionate ointment, calcipotriol ointment and ointment vehicle in patients with psoriasis vulgaris.\n 1,603 patients were randomised to one of the 4 double-blind treatments used once daily for 4 weeks.\n The mean percentage change in the PASI at the end of treatment was -71.3 (combination), -57.2 (betamethasone), -46.1 (calcipotriol) and -22.7 (vehicle). The mean difference of combination minus betamethasone was -14.2 (95% CI: -17.6 to -10.8, p < 0.001), of combination minus calcipotriol -25.3 (95% CI: -28.7 to -21.9, p < 0.001) and of combination minus vehicle -48.3 (95% CI: -53.2 to -43.4, p < 0.001). 6.0% of patients (combination) reported local adverse reactions compared to 4.9% (betamethasone), 11.4% (calcipotriol) and 13.6% (vehicle).\n Calcipotriol/betamethasone dipropionate combination ointment used once daily is well tolerated and more effective than either active constituent used alone.\n Copyright 2002 S. Karger AG, Basel", "Calcipotriene has limited efficacy in treating psoriasis. By inhibiting proinflammatory cytokines such as interleukin-12, interleukin-23, and tumor necrosis factor-alfa, nicotinamide may enhance the efficacy of calcipotriene therapy when used in combination.\n We sought to determine if the combination of nicotinamide with calcipotriene is more effective than either component alone.\n In this randomized, double-blinded, multicenter 7-arm bilateral comparison-controlled trial, patients were randomized to two of 7 treatments--placebo, calcipotriene 0.005% alone, nicotinamide 1.4% alone, calcipotriene plus nicotinamide 0.05%, calcipotriene plus nicotinamide 0.1%, calcipotriene plus nicotinamide 0.7%, or calcipotriene plus nicotinamide 1.4%--each administered to lesions on one side of the body or to one of two lesions at least 5 cm apart, for 12 weeks. Efficacy was measured using a clear to almost clear outcome.\n In all, 50.0% of patients in the calcipotriene and nicotinamide 1.4% combination group achieved a clear to almost clear outcome at week 12, compared with only 18.8% of patients treated with placebo (P = .002), 25% of patients treated with nicotinamide 1.4% alone (P = .02), and 31.5% of patients treated with calcipotriene alone (P = .096). A dose-response trend existed for increasing concentrations of nicotinamide, but it was not significant.\n The relatively small patient numbers, relatively high placebo effect, and maximum in-life portion of only 12 weeks of dosing are weaknesses of the study.\n This study provides evidence that using the combination nicotinamide and calcipotriene may provide additional benefit in the topical treatment for patients with psoriasis and may be an adequate steroid-sparing substitute treatment.\n Copyright © 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.", "The comparative efficacy, tolerability and acceptability of calcipotriol ointment (50 micrograms/g) and 5% coal tar/2% allantoin/0.5% hydrocortisone cream were determined in 122 patients with chronic plaque psoriasis affecting at least 100 cm2 of skin. Both preparations were applied twice daily for up to 8 weeks. At the end of treatment, investigators considered calcipotriol significantly more effective in the proportion of patients 'cleared' or 'markedly improved' (calcipotriol 72.3%, coal tar/allantoin/hydrocortisone 49.1%: p < 0.02). Calcipotriol was also superior in reducing the total sign score (p = 0.002), and individual scores for scaliness (p < 0.0001) and thickness (p = 0.001). The proportion of patients with less than 100 cm2 of affected skin at the end of treatment was significantly greater in the calcipotriol group (p < 0.05). Patients considered calcipotriol significantly more effective overall (p < 0.02) and in reducing flakiness/scaliness of skin (p = 0.001). Adverse events, most of which were application related and mild to moderate, were recorded in 15 (23.1%) patients using calcipotriol and in 10 (17.5%) patients using coal tar/allantoin/hydrocortisone (n.s.), and contributed to treatment withdrawal in one (1.5%) and three (5.3%) patients, respectively.", "A preliminary double-blind controlled trial was carried out in 8 patients with active chronic psoriasis, whose lesions were more or less bilaterally symmetrical, to assess the efficacy of topical treatment with 0.1% dithranol in a specialized carbamide (17% urea) base. The trial preparation was applied twice daily to one side only over a period of 3 weeks, and lesions on the other side of the body were treated in a similar manner with the base alone. Assessments of clinical improvement, based on severity rating scores, were carried out at weekly intervals. The results showed that, although use of the base alone led to some improvement, the preparation including dithranol was twice as effective, and this finding was supported by the patients' preference. It was easy to apply and remove and was well tolerated, the only side-effects reported being stinging and/or smarting.", "Mycophenolic acid is effective for systemic treatment of psoriasis. However, there is no report about its topical use in this cutaneous disorder so far. We undertook a randomized, placebo-controlled, within subject comparison of mycophenolic acid 1% incorporated in an ointment base and the corresponding vehicle alone (placebo) using the psoriasis plaque test in 7 patients with plaque-type psoriasis over a period of 3 weeks. Scoring of erythema and induration was performed 3 times weekly. After 3 weeks of occlusive treatment there was a reduction of the sum score for erythema and induration in the mycophenolic acid-treated sites of 23% and of 5.7% in the vehicle-treated sites, which was not statistically significant. No adverse advents were noted during the time of study. We conclude that mycophenolic acid is ineffective when applied topically in psoriasis even under occlusion.", "A double-blind, vehicle-controlled comparison of two glucocorticosteroid ointments demonstrated that once-daily therapy for psoriasis was effective. After 3 weeks of once-daily therapy, psoriasis subjects treated with betamethasone dipropionate (BD) ointment or diflorasone diacetate (DD) ointment showed statistically significant (p less than 0.01) improvement compared to subjects using vehicle alone.", "Topical corticosteroids are the primary treatment for mild to moderate psoriasis. Foam preparations of corticosteroids offer potential cosmetic and pharmacodynamic advantages over cream and ointment vehicles. A clobetasol propionate foam product is as effective as clobetasol propionate solution in the treatment of scalp psoriasis.\n To evaluate the safety and efficacy of clobetasol propionate foam in the treatment of psoriasis involving sites other than the scalp.\n Eighty-one subjects with mild to moderate psoriasis were randomized in a 3 : 1 ratio to receive clobetasol propionate foam vs. placebo foam treatment in this double-blind study of psoriasis involving nonscalp sites. The investigator's and subject's global assessment of the response at week 2 (or at the end of treatment) and at week 4 (follow-up) and the severity of erythema, scaling, and plaque thickness were assessed. Safety was assessed from reported adverse events.\n After 2 weeks of treatment, there was significantly greater improvement with clobetasol propionate foam compared with placebo foam in both investigator's and subject's global assessment of the response (P < 0.0005). The improvement with clobetasol propionate foam was still present at the 4-week follow-up visit. Adverse effects were generally limited to mild to moderate application site reactions. No subjects withdrew because of adverse events.\n Clobetasol propionate foam is more effective than placebo in the treatment of nonscalp psoriasis. Twice-daily applications are well tolerated, compliance exceeds 90%, cosmetic characteristics are acceptable, and the medication may eliminate the need for separate scalp and body prescriptions.", "Cyclosporine for the treatment of psoriasis constitutes a new approach. Alternative systemic cyclosporine derivatives have been studied to find an immunosuppressive drug with fewer adverse effects. Tacrolimus is one of these new immunosuppressive drugs. Systematically, it has been proven effective in treating psoriasis. A topical formulation of tacrolimus is attractive because it has fewer adverse effects and is useful for a large group of patients. We report for the first time on the efficacy of nonocclusive topical tacrolimus in the treatment of psoriasis.\n After a washout phase of 2 weeks, patients were randomized to receive 0.005% calcipotriol ointment twice daily, placebo ointment once daily, or 0.3% tacrolimus ointment once daily. One psoriatic plaque was treated with a surface area of 40 to 200 cm2. Efficacy was estimated using the local psoriasis severity index. The reduction in the local psoriasis severity index score after 6 weeks was 62.5% in the calcipotriol group, 33.3% in the tacrolimus group, and 42.9% in the placebo group.\n There was no statistically significant difference between the efficacy of tacrolimus and placebo ointment (P = .77). Calcipotriol ointment, applied twice daily, had a better effect than tacrolimus ointment and placebo ointment once daily.", "Although potent, topical corticosteroids offer effective and rapid healing of psoriatic lesions. Their long term use is limited because of the risk of side effects. Calcipotriol is safe for long-term treatment, but its initial efficacy is lower than with topical corticosteroids.\n To investigate whether 2 weeks of treatment with clobetasol propionate 0.05% ointment bd followed by 4 weeks of treatment with calcipotriol 50 microg/g bd would offer therapeutic advantages over 6 weeks of continuous treatment with calcipotriol.\n Forty-nine patients with moderate to severe plaque psoriasis were recruited from five centres in Norway. In a randomised, double-blind, right- versus left-side comparison, ointments were applied to two symmetrically-located areas.\n Two weeks of treatment with clobetasol propionate produced a significantly greater decrease in total symptom score (combined scores of erythema, induration and scaling) than calcipotriol treatment (P < 0.0001). This improvement on the clobetasol propionate-treated side of the body was maintained throughout a subsequent 4-week treatment period when calcipotriol was applied to both sides of the body (P < 0.0001). The superiority of the clobetasol propionate followed by calcipotriol treatment was maintained during a 4-week, treatment-free, observation period. Treatments were well tolerated with no rebound effect.\n Clobetasol propionate ointment bd for 2 weeks followed by treatment with calcipotriol ointment bd for 4 weeks was superior to calcipotriol ointment alone in the treatment of plaque psoriasis.", "Psoriasis is a chronic skin disorder affecting approximately 2% of the US population. Psoriasis may occur anywhere on the body with initial presentation usually seen between 15 and 30 years of age. Calcitriol 3 microg/g ointment has demonstrated good clinical efficacy as well as topical and systemic safety when used to treat psoriasis.\n To confirm the efficacy and safety of calcitriol 3 microg/g ointment versus its vehicle in the treatment of subjects with mild to moderate chronic plaque psoriasis.\n Suitable subjects were randomized to receive either calcitriol 3 microg/g ointment or its vehicle twice daily for up to 8 weeks in 2 multicenter, randomized, vehicle-controlled, double-blind parallel group studies. Efficacy was evaluated through a Global Severity Score dichotomized in success (clear and minimal) or failure. Erythema, plaque elevation, scaling and dermatologic sum score (sum of the scores for erythema, plaque elevation, and scaling), pruritus, and global improvement were also assessed. Routine safety and clinical laboratory parameters, including calcium homeostasis, were evaluated throughout the study.\n In total, 839 subjects were included in the 2 studies: 419 patients received calcitriol 3 microg/g ointment and 420 received the vehicle. In both studies, calcitriol 3 microg/g ointment was shown to be significantly more effective than its vehicle, with onset of therapeutic effect seen as early as week 2 and sustained at all subsequent visits. Calcitriol 3 microg/g ointment demonstrated good systemic and local safety profile comparable to its vehicle with no effect on calcium homeostasis.\n Calcitriol 3 microg/g ointment applied for 8 weeks is effective and safe in the treatment of mild to moderate psoriasis.", "Intertriginous and facial involvement are manifestations of psoriasis that require a different approach than is used for typical plaque psoriasis on other skin areas. Topical corticosteroids are the primary treatment for psoriasis; however, the side effects of corticosteroids are magnified on intertriginous and facial skin. Topical tacrolimus offers the potential for anti-inflammatory effect without the atrophy or other local side effects associated with the use of topical corticosteroids.\n To determine the efficacy and tolerability of 0.1% tacrolimus ointment for the treatment of facial or intertriginous psoriasis.\n One hundred sixty-seven patients 16 years or older were evaluated in an 8-week, randomized, double-blind, vehicle-controlled, multi-center study. Upon entry into the study, patients were randomized 2:1 to apply the tacrolimus ointment 0.1% or vehicle twice daily to all psoriatic lesions of the face or intertriginous areas for 8 weeks. The physician's global assessment was used to assess improvement from baseline. The inverse psoriasis severity for patients was measured using a 6-point scale from clear to very severe.\n As early as day 8, more patients ( P = .004) had cleared or achieved excellent improvement in the 0.1% tacrolimus ointment group compared to the vehicle group (24.8% vs 5.8%). At the end of the 8-week treatment period 65.2% of the tacrolimus ointment group and 31.5% of the vehicle were clear or almost clear ( P < .0001) based on a Static Severity Score. Adverse events were similar in the 0.1% tacrolimus ointment and vehicle groups. Conclusion Tacrolimus ointment is an effective treatment for psoriasis of the face or intertriginous areas.", "The efficacy, safety and tolerability of calcipotriol cream was compared with betamethasone 17-valerate cream in the treatment of plaque-type psoriasis in a multicentre double-blind, parallel group study. Patients with stable mild-to-moderate chronic disease were randomized to treatment with either calcipotriol, 50 micrograms/g, in a cream formulation (210 patients) or betamethasone 17-valerate cream, 1 mg/g (211 patients). After a wash-out period of 2 weeks, the treatment was applied twice daily, without occlusion, for 8 weeks or to complete clearing. The severity of psoriasis was assessed using the PASI at baseline and after 4 and 8 weeks treatment. The mean percentage reduction of PASI from baseline to end of treatment was 47.8% in the calcipotriol group and 45.4% in the betamethasone group. The reduction from baseline was highly significant in both groups, but the difference between the groups was not significant. There was a difference in the reduction in thickness of the lesions in favour of calcipotriol. The investigator's as well as the patient's overall assessment of treatment response at end of treatment showed no difference between the two treatment groups. Treatment-related adverse events were more frequent with calcipotriol than betamethasone. Lesional/perilesional irritation was reported in 16% and 9% (P = 0.03), and facial irritation in 10% and 0.5% (P < 0.001), respectively. No change was found in serum levels of calcium. Calcipotriol in a cream formulation was effective, safe, well-tolerated, and equal in effect to betamethasone valerate cream.", "A clinical trial was performed to evaluate the efficacy, speed of response, side effects and quality of life of patients treated with calcipotriol/betamethasone dipropionate (Dovobet) for 4 weeks followed by maintenance with calcipotriol for 8 weeks (group A) versus calcipotriol (Daivonex) alone for 12 weeks (group B) for the treatment of psoriasis.\n A total of 150 patients were enrolled and randomized to groups A and B. PASI and Skindex-29 were considered the outcome measures.\n Ninety-six patients completed the trial. At weeks 2 and 4, both groups showed a significant clinical improvement compared to baseline; group A demonstrated a higher clinical response compared with group B (p< 0.001). Treatment with calcipotriol was associated with a gradual improvement in group B and maintenance of the results in group A. Similarly, the quality of life assessment showed a marked improvement in terms of Skindex-29 in both groups at weeks 2 and 4 compared to baseline. Both treatments were safe and well tolerated.\n Our results demonstrate a higher efficacy and more rapid onset of action with the two-compound ointment compared with calcipotriol cream alone in short-term treatment. However, sequential application of calcipotriol allows maintenance of the results.", "Although topical vitamin D3 derivatives have been used in the treatment of patients with psoriasis for the past 15 years, questions remain about the indications and limitations of application. Extensive personal experience gained during the development of calcitriol (1alpha25-dihydroxyvitamin D3) is therefore reviewed. Three double-blind, vehicle-controlled trials have revealed that calcitriol 3 microg g(-1) ointment (Silkis ointment, Galderma Laboratories) has very good clinical efficacy. In a left-right comparison with vehicle ointment, complete clearance of psoriatic lesions was achieved in 48% of sites treated with calcitriol and a further 41% showed considerable or definite improvement. The clinical response to calcitriol in another study was as good as, or even better than, that achieved with betamethasone valerate 0.1% ointment. A preparation containing calcitriol 15 microg g(-1) did not show any clinical superiority to the lower dose but was associated with a higher risk of hypercalciuria, particularly when applied to extensive skin lesions. These results suggest that calcitriol 3 microg g(-1) ointment is an effective and safe treatment for chronic plaque psoriasis.", "Current topical therapies for scalp psoriasis are difficult or unpleasant to apply, resulting in decreased adherence and efficacy.\n To compare the efficacy and safety of once-daily treatment with a combination of calcipotriol 50 microg g(-1) plus betamethasone 0.5 mg g(-1) (as dipropionate) (Xamiol; LEO Pharma A/S, Ballerup, Denmark) and twice-daily calcipotriol 50 microg mL(-1) scalp solution in patients with scalp psoriasis.\n This 8-week, multicentre, randomized, investigator-blind, parallel-group study compared two-compound calcipotriol/betamethasone scalp formulation with calcipotriol scalp solution in patients with moderately severe scalp psoriasis. Primary efficacy outcome was the proportion of patients who achieved 'clear' or 'minimal' disease severity according to investigator's global assessment of disease severity at week 8. Secondary efficacy outcomes and adverse events were also evaluated. Relapse and rebound were assessed in an 8-week, post-treatment observation phase.\n In total, 207 patients received the two-compound scalp formulation and 105 patients received calcipotriol scalp solution. The proportion of patients with 'clear' or 'minimal' disease at week 8 was significantly greater in the two-compound scalp formulation group (68.6%) than in the calcipotriol scalp solution group (31.4%; P < 0.001). Improvement was more rapid with the two-compound scalp formulation than with calcipotriol scalp solution. Further evidence of the superiority of the two-compound scalp formulation over the scalp solution was demonstrated through greater improvements in clinical signs and fewer adverse events.\n A once-daily combination of calcipotriol plus betamethasone dipropionate was significantly more effective and better tolerated than twice-daily calcipotriol scalp solution in the treatment of scalp psoriasis.", "The calcipotriol/betamethasone dipropionate two-compound product is safe and effective in the short-term treatment of psoriasis.\n The primary objective was to investigate the safety of two treatment regimens involving use of the two-compound product over 52 weeks. The efficacy results are presented here.\n Six hundred and thirty-four patients were randomised double-blind to treatment (once daily, when required) with either: 52 weeks of two-compound product (two-compound group), 52 weeks of alternating 4-week periods of two-compound product and calcipotriol (alternating group), or 4 weeks of two-compound product followed by 48 weeks of calcipotriol (calcipotriol group).\n There was a trend towards a difference between treatments from the overall treatment effect for the percentage of satisfactory responses for each patient during the study (p = 0.071). This appeared to be due to the comparison of the two-compound and calcipotriol groups (p = 0.025).\n There was a trend towards the efficacy of the two-compound product used for up to 52 weeks being better than that of 4 weeks of the two-compound product followed by 48 weeks of calcipotriol.\n Copyright (c) 2006 S. Karger AG, Basel.", "A two-compound ointment containing calcipotriol 50 micro g g-1 and betamethasone dipropionate 0.5 mg g-1 has recently been shown to be an effective treatment for psoriasis.\n This study was designed to investigate efficacy and safety of different treatment regimens with the two-compound product (Daivobet/Dovobet; LEO Pharma, Ballerup, Denmark) and calcipotriol 50 micro g g-1 ointment (Daivonex/Dovonex; LEO Pharma).\n In total, 972 patients with psoriasis vulgaris were randomized to one of three treatment regimens: group 1, the two-compound product once daily for 8 weeks followed by calcipotriol ointment once daily for 4 weeks; group 2, the two-compound product once daily for 4 weeks followed by 8 weeks of treatment with calcipotriol ointment once daily on weekdays and the two-compound product once daily at weekends; and group 3, calcipotriol ointment twice daily for 12 weeks. The efficacy was evaluated by Psoriasis Area and Severity Index (PASI) and investigators' global assessments of disease severity. The primary response criteria were percentage reduction in PASI and proportion of patients with absent/very mild disease according to the investigators' global assessments after 8 weeks of treatment.\n The mean reduction in PASI from baseline to the end of 8 weeks of treatment was 73.3% for group 1, 68.2% for group 2 and 64.1% for group 3. The proportion of patients with absent/very mild disease at the end of 8 weeks of treatment was 55.3% for group 1, 47.7% for group 2 and 40.7% for group 3. For both primary response criteria, group 1 was statistically superior to group 3 (P < 0.001), whereas group 2 did not differ significantly from group 3. The difference between group 1 and group 2 was statistically significant with regard to PASI but not regarding the proportion of patients with absent/very mild disease. Patients receiving initial therapy with the two-compound product achieved the fastest treatment response, and the maximum treatment effect for these patients was seen after 5 weeks. This effect was maintained with continued treatment with the two-compound product for up to 8 weeks. After 12 weeks of treatment, no significant differences were seen between the three groups with regard to reduction in PASI, whereas the proportion of patients with absent/very mild disease in group 2 was superior to that in group 3. Patients receiving therapy with the two-compound product experienced fewer lesional/perilesional adverse drug reactions than the calcipotriol-treated patients (P < 0.001): 10.9% in group 1, 11.5% in group 2 and 22.3% in group 3.\n Two different short-term treatment regimens employing a recently developed two-compound product (calcipotriol/betamethasone dipropionate) provided rapid and marked clinical efficacy and were shown to be safe therapies for psoriasis vulgaris.", "Studies of antipsoriatic therapy often rely on subjective scoring. Objective measures have been developed but have not previously been compared with subjective scoring.\n Our purpose was to compare subjective and objective measures of reduction of psoriasis with topical therapy.\n A 2-week, double-blind, left-to-right comparative trial of betamethasone valerate against white soft paraffin was performed in 12 patients. The subjective scores were erythema, elevation, scale, and a composite total. Objective measures were nitric oxide production measured by chemiluminescence; erythema reflectance; ultrasound scan for thickness, scale, and echo-poor zone; and computerized image analysis of video images.\n Subjective and objective measures had similar power to detect therapeutic effect. The subjective measures showed greater variation and relatively overestimated improvement. There was correlation between measures and estimates for area, redness, and thickness. Nitric oxide production was the most powerful objective measure.\n Thickness determined by ultrasound scan and nitric oxide production are useful measures of reduction of psoriasis, which lend themselves to more powerful statistical tests than subjective interval data.", "A double-blind, randomized clinical study was conducted to compare the efficacy and tolerability of twice-daily topical calcipotriol treatment with a combination treatment of calcipotriol once a day in the morning and diflucortolone valerate in the evening. Sixty-three patients with a clinical diagnosis of chronic plaque psoriasis and comparable psoriatic lesions on both sides of the body were included. After a washout phase of 1 week, psoriatic lesions were treated for 4 weeks with calcipotriol ointment twice daily on one side of the body and a combination of calcipotriol and diflucortolone valerate ointment on the other side. The treatment period was followed by a period of 4 weeks without any treatment. The psoriasis area and severity index (PASI) was used to compare the 2 groups. Furthermore, the overall therapeutic results were assessed independently by the investigators and by the patients. Both treatment regimens showed a significant, nearly identical, reduction in PASI. The mean PASI for calcipotriol alone was 5.7 at baseline, 1.9 after 4 weeks of treatment and 3.8 at the end of the follow-up period. For combination therapy, these values were 5.7, 1.8 and 3.8, respectively. There was a statistically significant advantage in favor of combined calcipotriol and diflucortolone valerate treatment at weeks 1 and 2 (p < 0.05); however, at the end of the treatment phase the difference between the 2 therapies was not significant. Subjective evaluation of efficacy by both the investigators and the patients revealed no difference between the 2 treatments. The frequency of side effects (e.g. irritation) was low in both groups. In conclusion, both therapies were effective for the treatment of chronic plaque-type psoriatic lesions. The combination of calcipotriol and a topical steroid appeared to produce a more rapid clinical response and was shown to be as effective as calcipotriol therapy alone.", "1alpha, 25-Dihydroxy-22-oxacalcitriol (maxacalcitol) is a vitamin D3 analogue which displays approximately 10 times greater efficacy at suppressing keratinocyte proliferation in vitro than calcipotriol and tacalcitol. To determine clinical efficacy, a phase II double-blind, randomized, left vs. right, concentration-response study was performed with once-daily topical maxacalcitol in patients with mild to moderate chronic plaque psoriasis. Primary efficacy parameters were psoriasis severity index (PSI) based on sum of scores for erythema, scaling and induration and investigators' overall assessment of patients' response to therapy at 8 weeks of treatment. One hundred and forty-four patients participated. All concentrations of maxacalcitol ointment (6, 12.5, 25 and 50 microg/g) were significantly more effective at reducing PSI than placebo (P < 0.01), with greatest effect noted for maxacalcitol 25 microg/g. Calcipotriol ointment 50 microg/g once daily as active comparator had a similar effect. Marked improvement or clearance of psoriasis was greatest for maxacalcitol 25 microg/g (55% of subjects) which compared favourably with calcipotriol (46%). Improvement continued throughout the study period, with no plateau at week 8. Investigators' and patients' side preference (secondary efficacy parameters) rated maxacalcitol more effective than placebo and 25 microg/g maxacalcitol better than calcipotriol (P < 0.05 for investigators' assessment). Twelve patients withdrew from the study due to adverse events, of which four were judged to be due to study medication. This study indicates that once-daily maxacalcitol ointment is effective in the management of plaque psoriasis, with greatest effect noted at 25 microg/g. As no response plateau was noted at 8 weeks, these data suggest that further benefit might be obtained if maxacalcitol ointment were applied for longer. Finally, investigators' overall assessment and side preference suggest that maxacalcitol 25 microg/g may be more effective than once-daily calcipotriol.", "Both tazarotene (a retinoid prodrug) and calcipotriene (a synthetic analog of vitamin D3) are effective in the treatment of plaque psoriasis, but no reports in the literature directly compare the efficacy and tolerability of these 2 drugs. Tazarotene is commonly used in conjunction with a topical corticosteroid. In this study, tazarotene was used with mometasone furoate (a synthetic corticosteroid), and the 2-drug regimen was compared with calcipotriene monotherapy.\n This study was conducted to compare the efficacy and tolerability of tazarotene 0.1% gel once daily plus mometasone furoate 0.1% cream once daily with those of calcipotriene 0.005% ointment twice daily in the treatment of plaque psoriasis.\n In this multicenter, investigator-blinded, parallel-group study, adult patients with chronic, stable plaque psoriasis affecting 5% to 20% of their body surface area were randomly allocated to receive up to 8 weeks of treatment with either tazarotene 0.1% gel once daily (in the evening) plus mometasone furoate 0.1% cream once daily (in the morning) or calcipotriene 0.005% ointment twice daily. Patients were assessed at baseline and at weeks 2, 4, and 8 of treatment. Patients who demonstrated complete clearance of plaque psoriasis after 2 or 4 weeks of treatment and those whose psoriasis had improved > or = 50% after 8 weeks of treatment entered a 12-week posttreatment follow-up phase during which they applied only moisturizer. Patients were reassessed after 4, 8, and 12 weeks of posttreatment follow-up. Physician-rated measures of efficacy included global improvement, plaque elevation, scaling, erythema, and percentage of body surface area involvement. Patient-rated assessments included efficacy of study treatment compared with previous therapies, comfort of treated skin, outlook for long-term control of psoriasis, and overall impression of treatment.\n Of 120 patients with moderate to severe psoriasis enrolled from 3 centers, 106 (88%) completed the study. No significant differences in baseline clinical variables were observed between the 2 groups. Twenty-seven patients (45%) in the tazarotene plus cortico-steroid group achieved marked improvement (> or = 75% global improvement) after 2 weeks of treatment compared with 15 patients (26%) in the calcipotriene group (P < or = 0.05). Between-group comparisons of the percentage of patients achieving complete or almost complete clearance (> or = 90% global improvement) did not reach statistical significance at any time point. When compared with the calcipotriene regimen, the tazarotene plus corticosteroid regimen resulted in significantly greater efficacy on trunk lesions in reducing plaque elevation (at the end of treatment and at week 4 of the posttreatment phase, P < or = 0.05), scaling (week 4 of treatment and week 4 of the posttreatment phase, P < or = 0.05), erythema (week 4 of treatment and at the end of treatment, P < or = 0.05), and percentage of body surface area involvement (weeks 2 and 4 of treatment, P < or = 0.01). In addition, the tazarotene plus corticosteroid regimen was significantly more effective in reducing the percentage of body surface area involvement in upper limb lesions (weeks 2 [P < or = 0.05] and 4 [P < or = 0.01] of treatment). Forty-two of 55 patients (76%) in the tazarotene plus corticosteroid group rated their medication as more or much more effective than previous therapies compared with 30 of 52 patients (58%) in the calcipotriene group (P < or = 0.05). Although adverse events (burning, pruritus, irritation, and erythema) occurred in a significantly greater proportion of patients who received tazarotene plus corticosteroid than in those who received calcipotriene (P < or = 0.05), 47 of 55 patients (85%) in both groups rated the comfort of their treated skin as \"somewhat comfortable\" or better and both groups had similar discontinuation rates due to treatment-related adverse events (3% and 5%, respectively). CONCL", "Although betamethasone valerate (BMV) foam, 0.12% (Luxiq, Connectics Corporation, Palo Alto, CA) is approved by the Food and Drug Administration for the treatment of corticosteroid-responsive scalp dermatoses, no data are available for its use on nonscalp psoriasis.\n We evaluated the safety and efficacy of BMV foam in treating psoriatic lesions at nonscalp sites.\n We conducted a randomized, double-blind, placebo-controlled, paired-comparison, split-body study of 40 patients with mild to moderate plaque-type psoriasis. Patients applied BMV foam and placebo foam twice daily for 12 weeks.\n At the end of the treatment period, 70% of patients had greater than 50% improvement of lesions on their active foam-treated side compared with 24% of patients with similar improvement on their placebo foam-treated side. Adverse effects were limited to temporary stinging, burning, or itching in several patients. Three patients (7.5%) withdrew because of stinging or itching.\n The results indicate that BMV foam is effective against nonscalp psoriasis. Twice-daily applications are well tolerated, compliance exceeds 90%, cosmetic characteristics are acceptable, and the medication may reduce the need for multiple prescriptions.", "A calcipotriene/betamethasone dipropionate two-compound product (Taclonex ointment) has been shown to be safe and effective in the treatment of psoriasis over 4 weeks. Since treatment of psoriasis is generally long-term, the objective of this study was to investigate the efficacy and safety of transferring patients to maintenance treatment with calcipotriene cream (Dovonex cream) following a 4-week treatment period with the two-compound product.\n Patients with psoriasis were randomized to one of the following three treatment groups: 4 weeks of the two-compound product followed by 8 weeks of calcipotriene cream (calcipotriene cream group); 4 weeks of the two-compound product followed by 8 weeks of calcipotriene cream on weekdays and the two-compound product on weekends (alternating group); 4 weeks of the two-compound product followed by 8 weeks of vehicle of calcipotriene cream (vehicle group). All medications were applied once daily.\n A total of 1136 patients were randomized: 383 to the calcipotriene cream group, 377 to the alternating group, and 376 to the vehicle group. The mean percentage change in the Psoriasis Area and Severity Index from baseline to the end of the trial was -44.5% in the calcipotriene cream group, -58.4% in the alternating group, and -33.1% in the vehicle group. The mean difference between the calcipotriene cream and vehicle groups (primary treatment comparison) was -11.7% (95% CI -17.9, -5.5), which was statistically significant (p<0.001), and the mean difference between the alternating and vehicle groups was -24.7% (95% CI -30.9, -18.5), which was also statistically significant (p<0.001). For the investigators' global assessment of disease severity at the end of the trial, the differences between the calcipotriene cream and vehicle groups, and between the alternating and vehicle groups, were statistically significant (p<0.001), showing superior efficacy in the nonvehicle groups. The results were similar for the patients' global assessment of response to treatment. There were 43 patients (11.3%) with adverse drug reactions in the calcipotriene cream group, 28 (7.6%) in the alternating group, and 32 (8.6%) in the vehicle group. There were no statistically significant differences in the incidence of adverse drug reactions in the calcipotriene cream group relative to the vehicle group (odds ratio 1.36; 95% CI 0.84, 2.21; p=0.21), or in the alternating group relative to the vehicle group (odds ratio 0.87; 95% CI 0.51, 1.48; p=0.61).\n Four weeks of treatment with the calcipotriene/betamethasone dipropionate two-compound product followed by 8 weeks of maintenance treatment with calcipotriene cream is effective and safe. As an alternative maintenance regimen, treatment with calcipotriene cream on weekdays and the two-compound product on weekends is also effective and safe.", "In a double-blind, randomized multi-centre study, 116 patients with psoriasis have been treated for 1-3 weeks with budesonide ointment (Preferid, Draco/Tika; a subsidiary of AB ASTRA), a new non-halogenated topical steroid. In a series of 11 patients a 0.025% budesonide ointment was significantly superior to placebo. In a second series, of 54 patients, a 0.025% fluocinolone acetonide ointment (Synalar, ICI). In a third series, of 51 patients, a 0.010% budesonide ointment was compared with 0.025% fluocinolone acetonide ointment. No statistically significant difference between these two preparations was found to exist. No adverse reactions were observed.", "Calcitriol and calcipotriol are effective treatments for psoriasis, although the two have never been directly compared. We compared the efficacy and toxicity of each agent in 24 patients with moderately extensive chronic plaque psoriasis, who were randomized in double-blind fashion to apply 90 g per week of either calcitriol (3 micrograms/g) ointment or calcipotriol (50 micrograms/g) ointment over an 8-week period. Mean PASI in patients applying calcitriol fell from 13 to 8.8 (p < 0.05) and in patients applying calcipotriol from 14.9 to 4.7 (p < 0.005). The reduction was significantly greater in the calcipotriol-treated group (p < 0.05). There was a small increase in serum ionized calcium in the calcipotriol-treated group (from 1.21 mmol/L to 1.25 mmol/L, p < 0.05) but no effect on calcium homeostasis in the calcitriol group.", "A study was done of extended maintenance therapy using either betamethasone dipropionate (Diprolene) in optimized vehicle (OV) (ointment) or placebo in patients with psoriasis vulgaris. Of 59 patients originally enrolled in the study, 38 assessable patients achieved clearing of at least 85% improvement from baseline with traditional betamethasone in OV twice a day for two to three weeks before intermittent pulse dosing was attempted. Thereafter, the test medication was used on weekends (three consecutive doses at 12-hour intervals) once a week. Fourteen patients (74%) of the betamethasone in OV group and four patients (21%) of the placebo group maintained a remission status for 12 weeks. Intermittent pulse dosing with betamethasone in OV seems safe and efficacious maintenance therapy in selected psoriatic patients.", "The antipsoriatic efficacy, tolerability and safety of calcipotriol ointment was compared with tar in a prospective, right/left randomized, investigator-blinded controlled study. Calcipotriol ointment 50 micrograms/g twice daily was applied to one-half of the body. On the opposite side, white soft paraffin was applied in the morning, and coal tar solution BP 15% v/w in aqueous cream in the evening. Thirty patients with stable chronic plaque-type psoriasis were recruited. Assessments were made at 2, 4 and 6 weeks. Three patients were withdrawn from the study. A decrease in PASI score was seen on both sides at 2, 4 and 6 weeks. The differences from baseline between the two treatments were statistically significant in favour of calcipotriol. Improvement with calcipotriol was rapid in the first 2 weeks of treatment. With tar, significant improvement occurred only after 4 weeks of treatment. The differences in the scores for erythema, induration and desquamation from baseline between the two treatments were also statistically significantly in favour of calcipotriol at all evaluation points. Seven patients developed irritation on the calcipotriol-treated side, but there were no adverse effects on the tar-treated side. In two patients, itching associated with psoriasis was reduced by the calcipotriol. Although the mean serum calcium and phosphate levels remained within the normal ranges after 6 weeks' treatment, there were significant changes in their values compared with baseline.", "The merit of topical sequential therapy involving clobetasol foam and calcipotriene ointment has not been experimentally demonstrated.\n We sought to assess the short-term efficacy of twice-daily clobetasol foam plus calcipotriene ointment compared with either agent alone as monotherapy and to compare long-term use of weekday calcipotriene ointment with or without clobetasol foam weekend pulse therapy.\n Eighty-six subjects with plaque-type psoriasis received twice-daily treatment with clobetasol foam plus calcipotriene ointment or either agent as monotherapy for 2 weeks. Subjects in the combination group who achieved remission received weekday calcipotriene plus weekend pulse therapy with either clobetasol foam or vehicle for 6 months.\n After 2 weeks, psoriasis scores were significantly lower (P < .001) in the combination therapy group (adjusted trunk lesion score = 0.67) compared with monotherapy with either agent (lesion scores = 1.40 calcipotriene, 1.13 clobetasol foam). During the follow-up \"weekday-weekend\" phase, after 6 months, weekend pulse clobetasol foam was associated with a trend toward greater maintenance of remission compared with vehicle (92% improvement of trunk lesion vs 62%).\n Small sample size may have hampered the detection of statistical significance during long-term therapy.\n The combination of clobetasol foam and calcipotriene ointment is significantly more effective than monotherapy for short-term treatment. Weekday calcipotriene plus weekend pulse clobetasol foam shows a consistent trend toward greater maintenance of remission.", "Clobetasol propionate (CP) shampoo 0.05% is an efficacious and safe treatment for scalp psoriasis. The aim of this double-blind, randomized, placebo-controlled study was to determine if CP shampoo is suitable for long-term disease control. Participants with moderate to severe scalp psoriasis (global severity score [GSS] of 3 or 4 on a scale of 0 [clear] to 5 [very severe]) first received once daily CP shampoo treatment for up to 4 weeks. Responders were subsequently randomized to receive the CP shampoo or vehicle twice weekly maintenance regimen for up to 6 months. When relapse occurred (defined as GSS > 2), participants resumed once daily CP shampoo treatment; when symptoms diminished (GSS < or = 2), they readopted the twice weekly maintenance regimen. At all visits significantly more participants treated with CP shampoo did not relapse compared with participants treated with vehicle (P < .001). Only approximately one-third of participants treated with vehicle remained relapse free at 1 month, while this rate was observed approximately 3.5 months later (4.5 months after baseline of maintenance phase) in the CP shampoo group. After 6 months 31.1% (33/106) of participants in the CP shampoo group were still relapse free versus 8.1% (9/111) of participants in the vehicle group. There was no greater incidence of skin atrophy, telangiectasia, or hypothalamic-pituitary-adrenal (HPA) axis suppression in the CP shampoo group compared with the vehicle group. Clobetasol propionate shampoo is efficacious and safe for acute management and long-term maintenance of moderate to severe scalp psoriasis.", "In this study, we compared a new combination ointment containing both calcipotriol and betamethasone dipropionate with betamethasone dipropionate ointment (Diprosone) and calcipotriol ointment (Daivonex) in patients with psoriasis vulgaris; 1106 patients were randomized to twice daily double-blind treatment with combination, betamethasone dipropionate or calcipotriol for 4 weeks. Patients then received twice daily calcipotriol, unblinded, for a further 4 weeks. Mean percentage change in PASI at end of the double-blind phase was -74.4 (combination group), -61.3 (betamethasone group) and -55.3 (calcipotriol group). Mean difference (95% Cl) combination-betamethasone was -13.1 (-16.9 to -9.3, p < 0.001) and for combination-calcipotriol -19.0 (-22.8 to -15.2, p <0.001). The differences in PASI were also statistically significant after 1 week. In the double-blind phase, 8.1% of patients (combination) reported lesional/ perilesional adverse reactions compared to 4.7% (betamethasone) and 12.0% (calcipotriol). In the combination group, mean PASI at the end of the double-blind phase was 2.5, and at end of the unblinded phase 3.6, compared with 3.9 and 4.1 (betamethasone) and 4.4 and 3.7 (calcipotriol). Calcipotriol/betamethasone combination is more effective and has a more rapid onset of action than either active constituent used alone, and is well tolerated. It is safe to transfer patients from combination to calcipotriol, with maintenance of clinical effect.", "Tazarotene in a gel formulation is widely used in the treatment of psoriasis.\n To determine the efficacy and safety of tazarotene 0.1% and 0.05% creams in the treatment of psoriasis.\n A total of 1303 patients participated in 2 clinical trials. Patients applied tazarotene creams 0.1% and 0.05% or vehicle once daily to all psoriatic lesions for 12 weeks followed by a 12-week posttreatment period.\n Both creams were significantly more effective than vehicle on the basis of an overall assessment of psoriasis, a global response to treatment, and reduction in plaque elevation and scaling. Therapeutic effect was maintained during the posttreatment period. Common adverse events included signs and symptoms of skin irritation.\n Tazarotene creams were associated with significant reductions in the severity of the clinical signs of psoriasis and were found to be safe with acceptable tolerability. Tazarotene cream 0.1% was generally more effective, although slightly less well tolerated, than the 0.05% cream.", "nan", "A randomized, double-blind, left-right, vehicle-controlled study to assess the therapeutic efficacy and safety of twice daily application of 15 micrograms/g calcitriol ointment for a period of 6 weeks was performed in 32 patients suffering from bilateral, symmetrical, severe chronic plaque psoriasis. Twice daily 15 micrograms/g calcitriol ointment significantly improved erythema, induration, scaling and global severity of psoriatic plaques, and was much more effective than vehicle ointment. The difference in overall clinical efficacy between calcitriol and vehicle was statistically significant from week 1 onwards, and was maintained over the entire study. On completion of the study, clearance of psoriatic lesions was found in 47% of calcitriol-treated sides and in 13% of vehicle-treated sides. Skin histopathology of calcitriol-treated sides revealed a return to normal keratinization, with decreased inflammatory cell infiltration in the dermis and disappearance of the inflammatory infiltrate from the epidermis. Three patients had asymptomatic hypercalcaemia during the study. Mean serum levels of total calcium, albumin-adjusted total calcium, phosphorus, 25-hydroxyvitamin D and calcitriol did not show statistically significant changes in the baseline/end-point comparisons.", "nan", "Topical calcipotriene is frequently prescribed for the treatment of plaque-type psoriasis. Calcipotriene is currently available in the US as an ointment, a solution, a cream, and in a fixed-dose combination ointment with betamethasone dipropionate. Calcipotriene 0.005% has recently been formulated as a foam using a novel aqueous-based formulation to provide a new topical treatment option for patients with psoriasis.\n The objective of this study was to evaluate the efficacy and safety of topical calcipotriene 0.005% foam for the treatment of mild to moderate plaque-type psoriasis.\n Two identical, randomized, double-blind, vehicle-controlled, 8-week phase III clinical trials.\n Subjects with plaque-type psoriasis affecting 2-20% of the body surface area, with an identifiable target lesion affecting the trunk or extremities, were randomized in a 2:1 ratio to calcipotriene foam (n = 437) or vehicle foam (n = 222). Study medication was applied twice daily for 8 weeks.\n Treatment success was defined as a score of 0 or 1 (clear or almost clear) on the Investigator's Static Global Assessment (ISGA) psoriasis rating scale and a minimum improvement of ISGA score of at least 2 grades from baseline. Predefined target lesions were assessed for erythema, scaling, and plaque thickness. Primary endpoint was the proportion of subjects in each treatment group who achieved treatment success after 8 weeks, analyzed on an intent-to-treat (ITT) basis. In the primary endpoint analysis, subjects missing 8-week outcomes data were classified as treatment failures regardless of their outcomes at earlier evaluations. As part of the sensitivity analysis, a last-observation-carried-forward (LOCF) approach to impute missing 8-week efficacy outcomes also examined treatment. Secondary endpoints included treatment success as a function of baseline ISGA score (mild or moderate), ISGA score of 0 or 1 (clear or almost clear), and effects of treatment on target lesion. Adverse events (AEs) were recorded throughout the study.\n In the ITT population of Study 1, treatment success after 8 weeks was achieved by 14% of subjects in the calcipotriene foam group versus 7% of subjects in the vehicle foam group (p = 0.058). In the LOCF analysis, treatment success was achieved by more subjects with calcipotriene foam than with vehicle foam (15% vs 7%; p = 0.034). In Study 2, treatment success was achieved by more subjects in the calcipotriene foam group for the primary endpoint (27% vs 16%; p = 0.016) and the LOCF analysis (28% vs 16%; p = 0.010). Subjects in the calcipotriene foam group exhibited better response rates than did the vehicle foam group for most of the secondary outcomes. Calcipotriene foam was safe with an overall incidence of AEs similar to those experienced in the vehicle foam group. Application-site reactions were noted in approximately 1-2% of subjects in each group. No AE was reported in more than 2% of subjects in the calcipotriene foam group. Treatment was discontinued because of AEs in approximately 2% of subjects in both groups.\n In two identically designed, phase III clinical trials, calcipotriene 0.005% foam was safe and effective for the treatment of mild to moderate plaque-type psoriasis for up to 8 weeks. Clinical Trial Registration: Registered at clinicaltrials.gov: NCT00688519 and NCT00689481.", "Two nonsteroidal topical agents, calcitriol and tacrolimus, have been reported to be effective and safe for psoriatic lesions on sensitive areas. However, no comparative studies between calcitriol and tacrolimus have been reported.\n To compare the tolerability and efficacy of calcitriol 3 microg g(-1) and tacrolimus 0.3 mg g(-1) ointment in chronic plaque psoriasis affecting facial and genitofemoral regions.\n This is a double-blind, parallel, 6-week study of 50 patients who were randomized in a 1 : 1 ratio to apply calcitriol or tacrolimus twice daily. The primary efficacy variable was the mean reduction of the target area score (TAS), and the secondary efficacy variable was the percentage of patients with the Physician's Global Assessment (PGA) score of 5 (clear) and 4 (almost clear) at the end of the study.\n Both calcitriol and tacrolimus were well tolerated. Although calcitriol induced perilesional erythema in a statistically significant higher proportion of patients than tacrolimus (55% vs. 16% at week 6; P < 0.05), it did not necessitate treatment discontinuation. At the end of the study, tacrolimus was significantly more effective than calcitriol based on a significant reduction of mean TAS (67% vs. 51%; P < 0.05) as well as more patients achieving complete or almost complete clearance by PGA (60% vs. 33%; P < 0.05).\n Both calcitriol 3 microg g(-1) and tacrolimus 0.3 mg g(-1) are safe and well-tolerated therapeutic agents in the treatment of psoriasis in sensitive areas. Tacrolimus demonstrated a more effective clinical outcome compared with calcitriol.", "Psoriasis is a chronic, papulosquamous condition that affects up to 2% of the U.S. population. Approximately 50% of patients with psoriasis have involvement of the scalp. This was a multicentre, randomized, vehicle-controlled, double-masked and parallel-group study. The aim was to evaluate the efficacy and safety of clobetasol propionate shampoo, 0.05% versus its corresponding vehicle in subjects aged 12 years and older with moderate to severe scalp psoriasis over a treatment period of 4 weeks. Recurrence of scalp psoriasis was assessed during a two week follow-up period. A total of 142 subjects were treated. Results after 4 weeks demonstrated that clobetasol propionate shampoo, 0.05% was with a similar safety profile significantly more effective than its vehicle. The novel short contact shampoo formulation of clobetasol propionate is convenient and efficacious and minimizes systemic exposure while being efficient, safe and well-tolerated in the treatment of moderate to severe scalp psoriasis.", "Plaque-type psoriasis has been successfully treated with topical calcitriol, but there has been no long-term follow-up study of the safety and efficacy of this calciotropic hormone. In a single-centre study, patients with plaque or erythrodermic psoriasis were enrolled in a double-blind, right/left comparison, placebo-controlled study, and received 1.5 micrograms of calcitriol (15 micrograms/g of Vaseline) per day, or a placebo consisting of Vaseline alone. A subset of these patients (n = 22), with at least 25% involvement, applied 0.1 g of calcitriol ointment/50 cm2 on an area of from 2,500 to 5,000 cm2. Of the 84 patients enrolled in the double-blind control study, 96.5% responded to topical calcitriol therapy, compared with 15.5% whose lesions improved with Vaseline alone, after 2.4 months. After completion of the double-blind study, 22 patients applied calcitriol ointment (15 micrograms/g Vaseline) to all of their lesions (up to 10 g of calcitriol ointment; 150 micrograms calcitriol lesions showed either excellent or moderate clearing in 90.9% of all cases. The remaining 9.1% of cases showed slight improvement of their lesions. No abnormalities in calcium metabolism were noted in any of the patients using topical calcitriol. None of the patients experienced any local cutaneous side-effects, including six patients who applied calcitriol ointment to the face. Topical calcitriol is safe and effective for the treatment of psoriasis.", "Forty-eight patients with symmetrical chronic plaque psoriasis affecting the limbs were recruited for a single-blind right/left within patient study to assess the effect of combining occlusion with topical calcipotriol. Subjects were randomized into two groups. Sites of similar severity on opposing limbs were selected as target areas. The first (group A) treated one side with calcipotriol alone and the opposite side with calcipotriol plus occlusion. The second (group B) treated one side with placebo plus occlusion and the opposite side with calcipotriol plus occlusion. In group A the mean improvements were 40% (P < 0.001) for calcipotriol alone and 61% (P < 0.001) for calcipotriol plus occlusion. In group B, occlusion plus calcipotriol resulted in a mean 62% improvement (P < 0.001) while occlusion plus placebo produced no significant change. The combination of calcipotriol plus occlusion was significantly better than calcipotriol alone (P < 0.005). The results indicate that occlusion improves the response to calcipotriol by enhancing its penetration. Indices of calcium metabolism remained unchanged throughout the study.", "Twenty-seven patients with psoriasis of the scalp participated in a double-blind, paired comparison study between halcinonide solution (0.1%) and placebo. The therapeutic response was excellent in sixteen patients treated with halcinonide and in one patient treated with placebo. In the comparative evaluation halcinonide was superior in twenty-two patients, the placebo was superior in four patients, and both drugs were equally effective in one patient. There were no adverse reactions due to halcinonide, but one patient experienced pruritus with the placebo solution.", "Several open studies with active forms of vitamin D3 have been reported to be effective in the treatment of psoriasis. We report a double-blind study of 1 alpha,25-dihydroxycholecalciferol in psoriasis using 0.5 microgram of active substance applied topically twice daily. In contrast to previous studies, the present investigation does not provide evidence of clinical efficacy for the drug at that dosage and with the vehicle that was used.", "Various formulations of clobetasol propionate are currently used to treat psoriasis due to its anti-inflammatory, anti-pruritic, vasoconstrictive and immunomodulating properties.\n To assess the efficacy, safety and remission profile of clobetasol propionate lotion compared to that of clobetasol propionate emollient cream and lotion vehicle in subjects with moderate to severe plaque-type psoriasis.\n Multicentre, investigator-blind, randomized, active- and vehicle-controlled, parallel-group study.\n A total of 192 subjects were treated: 82 with clobetasol propionate lotion, 81 with clobetasol propionate cream and 29 with the vehicle. Clobetasol propionate lotion was significantly more effective than vehicle lotion and was comparable in efficacy to the emollient cream after 4 weeks of treatment. Treatment success was higher for subjects in the clobetasol propionate lotion group than in the emollient cream group after 4 weeks of a treatment-free follow-up period. Clobetasol propionate lotion was safe and well tolerated.\n The present study demonstrates that clobetasol propionate lotion is an efficacious, safe and well-tolerated alternative to the currently available emollient cream formulation, while showing a better remission profile after 4 weeks of treatment-free follow-up period.", "To establish the efficacy and safety of once daily treatment of Daivobet®/Dovobet® gel in patients with psoriasis vulgaris, relative to tacalcitol ointment and the gel vehicle alone.\n 458 patients with at least moderately severe disease were randomized in 3 treatment arms for an 8-week period. Treatment was investigator blinded, and treatment success was defined as patients with an Investigator's Global Assessment of 'clear' or 'almost clear' at week 8.\n The proportion of patients who were 'clear or almost clear' was significantly higher in the 2-compound gel group (39.9%) compared with 17.9% in the tacalcitol group and 5.5% in the gel vehicle group: p < 0.001 in both comparisons. The proportion of patients with at least 1 adverse drug reaction was significantly lower in the 2-compound gel group compared to the other 2 treatment groups.\n Once-a-day treatment with the 2-compound Daivobet/Dovobet gel is a safe and efficacious therapeutic regimen for individuals with psoriasis on the body.\n Copyright © 2011 S. Karger AG, Basel.", "The efficacy and safety of halobetasol propionate 0.05% cream, an ultra high-potency corticosteroid preparation, was evaluated in a double-blind, vehicle-controlled, paired comparison study. Patients' psoriatic lesions were evaluated before treatment and after 1 and 2 weeks of twice-daily treatment with halobetasol propionate and vehicle. Response measures (plaque elevation, erythema, scaling, and pruritus) were evaluated with a 4-point severity scale whereby the sum provided a total score. Patient self-assessment measures were obtained at the 2-week visit by categorizing his or her global responses to queries about each treatment's \"effectiveness\" and \"overall rating.\" All efficacy parameters, as judged by the physician, showed statistically significant (p = 0.0001) treatment differences favoring halobetasol propionate at both week 1 and week 2 evaluations. Patient global responses for \"effectiveness\" and \"overall rating\" favored halobetasol propionate 0.05% cream over vehicle after 2 weeks of use. No systemic adverse drug effects were reported during the study. No patient was discontinued from the study because of an adverse event, and there was no evidence of skin atrophy after 2 weeks of treatment with either agent. Patient reports of \"stings\" or \"burns\" were equally distributed between the active and vehicle treatment groups. This trial demonstrates that halobetasol propionate 0.05% cream is clinically beneficial and without evidence of significant risk in the treatment of plaque psoriasis.", "nan", "A two-compound ointment containing calcipotriol plus betamethasone dipropionate is an effective treatment for psoriasis vulgaris. The same active ingredients have now been combined in a gel formulation. Our objective was to compare the efficacy and safety of once daily treatment of the two-compound gel with the single components in the same gel vehicle and the gel vehicle alone, in patients with psoriasis vulgaris on the trunk and/or limbs. 364 patients received once daily treatment for up to 8 weeks with either the two-compound gel, the single components in the gel vehicle or the gel vehicle alone. The percentage of patients whose disease was clear or very mild and who had at least a two-step improvement in the Investigator's Global Assessment of disease severity at week 8, was significantly higher with calcipotriol plus betamethasone dipropionate (27.2%) than with betamethasone dipropionate (16.9%, p = 0.027), calcipotriol (11.4%, p = 0.006) or gel vehicle (0.0%, p < 0.001). This exploratory study showed that the two-compound gel was safe and more efficacious than its individual ingredients in the treatment of psoriasis vulgaris.", "Calcipotriene and betamethasone dipropionate are topical treatments for psoriasis vulgaris. Their mode of action is different. Improved risk/benefit may result with concomitant use of the two compounds together. A new vehicle has been created with the objective of obtaining optimal stability of both calcipotriene and betamethasone dipropionate in the combination product.\n We compared the clinical efficacy of a fixed combination of calcipotriene and betamethasone dipropionate in a new vehicle to calcipotriene in the new vehicle, betamethasone in the new vehicle, and the new vehicle alone.\n This was an international, multicenter, prospective, randomized, double-blind, parallel-group, 4-week study in patients with psoriasis vulgaris amenable to topical treatment.\n The mean percentage reduction in PASI from baseline to end of treatment was 73.2% in the combination group (n = 301), 48.8% in the calcipotriene group (n = 308), 63.1% in the betamethasone dipropionate group (n = 312) and 28.8% in the new vehicle group (n = 107), (P < .001). The mean percentage reduction in PASI during the first week was 48.1%, 28.4%, 41.4%, and 21.5%, respectively (P < .001).\n A combination product of calcipotriene 50 microg/g and betamethasone dipropionate 0.5 mg/g in the new vehicle shows superior efficacy with a more rapid onset of action than the new vehicle containing either constituent alone in the treatment of psoriasis vulgaris.", "For psoriasis therapy, topical derivatives of vitamin D3 represent a versatile option: they can be used either alone or in combination with other agents such as topical corticosteroids. In this two-phase parallel-group study, the naturally occurring vitamin D3 analogue, calcitriol, was compared with the vitamin D analogue calcipotriol in 125 patients with chronic plaque-type psoriasis. The proposed treatment regimen was an initial bitherapy for 2 or 4 weeks, with clobetasol propionate 0.05% cream, a super potent topical corticosteroid applied in the morning and either calcitriol 3 mug/g ointment or calcipotriol 50 mug/g ointment applied in the evening, followed by monotherapy with either calcitriol or calcipotriol applied twice daily until endpoint week 12. Efficacy evaluations (global assessment of improvement, PASI and body surface area (BSA) affected) showed no significant differences between the two regimen groups at the primary endpoints (week 2 and week 12) or at any interim points. At week 2 the investigator's global assessment showed clinical success (psoriasis markedly improved, almost clear or clear) for more than 50% of the patients in both groups and for 48 (79%) and 56 (88%) patients, respectively in the calcitriol and calcipotriol regimen group at week 12. Least-square means analysis of PASI indicated the calcitriol regimen to be equivalent to the calcipotriol regimen. There were no significant differences between the two groups with regards to cutaneous safety or to incidence of adverse events. The present study shows that for the treatment of mild to moderate plaque psoriasis calcitriol 3 mug/g ointment can provide a safe and effective alternative to calcipotriol 50 mug/g ointment while being administered within a regimen based on a bitherapy with corticosteroids followed by a vitamin D3 maintenance monotherapy.", "Tazarotene and calcipotriol are both effective in the treatment of psoriasis. An investigator-blind, bilateral comparison of 44 lesion pairs in 19 patients was conducted to evaluate the efficacy, side effects and duration of therapeutic effects of once-daily tazarotene 0.1% gel plus petrolatum with twice-daily calcipotriol 0.005% ointment in plaque psoriasis. It consisted of a 12-week treatment phase, followed by a 4-week post-treatment observation phase. At the end of the treatment phase, tazarotene-petrolatum was as effective as calcipotriol in both objective and subjective overall efficacy assessment. Calcipotriol had a significantly greater effect in reducing erythema than tazarotene-petrolatum at weeks 2-8. At week 16, tazarotene-petrolatum demonstrated a significantly better maintenance effect in all parameters. Local irritation was noted only in tazarotene-petrolatum-treated lesions. Once-daily tazarotene 0.1% gel plus petrolatum was as effective as twice-daily calcipotriol 0.005% ointment in the treatment of plaque psoriasis, but had a better maintenance effect after the cessation of therapy.", "The purpose of this double-blind, placebo-controlled study was to examine whether the vitamin D analogue calcipotriol, topically applied to psoriatic skin lesions, had any effect on calcium or bone metabolism. Thirty-four outpatients with psoriasis vulgaris were randomized to treatment with either calcipotriol ointment (50 micrograms/g) or vehicle ointment twice daily for 3 weeks. The patients were put on a calcium energy fixed diet and examined once weekly. The mean amount of calcipotriol ointment used was 40.3 g/week (range 8.2-95.4 g/week). The results of biochemical markers on calcium and bone metabolism showed no significant differences between the two groups. No correlation was found between the amount of ointment used and changes in parameters on calcium and bone metabolism during the 3-week treatment. It is concluded that calcipotriol ointment (50 micrograms/g), applied in doses of 8.2-95.4 g/week for 3 weeks to psoriatic skin lesions, has no effect on calcium or bone metabolism.", "The use of topical calcipotriol in adults with psoriasis is safe and effective.\n Our purpose was to study the efficacy and safety of calcipotriol in children.\n A multicenter, prospective, 8-week, double-blind, parallel group study was conducted in 77 children. Response to treatment was assessed by means of the Psoriasis Area and Severity Index (PASI) in that the intensity of redness, thickness, and scaliness as well as the area involved are scored. The children were 2 to 14 years of age and had stable psoriasis, involving less than 30% of the body surface. Forty-three children were assigned to receive calcipotriol ointment and 34 to receive placebo. Nine children dropped out of the study, six in the calcipotriol-treated group and three in the placebo-treated group.\n Both treatment groups (calcipotriol and placebo) showed significant improvement in PASI from baseline to the end of treatment, and the difference was not statistically significant. No serious side effects, in particular including those relating to calcium and bone metabolism, were recorded.\n Calcipotriol ointment was statistically significantly more effective than its vehicle in terms of the investigator's overall assessment and reduction in redness and scaliness but not in terms of PASI score.", "Methotrexate has been used as one of the first and systemic therapies for psoriasis. In general, 70% of patients with psoriasis prefer topical therapy as the treatment of choice.\n The purpose of this placebo-controlled double-blind study was to evaluate the clinical efficacy and tolerability of methotrexate 0.25% incorporated in a hydrophilic gel (hydroxyethylcellulose 1%) to treat patients afflicted with psoriasis vulgaris.\n Sixty patients (37M/23F) ranging between 18 and 70 years of age, with slight to moderate chronic plaque-type psoriasis and PASI (Psoriasis Area and Severity Index) scores between 5.3 and 17.5 joined the study. The mean duration of the disease at entry was 9.6 years (range 1-24 years). The diagnosis of psoriasis was established by clinical and histopathologic methods. Patients were sequentially randomized into two parallel groups. Each patient was allocated a precoded 100-g tube (active or placebo) with instructions on how to self-administer the trial medication topically (without occlusion) to their lesions two times daily for 5 consecutive days per week. The study lasted for 12 weeks with 4 weeks of active treatment. Patients were examined on a weekly basis and those showing total clearing or remission of lesions were considered effectively treated.\n By the end of the treatment, breaking the code disclosed that methotrexate 0.25% gel had significantly treated more patients than placebo (83.3% vs. 6.7%; p < 0.0001), reduced the PASI score to a mean of 2.2, and cleared more plaques (82.2% vs. 4.3%; p < 0.0001). Laboratory evaluations, including CBC with differential and platelet count, renal function, liver chemistry [SGOT (aspartate transaminase) and SGPT (alanine transaminase)], and serum creatinine, were within the normal limits. The treatment was well-tolerated by all the patients, with no adverse drug-related symptoms and no dropouts. The study was followed up for 12 months from the first day of the treatment; two cured patients had relapsed after 8 months.\n The findings of this study demonstrate that methotrexate 0.25% in a hydrophilic gel is well tolerated and significantly more effective than placebo as a patient-applied topical medication to treat psoriasis vulgaris.", "nan", "This report describes the use of a new corticosteroid ointment in the treatment of psoriasis and atopic dermatitis. It further summarizes the results of treatment with the active medication versus the vehicle alone in these two disease categories. In the group with psoriasis 13 of 17 patients (76.4%) treated with the active drug showed either excellent or good clinical response (50% to 100% improvement) in three weeks. Five of 16 patients (31.2%) treated with the placebo showed excellent or good response. In the group with atopic dermatitis 16 of 17 patients (94.1%) treated with the active drug showed either excellent or good clinical response (50% to 100% improvement) in three weeks. Two of 16 (12.5%) treated with the placebo showed excellent or good response.", "Omega-3 polyunsaturated fatty acids compete with arachidonic acid as substrates for lipoperoxidases, which transform them into leukotrienes with low biological activity. As this process, in skin, may benefit psoriatic patients, a randomized controlled single blind-study was carried out on a sample of 25 patients. In the study fish oil (FO) was compared with liquid paraffin (LP); both were topically applied and administered daily for 6 h under an occlusive dressing over a 4-week period. Evaluations were performed weekly assessing erythema, scaling, plaque thickness (induration) and itching. The results showed statistically significant improvement in erythema and scaling for both treatments compared to basal values; significant differences between treatments were achieved in scaling but not in erythema. Compared to baseline, FO significantly improved plaque thickness while LP did not. After 4 weeks, FO proved to be significantly better than LP. All patients accepted the treatment despite its unpleasant smell. Irritation and a burning sensation were reported in the FO treated plaque of one patient. This adverse effect reverted after completing the treatment. These findings demonstrate that topical FO shows a better performance than LP under an occlusive dressing.", "Ninety psoriasis patients, who were either completely cleared of or manifested only a minimal presence of disease signs following 3-4 weeks of twice daily treatment with augmented betamethasone dipropionate (ABD) ointment 0.05%, were enrolled in this multicenter, double-blind, placebo-controlled study. The study was designed to determine if an intermittent pulse dose regimen of ABD ointment could safely and effectively maintain a remission disease status when treatment was applied in three consecutive applications 12 h apart, once a week for a maximum treatment period of 6 months. The disease of 60% of the patients in the active treatment group was successfully controlled for 6 months, while 80% of the placebo-treated patients experienced exacerbation of disease signs. No serious local or systemic treatment-related adverse experiences were reported. ABD ointment 0.05%, when applied using the intermittent treatment regimen described here, was shown to be a clinically beneficial and well-tolerated method of long-term (up to 6 months) maintenance therapy for psoriasis patients.", "Psoriasis involving sensitive skin areas remains difficult to treat because of the side-effects of topical corticosteroids and the irritancy potential of vitamin D3 derivatives. Several clinical trials have demonstrated that calcitriol, the naturally occurring and hormonally active form of vitamin D3, is effective and safe at the dose of 3 microg g(-1) for the treatment of psoriasis affecting the trunk and limbs.\n We compared the safety and efficacy of calcitriol 3 microg g(-1) ointment and calcipotriol 50 microg g(-1) ointment in a multicentre, randomized, investigator-blinded, left-right comparison in mild to moderate chronic plaque psoriasis affecting sensitive areas, defined as being the face, hairline, retroauricular and flexural areas. One pair of symmetrical and bilateral target lesions was selected from each area and assessed for perilesional erythema, oedema, and stinging/burning. Global assessment of local tolerability and global improvement were rated by the investigator, and the subjects were asked to evaluate the tolerability and efficacy of each product and to express their global preference.\n In the 75 subjects, calcitriol and calcipotriol both led to clearing of at least one target lesion in 21 (28%) of the subjects each. Perilesional erythema (P < 0.001), perilesional oedema (P < 0.02) and stinging/burning (P < 0.001) were all significantly less severe with calcitriol than with calcipotriol. The subjects' evaluation of local tolerability was significantly (P < 0.0001) in favour of calcitriol. Ten treatment-related dermatological events occurred in eight subjects, including one subject who experienced skin discomfort on both sides. All other events occurred only on the calcipotriol-treated side (irritant dermatitis, six subjects; contact dermatitis, one subject). Global assessment of improvement from baseline by the investigators was significantly greater for the calcitriol-treated lesions (P < 0.02). The subjects' global preference was significantly in favour of calcitriol (P < 0.02).\n In the present study, calcitriol ointment was found to be better tolerated and would appear to be more effective than calcipotriol ointment in the treatment of psoriasis in sensitive areas.", "A two-compound product containing calcipotriol 50 microg/g and betamethasone dipropionate 0.5 mg/g (Daivobet, Dovobet) has been demonstrated to be an effective, once daily, treatment for psoriasis vulgaris.\n To compare the efficacy and safety of treatment with the two-compound product for 4 weeks followed by calcipotriol for 4 weeks, with that of tacalcitol for 8 weeks in patients with stable psoriasis vulgaris.\n 501 patients were randomised to double-blind treatment with the two-compound product followed by calcipotriol 50 microg/g once daily, or to tacalcitol 4 microg/g once daily.\n Treatment with the two-compound product/calcipotriol was significantly more effective than tacalcitol in terms of mean percentage PASI reduction (65.0 vs. 33.3% at week 4 and 59.0 vs. 38.4% at week 8; p < 0.001 for both).\n A treatment regimen comprising calcipotriol/betamethasone ointment (Daivobet) for 4 weeks followed by calcipotriol for 4 weeks is superior to tacalcitol ointment for 8 weeks in patients with psoriasis vulgaris.\n Copyright (c) 2004 S. Karger AG, Basel.", "The efficacy and safety of 0.3% tacrolimus gel and 0.5% tacrolimus cream compared with calcipotriol ointment were evaluated in adults (n = 124) with mild to moderate plaque psoriasis. Treatment was twice daily for a maximum of 12 weeks. Clinical efficacy was assessed by the percentage change in the local psoriasis severity index of a target lesion between baseline and week 12. By week 12, the median percentage changes in local psoriasis severity index of the target lesions in the tacrolimus gel, tacrolimus cream and calcipotriol groups were 55.6%, 50.0% and 58.6%, respectively (no statistically significant differences). Clinical improvement was observed after one week and increased throughout the study. Tacrolimus-treated patients experienced more application site skin burning (tacrolimus gel and cream both 31.0% versus 7.5% for calcipotriol; p = 0.011). Skin burning was mostly mild in intensity and decreased substantially after 1 week of treatment. There were no differences in the nature and incidence of infections and no clinically relevant changes in laboratory values.", "The efficacy, tolerability and safety of calcipotriol solution and betamethasone 17-valerate solution were compared in a multicentre, prospective, randomized, double-blind, parallel group study. Four hundred and seventy-four patients with scalp psoriasis were recruited from six European countries and Canada. Following a 2-week washout period, either calcipotriol solution (50 micrograms/ml) or betamethasone 17-valerate solution (1 mg/ml) was applied twice daily for 4 weeks. After this time, patients who required no further active treatment were observed for relapse. Retreatment with calcipotriol was offered to those patients who relapsed, and who were originally in the calcipotriol-treated group. The two treatment groups were well matched at baseline. At the end of treatment, the proportion of patients who had 'cleared' or 'markedly improved' was statistically significantly greater in the betamethasone group (75%) than in the calcipotriol group (58%) (P < 0.001) (95% confidence interval of difference 25.3-->8.6). The decrease in total sign score (sum of scores for erythema, thickness and scaliness) at the end of treatment was also statistically significantly greater in the betamethasone group (61%) than the calcipotriol group (45%) (P < 0.001) (95% confidence interval of difference 9.7-->23.1). Adverse events were reported by 87 patients in the calcipotriol group, and 31 patients in the betamethasone group; the most common was lesional or perilesional irritation, which occurred significantly more frequently with calcipotriol (26%) than with betamethasone (8%) (P < 0.001). Fifteen patients (6%) in the calcipotriol group and four (1%) in the betamethasone group withdrew from the study because of adverse events or unacceptable treatment response (P = 0.017).(ABSTRACT TRUNCATED AT 250 WORDS)", "Forty adult out-patients with erythematous squamous dermatoses of the scalp were treated in this 21-day double-blind study with an alcohol base lotion containing either 0.05% betamethasone-17,21-dipropionate, 2% salicylic acid, 0.05% betamethasone-17,21-dipropionate + 2% salicylic acid or their respective placebo. The four treatments were assigned randomly to the patients according to a 2 x 2 orthogonal factorial design. Changes in severity of redness, scaling, pruritus and size of lesions were evaluated. Since very few patients presented with excoriation and lichenification, these symptoms could not be ascertained. Results were assessed for significance by covariance analysis where initial status was used as regressor. A potentiation of the betamethasone-17,21-dipropionate activity by salicylic acid was observed for scaling. An additive effect was noted for redness and pruritus. According to the physician's global evaluation, patients treated with the combination drug showed a better evolution than those treated with placebo. The results suggest that addition of a keratolytic agent enhances the corticosteroid effect in the treatment of erythematous squamous dermatoses.", "A double-blind paired comparison was made of once daily and three times daily regimens of 0.1% halcinonide cream in 149 patients with atopic dermatitis and 194 with psoriasis. In a simultaneously conducted study once daily application of 0.1% halcinonide was compared to the cream base alone (placebo) in 48 patients with atopic dermatitis and 78 with psoriasis. Results show that a once daily regimen can be an effective treatment in both conditions, and can be recommended as a starting regimen in certain circumstances such as the treatment of young children or pregnant women, or where long-term treatment is likely. The three times daily regimen, however, was superior overall, and is still recommended as the treatment of choice, at least in severe psoriasis.", "Calcipotriene is a synthetic analogue of 1,25-dihydroxyvitamin D3 established to be effective topically in the treatment of psoriasis. We investigated the early cellular and immunological events induced by calcipotriene in psoriasis. Thirty patients with moderate plaque-type psoriasis were randomly assigned to receive twice daily applications of either calcipotriene ointment 0.005% or matching vehicle for 6 weeks. Skin biopsies (6 mm) were performed from designated plaques at baseline and days 3 and 7. On these days and at weeks 2, 4 and 6, complete clinical evaluations were made in a double-blind fashion. Consistent with previous studies, significant clinical improvement (P < 0.05) in psoriasis was observed in patients receiving calcipotriene vs. those receiving vehicle by day 7 for scale and erythema, and by day 14 for thickness. No significant improvement, however, was seen on day 3. None of the immunohistological markers (CD1a, CD4, CD8, ICAM-1, VCAM-1, E-selectin, HLA-DR) semiquantitatively assessed in psoriatic plaques was significantly changed by calcipotriene treatment for 7 days. In the calcipotriene-treated group, interleukin (IL)-10 levels (pg/microgram of protein) increased by 57% from baseline (0.030 +/- 0.006; mean +/- SEM) to day 3 (0.047 +/- 0.011) (P = 0.05 vs. baseline; n = 10) and remained elevated at day 7 (0.046 +/- 0.012). IL-8 levels (pg/microgram of protein), however, declined by 70% from baseline (0.13 +/- 0.06) to day 3 (0.04 +/- 0.01), and remained low at day 7 (0.03 +/- 0.02) (P < 0.05 vs. baseline; n = 10). Both IL-8 and IL-10 were unaffected by vehicle treatment. Calcipotriene-induced clinical improvement of psoriasis is preceded by an increase in IL-10 and a concomitant decrease in IL-8 levels. The changes in the level of these two cytokines provide further evidence for immunological changes as a significant part of the mechanism of action of calcipotriene in psoriasis.", "The objectives of the study were to determine whether concurrent treatment with calcipotriol (50 microg/g) and either clobetasone 17-butyrate cream (0.5 mg/g) (moderate potency) or betamethasone 17-valerate cream (1 mg/g) (potent) or placebo (vehicle of calcipotriol) was more effective and/or caused less skin irritation than calcipotriol cream (50 microg/g) used twice daily. It was a multicentre, double-blind, parallel group study. Patients applied calcipotriol cream in the morning and either vehicle (n = 174), calcipotriol (n = 174), clobetasone (n = 175) or betamethasone creams (n = 176) in the evening for up to 8 weeks. Adverse events led to withdrawal in 20 patients (2.9%). The mean percentage change in PASI (psoriasis area and severity index) was -40.6 in the calcipotriol/vehicle group, -48.3 in the calcipotriol/calcipotriol group, -53.7 in the calcipotriol/clobetasone 17-butyrate group and -57.5 in the calcipotriol/betamethasone 17-valerate group. A statistically significant difference was seen between the four treatment groups (P = 0.006) with calcipotriol/vehicle being less effective than the other treatments. A statistically significant difference in favour of calcipotriol/betamethasone 17-valerate was seen between the calcipotriol/calcipotriol group and the calcipotriol/betamethasone 17-valerate group. The majority of adverse events were skin irritations, which were reported for 31.2% of patients treated with calcipotriol/vehicle, 34.3% of patients treated with calcipotriol twice daily and 23.8% vs. 17.1% of patients treated with calcipotriol/clobetasone 17-butyrate and calcipotriol/betamethasone 17-valerate, respectively. Skin irritation was seen statistically significantly less frequently in patients treated with calcipotriol/ clobetasone 17-butyrate or calcipotriol/betamethasone 17-valerate (P = 0.001), whereas no difference was seen between the other groups. In conclusion, calcipotriol applied twice daily was as effective as calcipotriol/clobetasone 17-butyrate, but slightly less effective than calcipotriol/betamethasone 17-valerate. The incidence of skin irritation was less for patients using concurrent corticosteroids, whereas treatment with calcipotriol/vehicle did not reduce the incidence of skin irritation when compared with calcipotriol twice daily.", "There are already many effective topical therapies available for use in the treatment of chronic plaque psoriasis. Unfortunately, these treatments are often associated with a rather significant risk of undesirable effects.\n In this randomized, prospective clinical trial, the effects of the vitamin D(3) analog calcipotriol were evaluated against those of a recently developed vitamin B(12) cream containing avocado oil in an intraindividual right/left-side comparison. The trial population consisted of 13 patients, 10 men and 3 women, with chronic plaque psoriasis. The observation period was 12 weeks; the effects of therapy were assessed on the basis of a PASI score adapted to the right/left-side comparison technique, the subjective evaluations of the investigator and patients and the results of 20-MHz sonography.\n There was a more rapid development of beneficial effects with the use of calcipotriol in the initial 8 weeks, although differences in effects were significant only at the time point of therapy week 8 (p < 0.05). After 12 weeks, neither the PASI score nor 20-MHz sonography showed significant differences between the two treatments. While the efficacy of the calcipotriol preparation reached a maximum in the first 4 weeks and then began to subside, the effects of the vitamin B(12) cream containing avocado oil remained at a constant level over the whole observation period. This would indicate that the vitamin B(12) preparation containing avocado oil may be suitable for use in long-term therapy, a hypothesis further supported by the fact that the investigator and the patients assessed the tolerability of the vitamin B(12) cream containing avocado oil as significantly better in comparison with that of calcipotriol.\n The results of this clinical trial provide evidence that the recently developed vitamin B(12) cream containing avocado oil has considerable potential as a well-tolerated, long-term topical therapy of psoriasis.\n Copyright 2001 S. Karger AG, Basel", "Tacalcitol is a vitamin D analogue which ahs been developed for the therapy of psoriasis vulgaris. The treatment with a twice daily application of 2 micrograms/g ointment is efficacious and safe in Japanese patients. The objective of this randomized, placebo-controlled, intraindividual right-left comparison was to investigate the efficacy and safety of 8 weeks' therapy with a once daily application of a 4 micrograms/g tacalcitol ointment in Caucasian psoriatics. The data on 122 male and female patients were analysed. The score sum of erythema, infiltration and desquamation was influenced significantly more by tacalcitol ointment than by placebo (P < 0.0001) at every control point, starting from week 2. With regard to the individual symptoms of desquamation, infiltration and erythema, the treatment with tacalcitol was also superior to placebo treatment beginning at week 2. Qualitatively, the same results were obtained with the preference assessment of both treated body sides and also the global assessments of efficacy and benefit. Symptoms of local skin irritation which may be related to the active compound or the ointment base were reported by 12.3% of patients. In only one patient, irritation required discontinuation of tacalcitol treatment. Laboratory criteria, including serum calcium, serum phosphate and serum levels of calcitonin, parathormone, 1 alpha, 24-dihydroxyvitamin D3 and 25-hydroxyvitamin D3, did not reveal any changes of clinical relevance during or after treatment. Furthermore, the global assessment of tolerance was good or very good in more than 90% of cases. The results of this study demonstrate that the once daily application of a 4 micrograms/g tacalcitol ointment is an efficacious therapy for psoriasis vulgaris in Caucasian patients, and that its tolerance is good, wherever the lesion is located, including on the face.", "The efficacy of home treatment of psoriasis with a new dithranol formulation, Micanol, was investigated in three studies. They were carried out according to a randomized, within-patient comparison design. In a 4-week pilot study Micanol was compared with placebo (10 patients) and in two 6-week studies Micanol was compared with dithranol 1% in petrolatum (33 patients) and with dithranol 1% in Amitase stick (16 patients). Micanol was found to be effective and well suited for treatment at home in all studies. The vehicle itself did not improve the psoriasis plaques. The rate of clinical improvement was faster for dithranol in petrolatum and Amitase stick than for Micanol. The prevalence and severity of erythema, burning and staining of skin and clothing were far less for Micanol. Approximately half the number of patients preferred dithranol in petrolatum or Amitase stick and the other half preferred Micanol.", "There continues to be a need to develop new pharmacological approaches for treating the common skin disease psoriasis. Human skin produces parathyroid hormone related peptide. This peptide is a potent inhibitor of epidermal cell growth.\n A programme was initiated to determine whether an agonist of this peptide's receptor, PTH (1-34), could be developed as a drug to treat psoriasis.\n PTH (1-34) was formulated in Novasome A cream. Fifteen adult patients with chronic plaque psoriasis who had failed to respond to at least one standard treatment were enrolled in a randomized double-blinded placebo self-controlled trial. The patients topically applied to a 25-cm2 psoriatic lesion 0.1 g of either Novasome A cream or Novasome A cream that contained 20 microg of PTH (1-34) twice a day for 2 months. At the end of the double-blind study, patients were enrolled in an open large area study. Ten patients applied PTH (1-34) (50 microg per 0.1 g) once daily to their psoriatic lesions. The patients were evaluated for their global improvement and calcium metabolism.\n Novasome A cream enhanced the percutaneous absorption of PTH (1-34) in human skin in comparison with formulations in propylene glycol or normal saline. Psoriatic lesions treated with PTH (1-34) showed marked improvement in scaling, erythema and induration. There was a 67.3% improvement in the global severity score for the lesion treated with PTH (1-34) compared with the placebo-treated lesion, which only showed a 17.8% improvement. Ten patients topically applied PTH (1-34) on all of their lesions in a stepwise manner. A Psoriasis Area and Severity Index score analysis of all the patients revealed improvement of 42.6% (P < 0.02). None of the patients experienced hypercalcaemia or hypercalciuria or developed any side-effect to the medication.\n Patients who were resistant to at least one standard therapy for psoriasis had a remarkable improvement in their psoriasis when they applied PTH (1-34) to their lesion(s). No untoward toxicity was observed in any of the subjects. This pilot study suggests that topical PTH (1-34) is a safe and effective novel therapy for psoriasis.", "Calcipotriol has become a first-line treatment for psoriasis. Its efficacy and safety have been shown in many comparative clinical trials carried out in outpatients. In a comparative study in patients visiting the outpatient department once every 14 days, it was shown that calcipotriol was more effective and better tolerated compared with dithranol.\n To compare the clinical efficacy of calcipotriol ointment with that of dithranol cream in a supervised treatment regimen.\n In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks.\n This study failed to prove that calcipotriol is as efficacious as dithranol when used in a day-care setting (noninferiority test). The mean percentage reduction in Psoriasis Area and Severity Index from baseline to end of treatment was 57.0% in the calcipotriol group vs. 63.6% in the dithranol group. However, the two-sided test for superiority indicated no statistically significant difference between the treatment groups (P = 0.39). At the end of treatment, 15% of the patients treated with calcipotriol ointment and 25% of those treated with dithranol cream did not require any further treatment. Although calcipotriol ointment appeared to be more effective during the first 8 weeks, a difference was no longer apparent at 12 weeks. In comparison with the high number of drop-outs due to cutaneous side-effects in the calcipotriol group, the frequency of a tolerable degree of irritation appeared to be higher in patients treated with dithranol. However, concomitant corticosteroid treatment of dithranol irritation in seven patients may have contributed to this difference between both treatments. Moreover, patients receiving therapy with calcipotriol ointment experienced fewer application-related skin and subcutaneous tissue disorders than patients treated with dithranol cream: 21 of 53 (40%) and 37 of 52 (71%), respectively. This difference is statistically significant (P = 0.001).\n The hypothesis that calcipotriol ointment might be at least as effective as dithranol cream in the day-care setting could not be proven in the present study. Whereas calcipotriol has become a mainstay in the routine outpatient treatment of psoriasis not requiring a day-care setting, dithranol treatment, being difficult as a routine outpatient therapy, has increased efficacy and improved tolerability if the treatment is carried out in a day-care setting.", "Numerous preparations that are available for the treatment of psoriasis of the scalp contain high potency steroids, such as betamethasone dipropionate lotion or clobetasol propionate solution. Of special interest is a currently marketed oil preparation that contains the steroid fluocinolone acetonide (0.01%), classified as low potency (Class 6) steroid. Because the combination of emollients in the vehicle base are present to aid in softening the stratum corneum and allow penetration of the steroid component into the lower skin layer, it was thought this preparation would be an efficient treatment for psoriasis of the scalp. This study was designed to demonstrate the efficacy, tolerance and safety of fluocinolone acetonide 0.01% in oil, compared to its vehicle, for the treatment of scalp psoriasis. This was a randomized, double-blind, vehicle-controlled multi-center study in patients with moderate to severe scalp psoriasis. At the completion of the treatment period (21 days) all signs of psoriasis had improved in both treatment groups, the improvements in the FA group being significantly greater compared to those in the vehicle-treated group. The results of the physician global assessments of improvement in the signs of psoriasis from baseline confirmed the findings. Significantly more patients in the FA group had a good or better improvement from baseline compared to the number in the vehicle-treated group. The results of this study conclusively show that FA in an oil base that aids in the softening of the skin and allows penetration of the steroid into the stratum corneum, is an effective treatment for psoriasis of the scalp. This study also showed that the vehicle alone causes an improvement in the signs of psoriasis, but that the addition of 0.1% of the low potency steroid, fluocinolone acetonide, leads to a significantly better improvement.", "There is a need for new treatments for scalp psoriasis, as many topical treatments are cosmetically unacceptable and difficult to apply, resulting in poor compliance.\n To compare the efficacy and safety of a new, once-daily, two-compound scalp formulation (Xamiol; LEO Pharma A/S, Ballerup, Denmark) containing calcipotriol 50 microg g(-1) plus betamethasone 0.5 mg g(-1) (as dipropionate), with the active ingredients as single compounds in the same vehicle.\n This 8-week, multicentre, double-blind, parallel-group study, randomized adult patients with scalp psoriasis involving > 10% of the scalp to the two-compound scalp formulation (n = 568), betamethasone dipropionate 0.5 mg g(-1) (n = 563), or calcipotriol 50 microg g(-1) (n = 286). The primary efficacy measure was the proportion of patients with 'absence of disease' or 'very mild disease' according to investigators' assessments at week 8.\n The proportion of patients with 'absence of disease' or 'very mild disease' at week 8 was significantly higher in the two-compound group (68.4%) than the betamethasone dipropionate (61.0%, P = 0.0079) or calcipotriol (43.4%, P < 0.0001) groups. The proportion of patients rating their scalp psoriasis as 'clear' or 'almost clear' was significantly higher for the two-compound scalp formulation (69.6%) than for betamethasone dipropionate (59.9%, P = 0.0006) or calcipotriol (44.7%, P < 0.0001). The incidence of lesional/perilesional adverse events was lower in the two-compound and betamethasone dipropionate groups than the calcipotriol group.\n The two-compound scalp formulation was well tolerated and more effective in the treatment of scalp psoriasis than either of its individual components in the same vehicle.", "Topical therapy providing initial improvement and maintenance of effect after treatment of the large majority of patients with limited, mild to moderate psoriasis is not presently available. Previous topical retinoids have generally been either ineffective or too irritating for therapy of psoriasis.\n Our purpose was to evaluate a new topical retinoid, tazarotene, in the treatment of stable plaque psoriasis during treatment and posttreatment periods.\n In a double-blind manner, 324 patients were randomly selected to receive tazarotene 0.1% or 0.05% gel, or vehicle control, once daily for 12 weeks and were then followed up for 12 weeks after treatment.\n Of the total, 318 patients could be evaluated. Tazarotene gels were superior (p < 0.05) to vehicle, often as early as treatment week 1, in all efficacy measures: plaque elevation, scaling, and erythema; treatment response; percentage treatment success (patients with > or = 50% improvement); and time to initial success. Efficacy was equivalent on target lesion sites (trunk or limbs and knees or elbows) and overall. A sustained therapeutic effect was observed for 12 weeks after treatment. Tazarotene gel was cosmetically acceptable. There was low systemic absorption, limiting toxicity to local irritation.\n Once-daily tazarotene was effective and safe as a topical monotherapy for plaque psoriasis, providing rapid reduction of signs and symptoms.", "Topical coal tar is a well known and effective treatment for psoriasis, but the messiness, staining, odor, and inconvenience associated with its use make patient satisfaction and compliance a challenge.\n To determine the efficacy, patient tolerability, and cosmetic acceptability of a new topical liquor carbonis distillate (LCD) 15% solution compared with calcipotriene (calcipotriol) cream in patients with moderate, chronic plaque psoriasis.\n A randomized, single-blind, active-controlled, parallel-group, clinical trial consisting of a 12-week treatment phase and a 6-week post-treatment follow-up phase.\n Outpatient dermatology research unit in an academic hospital.\n Sixty adults with moderate, chronic plaque psoriasis (3-15% body surface area affected) not receiving other psoriasis therapies.\n Patients were randomized to apply either an LCD 15% solution (Psorent) or a commercially available calcipotriene 0.005% cream (Dovonex) to their psoriasis areas (excluding the head) twice daily at home for 12 weeks.\n A blinded investigator evaluated the patients' psoriasis using a modified Psoriasis Area and Severity Index (PASI) that excluded the head, and a Physician's Global Assessment (PGA) scale at weeks 0 (baseline), 2, 4, 8, and 12 (end of treatment), and 18 (6 weeks after treatment was withdrawn). Patients assessed their psoriasis symptoms and quality of life and completed a cosmetic acceptability survey about their medication.\n The changes in the baseline PASI scores after 12 weeks of treatment were compared between LCD and calcipotriene groups. Additional comparisons were performed for success rates during treatment (PASI 75 and PASI 50), changes in PGA scores, patient-reported psoriasis symptom scores, patients' quality-of-life scores, and recurrence rates during post-treatment follow-up.\n Both treatment groups showed improvement in psoriasis severity and quality of life. However, the LCD group had greater mean reductions in PASI scores: 58% vs 37% in the calcipotriene group (p < 0.05) at week 12. Additionally, the LCD group had more patients (14/27) with absent or minimal psoriasis on the PGA scale than the calcipotriene group (6/28) by the end of treatment (p < 0.05). LCD-treated patients also maintained their improvement better than calcipotriene-treated patients through week 18 after treatment was withdrawn for 6 weeks. Both treatments were well tolerated and cosmetically acceptable to patients.\n The newly formulated LCD solution, applied twice daily at home for 12 weeks, was more effective and as well tolerated and cosmetically acceptable as the calcipotriene cream over 12 weeks of treatment and 6 weeks of follow-up. The LCD solution is a patient-accepted and effective corticosteroid-sparing treatment alternative for psoriasis patients.", "Psoriasis is usually treated with local and systemic medications that have varying degrees of efficacy and safety profiles. We investigated the efficacy and safety of an alternative treatment from natural sources, Mahonia aquifolium, for the management of mild to moderate psoriasis. Two hundred subjects participated in a randomized, double-blind, placebo-controlled study using either the topical cream Reliéva (a homeopathic product containing a proprietary M. aquifolium extract) or control (placebo) twice a day for 12 weeks. Efficacy and safety were assessed using the Psoriasis Area Severity Index (PASI) and the Quality of Life Index (QLI) questionnaires at different times throughout the 12-week study. The PASI was evaluated by the physician at the beginning (week 0) and end (week 12) of the study. The QLI was assessed by patients at weeks 0, 4, 8, and 12. The results indicate statistically significant (P < 0.05) improvements in PASI and QLI in the Mahonia-treated group, compared with the control group. The side effects reported were infrequent, < 1% and minor; the most frequent side effects were rash, a burning sensation when applying the cream, and clothing stain. These data indicate that Reliéva, a proprietary form of M. aquifolium, is effective and well tolerated in patients with mild to moderate psoriasis.", "Plaque psoriasis of mild to moderate severity is routinely treated with topical steroids and coal tar along with emollients. A safe and convenient new treatment modality would be of value to most patients with psoriasis.\n Our purpose was to evaluate the safety and efficacy of a new vitamin D3 analogue, calcipotriene, for the treatment of plaque psoriasis.\n Twice-daily dosing of calcipotriene was compared with its vehicle, for up to 8 weeks, in a double-blind study of 277 patients at 10 study centers in the United States. Two hundred forty-seven patients completed the trial. The clinical characteristics of plaque elevation, erythema, scaling, and overall disease severity were evaluated at baseline and after 1, 2, 4, 6, and 8 weeks of treatment. A Physician's Global Assessment of improvement or worsening of the disease was performed after 1, 2, 4, 6, and 8 weeks of treatment. Blood and urine samples, for routine clinical laboratory tests, were collected at baseline and after 1, 2, 4, and 8 weeks of treatment.\n As early as the week 1 evaluation, patients treated with calcipotriene ointment 0.005% had significantly lower mean scores (p = 0.043) than the vehicle-treated patients for the disease characteristics of plaque elevation, erythema, and scaling. This trend continued through week 8 of treatment when 70% of the calcipotriene-treated patients showed 75% or more improvement compared with only 19% of vehicle-treated patients. Only minor treatment-related adverse events were observed. There were no abnormal laboratory results judged related to treatment and the rare instances of elevated serum calcium values were equally distributed between active and vehicle treatments.\n This study provides evidence that calcipotriene is a safe, effective, and promising new agent for the treatment of moderately severe plaque psoriasis.", "To determine the safety and efficacy of topically applied tazarotene gel in the treatment of mild to moderate psoriatic plaques.\n Two multicenter, double-blind, randomized studies of 6- and 8-week duration, with an 8-week follow-up in the second study.\n Medical center outpatient dermatology services.\n One hundred fifty-three adults with 2 bilateral target plaques on the trunk, legs, or arms.\n Vehicle gel or 0.01% and 0.05% tazarotene gel administered twice daily to 45 patients (study A), or 0.05% and 0.1% tazarotene gel administered either once or twice daily to 108 patients (study B).\n Treatment success and plaque elevation, scaling, and erythema vs time.\n The 0.01% tazarotene gel showed minimal efficacy. Applications of 0.05% and 0.1% tazarotene gels administered once or twice daily, resulted in significant improvements in plaque elevation, scaling, erythema, and overall clinical severity as early as 1 week. Treatment success rates (defined as > 75% improvement from baseline) were 45% with 0.05% tazarotene gel vs 13% with vehicle gel after 6 weeks of treatment (P < .05; study A) and ranged from 48% to 63% with the various tazarotene treatment regimens after 8 weeks of treatment (study B). These improvements were evident at the 8-week follow-up. Treatment-related adverse effects were generally limited to mild or moderate local irritation and were less frequent with the treatment regimen administered once daily.\n The 0.05% and 0.1% tazarotene gels demonstrated significant efficacy in the treatment of mild to moderate psoriatic plaques that persisted after cessation of treatment.", "There is a need for more effective therapy for scalp psoriasis.\n To assess the efficacy and safety of a 2-compound scalp formulation including calcipotriol and betamethasone dipropionate in the treatment of scalp psoriasis.\n Patients (n = 218) with scalp psoriasis were randomized to treatment with the 2-compound scalp formulation (n = 108) or betamethasone dipropionate in the same vehicle (n = 110). The treatments were applied once daily on the scalp for up to 8 weeks.\n The 2-compound scalp formulation showed a significantly higher efficacy than betamethasone dipropionate on the total sign score at the end of treatment (p = 0.042) and after 2 weeks (p = 0.005).\n The calcipotriol plus betamethasone dipropionate scalp formulation was superior to betamethasone dipropionate in the same vehicle when used once daily for up to 8 weeks in the treatment of scalp psoriasis.\n (c) 2008 S. Karger AG, Basel.", "A calcipotriol/hydrocortisone combination ointment has been developed for treating psoriasis on sensitive skin areas such as the face. The efficacy and safety of two calcipotriol/hydrocortisone dose combinations were compared with two concentrations of calcipotriol in the same ointment vehicle in patients with psoriasis on the face and body. Patients were randomised to receive 8 weeks once daily treatment with calcipotriol 25 mcg/g or 50 mcg/g, either alone or combined with hydrocortisone 10 mg/g. On the body and face overall, no statistically significant differences in efficacy were observed between the calcipotriol/hydrocortisone formulations versus the calcipotriol alone formulations nor between the two concentrations of calcipotriol (50 mcg/g versus 25 mcg/g). On the face alone, calcipotriol/hydrocortisone was significantly more effective than calcipotriol alone (P < 0.001) but no consistent significant difference was found between the two concentrations of calcipotriol. There was a significant benefit of combining hydrocortisone with calcipotriol in the incidence of adverse drug reactions on the body and face (P = 0.006) and on the face (P < 0.001) but no significant difference was found between the two concentrations of calcipotriol either on the body and face or on the face. In facial psoriasis, combining hydrocortisone with calcipotriol resulted in an improved efficacy and tolerability compared to calcipotriol alone.", "Calcipotriol and betamethasone dipropionate are both widely used, effective treatments for psoriasis. Vitamin D analogues and topical corticosteroids have different mechanisms of action in the treatment of psoriasis. A new vehicle has been developed in order to contain both calcipotriol (50 micro g g-1) and betamethasone dipropionate (0.5 mg g-1) in an ointment form. By using calcipotriol and a corticosteroid together, greater efficacy may be achieved than by using either compound alone.\n The present study was conducted in order to compare the clinical efficacy and safety of the combined ointment formulation used once daily with the vehicle ointment used twice daily, calcipotriol ointment used twice daily and the combined formulation used twice daily in psoriasis vulgaris.\n This was an international, multicentre, prospective, randomized, double-blind, vehicle-controlled, parallel group, 4-week study in patients with psoriasis vulgaris amenable to topical treatment. Patients were randomized to one of four treatment groups: combined formulation once daily, combined formulation twice daily, calcipotriol twice daily or vehicle twice daily. Efficacy and safety were assessed.\n There was no statistically significant difference in the mean percentage change in the Psoriasis Area and Severity Index (PASI) from baseline to end of treatment between the two combined formulation groups, but the difference in PASI reduction was significantly higher in the combined formulation groups (68.6% once daily, 73.8% twice daily) than in both the twice daily calcipotriol group (58.8%) and the vehicle group (26.6%). Safety data showed the frequency of adverse events to be less in the combined formulation groups than in both the calcipotriol group and the vehicle group. The proportion of patients with lesional/perilesional adverse reactions was less in the combined formulation groups and vehicle group than in the calcipotriol group (9.9% combined formulation once daily, 10.6% combined formulation twice daily, 19.8% calcipotriol, 12.5% vehicle).\n No statistically significant nor clinically relevant difference in efficacy was seen between the combined formulation used once daily and twice daily. When compared to vehicle ointment or calcipotriol ointment alone, the combined formulation was shown to be clearly more efficacious.", "The efficacy and safety of clobetasol propionate 0.05% scalp application was evaluated in 378 patients with moderate to severe scalp psoriasis in a double-blind vehicle-controlled parallel group study. After 2 weeks of twice-daily applications, 81% receiving active drug versus 22% receiving vehicle had clearing of 50% or greater. Complete clearing was seen in 26% with active drug and 1% with vehicle. Local side effects were primarily burning or stinging in 11% and 10% of patients treated on an active or a vehicle regimen, respectively. The morning cortisol levels of 168 patients were checked at baseline and again after 2 weeks of drug therapy. Subnormal morning plasma cortisol values were seen in 5% of the patients receiving active drug and in 5% receiving vehicle; 13% of those taking active drug versus 5% taking vehicle had a 50% or greater decrease in morning cortisol at the 2-week visit compared with baseline values. Clobetasol propionate 0.05% scalp application appears to be a safe and an effective treatment for scalp psoriasis.", "New topical treatments in scalp psoriasis are needed because many current topical treatments are disliked by patients and associated with poor compliance.\n To compare the efficacy and safety of once-daily, two-compound scalp formulation containing calcipotriene plus betamethasone dipropionate with the individual components in the same vehicle and the vehicle alone.\n In this 8-week, multicenter, randomized, double-blind study, patients with scalp psoriasis were randomized to treatment with the two-compound scalp formulation (calcipotriene 50 microg/g plus betamethasone 0.5 mg/g, as dipropionate) (n = 541), betamethasone 0.5 mg/g (as dipropionate) in the same vehicle (n = 556), calcipotriene 50 microg/g in the same vehicle (n = 272), or vehicle alone (n = 136).\n More patients achieved \"absent\" or \"very mild\" disease at week 8 with the two-compound scalp formulation (71.2%) compared with betamethasone dipropionate in the same vehicle (64.0%, p = .011), calcipotriene in the same vehicle (36.8%, p < .0001), or the vehicle (22.8%, p < .0001).\n Efficacy of the active comparators in the study has not been established in relation to calcipotriene and betamethasone formulations available for clinical use.\n Calcipotriene plus betamethasone dipropionate scalp formulation was more effective than either of the individual components or the vehicle alone.", "Inverse psoriasis can be difficult to treat because of the high sensitivity of intertriginous areas to cutaneous side effects, such as irritation and striae. Pimecrolimus, a well-tolerated, nonatrophogenic, skin-selective inflammatory cytokine inhibitor, has been shown to be effective in the treatment of psoriasis when applied topically under occlusion.\n This study evaluated the efficacy and safety of pimecrolimus cream 1% versus vehicle twice a day in the treatment of inverse psoriasis. Methods This was a double-blind, randomized, vehicle-controlled study in 57 patients with moderate to severe inverse psoriasis. Patients were evaluated using Investigator's Global Assessment of overall severity, Target Area Score, and Patient Self-Assessment.\n A significant between-group difference was observed early on, with 54% of the pimecrolimus group versus 21% of the vehicle group having an Investigator's Global Assessment score of 0 or 1 (clear or almost clear) at week 2 ( P = .0169). By week 8, 71% of the pimecrolimus group had an Investigator's Global Assessment score of 0 or 1. Change from baseline in Target Area Score was -2.4 (pimecrolimus group) compared with -0.7 (vehicle) at day 3 ( P < .0001). By week 8, 82% of patients using pimecrolimus scored their disease as well or completely controlled versus 41% of the vehicle group ( P = .0007). Adverse events were similar between groups.\n Pimecrolimus cream 1% is an effective treatment for inverse psoriasis with a rapid onset of action, and is safe and well-tolerated.", "nan", "Becocalcidiol is a vitamin D(3) analogue which has not caused hypercalcaemia or significant irritation in preclinical trials.\n To evaluate the efficacy and safety of two dosing regimens of becocalcidiol ointment (low dose = 75 microg g(-1) once daily for 8 weeks; high dose = 75 microg g(-1) twice daily for 8 weeks) in the treatment of plaque-type psoriasis.\n One hundred and eighty-five subjects with chronic plaque-type psoriasis affecting 2-10% of their body surface area took part in a multicentre, double-blind, parallel-group, vehicle-controlled, randomized controlled trial comparing topical application of placebo, becocalcidiol 75 microg g(-1) once daily (low dose) or becocalcidiol twice daily (high dose) for 8 weeks. Main outcomes included Physician's Static Global Assessment of Overall Lesion Severity (PGA) score; Psoriasis Symptom Severity (PSS) score; adverse events; and laboratory assessment.\n In the intent-to-treat population at week 8, high-dose becocalcidiol was statistically superior to vehicle [P = 0.002; 95% confidence interval (CI) 6.7-32.2], with 16 of 61 (26%) subjects achieving a PGA score of clear or almost clear. Greater improvement in PSS score was seen with high-dose becocalcidiol than with vehicle, but this result did not quite achieve statistical significance (P = 0.052; 95% CI -16.2 to 0.1). In all groups, therapy was safe and well tolerated, with fewer subjects experiencing irritation than is reported in studies using calcipotriol.\n Treatment with high-dose topical becocalcidiol for 8 weeks led to almost or complete clearing of moderate plaque-type psoriasis in over a quarter of patients. Therapy was safe and well tolerated.", "A clinical study was conducted to determine whether, in the topical treatment of psoriasis, a combination of calcipotriol and betamethasone valerate after previous treatment with calcipotriol alone was more effective than the continuation of the monotherapy with calcipotriol, especially in 'low responders'. Patients (n = 169) with the clinical diagnosis 'chronic plaque-type psoriasis' were treated twice daily for 2 weeks with calcipotriol, followed by a 4-week treatment with calcipotriol monotherapy in 87 patients or combined calcipotriol/betamethasone valerate in 82 patients; all patients were followed for 8 weeks. The psoriasis area and severity index (PASI) was used to compare the two treatment groups. The overall therapeutic result was also assessed by the investigators and patients. The combination therapy was more effective, as assessed by all evaluated variables; moreover, patients showing insufficient response to calcipotriol alone after 2 weeks showed a regression of psoriatic lesions using the combination regimen. Thus, the combination of calcipotriol and topical steroids is recommended as the therapy of first choice for patients who do not respond well to treatment with 2 weeks of calcipotriol alone. Furthermore, this combination reduces the hazards associated with the long-term use of topical corticosteroids (atrophy and rebound) as well as the irritation associated with calcipotriol.", "Effective and safe products are needed for long-term management of scalp psoriasis. This study investigated the long-term safety and efficacy of a two-compound formulation (calcipotriol 50 microg/g plus betamethasone dipropionate 0.5 mg/g) for scalp psoriasis.\n In this 52-week, international, double-blind study, 869 patients with moderate-to-severe scalp psoriasis were randomized to either a two-compound scalp formulation (n = 429) or calcipotriol (n = 440).\n Adverse drug reactions were less frequent in the two-compound group compared with the calcipotriol group (17.2 vs. 29.5%; p < 0.001). Incidences of adverse events possibly associated with long-term corticosteroid use were low in both the two-compound (2.6%) and the calcipotriol (3.0%) groups. Disease was satisfactorily controlled in 92.3% of visits in the two-compound group versus 80.0% in the calcipotriol group (p < 0.001).\n The two-compound scalp formulation demonstrated a high level of safety and efficacy in long-term management of scalp psoriasis.\n 2008 S. Karger AG, Basel.", "The purpose of this double-blind, placebo-controlled study was to evaluate the clinical efficacy and tolerability of topical Aloe vera extract 0.5% in a hydrophilic cream to cure patients with psoriasis vulgaris. Sixty patients (36M/24F) aged 18-50 years (mean 25.6) with slight to moderate chronic plaque-type psoriasis and PASI (Psoriasis Area and Severity Index) scores between 4.8 and 16.7 (mean 9.3) were enrolled and randomized to two parallel groups. The mean duration of the disease prior to enrollment was 8.5 years (range 1-21). Patients were provided with a precoded 100g tube, placebo or active (with 0.5% Aloe vera extract), and they self-administered trial medication topically (without occlusion) at home 3 times daily for 5 consecutive days per week (maximum 4 weeks active treatment). Patients were examined on a weekly basis and those showing a progressive reduction of lesions, desquamation followed by decreased erythema, infiltration and lowered PASI score were considered healed. The study was scheduled for 16 weeks with 12 months of follow-up on a monthly basis. The treatment was well tolerated by all the patients, with no adverse drug-related symptoms and no dropouts. By the end of the study, the Aloe vera extract cream had cured 25/30 patients (83.3%) compared to the placebo cure rate of 2/30 (6.6%) (P < 0.001) resulting in significant clearing of the psoriatic plaques (328/396 (82.8%) vs placebo 28/366 (7.7%), P < 0.001) and a decreased PASI score to a mean of 2.2. The findings of this study suggest that topically applied Aloe vera extract 0.5% in a hydrophilic cream is more effective than placebo, and has not shown toxic or any other objective side-effects. Therefore, the regimen can be considered a safe and alternative treatment to cure patients suffering from psoriasis.", "Topical corticosteroids are widely used in the treatment of psoriasis. This study was conducted to compare the efficacy and safety of clobetasol propionate (CP) 0.005% spray to calcipotriene 0.005%-betamethasome diproprionate 0.064% (C-BD) ointment in patients with moderate to severe plaque psoriasis. Assessments were made at baseline, week 2, week 4 (end of treatment) and week 8 (4 weeks posttreatment). An assessment for Overall Disease Severity (ODS) found that 75% of CP spray-treated patients achieved a rating of clear or almost clear after 4 weeks of treatment compared to 45% of C-BD ointment-treated patients (P=.003). Adverse events were reported by less than one-third of patients from each treatment group (31% for CP spray and 33% for C-BD ointment).", "Forty-two patients aged between 6 and 61 years (mean: 33.5 years) with psoriasis of the scalp were enrolled in this study. Twenty-seven patients (69%) were males and 15 (31%) were females. The aim of our study was to evaluate the efficacy, safety and tolerability of topical calcipotriol 50 micrograms/g/ml solution vs. betamethasone valerate 1% lotion in the treatment of psoriasis of the scalp. The study was randomized with the twice-daily application of either calcipotriol solution or betamethasone valerate lotion for 6 weeks. Treatment evaluation was clinically based on signs of psoriasis (thickness, redness, scaliness) which were scored from 0 = absent to 4 = severest possible involvement and was performed at the start of treatment and at weeks 2 and 6 of treatment. The results showed a marked improvement and clearance at the end of treatment in 15 (72.8%) of the 24 patients in the calcipotriol group and in 13 of the 18 patients (72%) in the betamethasone group. The mean total sign score at baseline was 5.1 in the calcipotriol group and 5.4 in the betamethasone valerate group. At the end of treatment, this score was decreased to 2.1 and 1.49, respectively. No significant adverse effects were reported in either group except in two patients (8.3%) in the calcipotriol group who developed signs of irritation including itching and erythema. In conclusion, both drugs were effective and well tolerated in the treatment of scalp psoriasis but in some patients calcipotriol had to be given for more prolonged courses.", "Topical vitamin D analogues have been reported to be an effective treatment in patients with psoriasis. Comparative studies with existing treatments are required.\n Our purpose was to compare the effectiveness of calcipotriol (50 micrograms/gm) and betamethasone 17-valerate (1 mg/gm) ointments twice daily in the treatment of stable plaque psoriasis.\n This study was a randomized, double-blind comparison over 6 weeks in 409 patients. Efficacy, as measured by the Psoriasis Area and Severity Index (PASI), and safety were assessed at 2, 4, and 6 weeks.\n Reduction of PASI was statistically significant at all time points for both treatments but there were no significant between-treatment differences. At the completion of 6 weeks of treatment, the mean PASI reduction was 5.50 for calcipotriol and 5.32 for betamethasone (95% confidence interval [CI] -0.40 to 0.78). Analysis of patient assessment at 6 weeks showed clearance or marked improvement in 61.2% of the calcipotriol patients and 50.5% with betamethasone (95% CI 1.4 to 20.8). Calcipotriol produced significantly more local side effects (19.5% compared with 3.9%, p less than 0.001); however, these were minimal leading to withdrawal in only 3 of 205 patients.\n Calcipotriol ointment was as effective as betamethasone 17-valerate ointment as measured by the PASI and superior as measured by self-assessment in patients with stable plaque psoriasis. Both treatments were well tolerated.", "Psoriasis is a common disease which often requires long-term maintenance therapy. In psoriatic epidermis, the level of cyclic adenosine monophosphate (cAMP) decreases. It has been reported that beta-blockers exacerbate existing psoriatic plaque and decrease the concentration of intracellular cAMP. Caffeine is a methylxanthine that inhibits phosphodiesterase enzyme and results in a higher concentration of intracellular cAMP.\n Evaluation of the efficacy of topical caffeine 10% in the treatment of psoriasis.\n The patients were treated by topical application of 10% caffeine or placebo three times per day on the right or left side of the body (randomly selected by flipping a coin). Thirty-nine patients with stable plaque psoriasis were included in a randomized, double-blind, placebo-controlled, right/left comparison. The patients visited every other week for a period of 8 weeks. Their Psoriatic Area and Severity Index (PASI) scores were assessed at each visit.\n The reductions in PASI scores measured at the four visits for the caffeine-treated group were 2.64+/-2.89, 4.47+/-3.62, 5.73+/-4.16, 6.58+/-4.40 and for the placebo-treated group the values were 1.45+/-2.32, 3.04+/-2.68, 4.02+/-3.36, 4.43+/-3.45, respectively. Comparing the corresponding results of the two groups, p values at the second, fourth, sixth and eighth week were 0.081, 0.083, 0.079 and 0.047, respectively. Based on presented p values, the treatment with caffeine is more effective than with placebo after 8 weeks (p<0.05), and the only side effect of caffeine is mild itching.\n Based on the results of the trial, topical caffeine is an effective, safe and inexpensive treatment for psoriasis, with a delay in action.", "To establish the efficacy and duration of remission post-treatment of calcitriol 3 micro g/g ointment in comparison with betamethasone dipropionate 0.05% ointment.\n A randomized, multicentre trial was conducted in 258 adult patients with chronic plaque psoriasis. Calcitriol 3 microg/g ointment or betamethasone dipropionate 0.05% ointment was applied twice daily for 6 weeks or until complete clearance of lesions. Patients whose psoriasis cleared or were significantly improved and did not require treatment continuation at treatment endpoint were contacted over the following 8 weeks to determine whether relapse had occurred.\n Both treatments were efficacious; improvement in psoriasis or clearance of lesions (residual erythema was allowed) was recorded for 79% and 82% of patients receiving calcitriol or betamethasone dipropionate, respectively. Global improvement and global severity scores at treatment endpoint showed statistically significant differences in favour of betamethasone dipropionate (p<0.05); however, the absolute reduction in mean PASI (psoriasis area and severity index) was comparable between the groups. A statistically significantly (p<0.01) higher proportion of responders remained in remission (no worsening of the disease warranting new treatment) following calcitriol therapy (48%) than betamethasone therapy (25%). This is of potential importance to patients, physicians and healthcare suppliers.\n Twice-daily applications of either calcitriol 3 microg/g ointment or betamethasone dipropionate 0.05% ointment can be used to good effect in the treatment of chronic plaque psoriasis. However, the beneficial effect is likely to persist for longer following calcitriol treatment.", "nan", "The biologically active form of vitamin D3, calcitriol, may offer a new therapeutic approach to psoriasis. Calcipotriol, a new vitamin D3 analogue, is at least 100 times less calcemic than calcitriol.\n Our purpose was to study the efficacy and safety of calcipotriol in the treatment of psoriasis vulgaris.\n In a right/left comparative, double-blind study, treatment with calcipotriol ointment (50 micrograms/gm) twice daily and placebo was given for 4 weeks. The preferred treatment was continued, without opening the code, for another 4 weeks. Efficacy, as measured by the Psoriasis Area and Severity Index and by the investigator's and patient's global assessment, and safety were assessed every 2 weeks.\n The mean Psoriasis Area and Severity Index fell in 4 weeks from 14.2 to 6.3 with calcipotriol and from 14.1 to 9.2 with placebo (p < 0.001; 95% confidence interval for difference: 1.78-->3.94). Local side effects were equally common with calcipotriol and placebo. The mean serum calcium remained unchanged.\n Topical application of up to 50 gm of calcipotriol ointment per week was found to be an effective and safe treatment of psoriasis vulgaris.", "Two clinical trials were conducted to evaluate the safety and antipsoriatic efficacy of a new 0.05 percent emollient formulation of clobetasol propionate (CP). In a crossover study of hypothalamic-pituitary-adrenal (HPA)-axis effects in 12 patients with psoriasis or eczema, 1.5 gm of CP emollient, applied to lesions twice daily for seven consecutive days, resulted in fewer patients with serum cortisol concentrations < 10 micrograms/100 mL than CP cream 0.05 percent (1vs 4); such concentrations were seen in two other patients during both treatment phases. A double-blind, randomized, parallel-group clinical trial in patients with moderate to severe plaque-type psoriasis showed that four weeks' treatment with CP emollient 0.43 to 0.5 gm twice daily (n = 35) was significantly more effective than emollient vehicle (n = 39) in reducing total signs/symptoms and scaling by Day 4, erythema and skin thickening by Day 8, and pruritus by Day 15. CP emollient was rated superior to vehicle by Day 4 in physician's gross assessment ratings and by Day 15 in patient's self-assessment ratings. In all assessments, CP emollient continued to be superior to vehicle during the remainder of the treatment period and two-week posttreatment period. No significant differences were observed in tolerability or serum cortisol effects during the course of the study.", "nan", "In a double-blind left-right randomised comparison, 27 patients suffering from chronic plaque-type psoriasis vulgaris were treated for one minute with dithranol 2% ointment, Psoralon (Psoralon MT), on a selected psoriasis plaque on one half of the body and with a placebo ointment on a corresponding plaque on the other. The preparations were applied once daily for 8 weeks. Seventeen patients achieved clearing or considerable improvement with dithranol therapy, as compared with 6 patients with placebo (p = 0.002). Erythema, infiltration, scaling, pruritus and the overall result were assessed. Statistically significant differences in favour of dithranol treatment were seen for all five variables, except for pruritus. The average of these five variables, designated the mean score, was also analysed; dithranol was seen to yield significantly better results (p = 0.001). Staining of clothes and the bathroom was noted by 3 and 5 patients, respectively, but no medical side effects were seen.", "The efficacy and safety of calcipotriol solution in the treatment of scalp psoriasis was compared with placebo (vehicle solution), in a multicentre double-blind, randomized, parallel-group study of 49 adult patients. Calcipotriol solution (50 micrograms/ml), or placebo, was applied twice daily over a 4-week period. At the end of the study period 60% of patients on calcipotriol showed clearance or marked improvement of their psoriasis compared with 17% on placebo. Overall assessment of treatment response showed that calcipotriol was superior to placebo in both investigator (P < 0.001; 95% confidence interval for difference 19.0-67.6) and patient (P < 0.001; 95% confidence interval for difference 18.3-68.0) assessments. Total sign score for psoriasis (i.e. the sum of the scores for redness, thickness and scaliness) decreased by 48.9% in the calcipotriol group, and by 18.6% in the placebo group (P = 0.005). Calcipotriol was significantly superior to placebo in reducing redness, thickness, scaliness and extent of psoriasis, and in the patients' assessment in reducing scalp flaking and itching. No statistically significant changes in blood biochemistry were detected during the study, and the solution was generally well tolerated.", "The therapeutic efficacy and tolerability of calcipotriol ointment and betamethasone valerate ointment in psoriasis were compared in a multicentre, prospective, randomised, double-blind, right/left trial. 345 inpatients and outpatients with psoriasis vulgaris of symmetrical distribution were treated twice daily for 6 weeks with calcipotriol ointment 50 micrograms/g and betamethasone ointment 0.1% randomly assigned to opposite sides of the body. The main outcome measures--the psoriasis area and severity index (PASI), the investigators' assessments of erythema, thickness, and scaling, and the patients' own assessments of the overall response to treatment--were sought at weeks 2, 4, and 6. Both treatments significantly reduced the PASI scores and the investigator's assessment scores, but at each visit the PASI score was significantly (p less than 0.001) lower with calcipotriol than with betamethasone. At 6 weeks the mean PASI reduction was 68.8% with calcipotriol and 61.4% with betamethasone (95% confidence interval for difference 5.1-9.8, p less than 0.001). The scores for erythema, thickness, and scaling were significantly (p less than 0.001) lower with calcipotriol than with betamethasone at the end of treatment. The patients considered that 82.1% of calcipotriol-treated sides and 69.3% of betamethasone-treated sides had improved greatly or cleared up by the end of treatment (p less than 0.001). 57 adverse events were reported by 52 patients (15.1%). The most common adverse event, lesional/perilesional skin irritation, was slightly but not significantly (p = 0.12) more common with calcipotriol treatment. 15 (4.3%) patients were withdrawn from the study, 3 because of local adverse events. There were no changes in serum calcium during the study. Thus, calcipotriol ointment was superior to betamethasone valerate ointment in psoriasis vulgaris. Though long-term results are not yet available, calcipotriol holds great promise as an antipsoriatic agent.", "The efficacy and tolerability of topically applied oleum horwathiensis were evaluated in a double-blind, placebo-controlled study of 42 patients with chronic stable psoriasis. Both groups of patients, 19 receiving oleum horwathiensis treatment and 23 receiving placebo treatment for 12 weeks, showed clinically significant effects of treatment. Oleum horwathiensis was more effective than placebo throughout the treatment period but the difference was not statistically significant at any time. No changes in laboratory values attributable to treatment were recorded. The symptoms of the oleum horwathiensis-treated group continued to be less severe than those of the placebo-treated group throughout the 12 weeks of follow-up. The follow-up period, however, occurred partly during the summer and since the clinical status of the patients may have been affected by climate the difference between the treatment groups was not analysed statistically. The tolerability and cosmetic acceptance of oleum horwathiensis were remarkably good, and good clinical efficacy in scalp lesions--which was not the subject of this study--was spontaneously reported by several patients.", "nan", "Short-contact treatment with dithranol (anthralin) is a widely used treatment for chronic plaque psoriasis. Although effective, it causes staining and irritation, and is therefore inconvenient. Calcipotriol is a recently developed vitamin D analogue which is effective and easy to use. To evaluate the relative efficacy, safety and acceptability of these treatments a multicentre, open, randomized, parallel-group comparison was performed. Four hundred and seventy-eight patients with chronic plaque psoriasis were randomized to use one of the two treatments for 8 weeks. One group applied calcipotriol ointment (50 micrograms/g) twice daily. The other used a single application for 30 min each day of Dithrocream in the highest concentration tolerated. Severity of psoriasis was assessed by modified PASI score at baseline, and after 2, 4, and 8 weeks of treatment. A five-point scale was used by subjects and by investigators as an additional assessment of overall response, and a similar scale was used by subjects to grade acceptability. Total serum calcium was monitored at baseline and after 2 and 8 weeks on treatment. The mean PASI score fell from 9.1 to 4.7 after 8 weeks on dithranol (P < 0.001), and from 9.4 to 3.4 on calcipotriol (P < 0.001). The difference between the two treatments was significant in favour of calcipotriol at 2 weeks (P < 0.001), and remained so at subsequent assessments. At 8 weeks the difference between mean improvements in scores for the two groups was 1.6 (95% confidence interval 0.5-2.7). Efficacy grading by subjects and investigators, and acceptability grading by subjects, were all significantly better for calcipotriol.(ABSTRACT TRUNCATED AT 250 WORDS)", "In a multicentre, randomized, open study, 306 patients of either sex, over 18 years of age with stable chronic plaque psoriasis > 100 cm2 in surface area, and who gave informed consent, applied Dovonex (calcipotriol) ointment (50 micrograms/g) twice daily or Dithrocream (short-contact dithranol) 0.1-2% for up to 3 months. The number of patients 'cleared' or with 'marked improvement' at the end of treatment were: investigators' assessment--calcipotriol 92 of 153 (60.1%); dithranol 67 of 131 (51.1%); odds ratio 1.44 [95% confidence interval (CI) 0.90, 2.31; P = 0.128]; patients' assessment--calcipotriol 93 of 153 (60.8%); dithranol 65 of 131 (49.6%); odds ratio 1.57 (95% CI 0.98, 2.52; P = 0.059). Significant improvement in patients' quality of life as assessed by the Psoriasis Disability Index (PDI) and the Sickness Impact Profile (SIP) were seen in both treatment groups. Reduction in the total mean score for PDI was 6.5 in the calcipotriol group (95% CI 4.4, 8.6; P = 0.001) and 3.7 in the dithranol group (95% CI 1.1, 6.3; P = 0.005). The reduction in the total mean score for SIP was 2.8 in the calcipotriol group (95% CI 1.4, 4.3; P < 0.001) and 1.7 in the dithranol group (95% CI 0.2, 3.1; P = 0.024). Calcipotriol treatment tended to have advantages over treatment with dithranol in improving quality of life.", "Two multicenter, double-blind, randomized, vehicle-controlled parallel-group trials involving 388 patients were conducted to compare the efficacy and safety of fluticasone propionate 0.005% ointment to those of its vehicle in the treatment of moderate-to-severe psoriasis. The study medication (up to 100 gm/week) was applied topically to the affected target areas of the body twice daily for up to four consecutive weeks. Efficacy and safety were evaluated after one, two, three, and four weeks of treatment. In both studies, fluticasone ointment was clearly shown to be superior to vehicle throughout the four weeks of treatment. At the end of the treatment period, the superiority of fluticasone ointment was statistically significant for all efficacy measures. At the end of study 1, the skin of ten of eighty-eight patients (11%) who received fluticasone were rated as cleared by the investigators and fifty (57%) were rated as excellent or good. Of those who received vehicle, the skin of one of ninety (1%) was rated cleared and twenty-five (28%) were rated excellent or good. In study 2, the skin of three of 105 (3%) patients who received fluticasone were rated as cleared and sixty-nine (66%) were rated as excellent or good at the end of the study. Of those who were treated with vehicle, no patient's skin was rated cleared and thirty of 100 (30%) were rated excellent or good. Adverse events were few and mild. The most common drug-related adverse events were burning and pruritus at the site of application, which occurred in 6% of both the fluticasone-treated patients and those who received vehicle. These findings support the conclusion that fluticasone, 0.005%, ointment is clinically superior to its vehicle in the treatment of psoriasis.", "In the vast majority of psoriatic patients, psoriatic lesions are localised on the body as well as on the scalp. Therefore, safety data on the combined use of calcipotriol in lotion and calcipotriol in ointment are needed.\n This study investigated the effect of high-dose treatment with a combination of calcipotriol ointment and scalp solution on calcium metabolism, indices of bone turnover and PASI in patients with extensive psoriasis.\n Following a 2-week wash-out period, 88 patients were randomised to 4 weeks of treatment with either calcipotriol ointment/scalp solution (80-100 g/week and 30-50 ml/week, respectively; n = 41) or with a dithranol/tar regimen (n = 47). Patients were seen at weeks 1, 2 and 4 during treatment and 1 week following cessation of treatment.\n No significant differences at the end of treatment were found between the 2 groups with respect to 24-hour urinary excretion of calcium (expressed as calcium/creatinine ratio), phosphate or pyridinoline, serum concentrations of calcium (albumin corrected), creatinine, phosphate, parathyroid hormone, 25-hydroxyvitamin D(3), 1,25-dihydroxyvitamin D(3), osteocalcin, alkaline phosphatase (total and bone-specific iso-enzymes) or 1-collagen telopeptide. At the end of treatment, the psoriasis area and severity index had decreased by 57.4% in the calcipotriol group and by 36.1% in the dithranol/tar group (p = 0.004). Investigators' and patients' assessments of overall efficacy also favoured treatment with calcipotriol (p < 0.001).\n The combined use of calcipotriol ointment/scalp solution did not affect the indices of calcium metabolism or bone turnover and was significantly more effective than dithranol/tar in reducing disease severity and extent in patients with extensive psoriasis.\n Copyright 2002 S. Karger AG, Basel", "A comparison of efficacy, safety and tolerance of a twice-daily application of calcitriol 3 microg/g ointment with dithranol cream.\n The study was an 8-week, prospective, randomised, open, parallel-group trial with 114 patients. Subjects received either 3 microg/g calcitriol ointment (twice daily) or 0. 25-2% dithranol cream (once daily for 30 min). Results were measured using global improvement, global severity, PASI, quality of life (QOL) and Psoriasis Disability Index scores. Safety was determined from reports of adverse events and blood chemistry analysis.\n At final assessment, calcitriol and dithranol were comparably efficacious. Skin irritation was reported by 5% of calcitriol and 72% of dithranol patients. Patients rated QOL and overall acceptability of calcitriol more highly.\n Twice-daily calcitriol ointment (3 microg/g) is equally effective as a once-daily, short-contact dithranol regimen. However, calcitriol is better tolerated than dithranol, and provides a better QOL and a greater patient acceptability.\n Copyright 2000 S. Karger AG, Basel", "Clobetasol propionate foam 0.05% (Connetics Corporation, Palo Alto, CA) is approved by the United States Food and Drug Administration for the treatment of corticosteroid-responsive scalp dermatoses, but there is only limited data available for its efficacy and tolerability in treating dermatoses which affect nonscalp sites.\n The efficacy and tolerability of clobetasol propionate foam (clobetasol foam) in treating psoriatic lesions at nonscalp sites was evaluated in a multicenter, randomized, double-blinded, placebo-controlled study of 279 patients with mild to moderate plaque-type psoriasis.\n The patients applied clobetasol foam or placebo to the psoriatic lesions twice daily for two weeks. In addition to receiving clinical evaluations, the study patients completed a questionnaire evaluating various characteristics of the foam formulation, including their preference for its use and their projected likelihood to comply with similar therapy in a nonstudy environment.\n At Week 2 (or end of treatment), 68% (94/139) of patients who received clobetasol foam had a Physician's Static Global Assessment score of 0 (clear, except for minor residual discoloration) or 1 (majority of lesions have individual scores for plaque thickness, erythema, and scaling that averages 1). This was significantly more than the 21% (30/140) observed in the placebo group (P < 0.0001). Similar results were obtained for the Patient's Global Assessment score at Week 2 and in changes (from Baseline to Week 2) in the scores for the signs of psoriasis at a target lesion and for pruritus. Adverse effects were generally limited to mild and transient burning or other application site reactions in only a few patients in each treatment group. In the patient's poststudy questionnaire (completed at Week 2, or end of treatment) a majority of patients rated the characteristics of the foam formulation very highly. The patients ranked the foam formulation as superior to other topical formulations based on factors impacting their quality of life and indicated they would be more likely to comply with a recommended course of therapy with the foam formulation than with other topical formulations.\n Clobetasol propionate foam 0.05% is safe and effective for the treatment of plaque-type psoriasis on scalp and nonscalp areas, when applied twice daily for two weeks. As it is understood that patient dissatisfaction with select topical formulations affects their compliance with therapy, which necessarily affects the effectiveness of the therapy, the results of the patient's poststudy questionnaire suggest that there are multiple and integrated benefits for the use of clobetasol foam in the treatment of psoriasis of nonscalp sites.", "There continues to be a need to develop new pharmacological approaches for treating psoriasis. Topical active vitamin D compounds have proven to be both safe and effective for treating psoriasis. Paricalcitol (19-nor-1 alpha,25-dihydroxyvitamin D(2)) is a novel vitamin D analogue which has been developed for the prevention of secondary hyperparathyroidism in patients with chronic renal failure.\n To investigate the efficacy and safety of 12 weeks' therapy with a once-daily application of paricalcitol ointment (15 microg g(-1)) in comparison with placebo ointment.\n This pilot double-blinded self-controlled study was initiated in 11 patients with moderate plaque psoriasis. To characterize the biological effects further and to evaluate the efficacy of topical paricalcitol treatment in psoriasis, we have analysed immunohistochemically the expression of one of the markers for epidermal differentiation (transglutaminase K) in paricalcitol-treated skin as compared with placebo treatment.\n Treatment with paricalcitol was superior to placebo treatment beginning at week 1. The global severity score for erythema, plaque elevation and scaling was improved significantly more by paricalcitol ointment than by placebo (P < 0.001). Similar results were obtained for assessments of scaling, erythema and plaque elevation. No symptoms of local skin irritation were noted. Laboratory parameters including serum calcium, phosphorus, parathyroid hormone and urinary calcium/creatinine ratio did not reveal any changes of clinical relevance during treatment. The immunoreactivity of transglutaminase K changed after 12 weeks of paricalcitol treatment almost completely to the pattern characteristic for nonlesional psoriatic skin.\n Once-daily application of paricalcitol ointment was safe and effective for the treatment of plaque psoriasis.", "Plaque psoriasis affects about 2% of the US population. A new and unique spray formulation of clobetasol propionate (CP) 0.05% was developed to provide advantages over the currently available treatment formulations.\n To evaluate the efficacy and safety of CP 0.05% spray compared to its vehicle in the treatment of moderate to severe plaque psoriasis.\n A 4-week, single-center, randomized, double-blind, vehicle-controlled, intra-individual study in subjects with plaque psoriasis. Each of 2 target lesions per subject were randomized to receive either CP 0.05% spray or its vehicle twice daily over 4 weeks. Efficacy parameters included overall target plaque severity score, scaling, erythema, and plaque elevation at all visits. Adverse events were reported throughout the study.\n A total of 27 subjects were enrolled in the study. At all visits there was a significant intra-individual treatment effect for the overall target plaque severity (P < .001) in favor of CP spray. Throughout the study, results for scaling, erythema, and plaque elevation were significantly (P < .001) in favor of CP spray. After 4 weeks of treatment, all intra-individual response measures, with the exception of erythema, showed an average difference in severity scores of more than 4 points (based on a 9-point scale) between the lesions treated with CP 0.05% spray and the lesions treated with vehicle. No serious adverse event occurred during the course of the study. One local adverse event at the application site (5%) was considered probably related to study medication.\n CP 0.05% spray was effective and safe in reducing overall plaque severity, scaling, erythema, and plaque elevation from the first week of treatment continuing throughout the trial.", "Vitamin D analogues are useful in topical therapy of psoriasis.\n To evaluate the effect of hexafluoro-1,25-dihydroxyvitamin D3 (F6-1,25(OH)2D3) in treatment of psoriasis.\n Fifteen patients with plaque-type psoriasis were enrolled in a single centre double-blind, right/left comparison, placebo-controlled study, and received 0.1 g of petrolatum containing 5 microg of F6-1,25(OH)2D3 or 0.1 g of petrolatum (placebo) for 3 months. After completion of this double-blind study, a subset of these patients (n = 12) applied F6-1,25(OH)2D3 ointment (50 microg g-1 of petrolatum) to all their lesions (total area, 100-5000 cm2, mean area: 3300 m2) for 2 months as a single application at night.\n The mean severity score in the right/left-sided controlled topical F6-1,25(OH)2D3 (50 microg g-1) therapy group showed a decrease of 85%. In contrast, the mean severity score for the placebo-treated areas showed a decrease of 45% (P < 0.001). In the 12 patients who subsequently applied F6-1,25(OH)2D3 (50 microg g-1) ointment to all of their lesions, 91.6% showed moderate to excellent improvement. The mean Psoriasis Area and Severity Index score decreased by 44.9% (from 33.6 +/- 15 to 18.5 +/- 13). No effect on calcium homeostasis was noted. Adverse events included mild irritation in two patients that resolved during therapy.\n Topical F6-1,25(OH)2D3 is a safe and effective once a day treatment for psoriasis." ]

[ "15832486", "15386821", "15220018", "16882108", "11230779", "15978304", "15983299", "12679450", "12439788", "15860237", "15579760", "16026361", "11092281", "14693980", "14693964", "16214598", "15883215", "15220012", "15270789", "15787663", "15562376", "14739053" ]

[ "Improved glycemic control and lipid profile in a randomized study of pioglitazone compared with acarbose in patients with type 2 diabetes mellitus.", "Long-term therapy with addition of pioglitazone to metformin compared with the addition of gliclazide to metformin in patients with type 2 diabetes: a randomized, comparative study.", "Metabolic effects of pioglitazone and rosiglitazone in patients with diabetes and metabolic syndrome treated with glimepiride: a twelve-month, multicenter, double-blind, randomized, controlled, parallel-group trial.", "Metformin-pioglitazone and metformin-rosiglitazone effects on non-conventional cardiovascular risk factors plasma level in type 2 diabetic patients with metabolic syndrome.", "Concentration of the complement activation product, acylation-stimulating protein, is related to C-reactive protein in patients with type 2 diabetes.", "Metabolic effects of pioglitazone in combination with insulin in patients with type 2 diabetes mellitus whose disease is not adequately controlled with insulin therapy: results of a six-month, randomized, double-blind, prospective, multicenter, parallel-group study.", "A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia.", "Effect of pioglitazone compared with metformin on glycemic control and indicators of insulin sensitivity in recently diagnosed patients with type 2 diabetes.", "Metabolic efficacy and safety of once-daily pioglitazone monotherapy in patients with type 2 diabetes: a double-blind, placebo-controlled study.", "Effect of pioglitazone on arteriosclerosis in comparison with that of glibenclamide.", "Efficacy and safety of pioglitazone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial.", "Comparison of metabolic effects of pioglitazone, metformin, and glimepiride over 1 year in Japanese patients with newly diagnosed Type 2 diabetes.", "Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes: a 6-month randomized placebo-controlled dose-response study. The Pioglitazone 001 Study Group.", "One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes.", "Favorable effects of pioglitazone and metformin compared with gliclazide on lipoprotein subfractions in overweight patients with early type 2 diabetes.", "Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial.", "Pioglitazone decreases carotid intima-media thickness independently of glycemic control in patients with type 2 diabetes mellitus: results from a controlled randomized study.", "Effects of pioglitazone and glimepiride on glycemic control and insulin sensitivity in Mexican patients with type 2 diabetes mellitus: A multicenter, randomized, double-blind, parallel-group trial.", "Sustained effects of pioglitazone vs. glibenclamide on insulin sensitivity, glycaemic control, and lipid profiles in patients with Type 2 diabetes.", "A long-term comparison of pioglitazone and gliclazide in patients with Type 2 diabetes mellitus: a randomized, double-blind, parallel-group comparison trial.", "Effect of pioglitazone on body composition and energy expenditure: a randomized controlled trial.", "Treatment of type 2 diabetes with a combination regimen of repaglinide plus pioglitazone." ]

[ "To assess the efficacy of pioglitazone treatment in comparison with that of acarbose treatment in patients with type 2 diabetes mellitus.\n In this randomized, parallel-group, open-label study patients were assigned to treatment with either pioglitazone (n = 129) or acarbose (n = 136). During a 1-week run-in patients commenced an individualized dietary regimen which was maintained throughout the study. Patients received the assigned study medication for 26 weeks. Serum glycosylated hemoglobin (HbA1c) levels, insulin resistance and lipid profiles were determined at baseline and at endpoint.\n Mean HbA1c was reduced from 8.98+/-1.20% to 7.82+/-1.95% with pioglitazone treatment and from 9.03+/-1.32% to 8.55+/-1.96% with acarbose treatment during the 26-week study. The change from baseline to endpoint was significantly greater for pioglitazone compared with acarbose when analyzed for all patients (p < 0.001) and for those who had (p = 0.009) or had not (p < 0.001) received previous medication for diabetes mellitus. Compared with acarbose, pioglitazone produced a significantly greater decrease in fasting glucose, insulin and insulin resistance (p < 0.001 for each). Triglycerides were decreased by 71.1+/-184.1 mg/dl with pioglitazone compared with 38.1+/-171.3 mg/dl with acarbose (p = 0.001 for difference between groups). High density lipoprotein (HDL)-cholesterol level was increased by 7.8+/-10.2 mg/dl with pioglitazone compared with a decrease of 0.8+/-24.1 mg/dl with acarbose (p < 0.001). While serum low density lipoprotein (LDL)-cholesterol levels remained unchanged with both treatment regimens, the decrease from baseline in very low density lipoprotein (VLDL)-cholesterol was significantly greater with pioglitazone than with acarbose (p < 0.04). Pioglitazone decreased systolic blood pressure by 5.6+/-17.7mm Hg compared with a 0.4+/-18.4mm Hg increase during acarbose treatment (p < 0.001). Pioglitazone caused a significantly greater decrease compared with acarbose in serum levels of gamma-glutamyl aminotransferase (p < 0.001) and alanine aminotransferase (p = 0.004).\n Six months of pioglitazone treatment decreased insulin resistance and improved glycemic control to a significantly greater extent than acarbose treatment. Pioglitazone was also associated with a significantly improved lipid profile, suggesting a reduction in risk of coronary heart disease.", "This 52-week, randomized, double-blind study compared the efficacy and safety of metformin plus pioglitazone with the established combination of metformin plus gliclazide in type 2 diabetes mellitus.\n Patients with poorly controlled type 2 diabetes (HbA1c > or = 7.5% to < or =11.0%) received either pioglitazone 15 mg o.d. (titrated up to 45 mg; n = 317) or gliclazide 80 mg o.d. (titrated up to 320 mg; n = 313) and metformin at the pre-study dose. HbA1c, fasting plasma glucose (FPG), insulin, lipids and the urinary albumin/creatinine ratio were measured.\n There were no significant differences in HbA1c (1% decrease in both groups) and FPG between groups. There was a decrease in fasting insulin in the pioglitazone group compared to an increase in the gliclazide group (p < 0.001). There were significantly greater improvements in triglycerides and HDL-cholesterol in the metformin plus pioglitazone group compared to the metformin plus gliclazide group (p < 0.001). Mean LDL-cholesterol decreased with metformin plus gliclazide and increased with metformin plus pioglitazone (p < 0.001); however, this increase was considerably less marked than that in HDL-cholesterol. The mean urinary albumin/creatinine ratio was reduced by 10% in the metformin plus pioglitazone group compared to an increase of 6% in the metformin plus gliclazide group (p = 0.027). The incidence of adverse events was comparable between groups and both combinations were well tolerated.\n Compared to the established combination of metformin plus gliclazide, this study indicates potential benefits of addition of pioglitazone to metformin in terms of improvements in microalbuminuria and specific abnormalities associated with diabetic dyslipidemia.\n Copyright 2004 John Wiley & Sons, Ltd.", "Glimepiride is approved as monotherapy and in combination with metformin or with insulin, whereas the combination of glimepiride with other antihyperglycemic drugs is under investigation.\n The aim of this study was to assess the differential effect on glucose and lipid variables and tolerability of the combination of glimepiride plus pioglitazone or rosiglitazone in patients with type 2 diabetes mellitus (DM) and metabolic syndrome.\n This 12-month, multicenter, double-blind, randomized, controlled, parallel-group trial was conducted at 3 study sites in Italy. We assessed patients with type 2 DM (duration, > or =6 months) and with metabolic syndrome. All patients were required to have poor glycemic control with, or to have experienced > or =1 adverse effect (AE) with, diet and oral hypoglycemic agents such as sulfonylureas or metformin, both given up to the maximum tolerated dose. All patients received a fixed oral dose of glimepiride, 4 mg/d divided into 2 doses, self-administered for 12 months. Patients also were randomized to receive oral pioglitazone (15 mg once daily) (G + P group) or oral rosiglitazone (4 mg once daily) (G + R group), self-administered for 12 months. We assessed body mass index (BMI), glycemic control (glycosylated hemoglobin [HbA(1c)], fasting and postprandial plasma glucose and insulin levels [FPG, PPG, FPI, and PPI, respectively], and homeostasis model assessment index), lipid profile (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides [TG]), and lipoprotein variables (apolipoprotein [apo] A-I and apo B) at baseline and at 3, 6, 9, and 12 months of treatment. Treatment tolerability was assessed at each study visit using a thorough interview of patients, and comparisons of clinical and laboratory values to baseline levels.\n A total of 91 patients were enrolled in the study; 87 patients completed it (G + P group: 24 women, 21 men; mean [SD] age, 53 [6] years; G + R group: 20 women, 22 men; mean [SD] age, 54 [5] years). Patients in the G + P and G + R groups experienced significant increases in mean BMI at 12 months compared with baseline (4.92% and 6.17%, respectively; both, P < 0.05). The combination of glimepiride with pioglitazone or rosiglitazone significantly improved glycemic control in the study patients. At 12 months, we observed a 1.3% improvement in mean values for plasma HbA(1c) concentration (P < 0.01) 19.3% in FPG (P < 0.01), 16.3% in PPG (P < 0.01), 42.4% in FPI ), and 23.3% in PPI (P <0.05); no significant differences were found between treatment groups. Although the G + P group experienced a significant improvement at 12 months in almost all variables of lipid metabolism from baseline (TC, - 11%; LDL-C, -12%; HDL-C, 15%; and apo B, - 10.6% [all, P , 0.05]), the G + R group experienced a significant increase in mostly the lipid risk factors for cardiovascular disease (TC, 14.9%; LDL-C, 16.5%; TG, 17.9%; and apo B, 10.3% [all, P , 0.05]). Overall, no statistically significant changes in plasma aminotransferase activities were observed. Of the 87 patients who completed the study, 6.7% (3/45) of patients in the G + P group and 11.9% (5/42) of patients in the G + R group had transient, mild to moderate AEs that did not cause withdrawal from the trial.\n In this study of patients with type 2 DM and metabolic syndrome who did not respond adequately to, or experienced AEs with, diet and either a sulfonylurea or metformin previously, the combination of glimepiride plus pioglitazone was associated with a significant improvement in lipid and lipoprotein variables, whereas the combination of glimepiride plus rosiglitazone appears to not have had any clinically significant effect on lipid metabolism.", "Metformin is considered the gold standard for type 2 diabetes treatment as monotherapy and in combination with sulphonylureas and insulin. The combination of metformin with thiazolidinediones is less well studied. The aim of the present study was to assess the differential effect, and tolerability, of metformin combined with pioglitazone or rosiglitazone on glucose, coagulation and fibrinolysis parameters in patients with type 2 diabetes mellitus and metabolic syndrome.\n This 12-month, multicentre, double-blind, randomized, controlled, parallel-group trial was conducted at three study sites in Italy. We assessed patients with type 2 diabetes mellitus (duration >or=6 months) and with metabolic syndrome. All patients were required to have poor glycaemic control with diet, or experienced adverse effects with diet and metformin, administered up to the maximum tolerated dose. Patients were randomized to receive either pioglitazone or rosiglitazone self-administered for 12 months. We assessed body mass index (BMI), glycaemic control [glycosylated haemoglobin (HbA(1c)), fasting and postprandial plasma glucose and insulin levels (FPG, PPG, FPI, and PPI respectively), homeostasis model assessment (HOMA) index], lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG)], lipoprotein (a) [Lp(a)] and homocysteine (HCT) at baseline and at 3, 6, 9 and 12 months of treatment.\n No BMI change was observed at 3, 6, 9 and 12 months in either group. Significant HbA(1c) decreases were observed at 9 and 12 months in both groups. After 9 and 12 months, mean FPG and PPG levels decreased in both groups. Decreases in FPI and PPI were observed at 9 and 12 months compared with the baseline in both groups. Furthermore, in both groups, the HOMA index improved but only at 12 months. Significant TC, LDL-C, HDL-C, TG improvement was present in the pioglitazone group at 12 months compared with the baseline values, and these variations were significantly different between groups. No TC, LDL-C, TG improvement was present in the rosiglitazone group after 12 months. Significant Lp(a) and HCT improvement was present in the pioglitazone group at 12 months compared with the baseline values, and Lp(a) change was significant compared with the rosiglitazone group. Significant HCT decrease was observed in the rosiglitazone group at the end of the study. In our type 2 diabetic patients, both drugs were safe and effective for glycaemic control and improving HCT plasma levels. However, long-term treatment with metformin plus pioglitazone significantly reduced Lp(a) plasma levels, whereas metformin + rosiglitazone did not.\n For patients with type 2 diabetes mellitus and metabolic syndrome, combined treatment with metformin and rosiglitazone or pioglitazone is safe and effective, However, the pioglitazone combination also reduced the plasma Lp(a) levels whereas the rosiglitazone combination did not.", "Type 2 diabetes is characterized by increased acute phase serum proteins. We wanted to study how these proteins are related to complement activation in type 2 diabetes and how improvement of glycemic control affects them or complement activation. A total of 29 type 2 diabetic patients (age, 55.2 +/- 1.8 years, glycosylated hemoglobin [HbA(1c)] 8.9% +/- 0.2%, body mass index [BMI] 30.9 +/- 0.8 kg/m(2), duration 5.9 +/- 1.3 years) participated in the study. They were previously treated either with diet alone or in combination with 1 oral antihyperglycemic medication. After a period of at least 4 weeks run-in on diet only, the patients were randomized to pioglitazone, glibenclamide, or placebo. Blood samples were taken before the treatments and at the end of the 6-month therapy. Basal C-reactive protein (CRP) level was related to acylation-stimulating protein (ASP) concentration (r =.55, P <.01), and many acute phase serum protein concentrations were associated with each other. The treatment reduced HbA(1c) level in the pioglitazone (from 9.1 +/- 0.3% to 8.0 +/- 0.5%, P <.05) and glibenclamide (from 8.9 % +/- 0.3% to 7.7% +/- 0.2%, P <.05) groups. Glibenclamide treatment was associated with a reduction in alpha-1-antitrypsin (P <.05), ceruloplasmin (P <.01), and complement C3 protein (C3) (P <.05). Although ASP did not change significantly in any of the treatment subgroups, in the whole patient population, the change in HbA(1c) during the treatments correlated positively with the change in ASP, (r =.43, P <.05). The changes in many acute phase serum proteins and ASP were related to each other. In conclusion, (1) inflammatory factors and complement activation are associated in patients with type 2 diabetes, and (2) changes in hyperglycemia are related to changes in the concentration of the complement activation product, ASP.\n Copyright 2001 by W.B. Saunders Company", "Type 2 diabetes mellitus (DM) is a progressive disease. Initial therapy begins with dietary and lifestyle modifications. However, as the disease progresses, glycemic control becomes more difficult to attain, often requiring > or =1 oral antihyperglycemic medication (OAM), and finally the addition of insulin to the OAMs and insulin monotherapy.\n This study was designed to determine the effect of pioglitazone 30 mg plus insulin (PIO + INS) versus placebo plus insulin (PLB + INS) on glycemic control, the serum lipid profile, and selected cardiovascular risk factors in patients with type 2 DM whose disease was inadequately controlled with insulin therapy alone despite efforts to intensify such treatment.\n This was a 6-month, randomized, double-blind, prospective, multicenter, placebo-controlled, parallel-group study. Patients with type 2 DM and a glycosylated hemoglobin (HbA(1c)) value > or =7.5% who were using insulin (with or without OAMs) entered a 3-month insulin intensification phase to achieve blood glucose targets with insulin monotherapy. After insulin intensification, those patients with HbA(1c) values > or =7.0% were randomized to PIO + INS or PLB + INS. The primary end point was the change in HbA(1c) from baseline. Cardiovascular risk markers (highly sensitive C-reactive protein [hs CRP] and plasminogen activator inhibitor-1 [PAI-1]) were measured at baseline and end point.\n Of the 289 patients randomized to treatment (mean [SD] age, 58.9 [7.1] years; 164 women, 125 men), 142 received PIO + INS and 147 received PLB + INS. A total of 263 patients completed the study. After 6 months, PIO + INS reduced mean HbA(1c) (-0.69%; P < 0.002) and mean fasting plasma glucose ([FPG] -1.45 mmol/L; P < 0.002) from baseline. PLB + INS produced no significant changes in HbA(1c) or FPG. The between-treatment differences for HbA(1c) (-0.55%; P < 0.002) and FPG (-1.80 mmol/L; P < 0.002) occurred despite a reduction of insulin dose in the PIO + INS group from baseline (-0.16 U/d . kg; P < 0.002). Significant between-group differences were observed for high-density lipoprotein cholesterol (0.13 mM; P < 0.002), triglycerides (ratio of geometric mean [PIO/PLB], 0.871; P < 0.01), atherogenic index of plasma (-0.11; P < 0.002), PAI-1 (-5.10 U/mL; P < 0.001), and hs CRP (-1.47 mg/L; P < 0.05). The rate of clinical and biochemical hypoglycemia (blood glucose <2.8 mmol/L) did not differ statistically between treatment groups, but reported incidences of subjective hypoglycemia occurred more often with PIO + INS than with PLB + INS (90 vs 75; P < 0.05). Edema was more common with PIO + INS than with PLB + INS (20 vs 5 instances, respectively), as was gain (mean [SEM]) in body weight (4.05 [4.03] vs 0.20 [2.92] kg, respectively).\n Adding pioglitazone to insulin in these study patients with type 2 DM whose disease was inadequately controlled with insulin monotherapy further improved their glycemic control.", "Published reports suggest that pioglitazone and rosiglitazone have different effects on lipids in patients with type 2 diabetes. However, these previous studies were either retrospective chart reviews or clinical trials not rigorously controlled for concomitant glucose- and lipid-lowering therapies. This study examines the lipid and glycemic effects of pioglitazone and rosiglitazone.\n We enrolled subjects with a diagnosis of type 2 diabetes (treated with diet alone or oral monotherapy) and dyslipidemia (not treated with any lipid-lowering agents). After a 4-week placebo washout period, subjects randomly assigned to the pioglitazone arm (n = 400) were treated with 30 mg once daily for 12 weeks followed by 45 mg once daily for an additional 12 weeks, whereas subjects randomly assigned to rosiglitazone (n = 402) were treated with 4 mg once daily followed by 4 mg twice daily for the same intervals.\n Triglyceride levels were reduced by 51.9 +/- 7.8 mg/dl with pioglitazone, but were increased by 13.1 +/- 7.8 mg/dl with rosiglitazone (P < 0.001 between treatments). Additionally, the increase in HDL cholesterol was greater (5.2 +/- 0.5 vs. 2.4 +/- 0.5 mg/dl; P < 0.001) and the increase in LDL cholesterol was less (12.3 +/- 1.6 vs. 21.3 +/- 1.6 mg/dl; P < 0.001) for pioglitazone compared with rosiglitazone, respectively. LDL particle concentration was reduced with pioglitazone and increased with rosiglitazone (P < 0.001). LDL particle size increased more with pioglitazone (P = 0.005).\n Pioglitazone and rosiglitazone have significantly different effects on plasma lipids independent of glycemic control or concomitant lipid-lowering or other antihyperglycemic therapy. Pioglitazone compared with rosiglitazone is associated with significant improvements in triglycerides, HDL cholesterol, LDL particle concentration, and LDL particle size.", "Pioglitazone, a thiazolidinedione, improves glycemic control primarily by increasing peripheral insulin sensitivity in patients with type 2 diabetes, whereas metformin, a biguanide, exerts its effect primarily by decreasing hepatic glucose output. In the first head-to-head, double-blind clinical trial comparing these two oral antihyperglycemic medications (OAMs), we studied the effect of 32-wk monotherapy on glycemic control and insulin sensitivity in 205 patients with recently diagnosed type 2 diabetes who were naive to OAM therapy. Subjects were randomized to either 30 mg pioglitazone or 850 mg metformin daily with titrations upward to 45 mg (77% of pioglitazone patients) and 2550 mg (73% of metformin patients), as indicated, to achieve fasting plasma glucose levels of less than 7.0 mmol/liter (126 mg/dl). Pioglitazone was comparable to metformin in improving glycemic control as measured by hemoglobin A1C and fasting plasma glucose. At endpoint, pioglitazone was significantly more effective than metformin in improving indicators of insulin sensitivity, as determined by reduction of fasting serum insulin (P = 0.003) and by analysis of homeostasis model assessment for insulin sensitivity (HOMA-S; P = 0.002). Both OAM therapies were well tolerated. Therefore, pioglitazone and metformin are equally efficacious in regard to glycemic control, but they exert significantly different effects on insulin sensitivity due to differing mechanisms of action. The more pronounced improvement in indicators of insulin sensitivity by pioglitazone, as compared with metformin monotherapy in patients recently diagnosed with type 2 diabetes who are OAM-naive, may be of interest for further clinical evaluation.", "Pioglitazone is a novel oral anti-diabetic agent belonging to the thiazolidinedione class. Pioglitazone has been shown to be effective and well tolerated in the treatment of patients with type 2 diabetes, as it reduces insulin resistance and improves glycaemic control and abnormal lipid profiles. This double-blind, randomised, placebo-controlled study was conducted for further evaluation of the efficacy and tolerability of once-daily administration of pioglitazone monotherapy alongside dietary measures in patients with type 2 diabetes. Following a 10-week washout period, 251 patients received one of three treatment regimens for 26 weeks: placebo + diet (n = 84), pioglitazone 15 mg once-daily + diet (n = 89), or pioglitazone 30 mg once-daily + diet (n = 78). Pioglitazone, both 15 and 30 mg/day, in addition to dietary control, was associated with significant reductions (vs. placebo) in mean levels of both glycosylated haemoglobin (HbA 1C ) and fasting blood glucose (FBG). HbA 1C was reduced by 0.92 % and 1.05 %, respectively, and FBG was reduced by 34.3 and 36.0 mg/dl, respectively, compared with the control group. Pioglitazone at 15 and 30 mg/day significantly reduced postprandial blood glucose levels at all visits (- 163 and - 165 mg/dl/hour, respectively) compared with an increase of 47.7 mg/dl/hour on placebo. The profile and frequency of adverse events were similar in all treatment groups. These results indicate that pioglitazone monotherapy together with dietary control is both effective and safe in patients with type 2 diabetes.", "Pioglitazone is an insulin-sensitizing agent that has been reported to have anti-arteriosclerotic effects.\n To investigate the anti-arteriosclerotic effects of pioglitazone in patients with diabetes mellitus using pulse wave velocity (PWV) as an index of efficacy.\n Twenty-seven patients with type 2 diabetes mellitus were randomly assigned to two groups, and pioglitazone (n=13) or glibenclamide (n=14) was administered for 6 months. The TG, TC, LDL-C, and HDL-C, FPG, HbA1c, IRI levels, HOMA-IR, and ba-PWV data were examined before and after administration of each agent.\n FPG and HbA1c were significantly improved in both the groups after treatment, but IRI, HOMA-IR and were improved only in the PIO group. The percent change of ba-PWV from the baseline after treatment in the PIO group improved significantly than that in the GC group (-6.3 +/- 5.6% versus 0.8 +/- 5.7%).\n The findings in this study suggested that pioglitazone has anti-arteriosclerotic effects. We concluded that drugs for the treatment of diabetes mellitus should be selected taking into consideration such endpoints as blood sugar control, and also the risk of complications such as cardiovascular events in the future.", "Pioglitazone increases the insulin sensitivity of peripheral tissues and may provide an alternative first-line treatment for type 2 diabetes. This study compared metabolic control in drug-naive type 2 diabetes patients given either pioglitazone or metformin. Eleven hundred and ninety-nine patients with poorly controlled type 2 diabetes mellitus [glycosylated hemoglobin (HbA1c), 7.5-11%; normal, 4.3-6.1%] were randomized to receive either pioglitazone (< or =45 mg/d) or metformin (< or =850 mg, three times daily). HbA1c, fasting plasma glucose (FPG), insulin levels, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol, triglycerides, free fatty acids, and urinary albumin/creatinine ratio were measured. Mean HbA1c decreased in both treatment groups from baseline to wk 52 (-1.4% and -1.5%). Significantly greater mean reductions in FPG were observed in the pioglitazone group (-45.0 mg/dl; -2.5 mmol/liter) than in the metformin (-39.6 mg/dl; -2.2 mmol/liter) group (P = 0.016). Favorable changes in triglycerides and HDL-C were more pronounced with pioglitazone. Although low density lipoprotein cholesterol and TC levels increased with pioglitazone, TC/HDL-C ratios decreased similarly with both treatments. The urinary albumin/creatinine ratio was reduced by 19% with pioglitazone treatment, but remained unchanged with metformin therapy (-1%; P = 0.002). There was an increase in body weight of 1.9 kg in the pioglitazone group and a decrease of 2.5 kg in the metformin group. The overall frequency of adverse events was similar between treatment groups, but adverse event profiles were different between treatment groups. HbA1c reduction is similar after pioglitazone and metformin monotherapies, but differences in FPG, plasma lipids, and adverse effects between the two compounds may influence decision-making in individual prescribers.", "To compare the metabolic effects of pioglitazone, metformin, and glimepiride in the treatment of Japanese patients with newly diagnosed Type 2 diabetes.\n A total of 114 patients with Type 2 diabetes who had never used oral hypoglycaemic drugs were studied for 12 months. Patients were randomly assigned to pioglitazone (30-45 mg/day, n = 38), metformin (750 mg/day, n = 39), or glimepiride (1.0-2.0 mg/day, n = 37). The effect of treatment on fasting plasma glucose (FPG), glycated haemoglobin (HbA(1c)), 1,5-anhydroglucitol (1,5AG), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, free fatty acids (FFA), and fasting plasma insulin levels was monitored monthly. Body weight and safety data were also collected.\n Eight patients withdrew from the study (three in the pioglitazone group, two in the metformin group, and three in the glimepiride group). The rate of reduction of HbA(1c) was fastest in patients receiving glimepiride and slowest in patients receiving pioglitazone. Although there were no significant differences among the three groups in HbA(1c) levels at the end of the study, patients taking pioglitazone had relatively lower FPG and 1,5AG levels than patients taking the other two drugs. These results suggest that pioglitazone acts predominantly on nocturnal metabolism rather than at mealtimes. FFA were reduced significantly in those taking pioglitazone (542.2 microEq/l vs. 237.3 microEq/l; P < 0.01) before a decrease in HbA(1c) was apparent. The change in FFA levels correlated with the change in HbA(1c) (r = 0.409, P < 0.01). There were no significant differences in other lipid parameters among the groups.\n Pioglitazone, metformin, and glimepiride are equally effective in reducing blood glucose in patients with newly diagnosed Type 2 diabetes. However, their specific characteristics, such as the rapid action on blood glucose levels of glimepiride and the favourable action on FPG and FFA of pioglitazone, should be considered when choosing an appropriate agent.", "To evaluate the efficacy and safety of four doses of pioglitazone monotherapy in the treatment of patients with type 2 diabetes.\n There were 408 patients randomized in this multicenter double-blind placebo-controlled clinical trial. Patients who had HbA1c > or = 7.0%, fasting plasma glucose (FPG) > or = 140 mg/dl, and C-peptide > 1 ng/ml were randomized to receive placebo or 7.5, 15, 30, or 45 mg pioglitazone administered once a day for 26 weeks.\n Patients treated with 15, 30, or 45 mg pioglitazone had significant mean decreases in HbA1c (range -1.00 to -1.60% difference from placebo) and FPG (-39.1 to -65.3 mg/dl difference from placebo). The decreases in FPG were observed as early as the second week of therapy; maximal decreases occurred after 10-14 weeks and were maintained until the end of therapy (week 26). In the 15-, 30-, or 45-mg pioglitazone groups, there were significant mean percent decreases in triglycerides, significant mean percent increases in HDL cholesterol, and only small percent changes in total cholesterol and LDL. The subset of patients naive to therapy had greater improvements in HbA1c and FPG (difference from placebo of -2.55% and -79.9 mg/dl for the 45-mg group) compared with previously treated patients. The overall adverse event profile of pioglitazone was similar to that of placebo. There was no evidence of drug-induced hepatotoxicity or drug-induced elevations of alanine aminotransferase levels in this study\n Pioglitazone monotherapy significantly improves HbA1c and FPG while producing beneficial effects on serum lipids in patients with type 2 diabetes with no evidence of drug-induced hepatotoxicity.", "The goal was to assess the 1-year efficacy and safety of the addition of pioglitazone or metformin to existing sulfonylurea (SU) therapy in patients with inadequately controlled type 2 diabetes.\n In this multicenter, double-blind study, patients were randomized to receive either pioglitazone 15 mg (n = 319) or metformin 850 mg (n = 320) and up to 45 mg/day and 2,550 mg/day, respectively. The primary efficacy endpoint was HbA(1c) at week 52. Fasting plasma glucose, insulin, and lipid profiles were also measured.\n HbA(1c) was reduced by 1.20% in the SU plus pioglitazone group and 1.36% in the SU plus metformin group, and fasting plasma glucose was reduced by 2.2 and 2.3 mmol/l in the respective groups. Fasting insulin levels were also reduced (pioglitazone arm -1.3 micro IU/ml; metformin arm -0.8 micro IU/ml). There were no significant between-treatment differences in these three parameters. Pioglitazone addition to SU significantly reduced triglycerides (-16 vs. -9%; P = 0.008) and increased HDL cholesterol (14 vs. 8%; P < 0.001) compared with metformin addition. LDL cholesterol was increased 2% by the addition of pioglitazone and decreased 5% by the addition of metformin to SU (P < 0.001). Urinary albumin-to-creatinine ratio was reduced by 15% in the SU plus pioglitazone group and increased 2% in the SU plus metformin group (P = 0.017). Both combinations were well tolerated with no evidence of hepatic or cardiac toxicity in either group.\n Clinically equivalent improvements in glycemic control were observed for both combinations. Compared with metformin plus SU, addition of pioglitazone to SU resulted in a reduction of the urinary albumin-to-creatinine ratio, a small but significant rise in LDL cholesterol, and significantly greater improvements in triglyceride levels and HDL cholesterol levels. Metformin plus SU was associated with a significant reduction in LDL cholesterol. SU plus pioglitazone is an effective and well-tolerated combination regimen that may provide additional beneficial effects for patients with type 2 diabetes.", "To compare effects of different oral hypoglycemic drugs as first-line therapy on lipoprotein subfractions in type 2 diabetes.\n Sixty overweight type 2 diabetic patients not on lipid-lowering therapy were randomized to metformin, pioglitazone, or gliclazide after a 3-month dietary run-in. Drug doses were uptitrated for 3 months to optimize glycemia and were kept fixed for a further 3 months. LDL subfractions (LDL(1), LDL(2), and LDL(3)) were prepared by density gradient ultracentrifugation at randomization and study end. Triglycerides, cholesterol, total protein, and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. The primary end point was change in proportion of LDL as LDL(3).\n HbA(1c), triglycerides, glucose, and cholesterol were comparable across groups at baseline and over time. LDL(3) mass and the LDL(3)-to-LDL ratio fell with pioglitazone (LDL(3) mass 36.2 to 28.0 mg/dl, P < 0.01; LDL(3)-to-LDL 19.2:13.3%, P < 0.01) and metformin (42.7 to 31.5 mg/dl, P < 0.01; 21.3:16.2%, P < 0.01, respectively) with no change on gliclazide. LDL(3) reductions were associated with reciprocal LDL(1) increases. Changes were independent of BMI, glycemic control, and triglycerides. Total HDL cholesterol increased on pioglitazone (1.28 to 1.36 mmol/l, P = 0.02) but not gliclazide (1.39 to 1.37 mmol/l, P = NS) or metformin (1.26 to 1.18 mmol/l, P = NS), largely due to an HDL(2) increase (0.3 to 0.4 mmol/l, P < 0.05). HDL(3) cholesterol fell on metformin (0.9 to 0.85 mmol/l, P < 0.01). On pioglitazone and metformin, the HDL(2)-to-HDL(3) ratio increased compared with no change on gliclazide.\n For the same improvement in glycemic control, pioglitazone and metformin produce favorable changes in HDL and LDL subfractions compared with gliclazide in overweight type 2 diabetic patients. Such changes may be associated with reduced atherosclerosis risk and may inform the choice of initial oral hypoglycemic agent.", "Patients with type 2 diabetes are at high risk of fatal and non-fatal myocardial infarction and stroke. There is indirect evidence that agonists of peroxisome proliferator-activated receptor gamma (PPAR gamma) could reduce macrovascular complications. Our aim, therefore, was to ascertain whether pioglitazone reduces macrovascular morbidity and mortality in high-risk patients with type 2 diabetes.\n We did a prospective, randomised controlled trial in 5238 patients with type 2 diabetes who had evidence of macrovascular disease. We recruited patients from primary-care practices and hospitals. We assigned patients to oral pioglitazone titrated from 15 mg to 45 mg (n=2605) or matching placebo (n=2633), to be taken in addition to their glucose-lowering drugs and other medications. Our primary endpoint was the composite of all-cause mortality, non fatal myocardial infarction (including silent myocardial infarction), stroke, acute coronary syndrome, endovascular or surgical intervention in the coronary or leg arteries, and amputation above the ankle. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN NCT00174993.\n Two patients were lost to follow-up, but were included in analyses. The average time of observation was 34.5 months. 514 of 2605 patients in the pioglitazone group and 572 of 2633 patients in the placebo group had at least one event in the primary composite endpoint (HR 0.90, 95% CI 0.80-1.02, p=0.095). The main secondary endpoint was the composite of all-cause mortality, non-fatal myocardial infarction, and stroke. 301 patients in the pioglitazone group and 358 in the placebo group reached this endpoint (0.84, 0.72-0.98, p=0.027). Overall safety and tolerability was good with no change in the safety profile of pioglitazone identified. 6% (149 of 2065) and 4% (108 of 2633) of those in the pioglitazone and placebo groups, respectively, were admitted to hospital with heart failure; mortality rates from heart failure did not differ between groups.\n Pioglitazone reduces the composite of all-cause mortality, non-fatal myocardial infarction, and stroke in patients with type 2 diabetes who have a high risk of macrovascular events.", "Patients with type 2 diabetes mellitus are at high risk of cardiovascular disease. Carotid intima-media thickness (IMT) is a strong predictor of myocardial infarction and stroke.\n We compared the effects of pioglitazone-based therapy (45 mg/d) and glimepiride-based treatment (2.7+/-1.6 mg/d) for 12 and 24 weeks on metabolic control (HbA1c), insulin resistance (homeostasis model assessment), and carotid IMT (B-mode ultrasonography) in a randomized controlled study in 173 orally treated patients with type 2 diabetes (66 women, 107 men; mean+/-SD age, 62.6+/-7.9 years; body mass index, 31.8+/-4.6 kg/m2; HbA1c, 7.5+/-0.9%). Treatment was generally well tolerated in both groups. Despite similar improvements in metabolic control (HbA1c) after 24 weeks (-0.8+/-0.9% [pioglitazone] versus -0.6+/-0.8% [glimepiride]; P=NS), carotid IMT was reduced only in the pioglitazone group after 12 weeks (-0.033+/-0.052 versus -0.002+/-0.047 mm [glimepiride]; P<0.01 between groups) and 24 weeks (-0.054+/-0.059 versus -0.011+/-0.058 mm [glimepiride]; P<0.005 between groups). Insulin resistance was also improved only in the pioglitazone group (homeostasis model assessment, -2.2+/-3.4 versus -0.3+/-3.3; P<0.0001 between groups). Reduction of IMT correlated with improvement in insulin resistance (r=0.29, P<0.0005) and was independent of improvement in glycemic control (r=0.03, P=0.68).\n We found a substantial regression of carotid IMT, independent of improved glycemic control, after 12 and 24 weeks of pioglitazone treatment. This finding may have important prognostic implications for patients with type 2 diabetes mellitus.", "Pioglitazone and glimepiride improve glycemic control in patients with type 2 diabetes mellitus by different mechanisms. Pioglitazone is a thiazolidinedione that reduces insulin resistance, and glimepiride is a sulfonylurea insulin secretagogue.\n The goals of this study were to compare changes in measures of glycemic control and insulin sensitivity in Mexican patients with type 2 diabetes who received pioglitazone or glimepiride for 1 year.\n This was a multicenter, 52-week, double-blind, parallel-group trial. Patients were randomized to receive monotherapy with either glimepiride (2 mg QD initially) or pioglitazone (15 mg QD initially). Doses were titrated (maximal doses: pioglitazone 45 mg, glimepiride 8 mg) to achieve glycemic targets (fasting blood glucose < or =7 mmol/L and 1-hour postprandial blood glucose < or =10 mmol/L). Insulin sensitivity (primary end point) was evaluated in terms of the Homeostasis Model Assessment for Insulin Sensitivity (HOMA-S), the Quantitative Insulin Sensitivity Check Index (QUICKI), and fasting serum insulin (FSI) concentrations. Glycemic control was evaluated in terms of glycosylated hemoglobin (HbA(1c)) values and fasting plasma glucose (FPG) concentrations. Patients were encouraged to maintain their individual diet and exercise regimens throughout the study.\n Two hundred forty-four patients (125 women, 119 men; all but 1 Hispanic) were randomized to receive pioglitazone (n = 121) or glimepiride (n = 123). In the intent-to-treat sample, pioglitazone and glimepirede produced comparable reductions in HbA(1c) from baseline to the end of the study (-0.78% and -0.68%, respectively). The pioglitazone group had significantly higher HbA(1c) values compared with the glimepiride group after 12 weeks of therapy (8.66% vs 7.80%; P = 0.007) but had significantly lower values after 52 weeks (7.46% vs 7.77%; P = 0.027). Pioglitazone significantly reduced FPG compared with glimepiride (-0.6 vs 0.6 mmol/L; P = 0.01). Pioglitazone therapy was associated with significant increases in insulin sensitivity (reduced insulin resistance), whereas glimepiride had no effect. HOMA-S values changed 18.0% for pioglitazone and -7.9% for glimepiride (P < 0.001), QUICKI values changed a respective 0.013 and -0.007 (P < 0.001), and FSI values were -21.1 and 15.1 pmol/L (P< 0.001). Both drugs were well tolerated, with pioglitazone associated with more peripheral edema (number of treatment-emergent cases: 35/121[28.9%] vs 17/123 [13.8%]; P = 0.005) and fewer hypoglycemic episodes (19 [15.7%] vs 38 [30.9%]; P = 0.024). The incidence of weight gain was not significantly different between treatment groups. Conclusions: These data suggest that long-term treatment with pioglitazone enhances insulin sensitivity relative to glimepiride in Mexican patients with type 2 diabetes and that pioglitazone may have a more sustained antihyperglycemic effect.", "This study compared the effects of 52 weeks' treatment with pioglitazone, a thiazolidinedione that reduces insulin resistance, and glibenclamide, on insulin sensitivity, glycaemic control, and lipids in patients with Type 2 diabetes.\n Patients with Type 2 diabetes were randomized to receive either pioglitazone (initially 30 mg QD, n = 91) or micronized glibenclamide (initially 1.75 mg QD, n = 109) as monotherapy. Doses were titrated (to 45 mg for pioglitazone and 10.5 mg for glibenclamide) to achieve glycaemic targets during the next 12 weeks: fasting blood glucose of < or = 7 mmol/l and 1-h postprandial blood glucose of < or = 10 mmol/l. Patients were maintained on the titrated dose for 40 weeks.\n Pioglitazone significantly increased insulin sensitivity compared with glibenclamide, as assessed by homeostasis model assessment (17.0% vs. -13.0%; P < 0.001), quantitative insulin sensitivity check index (0.011 vs. -0.007; P < 0.001) and fasting serum insulin (-1.3 pmol/l vs. 23.8 pmol/l; P = 0.007). The glibenclamide group had significantly lower HbA1c than the pioglitazone group after 12 weeks of therapy (7.8% vs. 8.3%, P = 0.015), but significantly higher HbA1c after 52 weeks of therapy (7.8% vs. 7.2%, P = 0.001). Pioglitazone significantly (vs. glibenclamide) increased mean HDL-C (P < 0.001), decreased mean triglycerides (P = 0.019), and decreased mean atherogenic index of plasma (AIP; P = 0.001) and mean total cholesterol/HDL-C (P = 0.004), without significantly elevating mean total cholesterol or mean LDL-C compared with glibenclamide. CONCLUSIONS These data suggest that the effects of pioglitazone are more sustained than those of glibenclamide for improving insulin sensitivity in patients with Type 2 diabetes, and that 52 weeks' treatment with pioglitazone has favourable effects on glycaemic control and lipoprotein profile.\n Copyright 2004 Diabetes UK", "This study compared the effects of pioglitazone and gliclazide on metabolic control in drug-naive patients with Type 2 diabetes mellitus.\n A total of 1270 patients with Type 2 diabetes were randomized in a parallel-group, double-dummy, double-blind study. Patients with poorly controlled Type 2 diabetes (HbA1c 7.5-11%), despite dietary advice, received either pioglitazone up to 45 mg once daily or gliclazide up to 160 mg two times daily. Primary efficacy endpoint was change in HbA1c from baseline to the end of the study. Secondary efficacy endpoints included change in fasting plasma glucose, fasting plasma insulin and plasma lipids. At selected centres, oral glucose tolerance tests were performed and C-peptide and pro-insulin levels were measured.\n Mean HbA1c values decreased by the same amount in the two treatment groups from baseline to week 52 [pioglitazone: -1.4%; gliclazide: -1.4%; (90% CI: -0.18 to 0.02)]. A significantly greater mean reduction in fasting plasma glucose was observed in the pioglitazone group (2.4 mmol/l) than in the gliclazide group [2.0 mmol/l; treatment difference -0.4 mmol/l in favour of pioglitazone; P = 0.002; (95% CI: -0.7 to -0.1)]. Improvements in high-density lipoprotein cholesterol (HDL-C) and total cholesterol/HDL-C were greater with pioglitazone than with gliclazide (P < 0.001). The frequencies of adverse events were comparable between the two treatment groups, but more hypoglycaemic events were reported for gliclazide, whereas twice as many patients reported oedema with pioglitazone than with gliclazide.\n Pioglitazone monotherapy was equivalent to gliclazide in reducing HbA1c, with specific differences between treatments in terms of mechanism of action, plasma lipids and adverse events.", "Several clinical studies have demonstrated that body weight increases after treatment with thiazolidinediones (TZDs). Prior studies have demonstrated an increase in insulin-stimulated lipid storage in adipose tissue. Some, but not all, studies demonstrate reductions in visceral adipose tissue. Changes in body weight are the result of changes in energy intake, energy expenditure, or both.\n Based on these findings, the primary aim of this study was to evaluate the effect of TZDs on visceral, subcutaneous, and total body fat. Secondary aims were to determine the effects of pioglitazone on (a) energy expenditure, (b) hunger and satiety, (c) blood lipids, and (d) the role of insulinemia/sulfonylurea usage on weight gain in patients with type 2 diabetes.\n We performed a randomized, double-blind, placebo-controlled trial in 48 men and women with type 2 diabetes who had not previously received treatment with TZDs. Patients were treated for 24 weeks with 45 mg/d of pioglitazone or a matching placebo. Body composition was measured by dual-energy x-ray absorptiometry. Visceral and subcutaneous fat were measured by computed tomography. Resting metabolic rate and thermogenic response to a test meal were measured by indirect calorimetry before and after a standardized meal. Hunger and satiety were measured with visual analog scales before and after the same test meal. Blood was collected for the measurement of fasting glucose and insulin levels, hemoglobin A 1c levels, and lipid content.\n Pioglitazone treatment resulted in a decrease in hemoglobin A(1c) level by 0.96 +/- 1.1% vs 0.11 +/- 0.8% in the placebo group (P < .005). Body weight and fat increased steadily in the patients treated with pioglitazone during the 6 months of the study (+3.9 +/- 3.1 kg at 6 months in pioglitazone-treated patients vs -0.8 +/- 3.4 kg in the placebo-treated patients). Subcutaneous fat in the trunk, arms, and legs were all increased in the pioglitazone-treated group. Visceral fat did not change significantly in either group. Neither resting metabolic rate nor the thermogenic responses to a meal were altered by pioglitazone. Subjective measures of hunger (visual analog scale) did not change with pioglitazone treatment. Triglycerides fell in the pioglitazone-treated group (-58.5 +/- 124 mg/dL, P < .003). Neither the prior use of sulfonylureas nor the level of insulinemia before treatment was a predictor of weight or fat change.\n Pioglitazone increased subcutaneous body fat, but not visceral fat. There was no measurable effect on energy expenditure or hunger/satiety. In contrast to the placebo-treated patient with diabetes, weight gain occurs in the face of falling hemoglobin A(1c) and triglyceride levels.", "The efficacy and safety of combination therapy (repaglinide plus pioglitazone) was compared to repaglinide or pioglitazone in 24-week treatment of type 2 diabetes. This randomized, multicenter, open-label, parallel-group study enrolled 246 adults (age 24-85) who had shown inadequate response in previous sulfonylurea or metformin monotherapy (HbA(1c) > 7%). Prior therapy was withdrawn for 2 weeks, followed by randomization to repaglinide, pioglitazone, or repaglinide/pioglitazone. In the first 12 weeks of treatment, repaglinide doses were optimized, followed by 12 weeks of maintenance therapy. Pioglitazone dosage was fixed at 30 mg per day. Baseline HbA(1c) values were comparable (9.0% for repaglinide, 9.1% for pioglitazone, 9.3% for combination). Mean changes in HbA(1c) values at the end of treatment were -1.76% for repaglinide/pioglitazone, -0.18% for repaglinide, +0.32% for pioglitazone. Fasting plasma glucose reductions were -82 mg/dl for combination therapy, -34 mg/dl for repaglinide, -18 mg/dl for pioglitazone. Minor hypoglycemia occurred in 5% of patients for the combination, 8% for repaglinide, and 3% for pioglitazone. Weight gains for combination therapy were correlated to individual HbA(1c) reductions. In summary, for patients who had previously failed oral antidiabetic monotherapy, the combination repaglinide/pioglitazone had acceptable safety, with greater reductions of glycemic parameters than therapy using either agent alone." ]

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[ "Axillary block by \"selective\" injections at the nerves involved in surgery using a peripheral nerve stimulator: a comparison with a \"standard\" triple-injection technique.", "Radial plus musculocutaneous nerve stimulation for axillary block is inferior to triple nerve stimulation with 2% mepivacaine.", "A comparison of three methods of axillary brachial plexus anaesthesia.", "[Axillary brachial plexus anesthesia. How many nerve stimulation responses do we look for?].", "Axillary brachial plexus block using peripheral nerve stimulator: a comparison between double- and triple-injection techniques.", "Comparison of the clinical efficacy of three perivascular techniques for axillary brachial plexus block.", "A comparison of four stimulation patterns in axillary block.", "Axillary brachial plexus blockade: an evaluation of three techniques.", "A comparison of three methods of axillary approach to brachial plexus blockade for upper extremity surgery.", "[Comparison of transarterial and multiple nerve stimulation techniques for axillary block using lidocaine with epinephrine.].", "Comparison of two neurostimulation techniques for axillary brachial plexus blockade.", "Clinical and radiological comparison of perivascular and transarterial techniques of axillary brachial plexus block.", "Readiness for surgery after axillary block: single or multiple injection techniques.", "Comparison of transarterial and multiple nerve stimulation techniques for an initial axillary block by 45 mL of mepivacaine 1% with adrenaline.", "Comparison of transarterial and multiple nerve stimulation techniques for axillary block using a high dose of mepivacaine with adrenaline.", "Low dose axillary block by targeted injections of the terminal nerves.", "Axillary plexus block using a peripheral nerve stimulator: single or multiple injections.", "Double-injection method using peripheral nerve stimulator is superior to single injection in axillary plexus block." ]

[ "A triple-injection technique (injections at the median, musculocutaneous, and radial nerves) for axillary block affords a high incidence of complete block (all the nerves below the elbow). However, in certain surgeries, only 1 or 2 nerves are involved in the surgical field. The aim of this prospective randomized study was to test the effectiveness of surgical anesthesia of a \"selective\" approach in which only the nerves involved in surgery were electrically located and injected.\n Three types of surgery were selected. Type 1 included surgery on the fifth finger, type 2 included superficial surgery (without bone involvement) on the palm or on the dorsum of the hand, and type 3 included any surgery on the first 3 fingers. For each type, 138 patients were enrolled and divided into 2 groups: group SEL in which only the nerves involved in the surgical field (1 or 2) were located and injected and group TNS in which a standard triple-nerve stimulation technique was used.\n A lower rate of surgical anesthesia (84% vs 92%; P G 0.05)was recorded in group SEL considered as a whole: this was mainly due to the significant difference recorded in type 2 surgery (75% vs 93%;P G 0.05). More patients needed intravenous administration of fentanyl for tourniquet pain (18% vs 8%; P G 0.005) and of midazolam for intraoperative anxiety (20% vs 8%; P G 0.005) in group SEL considered as a whole. In type 1, improved patient comfort at block performance(P G 0.05), a 7-min saving on total anesthetic time (P G 0.001), and a higher need for midazolam administration (P G 0.05) were recorded in group SEL. In type 2, a higher need for midazolam administration(P G 0.05) was recorded in group SEL. In type 3, no clinically significant differences between the groups were recorded.\n A standard triple-nerve stimulation technique seems to be preferable to the selective approach even when a limited number of nerves are involved in the surgical field.", "To compare the extent of sensory and motor block with two different nerve stimulation techniques in axillary blocks.\n Prospective, randomized, investigator-blinded study.\n Ambulatory surgery unit of a university hospital.\n 60 ASA physical status I, II, and III patients undergoing surgery at or below the elbow.\n Patients receiving axillary block were randomized into two nerve stimulation groups with either radial plus musculocutaneous or triple nerve stimulation (radial, median, and musculocutaneous nerves). Thirty milliliters of plain 2% mepivacaine was given to all patients either in a single or fractionated dosing for radial or for radial and median nerves, according to group assignment. Five milliliters of plain 1% mepivacaine for the musculocutaneous nerve was given to all patients.\n Blocks were assessed at 10, 20, and 30 minutes. Rates of supplementation given as a result of insufficient surgical anesthesia were also noted.\n Statistically significantly higher rates of anesthesia at the cutaneous distributions of median and medial cutaneous of the arm nerves with multiple nerve stimulation at 30 minutes were found as compared with radial plus musculocutaneous nerve stimulation. The rate of supplementation was lower with multiple nerve stimulation.\n Radial plus musculocutaneous nerve stimulation showed lower efficacy of axillary block than did triple nerve stimulation when using 2% mepivacaine.", "One hundred patients scheduled for elective outpatient hand surgery had blockade of the axillary brachial plexus by one of three techniques; insertion of a catheter into the brachial plexus sheath (n = 25), use of paraesthesia (n = 50) or use of the nerve stimulator (n = 25) to localise the plexus. Only two patients required general anaesthesia for the planned surgery. Assessment of the dermatomes blocked did not demonstrate a statistical difference between the success rates of the three groups. The more nerves detected in the paraesthesia and the nerve stimulator groups before injection of local anaesthetic the higher the success rate of the block. We advocate use of the nerve stimulator technique in view of the possible risk of neurological damage associated with paraesthesia and the technical difficulties with the catheter technique, for routine brachial plexus blockade.", "To determine whether axillary block with nerve stimulation involving the location of four motor responses is more effective than other techniques using fewer locations, without increasing patient discomfort or the rate of complications.\n Prospective, randomized single blind study enrolling 100 patients undergoing orthopedic surgery under axillary block with nerve stimulation. Patients were randomly assigned to five groups of 20 patients: in group A, 4 motor responses were located; in group B three were located (musculocutaneous nerve and two more); in group C two responses, the musculocutaneous nerve and one more; in group D two non-musculocutaneous responses; and in group E only one non-musculocutaneous response was located (medial, cubital or radial). We used 40 ml of 1% mepivacaine. Data collected were location of responses, duration of blockade, adverse events occurring during the technique; level of motor and sensory block; tolerance to the tourniquet; level of patient discomfort; and presence of complications.\n A full sensory block was achieved for 100% in group A, 90% in group B, 60% in group C, 75% in group D and 40% in group E. Patient discomfort was similar in all groups. One patient continued to suffer postoperative neurologic dysfunction three months after the block.\n Locating 4 responses gives the greatest degree of assurance of obtaining full sensory block without increasing patient discomfort or rate of complications.", "The multiple-injection technique for axillary block, in which the main 4 nerves of the plexus are located by a nerve stimulator and separately injected, has been shown to produce a high success rate. However, this technique may prove to be more difficult and time-consuming than other methods. Therefore, a simplified technique, with a reduced number of injections, might be desirable. A comparison between 2- and 3-injection techniques was made in the present double-blind study.\n One hundred patients were randomly allocated to 2 groups. In group 3N, the radial, median, and musculocutaneous nerves were located by a nerve stimulator and injections made. In group 2N, the radial and median nerves were located and injections made. Forty milliliters of local anesthetic was used.\n A greater success rate for anesthetizing the musculocutaneous nerve was found in group 3N (98% v 80%; P <.005). No differences between the groups were found in the success rate for blocking the radial, median, and ulnar nerves. The rate of complete block (all the sensory areas distal to the elbow) was 90% in group 3N and 76% in group 2N. The time to perform the block was shorter in group 2N (5 +/- 1 v 6 +/- 1 minutes; P <.001).\n The 2-injection technique offers a success rate in blocking the 3 nerves innervating the hand similar to that obtained with the 3-injection technique. The latter approach should be considered when the musculocutaneous nerve distribution is involved in the surgical area.", "This study compared the efficacy of three perivascular techniques of axillary block.\n In group 1, all of the local anesthetic was injected after advancing the needle through the axillary artery (back of artery, n = 20); in group 2, after withdrawing slightly from the artery (front of artery, n = 20); and in group 3, half of the anesthetic was injected after advancing through and half after withdrawing from the axillary artery (half and half, n = 20). The local anesthetic used for the axillary block was 50 ml of 1.5% mepivacaine with epinephrine 1:200,000.\n The groups did not differ significantly in the incidence of analgesia or anesthesia expected in the median nerve distribution, where there was a significantly lower incidence of anesthesia in the back of the artery group. This group also had a slower onset of anesthesia for the median and the medial antebrachial cutaneous nerves.\n There was no significant difference in the number of patients requiring supplementation, with five patients in the back group (25%), three patients in the front group (15%), and one patient in the half and half group (5%) requiring supplementation for the surgical procedure.", "Insufficient spread of the local anesthetic toward the retroarterial region of the neurovascular space may be responsible for inconsistent anesthesia of the upper limb after single-injection axillary block. We hypothesized that injection of the local anesthetic on a single radial-nerve stimulation would produce the same extent of anesthesia as either a single median-nerve stimulation, a double-stimulation technique (radial and musculocutaneous nerves), or a triple-stimulation technique (radial, musculocutaneous, and median nerves).\n One hundred twenty patients were randomly assigned to receive an axillary block by either median-nerve, radial-nerve, radial-nerve plus musculocutaneous-nerve, or triple-nerve stimulation with 40 mL of plain 1.5% mepivacaine. Patients were assessed for sensory block by the pinprick method at 5 and 20 minutes.\n Radial-nerve stimulation produced more extensive anesthesia than did median-nerve stimulation. The rate of anesthesia at 20 minutes in the median-nerve cutaneous distribution was similar after median-nerve stimulation or radial-nerve stimulation. The ulnar nerve was more frequently blocked at 20 minutes after radial-nerve stimulation than after median-nerve stimulation. Extent of anesthesia at 20 minutes after radial-nerve plus musculocutaneous-nerve stimulation was similar to that produced by triple-nerve stimulation, except for lower rates of anesthesia that corresponded to the median nerve. All of the differences were statistically significant.\n Musculocutaneous-nerve stimulation and radial-nerve stimulation play predominant roles in the success of axillary brachial plexus block, although a triple-nerve stimulation technique is still required to produce complete anesthesia of the upper limb.", "Surgical procedures to the distal humerus, elbow, and proximal forearm are ideally suited to regional anesthetic techniques. Selection of the preferred approach is determined by the innervation of the surgical site, the risks of regional anesthesia-related complications, and the preference and experience of the anesthesiologist. The axillary approach to the brachial plexus is the most commonly used because of its ease of performance, patient acceptance, safety, and reliability, particularly for hand and forearm surgery. Nerve location technique does not affect success rate with the supraclavicular and interscalene approaches but it does with axillary approaches. The purpose of this study was to evaluate three techniques of plexus identification in axillary blockade. Sixty-nine American Society of Anesthesiologists grade I to II patients who had undergone orthopedic or traumatological surgical procedures on the upper extremity during a period of 1 year were chosen. After premedication, patients were divided randomly into three groups according to the technique of plexus identification. Group A (n = 23) consisted of those treated with the Winnie technique; group B (n = 23) consisted of those treated with the transarterial technique; group C (n = 23) consisted of those treated with the combination technique. Axillary blockade performed using the combined technique had higher a success rate than blockade performed with the transarterial and Winnie techniques. Our results suggest that all three techniques are reliable for axillary blockade. But the onset, complete blockade time, and quality of analgesia were better with the combined technique than with the transarterial and Winnie techniques.", "nan", "High-dose transarterial technique results in highly effective axillary block. The multiple nerve stimulation technique (MNS) requires more time and experience. This prospective study aimed at comparing onset and success rate of multiple-injection axillary brachial plexus block using two methods of nerve location: transarterial or multiple nerve stimulation technique.\n Axillary block was initially induced with 800 mg lidocaine with epinephrine. The transarterial group received deeply injected 30 mL of 1.6% lidocaine with epinephrine, and 20 mL superficially to the axillary artery. For the multiple nerve stimulation group, three terminal motor nerves were electrolocated and blocked with 20 mL, 20 mL and 10 mL. Blockade was considered effective when analgesia was present in all sensory nerves distal to the elbow.\n Onset (8.8 +/- 2.3 min versus 10.2 +/- 2.4 min; p-value = 0.010) was significantly shorter in the transarterial group. Complete sensory block of all four nerves (median, ulnar, radial and musculocutaneus) was achieved in 92.5% versus 83.3% for multiple nerve stimulation group and transarterial group, respectively, without significant difference (p = 0.68). Musculocutaneous nerve was significantly easier to be blocked with the aid of peripheral nerve stimulator (p = 0.034).\n Both MNS technique for axillary block with nerve stimulator (3 injections) and transarterial technique (2 injections) promote similar results. Musculocutaneous nerve is more easily blocked with the aid of peripheral nerve stimulator. MNS technique has required less supplementary blocks and has delayed beginning of surgery.", "This prospective, randomized, double-blind study compared two techniques of axillary brachial plexus block using a peripheral nerve stimulator. Both groups received initial musculocutaneous nerve block followed by either a single injection on median nerve stimulation (group 1) or a double injection divided between median and radial nerves (group 2). All 60 patients received a total of 30 ml of lidocaine 15 mg/ml with epinephrine 5 microg/ml. Complete sensory blockade of all six peripheral nerves occurred in 53% and 97% of patients in groups 1 and 2, respectively (P<0.001), with a more rapid onset of blockade occurring in group 2 patients (P<0.001). Complete motor blockade was evident in 30% and 83% of patients in groups 1 and 2, respectively (P<0.001).", "The perivascular technique of axillary brachial plexus block results in incomplete block of radial and musculocutaneous nerves in 10-20% of patients. With the transarterial technique and a large dose of mepivacaine, success rates of 99% have been reported. We have compared the clinical efficacy of these techniques in 50 patients using 1% mepivacaine 45 ml with adrenaline. If required, the block was supplemented with additional blocks of single nerves or i.v. alfentanil. Additionally, eight patients in each group were studied with computed tomography after contrast medium was added to 0.5% bupivacaine 40 ml. There were no statistically significant differences in sensory or motor block between the groups at 20 min or in the plasma concentrations of mepivacaine measured 0-45 min after injection. In the CT scans, both proximal and distal spread of the contrast medium were more common after perivascular than after transarterial block. The distribution of the contrast medium was not related to the efficacy of the block.", "We have assessed prospectively the time to readiness for surgery following axillary block (sum of block performance and latency times) in 80 patients. The brachial plexus was identified using a nerve stimulator, and anaesthetized with 45 mL of mepivacaine 1% with adrenaline 5 micrograms mL-1. In group 1 (single injection) the whole volume of mepivacaine was injected after locating only one of the plexus nerves. In group 2 (multiple injections) at least three plexus nerves were located, and the volume of mepivacaine was divided between them. Sensory block was assessed by a blinded observer every 10 min. Patchy analgesia was supplemented after electrolocating the unblocked nerves after 20, 30 or 40 min. The patient was pronounced ready for surgery when analgesia was present in all areas to be operated upon, which always included the three nerves to the hand. The single injection technique required less time for block performance (mean 5.5 min) than multiple injections (mean 9.5 min), P < 0.0001. However, latency of the block was longer and the requirement for supplemental nerve blocks was greater, after single injections (33 min and 57%) than after multiple injections (15.5 min and 7%, respectively), P < 0.0001. As a result, readiness for surgery was achieved faster in group 2 (25 min), than in group 1 (38.5 min), P < 0.0001. After supplementation, block effectiveness was 100% in group 1 and 98% in group 2 (NS). The frequency of adverse effects (vessel puncture or paraesthesia) was similar in both groups. No neurological sequelae were observed. We conclude that the multiple injection technique takes longer to perform than single injection, but that readiness for surgery is faster because of shorter block latency and better spread of analgesia.", "The single-injection axillary block is rapidly performed but gives unpredictable results. Axillary block by multiple nerve stimulation technique (MNS) gives better results, but takes longer to perform. Transarterial (TA) injections of high doses of local anaesthetics are very successful. This double-blind study compared both block effectiveness and anaesthesiologic time consumption in 100 patients, having an axillary block by either TA or MNS techniques.\n 45 mL of 1% mepivacaine with adrenaline 5 microg/mL was used in each patient. Five mL was injected subcutaneously. In the TA group, 20 mL was injected deep to, and 20 mL superficial to the axillary artery. In the MNS group, four terminal motor nerves were electrolocated in the axilla, and injected with 10 mL each. Analgesia was assessed every 10 min and when needed supplemented after 30 min. The block was considered successful when analgesia was present in all sensory nerve areas distal to the elbow.\n MNS group required 10+/-2 min (mean+/-1 SD) for the initial block performance compared with 7+/-2 min for TA group, P<0.001. Latency of the initial block was shorter and the frequency of supplemental analgesia lower in the MNS group (mean 17 min and 12%), than in the TA group (25 min and 38%, respectively), P<0.001. All incomplete blocks were successfully supplemented by electrolocating the unblocked nerves. However, the total time to obtain 100% success rate was shorter in the MNS group (30 min), than in the TA group (38 min), P<0.001. The adverse effects (accidental intravascular injections and axillary haematomas) were fewer in the MNS group.\n In the hands of anaesthetists experienced in nerve electrolocation, the MNS technique of an initial axillary block by four separate injections of 10 mL of mepivacaine produces faster and more extensive block than the TA technique by two separate injections of 20 mL. Hence, the MNS technique requires fewer supplementary blocks and results in faster patient readiness for surgery than the TA technique.", "High-dose transarterial (TA) technique results in high effectiveness of the axillary block. The technique is fast and simple, but does not produce a satisfactory success rate when using the manufacturer's recommended dose of mepivacaine. The multiple nerve stimulation (MNS) technique requires more time and experience. This double-blind study compared effectiveness, safety and the time used to obtain an effective analgesia in 101 patients, having an axillary block by either TA or MNS techniques.\n Mepivacaine with adrenaline (MEPA), 850 mg, was used for the initial block. Five millilitres of 1% solution was injected subcutaneously. In the TA group, 20 mL of 2% solution was injected deep to, and 20 mL superficial to the axillary artery. In the MNS group, four terminal motor nerves were electrolocated in the axilla, and injected with 10 mL each. Analgesia was assessed every 10 min and, when needed, supplemented after 30 min. The block was effective when analgesia was present in all sensory nerve areas distal to the elbow.\n The MNS group required median 11 min for block performance compared with 8 min for the TA group (P < 0.001). Latency of the initial block was shorter and the frequency of supplemental analgesia lower in the MNS group (median 10 min and 6%) than in the TA group (30 min and 36%, respectively), P < 0.001. All incomplete blocks were successfully supplemented. However, the total time to obtain an effective block was shorter in the MNS group (23 min) than in the TA group (37 min), P < 0.001. Two patients in each group had signs and symptoms of systemic toxicity, the most serious being atrial fibrillation and temporary loss of consciousness in a cardiovascularly medicated patient. The local adverse effects (intravascular injections and haematomas) were fewer in the MNS group, P < 0.001.\n The MNS technique of axillary block by four injections of 10 mL of 2% MEPA produces faster and more extensive block than the TA technique by two injections of 20 mL. Therefore, the MNS technique requires fewer supplementary blocks and results in faster patient readiness for surgery. However, high doses of MEPA may result in dangerous systemic toxic reactions.", "To compare anesthetic time, success rate and adverse effects of axillary block by single or multiple injections of local anesthetic.\n Two groups of patients were studied. In group T (targeted injections, n = 53) the four terminal nerves were located by electrical stimulation, and anesthetized with 5 ml mepivacaine 1% with epinephrine 5 microg x ml(-1) (MEPE). In group S (single injection, n = 53) 80 mL MEPE 1% were injected into the neurovascular sheath, transarterially or after eliciting paresthesia. Patchy blocks were supplemented after 30 min. The patient was ready for surgery when analgesia was present in all areas distal to the elbow.\n The block was complete at 11 min (6-15) in Group T and 7 min (5-13) in group S, P<0.01. Supplementation was required in 46% in group S compared with 13% in group T P<0.001: anesthesia time was 32 min (19-52) in group T, and 39 min (16-58) in group S, P = 0.02. The average doses of MEPE were 3.5 mg x kg(-1) (2.4-5.6) in T group and 12.0 mg x kg(-1) (8.9-16.4), in S group. However, 22% of patients in group T and 4% in group S reported tourniquet pain, P = 0.02. Paresthesia was elicited in 42% of patients in group S and 8% in group T, P<0.001.\n Small targeted injections of MEPE reduce total anesthetic time, give better spread of analgesia in the hand and forearm, and may be safer than a single large injection.", "This prospective, randomized, double-blind study was undertaken to evaluate the success rates of axillary brachial plexus block performed with the help of a peripheral nerve stimulator when either one, two or four of the major nerves of the brachial plexus were located. Seventy-five patients undergoing upper limb surgery were randomly allocated to one of the following five groups according to the nerve and number of nerves to be located; G-1: musculo-cutaneous, radial, median and ulnar nerves; G-2: musculo-cutaneous plus one of the other three nerves; G-3: radial nerve; G-4: median nerve; G-5: ulnar nerve. The sensory block was evaluated before surgery and cutaneous anaesthesia was considered to be present when the needles of a Wartenberg Pinwheel were no longer felt in all the dermatomes of the nerves implicated in the surgical site. Otherwise, the block was considered to need completion before surgery. Only one out of the 15 patients in G-1 and G-2 needed completion of their block before surgery whereas seven out of 15 for G-3 and eight out of 15 for G-4 and G-5 needed completion of their block (P less than 0.01). We conclude that when performing an axillary block with the help of a peripheral nerve stimulator, stimulation of the musculo-cutaneous nerve and one other nerve or stimulation of all four major nerves of the brachial plexus gives a higher success rate than stimulation of only one nerve, whether the stimulated nerve is the median, radial or ulnar.", "Axillary block using a single-injection method does not always provide effective analgesia. This study examined whether a double axillary block injection technique is superior to a single injection axillary block.\n Fifty patients were randomly allocated to two groups. In group I (single injection), the whole volume of local anesthetic (0.7 mL/kg) was injected after locating only one of the median, radial, or ulnar nerves. In group 2 (double injection), half of the volume was injected after locating one nerve and the other half after locating another peripheral nerve. Bupivacaine 0.5% and prilocaine 1% (1:1 volumes) were used as local anesthetic. A peripheral nerve stimulator was used to identify the nerves. Sensory block of seven nerves and motor block of four nerves were tested after 40 minutes.\n Complete sensory and motor block (scores 2 or 3 on scale 0-3) in all four main nerves (median, ulnar, radial, musculocutaneous) was achieved in 3 (12%) versus 20 (80%) patients in groups 1 and 2, respectively (P = .000001). Primary success rate (no need for supplemental nerve block) was 52% in group 1 and 92% in group 2 (P = .0016).\n A double-injection method in axillary block provides excellent analgesia and motor block compared with a single-injection method. Moreover, the need for supplemental nerve blocks is significantly decreased." ]

[ "18925641", "11451173", "12072331", "12763375" ]

[ "A randomized study of adefovir dipivoxil in place of HBIG in combination with lamivudine as post-liver transplantation hepatitis B prophylaxis.", "Randomized trial of lamivudine versus hepatitis B immunoglobulin for long-term prophylaxis of hepatitis B recurrence after liver transplantation.", "Is lamivudine with 1-week HBlg as effective as long-term high-dose HBlg in HBV prophylaxis after liver transplantation?", "A randomized study comparing lamivudine monotherapy after a short course of hepatitis B immune globulin (HBIg) and lamivudine with long-term lamivudine plus HBIg in the prevention of hepatitis B virus recurrence after liver transplantation." ]

[ "Prior to effective prophylaxis, liver transplantation for hepatitis B virus (HBV)-related disease was frequently complicated by recurrence, which could be severe and rapidly progressive. Combination hepatitis B immunoglobulin (HBIG) and lamivudine prophylaxis reduces this rate of recurrence to <5% at 5 years; however, HBIG administration is costly and inconvenient. We conducted a multicenter randomized study of adefovir dipivoxil substitution for low-dose intramuscular (IM) HBIG in patients without HBV recurrence at least 12 months posttransplantation for HBV-related disease. Thirty-four patients were randomized, 16 to adefovir (1 patient withdrew consent at 3 months and is not considered in the results) and 18 to continue HBIG. All continued lamivudine. Groups were well matched by age, sex, and time since transplantation (median, 4.5 years), and background virological risk for HBV recurrence (30% of patients in the adefovir group, 24% in the HBIG group having detectable HBV DNA at transplantation). All patients were alive at study completion without recurrence. One patient in the adefovir group became hepatitis B surface antigen-positive at 5 months but was persistently HBV DNA undetectable via polymerase chain reaction (sensitivity 14 IU/mL) over the following 20 months. Median creatinine was not significantly changed over the course of the study in either group. One patient in the adefovir group with a background of diabetic and hypertensive nephropathy (baseline creatinine 150 micromol/L) developed increased creatinine leading to dose reduction and ultimately cessation of adefovir at 15 months. Yearly cost of combination adefovir/lamivudine prophylaxis was $8,290 versus $13,718 IM HBIG/lamivudine.\n Compared with combination HBIG plus lamivudine prophylaxis, combination adefovir plus lamivudine provides equivalent protection against recurrent HBV infection but with better tolerability and less cost.", "The long-term prophylaxis of hepatitis B after liver transplantation requires further optimization. In a randomized trial we investigated a regimen where the initially given hepatitis B immunoglobulin (HBIg) is replaced by long-term lamivudine treatment.\n Twenty-four liver transplant recipients (all HBsAg-positive/HBV DNA-negative before transplantation), who had received HBIg for at least 6 months without HBV recurrence, were randomized to receive lamivudine (n = 12) or HBIg (n = 12) for 52 weeks. The efficacy criteria involved seronegativity for HBsAg and undetectable HBsAg/ HBcAg in the liver.\n Twenty-one of 24 patients completed the study without hepatitis B virus (HBV) recurrence (11 on HBIg, ten on lamivudine), while three patients became HBsAg-positive. Amongst those without HBV recurrence HBV DNA was detectable only by polymerase chain reaction, intermittently in serum and lymphocytes, and in liver specimens from six of eight patients receiving HBIg and five of seven receiving lamivudine. YMDD variant was found in four cases with no viral antigen expression. Eight patients continued lamivudine after the study and during an additional 6-22 months remained HBsAg-negative with normal graft function.\n Substitution of HBIg with lamivudine is effective for prevention of HBV recurrence in low-risk liver transplant recipients and offers a convenient and cost-effective alternative for long-term HBV prophylaxis.", "nan", "To compare the efficacy in preventing hepatitis B virus (HBV) recurrence of lamivudine vs. lamivudine plus hepatitis B immune globulin (HBIg) after a short course of HBIg and lamivudine in liver transplanted chronic hepatitis B patients.\n Forty-six patients with HBV cirrhosis received lamivudine before liver transplantation and were then randomized to receive lamivudine plus HBIg for 1 month followed by lamivudine or both drugs for 17 months.\n Thirty-two patients were transplanted and 29 were randomized to receive combination therapy (15 cases) or lamivudine monotherapy (14 cases). HBV DNA was undetectable in all cases (17 induced by lamivudine therapy) at the time of liver transplantation. After 18 months of follow-up, all patients survived without HBV recurrence: hepatitis Bs antigen and HBV DNA were negative; however, HBV DNA was detected by polymerase chain reaction in four cases (three with HBIg plus lamivudine and one with lamivudine). Alanine aminotransferase levels were normal except in six cases (one HCV and two HDV coinfections). There were no drug-related adverse events.\n Lamivudine monotherapy after a short course of lamivudine and HBIg is equally as efficacious in preventing HBV recurrence as HBIg plus lamivudine during the first 18 months after liver transplantation. This strategy is more economic and convenient to administer than long-term HBIg plus lamivudine." ]

[ "10865316" ]

[ "Ischemic Optic Neuropathy Decompression Trial: twenty-four-month update." ]

[ "To describe visual acuity outcomes of patients in the Ischemic Optic Neuropathy Decompression Trial (IONDT) after 24 months of follow-up.\n The IONDT is a single-masked, multicenter, randomized clinical trial.\n Patients were evaluated and followed up at 25 clinical centers located throughout the United States. Data were sent to and analyzed at a central coordinating center.\n Two hundred fifty-eight patients 50 years or older with nonarteritic anterior ischemic optic neuropathy and visual acuity of 20/64 or worse, but better than no light perception, were randomized to either a careful follow-up group (n=131) or an optic nerve decompression surgery (ONDS) group (n=127). Of these, 174 continued participation for at least 24 months, 89 in the careful follow-up group and 85 in the ONDS group.\n Randomized patients underwent a standard visual acuity examination at 3, 6, 12, 18, and 24 months of follow-up. The primary outcome was a change of 3 lines or more of visual acuity, defined as a difference of 0.3 in logMAR scores, between baseline and 6 months of follow-up. A secondary outcome was mean change in visual acuity (in logMAR units) at 3, 6, 12, 18, and 24 months following baseline. These changes were estimated using available data from all randomized patients for whom we had data.\n Of the 258 patients randomized, 143 (55.4%) were male, and 169 (65.5%) were 65 years or older. Mean visual acuity was statistically significantly improved from baseline value at all study visits and for both treatment groups, although visual acuity declined gradually in both groups after the 3-month visit. There were no significant differences between careful follow-up and ONDS in mean change in vision from the baseline and any follow-up time point. At 24 months of follow-up, 31.0% of patients in the careful follow-up group and 29.4% of patients in the ONDS group experienced an increase of 3 or more lines of vision compared with baseline acuity; 21.8% of patients in the careful follow-up group and 20.0% of patients in the ONDS group experienced a decrease of 3 or more lines. In patients who could read at least 1 letter on the Lighthouse chart, there was a gradual decline in mean visual acuity noted over time for both treatment groups, although acuity remained significantly better than at baseline.\n Analysis of visual acuity data from patients enrolled in the IONDT at 24 months of follow-up confirms that there is no benefit of ONDS compared with careful follow-up in patients with nonarteritic anterior ischemic optic neuropathy. Arch Ophthalmol. 2000;118:793-798" ]

[ "971383", "389259", "1030974", "1089884", "2705373", "840119", "4108259", "4573122", "6817596", "4843149", "13218503", "484261", "937882" ]

[ "Lack of effect of bed rest and cigarette smoking on development of deep venous thrombosis after myocardial infarction.", "Randomised multicentre trial of early mobilisation after uncomplicated myocardial infarction.", "[Early mobilization in myocardial infarct].", "Value of early ambulation in patients with and without complications after acute myocardial infarction.", "Effect of rapid mobilization on ejection fractions and ventricular volumes after acute myocardial infarction.", "[A controlled clinical study of early mobilisation of patients with myocardial infarction (author's transl)].", "Controlled trial of early mobilisation and discharge from hospital in uncomplicated myocardial infarction.", "Early hospital discharge after myocardial infarction.", "Accelerated versus classical early mobilization after myocardial infarction.", "Early mobilization after myocardial infarction. A controlled study.", "The management of myocardial infarction with particular reference to the chair treatment.", "A controlled study of early discharge after uncomplicated myocardial infarction.", "Prevention of lower extremity venous thrombosis by early mobilization. Confirmation in patients with acute myocardial infarction by 125I-fibrinogen uptake and venography." ]

[ "In a prospective study of patients admitted to a coronary care unit, the incidence of isotopically diagnosed deep venous thrombosis was found to be related to the severity of illness rather than to the duration of bed rest. In addition, no negative correlation was found between cigarette smoking and deep venous thrombosis.", "In a multicentre trial 742 patients in 13 hospitals in Wales were randomly allocated on the fifth day after uncomplicated myocardial infarction to be mobilised on the fifth or the tenth day. The trial shows no difference in first year mortality, nor in morbidity assessed after a median period of 13 months. Follow-up after one year suggests an unexplained lower mortality during the second and third years in the late mobilisation group.", "nan", "A prospective, controlled, randomized study was done to compare the effect of early and late ambulation in hospitalized patients with acute myocardial infarction. All patients surviving longer than the first five days were studied; 64 patients were mobilized on day six and discharged on day 12, and 65 were mobilized on day 13 and discharged on day 19. Follow-up observation lasted from six to 52 weeks. Of patients without complications until day six, eight out of 32 in the early and 16 of 35 in the late groups manifested complications during the follow-up period (p smaller than 0.05). Of those who had complications before day six, seven of 32 and 26 of 30 still had or acquired new complications until last seen (p small than 0.0001). The number of serious complications in the two groups was eight and 24 respectively (p smaller than 0.001). We conclude that early ambulation is beneficial irrespective of complications on admission.", "Despite the current practice of early mobilization and early hospital discharge after uncomplicated acute myocardial infarction (AMI), physicians are reluctant to permit normal physical and social activity for several weeks after the AMI \"to allow the heart to heal.\" This study tested whether it was possible to identify a low risk group of patients on day 3 after AMI, and whether vigorous early mobilization from days 4 through 7 affected left ventricular function and volumes (studied by gated blood pool scan on days 4 and 14). There was 1 death in 3 months in 45 patients with uncomplicated AMI suitable for randomization to activity (group A) compared with 11 deaths in 55 patients unsuitable for rapid early mobilization (group B) (p less than 0.01). Early vigorous mobilization in 24 of the group A patients compared with sedentary care in 20 did not affect change in ejection fraction, end-diastolic volume, end systolic-volume, stroke volume, heart rate or cardiac output between days 4 and 14. A very low risk group suitable for early vigorous mobilization can be defined on day 3 after AMI; further, vigorous early mobilization does not affect left ventricular function or volumes. Early return to physical, social and occupational activity after uncomplicated AMI should result in marked reduction in direct and indirect costs of AMI.", "This is the report about 265 patients with recent transmural myocardial infarction. In the first week of hospital treatment 63 died. From the remaining 201 patients 101 fulfilled the conditions for early mobilisation of the WHO. In a controlled study these patients were divided in 2 groups: group 1 started the programme of early mobilisation the 7th day and group 2 was the control group which was mobilized after 3 weeks of bed rest. The 2 groups were comparable in the clinical course and had 2% of letality. The remaining 100 patients with conditions against early mobilisation were conservatively treated with 3 weeks of bed rest. The letality in this group was very high with 23%.", "nan", "nan", "nan", "nan", "nan", "Out of 383 myocardial infarction (MI) patients aged below 70 years, 252 (66%) were judged after the third day in hospital to have had uncomplicated infarctions. These patients were allocated at random to two groups, one of which was given treatment for 8 days and the other for 15 days. No significant differences in mortality, morbidity or incapacity for work could be detected during the three-month period of follow-up. The findings thus support previous conclusions that early discharge from hospital after uncomplicated MI is not associated with greater risk for the patient than later discharge.", "To determine the effects of early ambulation on peripheral venous thrombosis in the coronary care unit, 29 patients with acute myocardial infarction had daily 125I-fibrinogen point counting of both legs using a standard portable technique in the first 3 to 7 days after admission. Twenty-one patients underwent early ambulation during the initial 3 days, while 8 remained at complete bed rest for 5 days. Only 2 of 21 early ambulated patients had positive fibrinogen point counts, in contrast to 5 of 8 nonambulated patients (P less than 0.01). With heart failure, only 2 of 9 ambulated patients had positive point counts, compared with 4 of 5 nonambulated patients (P less than 0.05). In 16 patients undergoing venography, point counts were confirmed in 6 positive and 10 negative findings. These results show that the high frequency of peripheral venous thrombosis in immobilized acute myocardial infarction patients, particularly those with heart failure, can be effectively reduced by early ambulation." ]

[ "17383291" ]

[ "A randomized trial of carvedilol after renin-angiotensin system inhibition in chronic Chagas cardiomyopathy." ]

[ "The objective of this study was to determine the safety and efficacy of renin-angiotensin system (RAS) inhibitors and beta-blockers in chronic Chagas cardiomyopathy.\n Chronic Chagas cardiomyopathy causes substantial morbidity and mortality in Latin America. Whether RAS inhibitors and beta-blockers are safe and beneficial has been challenged because of the lack of formal trials.\n We conducted a double-blind, placebo-controlled, and randomized trial in 42 patients with Trypanosoma cruzi infection and cardiomyopathy. All patients received enalapril (up-titrated to 20 mg BID) and spironolactone (25 mg QD). Subsequently, the patients were randomly assigned to receive placebo (n = 20) or carvedilol up-titrated to 25 mg BID (n = 19). The primary end points were change in left ventricular ejection fraction (LVEF) after RAS inhibition and that after the addition of carvedilol. The secondary end points were changes in other echocardiographic parameters, Framingham score, quality of life (36-item Short-Form Health Survey), New York Heart Association class, radiographic indices, brain natriuretic peptide levels, and chemokines as well as safety end points.\n Optimization of RAS inhibition was safe, hemodynamically well tolerated, and associated with improvements in Framingham score (P = .001) and quality of life as well as reductions in the cardiothoracic index (P = .002), brain natriuretic peptide level (P = .032), and RANTES (regulated on activation, normal T expressed and secreted) level (P = .001). Left ventricular ejection fraction increased by 2.3% (P = .25); in patients with an LVEF < or = 45% at baseline, it increased by 2.8% (P = .017). Treatment with carvedilol was associated with a trend toward an increase in LVEF (absolute difference between groups, 2.3%; P = .094). The addition of carvedilol was safe, hemodynamically well tolerated, and not associated with symptomatic bradycardia.\n In patients with chronic Chagas cardiomyopathy, optimization of treatment with enalapril and spironolactone and subsequent addition of carvedilol were safe and associated with benefits in cardiac function and clinical status. Larger trials are needed to show effects on mortality and/or hospitalization." ]

[ "8684407", "14681504", "7495111", "8911291", "1383816", "10971268", "9475762", "8595647", "7678871", "8876706", "9285305", "9152564", "9146609", "1283370", "14663474", "12559281", "7542109", "7678931", "9610579", "12526285", "10210385" ]

[ "The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group.", "The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia.", "Can finasteride reverse the progress of benign prostatic hyperplasia? A two-year placebo-controlled study. The Scandinavian BPH Study Group.", "Efficacy and safety of finasteride therapy for benign prostatic hyperplasia: results of a 2-year randomized controlled trial (the PROSPECT study). PROscar Safety Plus Efficacy Canadian Two year Study.", "The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group.", "Combined sabal and urtica extract compared with finasteride in men with benign prostatic hyperplasia: analysis of prostate volume and therapeutic outcome.", "The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group.", "Efficacy, tolerability, and effect on health-related quality of life of finasteride versus placebo in men with symptomatic benign prostatic hyperplasia: a community based study. CUSP Investigators. Community based study of Proscar.", "Urodynamic effects of finasteride in the treatment of bladder outlet obstruction due to benign prostatic hyperplasia.", "Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign prostate hyperplasia: a randomized international study of 1,098 patients.", "Pharmacotherapy of benign prostatic hyperplasia: inhibitor of 5 alpha-reductase.", "Efficacy and tolerability of finasteride in symptomatic benign prostatic hyperplasia: a primary care study. Primary Care Investigator Study Group.", "Prostate tissue composition and response to finasteride in men with symptomatic benign prostatic hyperplasia.", "Scandinavian clinical study of finasteride in the treatment of benign prostatic hyperplasia.", "A comparison of the efficacy and tolerability of tamsulosin and finasteride in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.", "Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial.", "Therapeutic effects of finasteride in benign prostatic hyperplasia: a randomized double-blind controlled trial.", "The influence of finasteride on the volume of the peripheral and periurethral zones of the prostate in men with benign prostatic hyperplasia.", "Long-term effects of finasteride in patients with benign prostatic hyperplasia: a double-blind, placebo-controlled, multicenter study. PROWESS Study Group.", "Comparison of tamsulosin and finasteride for lower urinary tract symptoms associated with benign prostatic hyperplasia in Korean patients.", "Improvement of pressure flow parameters with finasteride is greater in men with large prostates. Finasteride Urodynamics Study Group." ]

[ "Men with benign prostatic hyperplasia can be treated with alpha 1-adrenergic-antagonist drugs that relax prostatic smooth muscle or with drugs that inhibit 5 alpha-reductase and therefore reduce tissue androgen concentrations. However, the effects of the two types of drugs have not been compared.\n We compared the safety and efficacy of placebo, terazosin (10 mg daily), finasteride (5 mg daily), and the combination of both drugs in 1229 men with benign prostatic hyperplasia. American Urological Association symptom scores and peak urinary-flow rates were determined at base line and periodically for one year.\n The mean changes from base line in the symptom scores in the placebo, finasteride, terazosin, and combination-therapy groups at one year were decreases of 2.6, 3.2, 6.1, and 6.2 points, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). The mean changes at one year in the peak urinary-flow rates were increases of 1.4, 1.6, 2.7, and 3.2 ml per second, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). Finasteride had no more effect on either measure than placebo. In the placebo group, 1.6 percent of the men discontinued the study because of adverse effects, as did 4.8 to 7.8 percent of the men in the other three groups.\n In men with benign prostatic hyperplasia, terazosin was effective therapy, whereas finasteride was not, and the combination of terazosin and finasteride was no more effective than terazosin alone.", "Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5alpha-reductase inhibitors. The long-term effect of these drugs, singly or combined, on the risk of clinical progression is unknown.\n We conducted a long-term, double-blind trial (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of benign prostatic hyperplasia.\n The risk of overall clinical progression--defined as an increase above base line of at least 4 points in the American Urological Association symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection--was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66 percent for the comparison with placebo, P<0.001) was significantly greater than that associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin. Doxazosin (P<0.001), finasteride (P=0.001), and combination therapy (P<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone.\n Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy.\n Copyright 2003 Massachusetts Medical Society", "To study if placebo-induced improvement in men with symptomatic benign prostatic hyperplasia (BPH) is maintained over 2 years, and to study the efficacy and safety from intervention with finasteride 5 mg for 24 months.\n This was a multicenter, double-blind, placebo-controlled study involving 707 patients with moderate symptoms of BPH enrolled at 59 centers in five Scandinavian countries. Following enrollment and a 4-week single-blind placebo run-in period, patients were randomized to receive finasteride 5 mg once daily or placebo for 24 months. Urinary symptoms, urinary flow rate, prostate volume, postvoiding residual urinary volume, and serum concentrations of prostate-specific antigen together with laboratory safety parameters were measured at entry and at months 12 and 24. Interim physical and laboratory examinations were performed when indicated clinically.\n In finasteride-treated patients the total symptom score improved throughout the study, with a significant difference between the two groups at 24 months (P < or = 0.01), whereas in placebo-treated patients, there was an initial improvement in the symptom score but no change from baseline at 24 months. The maximum urinary flow rate decreased in the placebo group, but improved in the finasteride group, resulting in a between-group difference of 1.8 mL/s at 24 months (P < or = 0.01). The mean change in prostate volume was +12% in the placebo group versus -19% in the finasteride-treated group (P < 0.01). Finasteride was generally well tolerated throughout the 2-year study period.\n The efficacy of therapy with finasteride 5 mg in improving both symptoms and maximum urinary flow rate and reducing prostate volume has been shown to be maintained during 24 months while patients receiving placebo experienced a return to baseline or deterioration of these parameters during the study. These results demonstrate that finasteride can reverse the natural progression of BPH.", "To evaluate the efficacy and safety of 2 years' treatment of moderate benign prostatic hyperplasia (BPH) with finasteride.\n Double-blind, parallel-group, placebo-controlled, multicentre, prospective randomized study.\n Outpatient care in 28 centres across Canada.\n Men aged 45 to 80, in good health, with moderate BPH and no evidence of prostate cancer. A total of 613 men were entered into the study; 472 completed the 2 years of treatment.\n After 1 month of receiving a placebo (run-in period), patients were given either finasteride (5 mg/d) or a placebo for 2 years.\n Efficacy: changes from baseline in BPH symptom scores, maximum urinary flow rates and prostate volume. Safety: onset, course and resolution of all adverse events during the treatment period.\n In the efficacy analyses the mean BPH symptom scores decreased 2.1 points (from 15.8 to 13.7) in the finasteride group, as compared with a decrease of 0.7 points (from 16.6 to 15.9) in the placebo group (P < or = 0.01). The maximum urinary flow rate increased by a mean of 1.4 mL/s (from 11.1 to 12.5 mL/s) in the finasteride group, as compared with an increase of 0.3 mL/s (from 10.9 to 11.2 mL/s) in the placebo group (p < or = 0.01). The mean prostate volume decreased by 21% (from a mean volume of 44.1 cm3 at baseline) in the treatment group; it increased by 8.4% (from a mean volume of 45.8 cm3 at baseline) in the placebo group (p < or = 0.01). In the safety analysis, the proportion of patients who experienced any adverse event was similar in the two groups (81.0% in the treatment group and 81.2% in the placebo group). However, the incidence of adverse events related to sexual dysfunction were significantly higher in the finasteride group than in the placebo group (ejaculation disorder 7.7% v. 1.7% and impotence 15.8% v. 6.3%; p < or = 0.01 for both parameters).\n Finasteride is a well-tolerated and effective alternative to watchful waiting in the treatment of moderate BPH.", "Benign prostatic hyperplasia is a progressive, androgen-dependent disease resulting in enlargement of the prostate gland and urinary obstruction. Preventing the conversion of testosterone to its tissue-active form, dihydrotestosterone, by inhibiting the enzyme 5 alpha-reductase could decrease the action of androgens in their target tissues; in the prostate the result might be a decrease in prostatic hyperplasia and therefore in symptoms of urinary obstruction.\n In a double-blind study, we evaluated the effect of two doses of finasteride (1 mg and 5 mg) and placebo, each given once daily for 12 months, in 895 men with prostatic hyperplasia. Urinary symptoms, urinary flow, prostatic volume, and serum concentrations of dihydrotestosterone and prostate-specific antigen were determined periodically during the treatment period.\n As compared with the men in the placebo group, the men treated with 5 mg of finasteride per day had a significant decrease in total urinary-symptom scores (P less than 0.001), an increase of 1.6 ml per second (22 percent, P less than 0.001) in the maximal urinary-flow rate, and a 19 percent decrease in prostatic volume (P less than 0.001). The men treated with 1 mg of finasteride per day did not have a significant decrease in total urinary-symptom scores, but had an increase of 1.4 ml per second (23 percent) in the maximal urinary-flow rate, and an 18 percent decrease in prostatic volume. The men given placebo had no changes in total urinary-symptom scores, an increase of 0.2 ml per second (8 percent) in the maximal urinary-flow rate, and a 3 percent decrease in prostatic volume. The frequency of adverse effects in the three groups was similar, except for a higher incidence of decreased libido, impotence, and ejaculatory disorders in the finasteride-treated groups.\n The treatment of benign prostatic hyperplasia with 5 mg of finasteride per day results in a significant decrease in symptoms of obstruction, an increase in urinary flow, and a decrease in prostatic volume, but at a slightly increased risk of sexual dysfunction.", "To test the hypothesis that in patients with benign prostatic hyperplasia (BPH), the outcome of drug therapy with finasteride may be predictable from the baseline prostate volume and that positive clinical effects might be expected only in patients with prostate volumes of > 40 mL, using a subgroup analysis of results from a previously reported clinical trial of finasteride and phytotherapy.\n A subgroup of 431 patients was analysed from a randomized, multicentre, double-blind clinical trial involving 543 patients with the early stages of BPH. Patients received a fixed combination of extracts of saw palmetto fruit (Serenoa repens) and nettle root (Urtica dioica) (PRO 160/120) or the synthetic 5alpha-reductase inhibitor finasteride. The patients assessed had valid ultrasonographic measurements and baseline prostate volumes of either </= 40 mL or > 40 mL. All 516 patients were included in the safety analysis. The results of the original trial showed equivalent efficacy for both treatments.\n The mean (SD) maximum urinary flow (the main outcome variable) increased (from baseline values) after 24 weeks by 1.9 (5.6) mL/s with PRO 160/120 and by 2.4 (6.3) mL/s with finasteride. There were no statistically significant group differences (P = 0.52). The subgroups with small prostates (</= 40 mL) showed similar improvements, with mean values of 1.8 (5.2) mL/s with PRO 160/120 and 2.7 (7.4) mL/s with finasteride. The mean values for the subgroups with prostates of > 40 mL were similar, at 2.3 (6.1) and 2. 2 (5.3) mL/s, respectively. There were improvements in the International Prostate Symptom Score in both treatment groups, with no statistically significant differences. The subgroup analysis showed slightly better results for voiding symptoms in the patients with prostates of > 40 mL, but there were also improvements in the subgroup with smaller prostates. The safety analysis showed that more patients in the finasteride group reported adverse events and also there were more adverse events in this group than in patients treated with PRO 160/120.\n The present analysis showed that the efficacy of both PRO 160/120 and finasteride was equivalent and unrelated to prostate volume. However, PRO 160/120 had better tolerability than finasteride.", "Finasteride is known to improve urinary symptoms in men with benign prostatic hyperplasia, but the extent to which the benefit is sustained and whether finasteride reduces the incidence of related events, including the need for surgery and the development of acute urinary retention, is not known.\n In this double-blind, randomized, placebo-controlled trial, we studied 3040 men with moderate-to-severe urinary symptoms and enlarged prostate glands who were treated daily with 5 mg of finasteride or placebo for four years. Symptom scores (on a scale of 1 to 34), urinary flow rates, and the occurrence of outcome events were assessed every four months in 3016 men. Prostate volume was measured in a subgroup of the men. Complete data on outcomes were available for 2760 men.\n During the four-year study period, 152 of the 1503 men in the placebo group (10 percent) and 69 of the 1513 men in the finasteride group (5 percent) underwent surgery for benign prostatic hyperplasia (reduction in risk with finasteride, 55 percent; 95 percent confidence interval, 41 to 65 percent). Acute urinary retention developed in 99 men (7 percent) in the placebo group and 42 men (3 percent) in the finasteride group (reduction in risk with finasteride, 57 percent; 95 percent confidence interval, 40 to 69 percent). Among the men who completed the study, the mean decreases in the symptom score were 3.3 in the finasteride group and 1.3 in the placebo group (P<0.001). Treatment with finasteride also significantly improved urinary flow rates and reduced prostate volume (P<0.001).\n Among men with symptoms of urinary obstruction and prostatic enlargement, treatment with finasteride for four years reduces symptoms and prostate volume, increases the urinary flow rate, and reduces the risk of surgery and acute urinary retention.", "This study sought to assess the efficacy, tolerability, and effect of finasteride on health-related quality of life (HRQL) in a diverse population of men with moderate-to-severe symptomatic benign prostatic hyperplasia (BPH). This double-blind study evaluated finasteride and placebo for 12 months in 2342 men with BPH (16.2% black, 14.5% Hispanic, 69.3% Caucasian/other) in a community-based setting. At 3-month intervals, urinary symptoms were measured by use of the American Urologic Association symptom index. HRQL was assessed by use of the BPH impact index (BII), which evaluated degree of bother, worry, physical discomfort, and restriction in activities as a result of urinary symptoms. Additional questions regarding activities of living were administered, and global assessments of change in urologic status were performed by both patients and investigators. Compared with placebo, patients treated with finasteride had a statistically significant decrease in symptom scores when first measured at month 3. Symptom scores continued to improve in finasteride-treated patients throughout the study; at month 12, the mean decrease in symptom scores in the finasteride-treated patients was -4.8 compared with -3.4 for placebo patients ( P = 0.0001). Statistically significant differences in favor of finasteride also were noted at month 12 on the BII (P = 0.0465), and finasteride-treated patients experienced less interference with activities of living (P = 0.0518). Patient and investigator global assessments of urologic status showed that significantly more patients in the finasteride group considered themselves improved and were considered improved by investigators at month 12 (P = 0.000). Finasteride was generally well tolerated. The incidence of drug-related sexual adverse experiences was significantly higher in the finasteride group (P = 0.000), but led to withdrawal in only 1.5% of patients. The demonstrated efficacy and tolerability of finasteride in reducing symptoms and improving quality of life confirm observations of previous trials and make finasteride a highly desirable treatment option for many men with symptomatic BPH.", "Urodynamic effects of the 5-alpha-reductase inhibitor, finasteride, were studied in the treatment of patients with bladder outlet obstruction due to benign prostatic hyperplasia (BPH). A total of 36 patients was randomly assigned in a double-bind manner to receive either 5 mg. finasteride daily (19) or placebo (17) for 6 months. The possible relief of bladder outlet obstruction was monitored with uroflowmetry and repeated urodynamics. The mean flow rate, detrusor opening pressure, detrusor pressure at maximum flow and maximum detrusor pressure improved significantly in the patients treated with finasteride. There were no significant differences in the improvement of symptom score or peak flow rate, or in the reduction of residual urine between the finasteride and placebo groups. The treatment resulted in 30% average decrease in prostatic size and 46% decrease in prostate specific antigen concentration. The efficacy of finasteride in relief of bladder outlet obstruction caused by BPH seems to be of the same degree as that achieved by chemical castration therapy but without any significant side effects. There were wide variations among BPH patient response to finasteride treatment. Further studies are needed to define the responders who benefit from this treatment.", "Controversy regarding the relative efficacy of treatments for the relief of the symptoms of benign prostatic hyperplasia (BPH).\n This was a 6-month double-blind randomized equivalence study that compared the effects of a plant extract (320 mg Permixon) with those of a 5 alpha-reductase inhibitor (5 mg finasteride) in 1,098 men with moderate BPH using the International Prostate Symptom Score (IPSS) as the primary end-point.\n Both Permixon and finasteride decreased the IPSS (-37% and -39%, respectively), improved quality of life (by 38 and 41%), and increased peak urinary flow rate (+25% and +30%, P = 0.035), with no statistical difference in the percent of responders with a 3 ml/sec improvement. Finasteride markedly decreased prostate volume (-18%) and serum PSA levels (-41%); Permixon improved symptoms with little effect on volume (-6%) and no change in PSA levels. Permixon fared better than finasteride in a sexual function questionnaire and gave rise to less complaints of decreased libido and impotence.\n Both treatments relieve the symptoms of BPH in about two-thirds of patients but, unlike finasteride, Permixon has little effect on so-called androgen-dependent parameters. This suggests that other pathways might also be involved in the symptomatology of BPH.", "We studied the effects of 5 alpha-reductase inhibitor (finasteride) in the treatment of benign prostatic hyperplasia (BPH). This study is a randomized controlled trial. Sixty-two patients were treated with 5 alpha-reductase (finasteride 5 mg/day) and 61 patients (control group) with placebo for one year. Prostatic volume, maximal urine flow rate, AUA symptom scoring, residual urine volume and prostate-specific antigen (PSA) levels were evaluated at 3, 6, 9 and 12 months. In the first 6 months prostatic volume decreased rapidly (20.5%), in the second 6 months it decreased slowly and reached the maximal rate (23.3%). Maximal urine flow rate increased in the second 6 months. AUA symptom scores decreased first at 3 months and were 4.6 points lower at the end of the 12th month. There were no significant changes in residual volume. The 5 alpha-reductase inhibitor caused a 50% decrease in PSA levels, like in other studies. Because of the prolonged use of the drug, treatment with 5 alpha-reductase inhibitor is not tolerated by many patients and being expensive its future in the pharmacotherapy of BPH is unclear.", "Because increasing numbers of men are seeking treatment for benign prostatic hyperplasia (BPH) from primary care physicians, we sought to assess the efficacy and tolerability of finasteride in a primary care setting. In this randomized, double-masked study, 2,112 men with symptomatic BPH received either finasteride (n = 1,589) or placebo (n = 523) for 1 year. At 3, 6, 9, and 12 months, urinary symptoms were measured using the American Urological Association Symptom Index (AUASI). Quality of life was assessed using the BPH Impact Index (BII), which assessed bother, worry, physical discomfort, and restriction in activities. Both patients and investigators assessed overall urologic status. Investigators assessed the effect of the drug on plasma lipids in a subset of patients. Patients treated with finasteride had a statistically significant mean decrease in AUASI scores compared with patients treated with placebo beginning at month 6 and continuing throughout the study. At month 12, adjusted mean decreases in AUASI scores were -4.96 for finasteride versus -3.71 for placebo. Statistically significant differences in favor of finasteride were also noted on BII at months 9 and 12. Patient and investigator overall assessments showed greater improvement in the finasteride group beginning at month 6. The incidence of drug-related sexual adverse experiences was significantly greater in finasteride-treated patients but led to withdrawal in only 2.2% of these patients. Overall lipid profile was not significantly altered in either group. Based on improvement in symptoms and quality of life, and on its favorable tolerability profile, finasteride should be considered by primary care physicians for management of symptomatic BPH.", "We sought to quantify prostate tissue changes induced by finasteride and to identify a predictor of finasteride response in men with symptomatic benign prostatic hyperplasia (BPH) via a randomized, placebo controlled, double-blind clinical trial.\n Men with symptomatic BPH (52 to 78 years old) were randomly assigned to 6 months of treatment with finasteride (26) or placebo (15). Outcome measures were clinical (urinary symptom score and flow rate), chemical (serum prostate specific antigen and dihydrotestosterone levels), volumetric (transrectal ultrasound, and magnetic resonance imaging for whole and zonal prostate volumes) and histological (morphometry of prostate sextant biopsies, separated into inner and outer gland segments, to measure the percent epithelium, stroma and glandular lumen).\n In the finasteride group we found a suggestion of decreasing symptom scores and increasing flow rates (not significant) with significant decreases (p < 0.01) in prostate specific antigen (48%), dihydrotestosterone (74%) and prostate volume (21%). Finasteride treatment induced a 55% decrease in inner gland epithelium (p < 0.01) with little effect on stroma or lumina. We also found a linear correlation between pretreatment inner gland epithelial content and prostate volume decrease induced by the drug (tau = 0.58, p = 0.01).\n Finasteride treatment results in a major suppression of prostate epithelium, which is most pronounced in the inner gland. Moreover, a finasteride induced prostate volume decrease was predictable by quantification of epithelial tissues of the inner gland. These data lend additional support to the emerging concept of transition zone primacy in symptomatic BPH.", "The effects of finasteride, a potent 5 alpha-reductase inhibitor, were assessed in patients with benign prostatic hyperplasia. Patients were treated with finasteride or placebo for 24 weeks in a double-blind multicenter study followed by a 12-month open-extension period. After 24 weeks, finasteride-treated patients, when compared to placebo-treated patients, showed a significant reduction in prostate volume (22.5% median decrease) and prostate significant antigen (32.4% median decrease), a significant increase in maximum urinary flow (1.6 ml/s mean increase from baseline) and a significant improvement in their obstructive symptom scores (two-point decrease from baseline). Finasteride was well tolerated, and the improvements in prostate volume, maximum urinary flow rate and obstructive symptom scores observed in the controlled study were maintained throughout the extension study.", "In this multicentre, double-blind study, patients with LUTS/BPH were randomised to 26 weeks with finasteride 5 mg once daily (n=204) or tamsulosin 0.4 mg once daily (n=199). Double-blind treatment was continued for another 26 weeks (total treatment duration: 1 y). The primary efficacy parameter was the difference in mean change in total Symptom Problem Index (SPI) from baseline to end point at week-26 in the intention-to-treat (ITT) and per protocol (PP) populations. Tamsulosin induced a greater improvement in total SPI (-5.2 points or -37%) compared to finasteride (-4.5 points or -31%) at week-26 (P=0.055 in ITT and P=0.032 in PP). Tamsulosin improved urinary symptoms (particularly the more bothersome storage symptoms) and flow more quickly than finasteride. The difference was statistically significant for the SPI from week-1 (reduction, respectively, -2.5 vs -1.8 points, P=0.043) to week-18 and for Qmax from week-1 (increase, respectively, 2.3 vs 0.7 ml/s, P=0.0007) to week-12. Both treatments were well tolerated with a comparable incidence of adverse events, including urinary retention.", "To evaluate the efficacy and tolerability of the selective alpha(1)-adrenergic antagonist doxazosin and the 5-alpha-reductase inhibitor finasteride, alone and in combination, for the symptomatic treatment of benign prostatic hyperplasia.\n In a prospective, double-blind, placebo-controlled trial, 1095 men aged 50 to 80 years were randomized to treatment for 52 weeks with doxazosin, finasteride, the combination of doxazosin and finasteride, or placebo. The dose of finasteride (or its matched placebo) was 5 mg/day. Doxazosin (or its matched placebo) was initiated at 1 mg/day, and titrated up to a maximum of 8 mg/day over approximately 10 weeks according to the response of the maximal urinary flow rate (Qmax) and International Prostate Symptom Score (IPSS). The IPSS and Qmax were assessed at baseline and at weeks 10, 14, 26, 39, and 52 or at the endpoint.\n An intent-to-treat analysis of 1007 men showed doxazosin and doxazosin plus finasteride combination therapy produced statistically significant improvements in total IPSS and Qmax compared with placebo and finasteride alone (P <0.05). Finasteride alone was not significantly different statistically from placebo with respect to total IPSS and Qmax. All treatments were generally well tolerated.\n Doxazosin was effective in improving urinary symptoms and urinary flow rate in men with benign prostatic hyperplasia, and was more effective than finasteride alone or placebo. The addition of finasteride did not provide further benefit to that achieved with doxazosin alone.", "The clinical effects of finasteride, a 5 alpha-reductase inhibitor, in patients with benign prostatic hyperplasia (BPH) were evaluated in a double-blind, placebo-controlled study. Forty-six patients with symptomatic BPH were randomly assigned to 2 groups, the finasteride group and the placebo group. The finasteride group received 5 mg of finasteride daily for 6 months. Prostate volume, urinary flow, urinary symptoms, serum prostate-specific antigen (PSA) and adverse events were determined before and after treatment. After 6 months of treatment the patients treated with 5 mg of finasteride per day had a 30% decrease in their total urinary symptom score, a 14% decrease in prostate volume and a 0.9 ng/dL decrease of PSA. Their maximal urinary flow rate increased by 1.42 mL per second and the mean urinary flow rate increased by 0.64 mL per second. The patients given placebo showed no significant changes in their prostate volume, serum PSA and maximal and mean urinary flow rate. However, the symptom scores in the placebo group also decreased significantly. When compared with the placebo group, those in the finasteride group had significantly lower prostate volume, serum PSA, maximal urinary flow rate and urinary symptoms, but not mean urinary flow rate. The frequency of adverse events was low in both the finasteride and placebo groups. These results show that finasteride may be an effective and safe alternative for the treatment of patients with BPH.", "To determine the influence of androgen deprivation induced by the potent 5 alpha-reductase inhibitor finasteride on the volume of the zones of the prostate, 20 symptomatic men with established BPH were randomized to one of three groups: placebo, finasteride 1 mg, and finasteride 5 mg/day. The volume of the entire prostate gland, periurethral zone, and peripheral zone and the seminal vesicles were determined by three dimensional reconstructions of magnetic resonance contoured images of the prostate. There was no significant difference between the results achieved with 1 and 5 mg of finasteride per day; thus the results in these two groups were combined. In the placebo group there was no significant change in the volume of any structure. Following treatment for 1 year with finasteride there was a significant (P < 0.02) 17% decrease in total gland size (11.5 +/- 3.2 cc). Similarly, there was a significant (P < 0.02) 17% decrease in total gland size (11.5 +/- 3.2 cc). Similarly, there was a significant (P < 0.03) decrease in the size of the periurethral zone of the prostate (6.2 +/- 3 cc). Although there was also a decrease in the size of the peripheral zone of the prostate (2.8 +/- 1.2 cc) this did not reach statistical significance. There was no significant change in the volume of the seminal vesicles. These findings indicate for the first time that androgen deprivation induces a significant decrease in the size of the periurethral zone of the prostate in men with established BPH.", "To compare the long-term effects of finasteride (5 mg/day) and placebo in patients with moderate symptoms of benign prostatic hyperplasia (BPH).\n Patients aged 50 to 75 years, with at least two urinary symptoms indicating moderate BPH, and an enlarged prostate, were followed in a 2-year double-blind, randomized, placebo-controlled multicenter study. The effects of finasteride versus placebo were assessed by total symptom score (modified Boyarsky), obstructive symptom score, maximal urinary flow rate, prostate volume, and urologic end points (acute urinary retention, BPH-related surgical intervention).\n Of the 3270 men enrolled, 3168 contributed data to the safety analysis, and 2902 to the efficacy evaluation. Significantly greater improvement with finasteride compared to placebo was observed at 12 and 24 months for total symptom score (mean -2.9 versus -1.9 at 12 months, P < or =0.001; -3.2 versus -1.5 at 24 months, P < or =0.001), obstructive symptom score (mean -1.9 versus -1.3 at 12 months, P < or =0.001; -2.1 versus -1.1 at 24 months, P < or =0.001), maximal urinary flow rate (mean +1.2 versus +0.6 mL/s at 12 months, P = 0.010; +1.5 versus +0.7 mL/s at 24 months, P = 0.002), and prostate volume (mean -14.2 versus +5.4% at 12 months, P < or =0.01; -15.3 versus +8.9% at 24 months, P < or =0.001). Greater improvements in placebo-adjusted total symptom score occurred in men with large prostates than in men with small prostates (mean -2.4 versus -1.1 at 12 months; -3.2 versus -1.3 at 24 months, placebo-adjusted data, P = 0.053). Fifteen of 1450 men (1.0%) in the finasteride group experienced an acute urinary retention event, compared with 37 of 1452 (2.5%) in the placebo group, and the corresponding figures for surgery were 51 of 1450 (3.5%) and 86 of 1452 (5.9%), respectively. The hazard rate for occurrence, computed using the log-rank statistic, decreased by 57% for acute urinary retention and by 40% for surgery accompanied by finasteride therapy compared to placebo.\n Finasteride causes long-term symptomatic improvement and reduces the risk of acute urinary retention or surgery. Men with enlarged prostates benefit most from finasteride treatment.", "Tamsulosin (0.2 mg) and finasteride (5 mg) once daily for 24 weeks were compared in a single-blind, randomized study as initial treatments for lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH) in 205 Korean patients. Symptom and quality of life (QOL) assessment by the International Prostatic Symptom Score (I-PSS), maximum urinary flow rate (Qmax) and adverse events were analysed at 4 weeks and 24 weeks. On intention-to-treat analysis, both drugs showed similar efficacy at endpoint (decreased I-PSS, increased Qmax and improved QOL score; 34.7%, 23.9% and 34.1% for tamsulosin, and 30.5%, 22.2% and 23.1% for finasteride, respectively). However, tamsulosin produced significant improvements in I-PSS and Qmax at 4 weeks compared with finasteride (17.6% versus 10.0% and 10.9% versus 3.1%, respectively), and a superior QOL score improvement during the study. Adverse events were observed significantly more frequently among finasteride than tamsulosin patients (23 versus four). Both were equally effective in long-term treatment of urinary outflow obstruction symptoms associated with BPH in Korean patients, but tamsulosin was more effective for short-term treatment, with a better safety profile.", "We assess the effect of finasteride, a 5alpha-reductase inhibitor, on objective voiding parameters in men with lower urinary tract symptoms and benign prostatic enlargement on digital rectal examination (known as clinical benign prostatic enlargement) in a double-blind placebo controlled multicenter study using strict standard pressure flow study techniques.\n A modification of the Abrams-Griffiths nomogram was used by 1 reader to ensure that all patients met objective criteria for bladder outlet obstruction at baseline. After performing a pressure flow study patients with obstruction were randomized 2:1 to receive 5 mg. finasteride (81) or placebo (40) daily. A second pressure flow study was performed at month 12. At baseline and month 12 free urinary flow studies and transrectal ultrasound were performed, and International Prostate Symptom Score questionnaires were completed. Patients were treated between May 1994 and July 1996.\n Finasteride caused a significant decrease (-8.1 cm. water) in detrusor pressure at maximum flow (p <0.05 versus placebo p = 0.02), increase (+1.1 ml. per second) in maximum flow rate (p <0.05 versus placebo p = 0.02) and decrease (-22.8%) in prostate volume (p <0.05 versus placebo p <0.001). Men with prostates larger than 40 cc had greater improvement in detrusor pressure at maximum flow (between group difference -14.5 cm. water, 95% confidence interval -26.2 to -2.6, p = 0.02) and maximum flow rate (mean treatment effect +1.6 ml. per second, 95% confidence interval -0.2 to 3.0, p = 0.02) compared to those with prostates 40 cc or less (between group differences not significant).\n Finasteride treatment resulted in improvements in urodynamic parameters, which were greater in men with large prostates." ]

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[ "Immediate versus delayed loading of single mandibular molars. One-year results from a randomised controlled trial.", "Replacement of mandibular molars with single-unit restorations supported by wide-body implants: immediate versus delayed loading. A randomized controlled study.", "Immediate loading versus immediate provisionalization of maxillary single-tooth replacements: a prospective randomized study with BioComp implants.", "Immediate versus early loading of flapless-placed implants supporting maxillary full-arch prostheses: a randomised controlled clinical trial.", "Implant-retained mandibular overdentures with Brånemark System MKII implants: a prospective comparative study between delayed and immediate loading.", "Immediate versus early loading of two implants placed with a flapless technique supporting mandibular bar-retained overdentures: a single-blinded, randomised controlled clinical trial.", "Immediate versus early loading of 7-mm-long flapless-placed single implants: a split-mouth randomised controlled clinical trial.", "In-patient comparison of immediate and conventional loaded implants in mandibular molar sites within 12 months.", "Immediate occlusal versus non-occlusal loading of single zirconia implants. A multicentre pragmatic randomised clinical trial.", "Immediate non-occlusal loading of single implants in the aesthetic zone: a randomized clinical trial.", "Early loading of ITI implants supporting a maxillary full-arch prosthesis: 1-year data of a prospective, randomized study.", "Immediate and early non-occlusal loading of Straumann implants with a chemically modified surface (SLActive) in the posterior mandible and maxilla: interim results from a prospective multicenter randomized-controlled study.", "Clinical and radiographic evaluation of implant-retained mandibular overdentures with immediate loading.", "Immediate versus early non-occlusal loading of dental implants placed flapless in partially edentulous patients. One-year results from a randomised controlled trial.", "Implant-retained mandibular overdentures with ITI implants.", "Conventional and early loading of unsplinted ITI implants supporting mandibular overdentures.", "Effect of flapless implant surgery on soft tissue profile: a randomized controlled clinical trial.", "Instant provisionalization of immediate single-tooth implants is essential to optimize esthetic treatment outcome.", "Restoration of partially edentulous patients using dental implants with a microtextured surface: a prospective comparison of delayed and immediate full occlusal loading.", "Early versus late loading of unsplinted TiUnite surface implants supporting mandibular overdentures: a 2-year report from a prospective study.", "Immediate nonocclusal versus early loading of dental implants in partially edentulous patients: 1-year results from a multicenter, randomized controlled clinical trial.", "Early loading of unsplinted implants supporting mandibular overdentures using a one-stage operative procedure with two different implant systems: a 2-year report.", "Immediate functional loading of implants in single tooth replacement: a prospective clinical multicenter study.", "Immediate versus delayed loading of dental implants placed in fresh extraction sockets in the maxillary esthetic zone: a clinical comparative study.", "A randomized controlled clinical trial of conventional and immediately loaded tapered implants with screw-retained crowns." ]

[ "To compare the outcome of immediate non-occlusal loading and that of delayed implant loading in the bilateral replacement of single mandibular molars.\n This study was designed as a randomised, controlled, split-mouth trial. Twenty patients with bilaterally missing first mandibular molars had one of the sites to be restored randomly assigned to be treated with immediately or conventionally loaded single implants. A total of 40 implants were bilaterally installed. All the implants were inserted in healed healthy bone with an insertion torque between 35 and 45 Ncm. One molar was restored with a non-occluding temporary crown within 24 h after implant placement, while the contralateral molar was restored with a definitive crown 4 to 5 months later, according to a two-stage procedure. Final restorations were provided 4 to 5 months after implant placement for all implants. Outcome measures were implant survival, complications, radiographic marginal bone-level changes, PPD and BOP.\n No patients dropped out and no implant failed. Only minor prosthetic complications were observed (2 provisional acrylic crown fractures in the immediate loading group and 2 ceramic chipping in the delayed loading group). Mean marginal bone loss was 0.83 ± 0.16 mm (95% CI 0.75 to 0.91) in the immediate loading group and 0.86 ± 0.16 mm (95% CI 0.78 to 0.94) in the conventional loading group and no statistically significant differences between the two groups were observed (P = 0.530). Mean PPD and BOP values were, respectively, 2.76 ± 0.48 (95% CI 2.55 to 2.97) and 1.30 ± 0.73 (95% CI 0.98 to 1.62) in the immediate loading group, and 2.70 ± 0.37 (95% CI 2.54 to 2.86) and 1.40 ± 0.75 (95% CI 1.07 to 1.73) in the conventional loading group. Also, a statistical comparison of BOP and PPD did not show any significant difference (P = 0.163 and P = 0.652, respectively).\n Within the limitations of this study, the present data seem to confirm the hypothesis that the clinical outcome of immediate versus delayed loading of implants in single mandibular molar sites is comparable.", "This prospective randomized controlled trial aimed to compare single implant-supported mandibular molar restorations using either an immediate or a delayed loading protocol.\n Thirty subjects requiring single mandibular molar replacement were consecutively treated. One implant was placed in each patient. Fifteen subjects were assigned to delayed loading protocol and 15 to immediate loading protocol according to a randomization table. After insertion, the delayed loaded implants were connected to a healing abutment and restored after 3 to 4 months of healing without loading. The immediately loaded implants were loaded within 24 hours of surgery with a provisional restoration. The interim prosthesis was placed in centric occlusion. All contacts in lateral excursions were eliminated. At implant placement the maximum value of insertion torque was recorded. Radiographic bone level change was measured on periapical radiographs obtained at the time of implant placement and 12 months after loading. Means of the 2 groups were compared by Student t test and analysis of variance (ANOVA). The level of significance was set at .05.\n No implants were lost in the delayed loading group (0/15), whereas 1 implant failed (1/15) in the immediate loading group. No differences were observed in relation to implant length or insertion torque between the groups. The average radiographic bone level change after 1 year of function was 1.2 +/- 0.55 mm (range, 0.5 to 2.6 mm) and 0.77 +/- 0.38 mm (range, 0.29 to 1.23 mm) for the delayed loaded and the immediately loaded implants, respectively. The difference in radiographic bone level change between the delayed and immediate loading groups was statistically significant (P = .022; CI = -0.79 to -0.06; Student t test).\n Immediate loading of wide-diameter implants supporting single restorations in mandibular molar sites seems to be a suitable clinical option. Moreover, the radiographic bone level change observed after 12 months of loading was significantly less for immediately loaded implants.", "The aim of this prospective randomized study was to evaluate the clinical outcome of immediately loaded solid plasma sprayed (TPS) BioComp (BioComp Industries BV, Vught, The Netherlands) implants versus immediate provisionalized but non-loaded BioComp implants in the anterior and premolar region of the maxilla.\n Forty-eight patients (31 females and 17 males) with a mean age of 42.3+/-13.1 years (range 19 to 78 years) were included in the study. Fifty threaded TPS implants were placed and provisionalized within 24 hours after surgery. The patients were randomly assigned to 2 groups. In the immediate loaded (IL) group (n=24) the occlusion of the provisional was designed with normal contacts in centric relation and at lateral excursions, while in the non-immediate loaded (IP) group (n=24) the provisional restoration was adjusted to clear all occlusal contacts or contacts at lateral excursions. Patients were instructed to eat a soft diet and to avoid placing food in the area of the provisional crown during the first 6 weeks. Regular clinical and radiographic controls were performed and the survival rate and implant stability quotient (ISQ) values were evaluated at delivery of the definitive restoration at 6 months. At 1 year, radiographic coronal bone defects and gingival esthetics between the 2 groups were assessed.\n Of the IL group, 2 fixtures were lost, while 3 implants were lost in the IP group. The failing implants showed increasing mobility at 2 to 3 weeks after insertion, and were removed. The remaining 45 implants were stable at every subsequent follow-up examination, and 6 months after implant placement, ISQ values were measured. The mean ISQ value in the IL group was 63.7+/-5.8 versus 63.2+/-4.3 for the IP group (P=.78). The mean mesial marginal bone loss after 12 months in the IL group was 0.27+/-0.2 mm versus 0.28+/-0.22 mm in the IP group (P=.9). The mean distal marginal bone loss after 12 months in the IL group was 0.19+/-0.15 mm versus 0.2+/-0.11 mm in the IP group (P=.87). All implants of the IL group had an ideal gingival buccal margin, versus 91% of the IP group. Full regeneration of the mesial interdental papilla was observed in 70% of the IL group versus 91% of the IP group, while full regeneration of the distal papilla was observed in 91% of both the IL and IP implants.\n No significant differences in ISQ mean values in radiographic bone loss and gingival esthetics were found between immediate non-loaded provisionalization and immediately loaded BioComp implants in the maxilla.", "To evaluate the efficacy of flapless placed implants immediately or early loaded at 2 months with full-arch prostheses.\n Thirty patients were randomised: 15 to the immediately loaded group and 15 to the early loaded group. All implants had to be inserted with a minimum torque > 48 Ncm. Outcome measures were prosthesis and implant failures, biological and biomechanical complications, peri-implant marginal bone level changes, patient satisfaction and implant stability quotient (ISQ) assessed with a resonance frequency analysis instrument.\n Ninety implants were placed in the immediately loaded and 87 in the early loaded group. Four localised flaps had to be elevated. Six implants in five patients did not reach the planned insertion torque. Four were immediately replaced by larger diameters ones, one was early loaded and another removed just after placement. After 1 year no drop-out occurred. One implant failed in the immediately loaded group versus three early loaded implants in two patients. There were no statistically significant differences between groups for implant losses, complications, and mean marginal bone level changes. There were borderline significant differences for mean ISQ values, and patients in the immediately loaded group were significantly more satisfied than those early loaded. When comparing mean ISQ values taken 2 months after placement with year 1 data within each group, values increased significantly.\n Maxillary cross-arch prostheses can be successfully loaded the same day of flapless implant placement, increasing patient satisfaction while decreasing treatment time and patient discomfort. No apparent advantages were seen when loading implants at 2 months.", "This study was designed to compare the results of immediate and delayed loading of implants with implant-retained mandibular overdentures. Ten patients (test group) received 40 Brånemark System MKII implants (4 per patient) placed in the interforaminal area of the mandible. Standard abutments were immediately screwed to the implants, rigidly connected with a bar, and immediately loaded with an overdenture. Ten patients (control group) received the same type and number of implants in the same area, but the implants were left to heal submerged. Four to 8 months later, standard abutments were screwed to the implants and the same prosthetic procedure was applied. Each implant was evaluated at the time of prosthetic loading and at 6, 12, and 24 months after the initial prosthetic load with the following parameters: modified Plaque Index (MPI), modified Bleeding Index (MBI), probing depth (PD), and Periotest. Peri-implant bone resorption was evaluated on panoramic radiographs taken 12 and 24 months after initial prosthetic loading. No significant differences were found between the 2 groups regarding MPI, MBI, Periotest, peri-implant bone resorption, and PD at 6 and 24 months (P > .05). The only difference was found regarding PD values on the mesial and lingual sites at 12 months (P < .05). The cumulative success rate of implants was 97.5% in both groups. Results from this study showed that immediate loading of endosseous implants rigidly connected with a U-shaped bar does not seem to have any detrimental effect on osseointegration. Conversely, this method significantly shortens the duration of treatment with relevant satisfaction for the patients.", "To evaluate the efficacy of immediate loading versus early loading at 6 weeks of bar-retained mandibular overdentures supported by two implants placed with a flapless technique.\n Sixty patients were randomised: 30 to the immediately loaded group and 30 to the early loaded group. To be immediately loaded, implants had to be inserted with a minimum torque > 48 Ncm. Outcome measures were prosthesis and implant failures, biological and biomechanical complications, patient satisfaction, and Implant Stability Quotient (ISQ) assessed with a resonance frequency analysis instrument.\n Sixty implants were placed in each group. Flaps had to be raised in nine patients to check drill direction or to better visualise the area after multiple teeth extraction. Two implants in two patients did not reach the planned insertion torque and were immediately replaced by larger diameters ones. After 1 year no drop out occurred and two early loaded implants failed in two patients. There were no statistically significant differences between groups for prosthesis failures, implant losses, complications, and mean ISQ values; however, patients in the immediately loaded group were significantly more satisfied than those loaded early. When comparing mean ISQ values taken 6 weeks after placement with 1-year data within each group, values decreased significantly.\n Mandibular overdentures can be successfully loaded the same day of implant placement with a minimally invasive surgery, increasing patient satisfaction while decreasing treatment time and patient discomfort. No apparent advantages were seen when loading the overdentures at 6 weeks.", "To evaluate the efficacy of 7-mm-long flapless placed single implants immediately or early loaded at 6 weeks.\n Thirty patients received two single Nanotite External Hex Biomet 3i implants that were then randomised for immediate or early loading. All implants had to be inserted with a minimum torque >40Ncm. Provisional crowns were put in slight occlusal contact and replaced by definitive crowns 3 months after loading. Outcome measures were implant failures, biological and biomechanical complications, peri-implant marginal bone level changes and patient preference.\n Twenty-nine implants were immediately loaded and 31 early loaded. Thirteen flaps had to be elevated in 12 patients. Eleven implants in ten patients did not reach the planned insertion torque. Eight implants in seven patients were immediately replaced by implants with a larger diameter, two were loaded anyway, and one implant that was randomised to immediate loading was early loaded instead. Nine months after loading, no drop-out occurred. One implant failed in each group. There were no statistically significant differences between groups for implant losses, complications, mean marginal bone level changes, and patient preferences.\n Flapless placed 7-mm-long single implants can be successfully loaded the day of insertion. Longer follow-ups are needed to monitor the long-term prognosis of short implants.", "The aim of this prospective clinical study was to evaluate the clinical outcomes of dental implants placed in the mandibular molar sites and immediately functionally restored compared with conventionally loaded controls in an in-patient study.\n Twenty-four dental implants were placed in 12 patients who had first molar loss bilaterally in the mandibular area. One site of the patient was determined as immediately loaded (IL) and the other side was conventionally loaded (CL). Resonance frequency analyses for implant stability measurements, radiographic examinations for marginal bone levels and peri-implant evaluations were performed during the clinical follow-up appointments within 12 months.\n During the 12-month follow-up period, only one implant was lost in the IL group. The mean implant stability quotient values were 74.18+/-5.72 and 75.18+/-3.51 for Groups IL and CL at surgery, respectively, and the corresponding values were 75.36+/-5.88 and 75.64+/-4.84 at 1-year recall, respectively. The difference was not statistically significant between the two groups during the 12-month study period (P>0.05). When peri-implant parameters were evaluated, excellent peri-implant health was demonstrated during the 1-year observation period and all implants showed less than 1 mm of marginal bone resorption during the first year.\n In the present study, immediate functionally loading did not negatively affect implant stability, marginal bone levels and peri-implant health when compared with conventional loading of single-tooth implants.", "To evaluate whether immediate non-occlusal loading of single zirconia implants could reduce early failures when compared to immediate occlusal loading.\n Forty partially edentulous patients who received one single zirconia implant (Z-Systems) at least 10 mm long and 3.25 mm wide inserted with a torque of at least 35 Ncm were randomised to immediate occlusal or non-occlusal loading groups. All patients received provisional acrylic crowns the same day of implant placement. Provisional crowns were replaced after 4 to 5 months by definitive full ceramic crowns. Outcome measures were implant success, any complications and peri-implant marginal bone levels.\n One year after loading, no patients had dropped out. Five implants (12.5%) failed early: three occlusally loaded and two non-occlusally loaded. Three complications occurred, all after delivery of the definitive crowns: one crown fractured (occlusal loading), one had to be remade after debridement because of hyperplastic tissues (occlusal loading), and one crown decemented (nonocclusal loading). These differences were not statistically significant. Both groups gradually lost periimplant bone in a highly statistically significant way. One year after loading, patients subjected to non-occlusal loading lost an average of 0.7 mm of peri-implant bone versus 0.9 mm in the occlusal group. This difference in bone loss between groups was not statistically significant. There was an association between immediate post-extractive implants and implant failures (P=0.01). Four of the 10 immediate post-extractive implants (40%) failed versus one out of 30 delayed implants (3%).\n The results of this study do not provide a conclusive answer to whether immediate non-occlusal loading may decrease implant failures. Immediately loaded zirconia implants placed in post-extractive sites had high failure rates.", "this study compared the outcome of immediate non-occlusal loading with conventional loading for single implants in the maxillary aesthetic zone. It was hypothesized that immediate non-occlusal loading is not inferior to conventional loading.\n sixty-two patients with a missing maxillary anterior tooth were randomly assigned to be treated with an implant that was either restored with a non-occluding temporary crown within 24 h after implant placement (the \"immediate group\") or was restored according to a two-stage procedure after 3 months (the \"conventional group\"). All implants were installed in healed sites. Follow-up visits were conducted after 6 and 18 months post-implant placement. Outcome measures were radiographic marginal bone-level changes, survival, soft tissue aspects (probing depth, plaque, bleeding, soft tissue level), aesthetics and patient satisfaction.\n no significant differences were found between both study groups regarding marginal bone loss (immediate group 0.91 ± 0.61 mm, conventional group 0.90 ± 0.57 mm), survival (immediate group 96.8%: one implant lost, conventional group 100%), soft tissue aspects, aesthetic outcome and patient satisfaction.\n within the limitations of this study (sample size, follow-up duration), it was demonstrated that, for single implants in the anterior maxilla, the outcome of immediate non-occlusal loading was not less favourable than conventional loading.", "This prospective, randomized study investigated the safety, feasibility, and reliability of the early loading of implants in edentulous maxillae.\n Twenty-four patients with completely edentulous maxillae were randomized into a test group (n = 16) and a control group (n = 8). All patients received 5 or 6 solid screw-type titanium implants. These were loaded with full-arch prostheses after 9 to 18 days in the test group and after 2.5 to 5.1 months in the control group. Periapical radiographs were taken and routine clinical assessments were made at loading, after 6 months, and after 12 months.\n The implant survival rate 1 year after loading was 100%. Modified Plaque index scores and Sulcus Bleeding index scores were better in the test group than in the control group (P < or = .05). There was a significant difference in peri-implant bone height between the 2 groups (P < .001) and this difference converged with time (P < .001).\n This clinical, prospective, randomized, controlled study fulfilled the criteria for a comparable study. Owing to the small patient sample, the conclusions drawn were based on feasibility analyses of the results. Standard materials and methods were used. Only patients with maxillary bone of sufficient height and width were selected. The use of a single operator in each discipline--maxillofacial surgery, prosthodontics, and dental technology--may have improved the chances of achieving consistent standards and opinions.\n These results indicate that early loading in selected patients was as safe and reliable as delayed loading in this small patient population and may offer a satisfactory alternative to the standard protocol.", "Immediate and early loading of dental implants can simplify treatment and increase overall patient satisfaction. The purpose of this 3-year prospective randomized-controlled multicenter study was to assess the differences in survival rates and bone level changes between immediately and early-loaded implants with a new chemically modified surface (SLActive). This investigation shows interim results obtained after 5 months.\n Patients > or =18 years of age missing at least one tooth in the posterior maxilla or mandible were enrolled in the study. Following implant placement, patients received a temporary restoration either on the day of surgery (immediate loading) or 28-34 days after surgery (early loading); restorations consisted of single crowns or two to four unit fixed dental prostheses. Permanent restorations were placed 20-23 weeks following surgery. The primary efficacy variable was change in bone level (assessed by standardized radiographs) from baseline to 5 months; secondary variables included implant survival and success rates.\n A total of 266 patients were enrolled (118 males and 148 females), and a total of 383 implants were placed (197 and 186 in the immediate and early loading groups, respectively). Mean patient age was 46.3+/-12.8 years. After 5 months, implant survival rates were 98% in the immediate group and 97% in the early group. Mean bone level change from baseline was 0.81+/-0.89 mm in the immediate group and 0.56+/-0.73 mm in the early group (P<0.05). Statistical analysis revealed a significant center effect (P<0.0001) and a significant treatment x center interaction (P=0.008).\n The results suggested that Straumann implants with an SLActive can be used predictably in time-critical (early or immediate) loading treatment protocols when appropriate patient selection criteria are observed. The mean bone level changes observed from baseline to 5 months (0.56 and 0.81 mm) corresponded to physiological observations from other studies, i.e., were not clinically significant. The presence of a significant center effect and treatment x center interaction indicated that the differences in bone level changes between the two groups were center dependent.", "The aim of this study was to evaluate and compare immediate-loaded implant-retained mandibular overdentures and delayed-loaded implant-retained mandibular overdentures.\n Ten completely edentulous male patients received 40 dental implants. Patients were randomly divided into 2 equal groups, 5 patients each. Patients of both groups received conventional maxillary complete denture and had stage 1 surgery for placing 4 dental implant fixtures, 2 on each side anterior to the mental foramina. Group A: One-stage surgical procedure and immediate loading. Patients in this group received mandibular bar-retained overdenture supported by 4 endosseous implants loaded immediately after implant placement. Group B: The original 2-stage concept and delayed loading. Patients in this group received mandibular bar-retained overdenture supported by 4 endosseous implants that remained submerged for a period of 4 months before loading. The patients were evaluated clinically and radiographically immediately after overdenture delivery and after 6 months, 12 months, 18 months, and 24 months.\n The results of clinical evaluation showed no statistical significant difference between the 2 groups regarding the effect of treatment. The radiographic assessment showed no statistical significant difference in mesial and distal alveolar bone loss at the different intervals of the follow-up period, except at the 12-month period, where immediately loaded implants showed a decrease in the amount of alveolar bone loss mesially and distally compared to delayed loaded implants.\n The results suggest that immediate-loaded implants provide promising results compared to delayed-loaded implants and can be a possible alternative procedure in implant dentistry.", "To compare immediate versus early (6 weeks) non-occlusal loading of dental implants placed flapless in partially edentulous patients 1 year after loading.\n Sixty patients were randomised: 30 to the immediately loaded group and 30 to the early loaded group. In order to be immediately loaded, implants were inserted with a minimum torque of > or = 40Ncm. Implants were fully occlusally loaded after 6 months. Outcome measures were prosthesis and implant failures, and biological and biomechanical complications.\n Five implants in five patients randomised to the immediately loaded group did not reach the required primary implant stability. Three of these implants (two prostheses) were not immediately loaded. Two patients who were randomised to the early loaded group were immediately loaded erroneously. Implants in five patients of the early loaded group were conventionally loaded. No patient dropped out and there were no failures. Two complications occurred in the early and one in the immediately loaded group (no statistically significant difference), but were solved.\n The use of a flapless technique for placing dental implants in conjunction with non-occlusal immediate or early loading in selected patients can provide excellent clinical results. No differences were observed when comparing implants that were loaded immediately or early. Therefore, when a high primary implant stability is obtained, it might be preferable to load the implants immediately rather than waiting for a few weeks.", "This prospective study has been designed to compare the results of immediate and delayed loading of implant-retained mandibular overdentures after a 2-year follow-up. Twenty patients have been randomly divided into two groups. Group 1 patients (test group) received four ITI implants in the intraforaminal area of the mandible. Octa abutments were immediately screwed on implants; 2 days after surgery, the implants were rigidly connected with a U-shaped Dolder gold bar and loaded with an overdenture. Group 2 patients (control group) received, in the same area, the same type and number of implants, which were left to heal according to the standard protocol. At 3-4 months, Octa abutments were screwed on the implants and the same prosthetic procedure of the test group was applied. The minimum follow-up period lasted 2 years, with recall appointments at 2 weeks, 1, 3, 6 months, 1 year and every following year postoperatively, evaluating: MPI, MBI, PD, Periotest and radiographic peri-implant bone resorption. Success criteria according to Albrektsson et al. were used. Only one implant out of the 40 of group 2 failed, whereas none failed in group 1. No statistical difference of the clinical parameters evaluated was noticed in the two groups. Therefore, immediate loading of implants, if connected with a U-shaped bar, can provide the same results of the 'traditional' technique as far as osseointegration and short-term survival rates of implants are concerned. Moreover, this method significantly shortens the treatment period, thus increasing patient satisfaction.", "The aim of this study was to compare the success rates after 1 and 2 years of conventionally and early loaded pairs of unsplinted ITI implants supporting mandibular overdentures in edentulous patients. Twenty-four participants (age range 55-80 years) were randomly allocated with maximum concealment to two treatment groups. In the first group, the implants were allowed to heal for 12 weeks before being functionally loaded (control) and the second group had 6 weeks of healing with identical loading. All participants had new conventional complete maxillary and mandibular dentures prior to the study. Two sandblasted large-grit acid-etched (SLA) surface ITI implants were placed in the mandibular interforaminal area, following a standardized nonsubmerged surgical protocol. After 6 or 12 weeks of healing, matrices were processed into the fitting surface of the pre-existing mandibular dentures and the implants loaded. Implant success was determined using mobility tests and radiographs taken at baseline and 52 and 104 weeks after surgery. Clinical peri-implant parameters were also documented. Results showed all implants successfully osseointegrated, according to accepted criteria, after 2 years. Mean loss of crestal bone height after 1 year was 0.35 +/- 0.22 mm (control) vs. 0.27 +/- 0.18 mm (test). After 2 years this reduced to 0.09 +/- 0.06 mm (control) vs. 0.12 +/- 0.17 mm (test). The mean Periotest value after 1 year was -4.9 (control) vs.-3.78 (test). After 2 years, the mean resonance frequency value for the control implants was 6797 Hz [mean implant stability quotient (ISQ) = 64.77] and for the test implants 6670 Hz (mean ISQ = 62.0). Shortened loading periods for these ITI implants did not cause any statistically significant differences in osseointegration or peri-implant parameters. We conclude that pairs of unsplinted SLA-surface ITI implants can be successfully loaded with mandibular overdentures 6 weeks after surgery.", "Flapless implant surgery has been suggested as one possible treatment option for enhancement of implant esthetics.\n Twenty-four patients with a missing tooth in the premaxillary region were randomly assigned to one of two groups (12 each): immediate loading (IL) or delayed loading (DL) (loading after 4 months). An endosseous implant was placed in each patient via a flapless surgery. Clinical measurements including the papillary index (PPI) (0, no papilla; 1, less than half; 2, more than half but not complete fill; 3, complete fill; and 4, overfill), marginal levels of the soft tissue (ML), probing depths (PDs), modified bleeding index (mBI), modified plaque index (mPI), and the width of the keratinized mucosa (WKM) were performed at baseline (at the time of loading) and at 2, 4, and 6 months.\n The soft tissue profile remained stable up to 6 months, without significant differences between the two groups (mean PPI and ML at 6 months, 2.16 and 0.30 mm, respectively). Mean PPI in the IL group significantly increased from 1.50 at baseline to 2.09 at 2 months, and the significance remained up to 6 months (2.30 at 6 months) (P <0.05), whereas in the DL group, no significant changes were found from baseline to 6 months in mean PPI (2.06 at both time points). Mean PPI increased over time when two treatment groups were combined; however, no statistical significance was found. In ML, the difference at baseline between the two groups (-0.28 mm for DL versus 0.17 mm for IL; P <0.05) was no longer significant at 2 months (0 versus 0.08 mm for DL and IL, respectively) and thereafter (P >0.05). No significant differences were detected between groups at each time and over time in the other clinical parameters, PD, mBI, mPI, and WKM (P >0.05).\n The results of this study indicate that creeping attachment (i.e., soft tissue recovery) might occur within 2 months after IL. The study suggests that flapless implant surgery provides esthetic soft tissue results in single-tooth implants either immediately or delayed loaded. Other long-term randomized controlled clinical trials with a large sample size and comparison group (i.e., implant surgery with flap) are recommended to verify the conclusions drawn in this preliminary study.", "The immediate single-tooth implant has become a viable treatment option. However, the impact of the restorative procedure on esthetics is currently unclear. The goal of this study was to compare the soft tissue outline at immediate implants following two restorative protocols: immediate connection of a temporary crown or submerged healing during which a removable partial denture is used.\n A 1-year single-blind randomized clinical study was performed in 49 patients. Twenty-four patients were assigned to the immediate restoration group and 25 to the delayed restoration group. Clinical and radiographic evaluations of soft and hard tissues were carried out after 3, 6 and 12 months.\n Implant survival, bone remodeling, probing depth and bleeding tendency were not influenced by the restorative protocol. Delayed restoration resulted in initial papilla loss taking up to 1 year to attain comparable height as for immediate restoration. Midfacial recession was systematically 2.5-3 times higher following delayed restoration pointing to a 0.75 mm additional loss in comparison with immediate restoration after 1 year.\n If the primary implant stability permits it, immediate single-tooth implants should be instantly provisionalized in the interest of optimal midfacial esthetics.", "The aim of this study was to determine the clinical effectiveness of placing dental implants with microtextured surfaces into full occlusal loading at the time of placement in partially edentulous patients.\n Two demographically similar groups of 14 patients each were treated with a total of 92 Spline Twist Implants (Centerpulse Dental, Carlsbad, CA). Test implants were placed into immediate full occlusal loading, and control implants were restored using a conventional delayed loading procedure. Otherwise, both groups of patients received similar therapy from the same treatment team. Radiographs, periodontal indices, and Periotest values were recorded every 6 months during routine clinical follow-up appointments. The mean loading time for all prostheses was 24 months at the time of this report.\n No implants failed in the test group, and 1 implant failed before loading in the control group. Cumulative implant success was 98.9% for all implants placed (test group = 100%; control group = 92.9%). Periodontal measurements indicated no significant clinical differences between implants placed into immediate full occlusal loading and those loaded via a conventional delayed protocol.\n Immediate full occlusal loading of partial prostheses supported by microtextured implants in partially edentulous patients demonstrated excellent clinical results, with no adverse periodontal effects after 24 months of function. Additional follow-up will provide invaluable information on the long-term effects of this technique.\n Immediate full occlusal loading of partial prostheses supported by microtextured implants can be successfully achieved for 24 months in highly motivated patients with excellent oral hygiene.", "The aim of this study was to evaluate the clinical performance of the implants supporting mandibular overdentures, and to investigate the prosthodontic outcomes of the mandibular implant overdentures. Twenty edentulous patients participated in this study. Forty implants were placed in the canine areas of the mandibles of all patients using the 1-stage approach. New maxillary complete dentures and the mandibular implant overdentures were delivered to 10 patients in the test group 1 week after surgery, while new maxillary and mandibular complete prostheses were delivered to 10 patients in the control group. These conventional mandibular prostheses were converted to mandibular implant overdentures 3 months after surgery. No implants were lost neither in test nor in control group. The average ISQ values between the two groups were not statistically significant during 2 years (P > 0.05). The average marginal bone resorptions were 0.4 and 0.5 mm for the test and the control group after 2 years. The number of appointments required for the prosthodontic maintenance of the mandibular implant overdentures in the first year was higher than that in the second year, which was statistically significant(P < 0.001). The results of the study suggest that the 1-week early loading approach does not adversely influence the clinical performance of the implants supporting mandibular overdentures.", "To compare the efficacy of immediate nonocclusal loading (test group) versus early loading (control group) in partially edentulous patients.\n Fifty-two patients in 5 Italian private practices were randomized to 1 of the treatments: 25 to the immediately loaded group and 27 to the early loaded group. To be immediately loaded, single implants had to be inserted with a torque of > 30 Ncm, and splinted implants had to be inserted with a torque of > 20 Ncm. Implants in the immediately loaded group were provided with full acrylic resin nonoccluding temporary restorations within 48 hours after placement. After 2 months, full occluding provisional restorations were provided. Implants in the early loading group were not submerged and were loaded after 2 months. At 8 months, provisional restorations were replaced with definitive metal-ceramic prostheses. Outcome measures were prosthesis and implant failures as well as biologic and prosthetic complications recorded by nonblinded assessors. The Fisher exact test was used to compare the proportion of implant failures.\n Fifty-two implants were placed in the immediately loaded group and 52 in the early loaded group. No dropouts or complications occurred up to 14 months postinsertion. One single implant failed in the immediately loaded group 2 months after placement. There was no statistically difference for the tested outcome measures between the 2 procedures (P > .99).\n The results of this randomized controlled clinical trial with 25 patients rehabilitated with immediately restored nonocclusally loaded implant-supported prostheses compared to 27 patients restored 2 months following placement suggest that there are no major clinical differences in implant survival between these 2 protocols. No biologic or prosthetic complications occurred.", "Step-wise reduction in loading protocols is necessary to evaluate early loading of implants with mandibular overdentures.\n To compare the success rates of two different dental implant systems following conventional or early loading protocols in patients being rehabilitated with mandibular overdentures.\n Forty-eight edentulous participants were randomly allocated to two different implant systems: one with a machined titanium implant surface (Sterioss, Nobel Biocare, Yorba Linda, California, USA) and the other with a roughened titanium surface (Southern Implants, Irene, South Africa). For each system, the participants were further divided into control groups, in whom mandibular implant overdentures and their respective matrices were inserted following a standard 12-week healing period, and test groups, in whom a 6-week healing period was followed prior to identical loading. Two unsplinted implants to support implant overdentures were placed in the anterior mandible of all participants, using a standardized one-stage surgical procedure. Mobility tests and marginal bone levels, as well as peri-implant parameters, were evaluated at each baseline and 52 and 104 weeks after surgery.\n There was no statistically significant difference in the success rates of the two systems in either control or test groups. At the 2-year evaluation, a success rate was found of 87.5% and 70.8% for the control and test Sterioss groups, respectively, and 83.3% and 100% for the control and test Southern Implants groups were observed. For the Sterioss groups, eight implants were lost at an early stage: seven in the test group and one in the control group. For the Southern Implants control and test groups, no failures were seen at any time interval. There were no significant differences in marginal bone loss, Periotest values, and peri-implant parameters between implant systems or between any of the control or test groups.\n Early loading, with step-wise reductions in loading protocols, of unsplinted machined Sterioss and roughened Southern Implants fixtures with mandibular overdentures is possible for up to 2 years.", "The aim of the present study was to evaluate the outcome of immediate functional loading of implants in single-tooth replacement using two different installation procedures.\n One hundred and fifty-one subjects, who required single-tooth rehabilitation in the area of 15-25 and 35-45, were enrolled in eight private clinics in Italy. The implant sites were randomly allocated to one of the following treatment groups. In the control group, in which a standard preparation procedure for implant placement and submerged healing of the implant was used, abutment connection and loading of the implants were performed 3 months after installation. In the test group 1, a standard preparation procedure for the implant placement and immediate functional loading of implant was carried out. In the test 2 group, however, a modified implant installation procedure (osteotome technique) was used followed by immediate functional loading of the implant. Clinical and radiographic examinations were performed at 3 and 12 months of follow-up at all sites.\n Three implants (5.5%) from the test 2 group (osteotome preparation) and one (2%) from the test 1 group (conventional drill preparation) failed to integrate and were removed one and three months after implant installation. The mean marginal bone loss assessed at 12 months was 0.31 mm (test 1), 0.25 mm (test 2) and 0.38 mm (control) (no statistically significant differences were found between the three treatment groups.)\n It is suggested that immediate functional loading of implants that are placed with a conventional installation technique and with sufficient primary stability may be considered as a valid treatment alternative in a single-tooth replacement.", "The aim of this study was to report a clinical comparative assessment of crestal bone level change around single implants in fresh extraction sockets in the esthetic zone of the maxilla either immediately loaded or loaded after a delay.\n Forty patients were included in a prospective, randomized study. All patients required 1 tooth extraction (ie, 1 tooth with a hopeless prognosis) and were randomized into either the test group or the control group. Implants were positioned immediately after tooth extraction and were loaded immediately in the test group (20 implants) and after 3 months in the control group (20 implants). The implant site was prepared, with at least 4 mm of sound apical bone below the implant apex, and the coronal margin of the implant was placed at the buccal level of the bone crest. All implants were 13 mm long; 30 implants had a diameter of 5 mm, and 10 had a diameter of 3.75 mm. Radiographic examinations were made at baseline, at 6 months, and at 24 months. To compare the mean values between test and control group, a paired t test was performed (considered statistically significant at P < .05).\n After a 24-month follow-up period, a cumulative survival rate of 100% was reported for all implants. The control group resulted in a mean mesial bone loss of 1.16 +/- 0.32 mm and a mean distal bone loss of 1.17 +/- 0.41 (mean bone loss, 1.16 +/- 0.51 mm). The test group resulted in a mesial bone loss of 0.93 +/- 0.51 mm and a distal bone loss of 1.1 +/- 0.27 mm (mean bone loss, 1.02 +/- 0.53 mm). No statistically significant difference between control and test groups (P > .05) was found.\n The success rate and radiographic results of immediate restorations of dental implants placed in fresh extraction sockets were comparable to those obtained in delayed loading group.", "Surgical, prosthodontic, and esthetic outcomes of conventional and immediately loaded, single, tapered, roughened-surface Southern implants in the anterior maxilla that were restored with screw-retained crowns were compared over 1 year.\n Standardized surgical and prosthodontic procedures were followed and accepted criteria were used for assessment.\n There were no significant differences within or between the control and test groups for age, gender, bone quality or quantity, implant stability measurements at surgery, or implant length.\n After 1 year, the implants that had been immediately loaded with single provisional crowns at surgery and definitive crowns 8 weeks later were as successful as conventionally loaded 2-stage implants." ]

[ "10675424", "8289849", "10232637", "14709187", "9822949", "12956024" ]

[ "The effect of weight loss in overweight, lactating women on the growth of their infants.", "A randomized study of the effects of aerobic exercise by lactating women on breast-milk volume and composition.", "Randomized trial of the short-term effects of dieting compared with dieting plus aerobic exercise on lactation performance.", "Structured diet and physical activity prevent postpartum weight retention.", "Reducing postpartum weight retention through a correspondence intervention.", "The effects of exercise and social support on mothers reporting depressive symptoms: a pilot randomized controlled trial." ]

[ "The retention of weight gained during pregnancy may contribute to obesity. Lactation should promote weight loss, but weight loss is highly variable among lactating women. The risks associated with the restriction of energy intake during lactation have not been adequately evaluated. The purpose of this study was to determine whether weight loss by women during lactation affects the growth of their infants.\n We randomly assigned 40 breast-feeding women who were overweight (defined as a body-mass index [the weight in kilograms divided by the square of the height in meters] of 25 to 30) at 4 weeks post partum either to restrict their energy intake by 500 kcal per day and to exercise for 45 minutes per day for 4 days per week (the diet-and-exercise group) or to maintain their usual dietary intake and not exercise more than once per week for 10 weeks (the control group). We measured the weight and fat mass of the women and the weight and length of the infants before, during, and at the end of the study period.\n The mean (+/-SD) energy intake decreased by 544+/-471 kcal per day in the diet-and-exercise group. As compared with the control group, the women in the diet-and-exercise group lost more weight (4.8+/-1.7 kg vs. 0.8+/-2.3 kg, P<0.001) and fat mass (4.0+/-2.0 kg vs. 0.3+/-1.8 kg, P<0.001). The gains in weight and length of the infants whose mothers were in the diet-and-exercise group (1925+/-500 g and 7.8+/-2.0 cm, respectively) were not significantly different from those of the infants whose mothers were in the control group (1861+/-576 g and 7.3+/-1.7 cm).\n Weight loss of approximately 0.5 kg per week between 4 and 14 weeks post partum in overweight women who are exclusively breast-feeding does not affect the growth of their infants.", "The potential risks and benefits of regular exercise during lactation have not been adequately evaluated. We investigated whether regular aerobic exercise had any effects on the volume or composition of breast milk.\n Six to eight weeks post partum, 33 sedentary women whose infants were being exclusively breast-fed were randomly assigned to an exercise group (18 women) or a control group (15 women). The exercise program consisted of supervised aerobic exercise (at a level of 60 to 70 percent of the heart-rate reserve) for 45 minutes per day, 5 days per week, for 12 weeks. Energy expenditure, dietary intake, body composition, and the volume and composition of breast milk were assessed at 6 to 8, 12 to 14, and 18 to 20 weeks post partum. Maximal oxygen uptake and the plasma prolactin response to nursing were assessed at 6 to 8 and 18 to 20 weeks.\n The women in the exercise group expended about 400 kcal per day during the exercise sessions but compensated for this energy expenditure with a higher energy intake than that recorded by the control women (mean [+/- SD], intake, 2497 +/- 436 vs. 2168 +/- 328 kcal per day at 18 to 20 weeks; P < 0.05). Maximal oxygen uptake increased by 25 percent in the exercising women but by only 5 percent in the control women (P < 0.001). There were no significant differences between the two groups in maternal body weight or fat loss, the volume or composition of the breast milk, the infant weight gain, or maternal prolactin levels during the 12-week study.\n In this study, aerobic exercise performed four or five times per week beginning six to eight weeks post partum had no adverse effect on lactation and significantly improved the cardiovascular fitness of the mothers.", "Limiting postpartum weight retention is important for preventing adult obesity, but the effect of weight loss on lactation has not been studied adequately.\n We evaluated whether weight loss by dieting, with or without aerobic exercise, adversely affects lactation performance.\n At 12+/-4 wk postpartum, exclusively breast-feeding women were randomly assigned for 11 d to a diet group (35% energy deficit; n = 22), a diet plus exercise group (35% net energy deficit; n = 22), or a control group (n = 23). Milk volume, composition, and energy output; maternal weight, body composition, and plasma prolactin concentration; and infant weight were measured before and after the intervention.\n Weight loss averaged 1.9, 1.6, and 0.2 kg in the diet, diet + exercise, and control groups, respectively (P < 0.0001) and was composed of 67% fat in the diet group and nearly 100% fat in the diet + exercise group. Change in milk volume, composition, and energy output and infant weight did not differ significantly among groups. However, there was a significant interaction between group and baseline percentage body fat: in the diet group only, milk energy output increased in fatter women and decreased in leaner women. The plasma prolactin concentration was higher in the diet and diet + exercise groups than in the control group.\n Short-term weight loss (approximately 1 kg/wk) through a combination of dieting and aerobic exercise appears safe for breast-feeding mothers and is preferable to weight loss achieved primarily by dieting because the latter reduces maternal lean body mass. Longer-term studies are needed to confirm these findings.", "Postpregnancy weight retention contributes to the near-epidemic prevalence of obesity in the United States. This study examines the impact of an individualized, structured diet and physical activity intervention on weight loss in overweight women during the first year postpartum.\n Forty overweight postpartum women were randomized to either a structured (STR) or a self-directed (SELF) intervention. Measurements included body weight, percent body fat, daily caloric intake, habitual physical activity, and cardiorespiratory fitness. Subjects in STR received individualized diet and physical activity prescriptions derived from baseline measurements. They met weekly for the first 12 weeks and kept daily food and activity diaries. Subjects in SELF received a single 1-hour educational session about diet and activity.\n Only 23 of 40 participants remained in the study at 1 year postpartum. Of those, STR (n = 13) had a significant weight loss (7.3 kg, p < 0.01), a significant decrease in percent body fat (6%, p < 0.01), and no change in fat-free mass. SELF (n = 10) had no significant change in weight, percent body fat, or fat-free mass.\n Women who committed to this one class per week for 12 weeks postpartum had a high likelihood of successful weight loss that persisted at 1 year. Women who were overweight before pregnancy were unlikely to lose the pregnancy-related weight without the help of a formal intervention. This suggests that healthcare professionals should strongly encourage postpartum women to enroll in a structured diet and exercise program.", "Since post-pregnancy weight retention may contribute to the development of obesity, we sought to determine whether a behavioral weight loss intervention was effective in returning women to their pre-pregnancy weight.\n Ninety women who had given birth in the past 3-12 months and whose weight exceeded their pre-pregnancy weight by at least 6.8 kg were randomly assigned to either: a) a six-month behavioral weight loss intervention, delivered via correspondence or b) a no-treatment control group. Assessments of body weight, physical activity and eating patterns were conducted at pre-treatment and six months (post-treatment).\n During the six month treatment, subjects in the correspondence condition lost significantly more weight than control subjects (7.8 kg vs 4.9 kg, P = 0.03) and lost a greater percentage of their excess postpartum weight (79% vs 44%, P = 0.01). Furthermore, a significantly greater percentage of correspondence subjects than controls returned to their pre-pregnancy weight (33% vs 11.5%, P < 0.05). Weight loss in the correspondence group was correlated with completion of self-monitoring records (r = 0.50, P < 0.005).\n A behavioral weight loss intervention, delivered via correspondence, appears to be effective in reducing women's postpartum weight retention. Future studies should examine the acceptability and the long-term impact of a correspondence postpartum weight loss intervention.", "A 12-week randomized controlled trial was conducted (n = 20) investigating the effects of a multi-intervention programme of exercise and social support compared to a control group. Both groups had given birth in the past 12 months and were experiencing depressive symptomatology. Pretest data of physical fitness and structured questionnaires were compared to post-test data. The results from the study showed that mothers who were in the multi-intervention group improved their fitness levels and depressive symptomatology significantly more than the control group. However, there were no significant changes to either group's social support levels. These results are encouraging and suggest that a pram push walking intervention might be an effective treatment for mothers suffering postnatal distress." ]

[ "9860069", "16344515" ]

[ "Double-blind, placebo-controlled, crossover study of lamotrigine in treatment-resistant generalised epilepsy.", "Double-blind, placebo-controlled study of lamotrigine in primary generalized tonic-clonic seizures." ]

[ "Lamotrigine (LTG) is recognised as effective add-on therapy for focal epilepsies, but this is the first double-blind, placebo-controlled, crossover study in treatment-resistant generalised epilepsy.\n The study consisted of 2 x 8-week treatment periods followed by a 4-week washout period. Patients received doses of either 75 or 150 mg daily, depending on their concomitant antiepileptic drugs (AEDs). Long-term continuation was offered at the end of the study with open-label LTG.\n Five centres in Australia recruited 26 patients who were having absence, myoclonic, or generalized tonic-clonic seizures or a combination of these. Twenty-two patients completed the study. There was a significant reduction in frequency of both tonic-clonic and absence seizure types with LTG. A 350% decrease in seizures was observed for tonic-clonic seizures in 50% of cases and for absence seizures in 33% of evaluable cases. Rash was the only adverse effect causing discontinuation. Twenty-three of 26 opted for open-label LTG, with 20 still receiving LTG for a mean of 26 months. In these 20, 80% had > or =50% seizure reduction and five (25%) were seizure free.\n This study shows that LTG is effective add-on therapy in patients with refractory generalised epilepsies. Statistically significant reduction in seizures in both absence and tonic-clonic seizure types was seen even with low doses of LTG.", "To evaluate the efficacy and tolerability of adjunctive lamotrigine in primary generalized tonic-clonic (PGTC) seizures in a randomized, double-blind, placebo-controlled trial.\n Patients with a diagnosis of epilepsy with PGTC seizures who were receiving one or two antiepileptic drugs at study entry were eligible. Patients with partial seizures were excluded on the basis of seizure history and screening EEGs. The study comprised a baseline phase, an escalation phase during which study medication was titrated to a target dose, and a 12-week maintenance phase during which doses of lamotrigine/placebo and concomitant antiepileptic drugs were maintained.\n Of the 121 randomized patients ages 2 to 55 years, 117 (58 lamotrigine, 59 placebo) entered the escalation phase and received study medication. During the escalation and maintenance phases combined, median percent reduction in PGTC seizure frequency was 66.5% with lamotrigine compared with 34.2% with placebo (p = 0.006). The corresponding numbers for lamotrigine and placebo were 60.6% and 32.8% (p = 0.038) during the escalation phase and 81.9% and 43.0% (p = 0.006) during the maintenance phase. During the maintenance phase, 72% of lamotrigine-treated patients compared with 49% of placebo-treated patients experienced a > or = 50% reduction in frequency of PGTC seizures (p = 0.014). A similar pattern of results was observed for all generalized seizures. The most common drug-related adverse events were dizziness (5% lamotrigine, 2% placebo), somnolence (5% lamotrigine, 2% placebo), and nausea (5% lamotrigine, 3% placebo).\n Adjunctive lamotrigine is effective in the treatment of primary generalized tonic-clonic seizures and has a favorable tolerability profile." ]

[ "17473143", "15330019", "1557840", "9258101", "8436990", "8549224", "16950076", "15795571", "2013589", "6195948" ]

[ "Rapid-inflation intermittent pneumatic compression for prevention of deep venous thrombosis.", "Prevention of deep-vein thrombosis after total hip and knee replacement. Low-molecular-weight heparin in combination with intermittent pneumatic compression.", "Prophylactic mini-dose heparin in patients undergoing radical retropubic prostatectomy. A prospective trial.", "Is heparin contraindicated in pelvic lymphadenectomy and radical prostatectomy?", "The effectiveness of intermittent plantar venous compression in prevention of deep venous thrombosis after total hip arthroplasty.", "The efficacy of pneumatic compression stockings in the prevention of pulmonary embolism after cardiac surgery.", "VenaFlow plus Lovenox vs VenaFlow plus aspirin for thromboembolic disease prophylaxis in total knee arthroplasty.", "Thromboembolic disease prophylaxis in patients with hip fracture: a multimodal approach.", "Intermittent pneumatic compression to prevent proximal deep venous thrombosis during and after total hip replacement. A prospective, randomized study of compression alone, compression and aspirin, and compression and low-dose warfarin.", "Prevention of postoperative deep venous thrombosis and pulmonary emboli with combined modalities." ]

[ "Current treatment regimens that are designed to prevent deep venous thrombosis in patients undergoing orthopaedic procedures rely predominantly on drug prophylaxis alone. The purpose of this randomized clinical study was to evaluate the effectiveness of a mechanical adjunct to chemoprophylaxis that involves intermittent compression of the legs.\n During a twenty-two month period, 1803 patients undergoing a variety of orthopaedic procedures were prospectively randomized to receive either chemoprophylaxis alone or a combination of chemoprophylaxis and mechanical prophylaxis. Nine hundred and two patients were managed with low-molecular-weight heparin alone, and 901 were managed with low-molecular-weight heparin and intermittent pneumatic compression of the calves for varying time periods. Twenty-four percent of the patients underwent total hip or knee joint replacement. Screening for deep venous thrombosis was performed on the day of discharge with duplex-color-coded ultrasound.\n In the chemoprophylaxis-only group, fifteen patients (1.7%) were diagnosed with a deep venous thrombosis; three thromboses were symptomatic. In the chemoprophylaxis plus intermittent pneumatic compression group, four patients (0.4%) were diagnosed with deep venous thrombosis; one thrombosis was symptomatic. The difference between the groups with regard to the prevalence of deep venous thrombosis was significant (p = 0.007). In the chemoprophylaxis plus intermittent pneumatic compression group, no deep venous thromboses were found in patients who received more than six hours of intermittent pneumatic compression daily.\n Venous thrombosis prophylaxis with low-molecular-weight heparin augmented with a device that delivers rapid-inflation intermittent pneumatic compression to the calves was found to be significantly more effective for preventing deep venous thrombosis when compared with a treatment regimen that involved low-molecular-weight heparin alone.", "After total hip (THR) or knee replacement (TKR), there is still an appreciable risk of developing deep-vein thrombosis despite prophylaxis with low-molecular-weight heparin (LMWH). In a prospective, randomised study we examined the efficacy of LMWH in combination with intermittent pneumatic compression in patients undergoing primary unilateral THR or TKR. We administered 40 mg of enoxaparin daily to 131 patients combined with either the use of intermittent pneumatic compression or the wearing of graduated compression stockings. Compression ultrasonography showed no evidence of thrombosis after LMWH and intermittent pneumatic compression. In the group with LMWH and compression stockings the prevalence of thrombosis was 28.6% (40% after TKR, 14% after THR). This difference was significant (p < 0.0001). In the early post-operative phase after THR and TKR, combined prophylaxis with LMWH and intermittent pneumatic compression is more effective than LMWH used with graduated compression stockings.", "We initiated a prospective, partially randomized trial of the effects of perioperative prophylactic mini-dose heparin on the incidence of clinically evident pulmonary emboli, intraoperative blood loss, blood transfusions, duration of postoperative pelvic drainage, and lymphocele formation in 68 consecutive patients undergoing radical retropubic prostatectomy. We treated 32 patients with mini-dose heparin and 36 without it. We detected pulmonary emboli in 4 (11%) patients not treated with mini-dose heparin and in none treated with heparin (p = 0.052). Anesthesiologists estimated a mean intraoperative blood loss of 2,152 cc in the heparinized patients compared with 1,886 cc in controls (p = 0.2). At a time when our policy was to replace all blood loss, we transfused a mean of 3.9 units to heparinized patients and 3.2 units to controls (p = 0.1). Persistent lymphatic drainage requiring more than six days of closed suction drainage occurred in 12 of 32 (38%) heparinized patients as compared with 4 of 36 (11%) controls (p = 0.01). We discontinued the study after 68 patients because of the morbidity associated with mini-dose heparin. Because of the associated morbidity we do not recommend the routine use of mini-dose heparin in patients undergoing radical prostatectomy.", "We initiated a prospective study to verify or refute the complications of lymphocele formation and excessive blood loss associated with heparin prophylaxis in pelvic lymphadenectomy and radical prostatectomy.\n A prospective study was completed on 579 men undergoing pelvic lymphadenectomy usually in association with radical prostatectomy. Patients were assigned to group 1 (given preoperative and postoperative subcutaneous heparin) and group 2 (no heparin). All patients were evaluated 2 to 3 weeks after surgery with ultrasound for pelvic lymphocele.\n There was no statistically significant difference in the number or size of pelvic lymphoceles or blood loss in group 1 versus group 2.\n The use of heparin prophylaxis to prevent thromboembolic complications in conjunction with pelvic lymphadenectomy and radical prostatectomy is not associated with increased blood loss or increased rate of lymphocele formation.", "The purpose of this study was to investigate the effectiveness of intermittent pneumatic compression of the plantar venous plexus with the newly developed arteriovenous impulse system. Seventy-four patients about to undergo primary unilateral total hip arthroplasty for osteoarthrosis, all receiving a standard thrombosis prophylaxis regime of thigh-length anti-embolic stockings, 5,000 IU heparin delivered subcutaneously twice daily, and 400 mg hydroxychloroquine sulfate delivered twice daily, were entered in a prospective trial. The patients were allocated at random to also receive the arteriovenous impulse system on the foot of the operated side. On approximately postoperative day 12 bilateral ascending venography was performed. There were 44 patients in the nonpumped group and 30 patients in the pumped group. The incidence of deep venous thrombosis was 6.6% in the pumped group and 27.27% in the nonpumped group. The incidence of thrombosis was significantly lower in the pumped group (P < .025). The authors conclude that chemical prophylaxis plus the use of the mechanical, pneumatic, and arteriovenous impulse system reduces the incidence of thromboembolic complications further than chemical prophylaxis alone.", "Pneumatic compression stocking (PCS) devices have been introduced to decrease the incidence of postoperative deep venous thrombosis (DVT). However, their role in the prophylaxis against pulmonary embolism (PE) remains unclear. This study was undertaken to compare the prophylactic effectiveness of subcutaneous heparin (SCH) alone vs the combined use of PCS and SCH in the prevention of PE following cardiac surgery.\n We studied 2,551 consecutive patients who underwent cardiac surgery over a 10-year period. They were randomly allocated to two groups. Group A included 1,196 patients who were treated with 5,000 U of SCH every 12 h and group B included 1,355 patients treated with a combined prophylactic regimen of PCS and SCH.\n The diagnosis of PE was established in 69 patients by either high-probability ventilation perfusion scan, pulmonary angiogram, or autopsy. The incidence of PE in group A patients was 4% (48/1,196) and in group B was 1.5% (21/1,355). The concomitant use of bilateral PCS and SCH reduced the frequency of postoperative PE in 62% in comparison to the prophylaxis with SCH alone (p < 0.001).\n These data suggest that the combined prophylactic method of bilateral PCS and SCH is superior to SCH alone in the prevention of PE after cardiac surgery.", "Two hundred seventy-five patients undergoing unilateral total knee arthroplasty were prospectively randomized to receive spinal epidural anesthesia (SEA), a VenaFlow calf compression device, and enoxaparin (group A) or SEA, VenaFlow, and aspirin (group B). Aspirin was started on the day of surgery, whereas enoxaparin was started 48 hours after surgery. Anticoagulants were continued for 4 weeks after surgery. All patients had an in-hospital ultrasound screening test on postoperative days 3 to 5 and a second follow-up ultrasound 4 to 6 weeks after surgery. The overall deep venous thrombosis rates in groups A and B were 14.1% and 17.8% (P = not significant), respectively. When used in combination with pneumatic compression devices and SEA, enoxaparin was not superior to aspirin in preventing deep venous thrombosis after total knee arthroplasty.", "To assess if pneumatic compression in conjunction with chemoprophylaxis is an effective way to reduce the incidence of deep vein thrombosis in orthopedic trauma patients sustaining fragility hip fractures.\n Two hundred patients admitted to the authors' institution between May 1998 and June 2002 for fractures of the hip were prospectively studied. All patients were treated operatively and received the VenaFlow calf compression device on both lower extremities immediately following surgery. Chemical prophylaxis of either aspirin (n = 67) or warfarin (n = 133) was administered in addition to mechanical compression. A noninvasive serial color flow duplex scan was performed 1 to 11 days postoperatively (mean 4.5 days) to determine the presence or absence of deep vein thrombosis. All patients were followed clinically 3 months postoperatively for a clinical evaluation of symptomatic deep vein thrombosis or pulmonary embolism.\n Overall, the incidence of deep vein thrombosis was 3.5% (7 of 200) and included only 1 proximal thrombosis (1 out of 200, or 0.5%) and no pulmonary embolism. Five of the 7 patients positive for deep vein thrombosis were in the mechanical compression and warfarin prophylaxis group and 2 were in the aspirin arm of the study. For patients with deep vein thrombosis, the average number of risk factors was 3.71, whereas patients without clots averaged 1.75 clinical risk factors (P < or = 0.05). Three patients in the warfarin group developed bleeding complications (1 with a gastrointestinal bleed and 2 with minor bleeding not at the operative site). No evidence of a symptomatic deep vein thrombosis or pulmonary embolism was reported within a 3-month period following hospitalization.\n Our findings suggest mechanical compression with the VenaFlow calf compression device in conjunction with chemoprophylaxis is an effective means of reducing thromboembolic disease in this high-risk population.", "A prospective, randomized study of the effectiveness of intraoperative and postoperative use of intermittent pneumatic compression, alone or in combination with oral administration of either aspirin or low-dose warfarin, was done of a consecutive series of patients who had a total hip replacement and were more than thirty-nine years old. All patients began walking by the third postoperative day. One hundred and ninety-six patients who had 217 total hip arthroplasties were included. Twenty-eight per cent of the procedures were revisions of a previous total hip replacement or of an endoprosthesis, and the remainder were primary arthroplasties. Patients were randomized as to the type of prophylaxis that they received: intermittent pneumatic compression alone, seventy-six hips; intermittent pneumatic compression and aspirin, seventy-two hips; or intermittent pneumatic compression and low-dose warfarin, sixty-nine hips. Before discharge from the hospital, and at an average of seven days after the operation, all patients were evaluated for the presence of proximal deep-vein thrombosis with either venography on the side of the operation or with bilateral venous ultrasonography. The relative frequency with which thrombosis occurred in a proximal vein was not significantly different in the three groups; the over-all relative frequency was 10 per cent. Intermittent compression during and after the operation effectively reduces the rate of proximal-vein thrombosis after total hip replacement. With the number of patients in our study, the effectiveness of this technique could not be shown to be augmented by oral administration of either aspirin or low-dose warfarin.", "Worldwide statistics reveal that 25 to 40 per cent of patients who are over the age of 40 years and operated on for 1 or more hours will develop a deep venous thrombosis (DVT). The studies reviewed in this paper were performed to evaluate several modalities and compare their effectiveness in preventing DVT in postoperative patients. In the first study, five modalities plus a control group were evaluated in 562 patients from five surgical specialties. The incidence of DVT in the control group was 35 per cent. Though most of the pharmacologic agents were effective in reducing the incidence of DVT, the antistasis devices (gradient elastic stockings and intermittent pneumatic compression) were most effective. The purpose of the second study was to evaluate the effectiveness of combining a pharmacologic drug with an antistasis modality. Deep venous thrombosis was virtually eliminated in this group of 328 patients. There was only a 1.5 per cent incidence of DVT in the treated population as compared to a 26.8 per cent incidence in the control group. Thus, it seems that combining one antistasis and one pharmacologic agent greatly reduces the incidence of lower extremity thrombi. I-125 fibrinogen scanning was the most sensitive test in detecting DVT and had an accuracy of 97 per cent." ]

[ "19007842", "19324530", "16816222" ]

[ "Bipolar I and II disorder residual symptoms: oxcarbazepine and carbamazepine as add-on treatment to lithium in a double-blind, randomized trial.", "Comparative efficacy and safety of oxcarbazepine versus divalproex sodium in the treatment of acute mania: a pilot study.", "A double-blind, randomized, placebo-controlled trial of oxcarbazepine in the treatment of bipolar disorder in children and adolescents." ]

[ "Bipolar affective disorders often require adjunctive therapy to treat persistent symptoms. In order to evaluate bipolar symptoms inadequately responsive to lithium, we have compared the effects of two structurally related compounds carbamazepine (CBZ) and oxcarbazepine (OXC). We evaluated the efficacy and safety of CBZ and OXC administration in residual symptoms as an adjunctive therapy in Bipolar I (BP I) and Bipolar II (BP II) patients while on lithium maintenance treatment. We selected from 153 bipolar patients in treatment those fulfilling Research Diagnostic Criteria for mania or hypomania, according to the SADS-L and conducted in 52 bipolar patients (27 BP I, 25 BP II) a double-blind, randomized, parallel-group, single centre, clinical trial. Bipolar I and II outpatients, were randomly assigned on a 1:1 ratio to OXC (n=26) or CBZ (n=26) for an 8-week period as add-on treatment to the existing lithium regimen. Outcome measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale 21 items (HDRS-21) and Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impression severity (CGI-S) and improvement illness (CGI-I). These scales were administered at baseline and at the end of weeks 2, 4 and 8. All the fifty-two patients completed the trial. Overall, females were 35 (65%) and mean (S.D.) age was 39.4 (11.9) years; final doses at the end of week 8 in OXC group was 637.7 (210) mg/day and in the CBZ group 673.5 (179) mg/day; lithium plasma levels were 0.73 (0.25) meq/l and 0.71 (0.28) meq/l, respectively. Both OXC and CBZ were effective in reducing bipolar scores from baseline to endpoint (p<0.01). OXC was more effective than CBZ at weeks 4 and 8 on all 5 outcome measures. OXC resulted in greater significant mean reductions in YMRS, HDRS-21, MADRS, CGI-S and CGI-I scores from baseline to week 4 (p<0.05) and from baseline to week 8 (p<0.001), except YMRS (p<0.01). OXC appeared to be significantly more effective and with better tolerability than CBZ as add-on strategy treatment in BP I and BP II patients. This pilot, randomized clinical trial, suggests the potential usefulness of OXC as adjunctive therapy to lithium both in acute and long-term treatment of bipolar disorder. However, further adequately placebo-controlled trials are needed to expand these findings.", "This study compared the efficacy and safety of oxcarbazepine and divalproex sodium in acute mania patients.\n In this 12 week, randomized, double-blind pilot study, 60 patients diagnosed with acute mania (DSM-IV) and a baseline Young Mania Rating Scale (YMRS) score of 20 or more received flexibly dosed oxcarbazepine (1,000-2,400 mg/day) or divalproex (750-2,000 mg/day). The mean decrease in the YMRS score from baseline was used as the main outcome measure of response to treatment. A priori protocol-defined threshold scores were <or=12 for remission and >or=15 for relapse. Number of patients showing adequate response and the time taken to achieve improvement was compared. Adverse events were systematically recorded throughout the study.\n Over 12 weeks, mean improvement in YMRS scores was comparable for both the groups including the mean total scores as well as percentage fall from baseline. There were no significant differences between treatments in the rates of symptomatic mania remission (90% in divalproex and 80% in oxcarbazepine group) and subsequent relapse. Median time taken to symptomatic remission was 56 days in divalproex group while it was 70 days in the oxcarbazepine group (p=0.123). A significantly greater number of patients in divalproex group experienced one or more adverse drug events as compared to patients in the oxcarbazepine group (66.7% versus 30%, p<0.01).\n Oxcarbazepine demonstrated comparable efficacy to divalproex sodium in the management of acute mania. Also the overall adverse event profile was found to be superior for oxcarbazepine.", "This multicenter trial examined the efficacy and safety of oxcarbazepine in the treatment of bipolar disorder in children and adolescents.\n A total of 116 outpatients 7 to 18 years of age with bipolar I disorder, manic or mixed, were recruited at 20 centers in the United States and randomly assigned to receive 7 weeks of double-blinded, flexibly dosed treatment with oxcarbazepine (maximum dose 900-2400 mg/day) or placebo. The primary efficacy measure was the mean change from baseline to endpoint in the Young Mania Rating Scale (YMRS), using the last-observation-carried-forward method.\n Oxcarbazepine (mean dose=1515 mg/day) did not significantly improve YMRS scores at endpoint compared with placebo [adjusted mean change: oxcarbazepine, -10.90 (N=55); placebo, -9.79 (N=55)]. Dizziness, nausea, somnolence, diplopia, fatigue, and rash were each reported in at least 5% of the patients in the oxcarbazepine group with an incidence at least twice that of the placebo group. The majority of adverse events were mild to moderate and occurred during the titration period. Eleven patients (19%) in the oxcarbazepine group discontinued the study because of adverse events, compared with two (4%) in the placebo group.\n Oxcarbazepine is not significantly superior to placebo in the treatment of bipolar disorder in youths. While the overall adverse event profile was similar to that reported for patients with epilepsy, the incidence of psychiatric adverse events for both the oxcarbazepine and placebo groups was higher than that reported for the epilepsy population." ]

[ "16788315", "12547542", "16442954", "16102099", "17382476", "16757825", "18496183", "12105840", "17692642", "18480205", "20838118", "19546387", "16035081", "17906567", "15681939", "16035095", "15569871", "18393319", "15734783", "16096533", "16269927", "15480990" ]

[ "Elective administration in infants of low-dose recombinant activated factor VII (rFVIIa) in cardiopulmonary bypass surgery for congenital heart disease does not shorten time to chest closure or reduce blood loss and need for transfusions: a randomized, double-blind, parallel group, placebo-controlled study of rFVIIa and standard haemostatic replacement therapy versus standard haemostatic replacement therapy.", "Effect of recombinant activated factor VII on perioperative blood loss in patients undergoing retropubic prostatectomy: a double-blind placebo-controlled randomised trial.", "Safety and hemostatic effect of recombinant activated factor VII in cirrhotic patients undergoing partial hepatectomy: a multicenter, randomized, double-blind, placebo-controlled trial.", "Recombinant activated factor VII in treatment of bleeding complications following hematopoietic stem cell transplantation.", "Recombinant FVIIa decreases perioperative blood transfusion requirement in burn patients undergoing excision and skin grafting--results of a single centre pilot study.", "Recombinant activated factor VII for acute intracerebral hemorrhage: US phase IIA trial.", "Recombinant factor VIIA in traumatic intracerebral hemorrhage: results of a dose-escalation clinical trial.", "Safety and efficacy of recombinant factor VIIa in patients with liver disease undergoing laparoscopic liver biopsy.", "Activated recombinant factor VII in orthotopic liver transplantation.", "Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage.", "Results of the CONTROL trial: efficacy and safety of recombinant activated Factor VII in the management of refractory traumatic hemorrhage.", "Safety and efficacy of recombinant activated factor VII: a randomized placebo-controlled trial in the setting of bleeding after cardiac surgery.", "Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease.", "Recombinant activated factor VII in spinal surgery: a multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial.", "Recombinant coagulation factor VIIa in major liver resection: a randomized, placebo-controlled, double-blind clinical trial.", "Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation.", "Safety and feasibility of recombinant factor VIIa for acute intracerebral hemorrhage.", "Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial.", "Use of activated recombinant coagulation factor VII in patients undergoing reconstruction surgery for traumatic fracture of pelvis or pelvis and acetabulum: a double-blind, randomized, placebo-controlled trial.", "Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials.", "Control of bleeding in children with Dengue hemorrhagic fever using recombinant activated factor VII: a randomized, double-blind, placebo-controlled study.", "Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial." ]

[ "We investigated the effectiveness of prophylactic administration of recombinant activated factor VII (rFVIIa) for cardiopulmonary bypass surgery in children under 1 year old with congenital heart disease (CHD) in a double-blinded, placebo-controlled study. The rFVIIa dose was 40 microg/kg and all patients also received standard haemostatic replacement therapy. The primary endpoint was the time to chest closure from neutralization of heparin with protamine sulphate as this could be most objectively and accurately measured during surgery. Secondary endpoints were volumes of transfused blood, platelet concentrates and fresh-frozen plasma. All adverse events were recorded. In the intention-to-treat analysis there were 76 patients (40 in rFVIIa group and 36 in placebo group). The demographics and severity of CHD were similar in both groups. No benefit of rFVIIa prophylaxis was found in the time to chest closure, which was significantly prolonged in the rFVIIa group (rFVIIa mean +/- SE, 98.8 +/- 27.27 versus 55.3 +/- 29.15, P = 0.0263). In the 41 patients available for a follow-up visit 6 weeks after discharge, the chest closure time was also prolonged in the rFVIIa group (P = 0.0515). There were no significant differences in the secondary endpoints. Adverse events were similar in both groups.", "Recombinant activated factor VII (factor VIIa) has prohaemostatic effects in bleeding patients with coagulation abnormalities. We aimed to test the hypothesis that recombinant factor VIIa could reduce perioperative blood loss in patients with normal coagulation systems. Therefore, we assessed safety and efficacy of this drug in patients undergoing retropubic prostatectomy, which is often associated with major blood loss and need for transfusion.\n In a double-blind, randomised placebo-controlled trial, we recorded blood loss and transfusion requirements in 36 patients undergoing retropubic prostatectomy, who were randomised to receive an intravenous bolus of recombinant factor VIIa (20 microg/kg or 40 microg/kg) or placebo in the early operative phase.\n Median perioperative blood loss was 1235 mL (IQR 1025-1407) and 1089 mL (928-1320) in groups given recombinant factor VIIa 20 microg/kg and 40 microg/kg, respectively, compared with 2688 mL (1707-3565) in the placebo group (p=0.001). Seven of twelve placebo-treated patients were transfused, whereas no patients who received 40 microg/kg recombinant factor VIIa needed transfusion. The odds ratio for receiving any blood product in patients treated with recombinant factor VIIa compared with control patients was 0 (95% CI 0.00-0.33) No adverse events arose.\n An injection of recombinant factor VIIa can reduce perioperative blood loss and eliminate the need for transfusion in patients undergoing major surgery.", "Coagulopathy caused by cirrhosis may contribute to excessive bleeding during hepatectomy. We evaluated the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in cirrhotic patients undergoing partial hepatectomy.\n Patients were randomized to rFVIIa 50 or 100 mug/kg or placebo, administered intravenously 10 minutes before surgery and every second hour during surgery. The primary efficacy end points were the proportion of patients receiving red blood cell (RBC) transfusions and the amount of RBCs transfused. The RBC transfusion trigger was blood loss of 500 mL. Safety end points included thromboembolic and adverse events.\n No statistically significant effect of rFVIIa treatment on efficacy end points was observed. Serious and thromboembolic adverse events occurred at similar incidences in the study groups.\n Using blood loss as a transfusion trigger, the efficacy of rFVIIa in reducing the requirement for RBC transfusion was not established in this study. No safety concerns were identified.", "Bleeding is a common complication following hematopoietic stem cell transplantation (HSCT) and standard hemostatic treatment is often ineffective. We conducted a multicentre, randomized trial of the efficacy and safety of activated recombinant factor VII (rFVIIa, NovoSeven) in the treatment of bleeding following HSCT.\n 100 patients with moderate or severe bleeding (52 gastrointestinal; 26 hemorrhagic cystitis; seven pulmonary; one cerebral; 14 other) were included from days +2 to +180 post-transplant (97 allogeneic; three autologous) to receive seven doses of rFVIIa (40, 80 or 160 microg kg(-1)) or placebo every 6 h. The primary efficacy endpoint was the change in bleeding score between the first administration and 38 h.\n No significant effect of increasing rFVIIa dose was observed on the primary endpoint. A post hoc analysis comparing each rFVIIa dose with placebo showed that 80 microg kg(-1) rFVIIa improved the bleeding score at the 38 h time point (81% vs. 57%, P = 0.021). This effect was not seen at 160 microg kg(-1). There were no differences in transfusion requirements across dose groups. There was no trend in the type or number of severe adverse events observed. Six thromboembolic events were observed in the active treatment groups: three during, and three following the 96-h observation period.\n Despite no overall effect of rFVIIa treatment on primary endpoint, post hoc analysis showed an improvement in the control of bleeding for 80 microg kg(-1) rFVIIa vs. standard hemostatic treatment. The heterogeneity of the population may have contributed to the lack of an increasing effect with increased dose. Further trials should focus upon identifying the patient populations that may benefit from treatment with rFVIIa.", "Excision of burn wounds is frequently associated with a large volume of blood loss requiring allogeneic blood transfusion. We conducted a pilot study to investigate the effect of activated recombinant coagulation factor VII (rFVIIa) on the reduction of blood transfusion requirements in burn patients undergoing excision and skin grafting.\n Eighteen consecutive patients scheduled for the surgery were randomised to receive either placebo or 40 microg/kg rFVIIa administered at first skin incision, and a second dose (40 microg/kg) at 90 min later. Blood transfusion requirements during, and up to 24h post-surgery per patient and percentage full thickness wound excised were compared. In addition, postoperative complications commonly seen in patients with burns as well as adverse events related to rFVIIa were monitored.\n rFVIIa significantly decreased the total number of units of blood components transfused per patient and percentage full thickness burn wound excised compared with placebo (0.9 versus 2.2, p=0.0013) including significant fewer red blood cell units (0.5 versus 1.1, p=0.004). We further observed a trend towards improved graft survival (p=0.1) and a reduction in multiple organ failures (p=0.08) in the rFVIIa-treated group. There were no adverse events, in particular thromboembolic events.\n rFVIIa might be useful in decreasing blood transfusion requirements in burn patients undergoing excision and skin grafting.", "Ultra-early hemostatic therapy may improve outcome after intracerebral hemorrhage (ICH) by preventing rebleeding and hematoma expansion. We conducted this trial to evaluate the safety of activated recombinant factor VII (rFVIIa; NovoSeven) for preventing early hematoma growth in acute ICH.\n In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial, 40 patients diagnosed with ICH by computed tomography within 3 hours of onset were treated with placebo or 5, 20, 40, or 80 microg/kg of rFVIIa ( n = 8 per group). Patients with any history of thromboembolic or vaso-occlusive disease were excluded. The primary endpoint was the frequency of adverse events (AEs).\n Mean age was 65 years (range 34 - 91) and the median admission Glasgow Coma Scale score was 14.5 (range 6 to 15). Mean ICH volume was 17 +/- 19 mL; nearly three-quarters were located in the basal ganglia ( n = 29). The mean interval from onset to treatment was 178 +/- 41 minutes. Thirty-three patients experienced 186 AEs, which occurred with similar frequency in the five groups. There were 10 thromboembolic AEs, including one case of deep vein thrombosis (20 microg g/kg group); one case of cerebral infarction (placebo); two cases of pulmonary embolism (20 and 40 microg g/kg groups); and six instances of ischemic ECG changes or cardiac enzyme elevation (placebo [ n = 2], 20 microg g/kg [ n = 1], 40 microg g/kg [ n = 1], and 80 microg g/kg [ n = 2] groups). No consumption coagulopathy or dose-related increase in edema-to-ICH volume ratio occurred.\n Ultra-early rFVIIa treatment for ICH was associated with a reasonable safety profile in this preliminary study across a wide range of dosages. Further research is warranted to investigate the safety and potential efficacy of rFVIIa for minimizing ICH growth.", "Intracerebral hemorrhages, whether spontaneous or traumatic (tICH), often expand, and an association has been described between hemorrhage expansion and worse clinical outcomes. Recombinant factor VIIa (rFVIIa) is a hemostatic agent that has been shown to limit hemorrhage expansion and which, therefore, could potentially reduce morbidity and mortality in tICH. This first prospective, randomized, placebo-controlled, dose-escalation study evaluated the safety and preliminary effectiveness of rFVIIa to limit tICH progression.\n Patients were enrolled if they had tICH lesions of at least 2 ml on a baseline computed tomographic scan obtained within 6 hours of injury. rFVIIa or placebo was administered within 2.5 hours of the baseline computed tomographic scan but no later than 7 hours after injury. Computed tomographic scans were repeated at 24 and 72 hours. Five escalating dose tiers were evaluated (40, 80, 120, 160, and 200 microg/kg rFVIIa). Clinical evaluations and adverse events were recorded until Day 15.\n No significant differences were detected in mortality rate or number and type of adverse events among treatment groups. Asymptomatic deep vein thrombosis, detected on routinely performed ultrasound at Day 3, was observed more frequently in the combined rFVIIa treatment group (placebo, 3%; rFVIIa, 8%; not significant). A nonsignificant trend for rFVIIa dose-response to limit tICH volume increase was observed (placebo, 21.0 ml; rFVIIa, 10.1 ml).\n In this first prospective study of rFVIIa in tICH, there appeared to be less hematoma progression in rFVIIa-treated patients (80-200 microg/kg) compared with that seen in placebo treated patients. The potential significance of this biological effect on clinical outcomes and the significance of the somewhat higher incidence of ultrasound-detected deep vein thromboses in the rFVIIa-treated group need to be examined in a larger prospective randomized clinical trial.", "Activated recombinant factor VII (rFVIIa) has been shown to be effective in correcting prolonged prothrombin time (PT) in cirrhotic patients. The main objective of this study was to evaluate the effect of 4 (5, 20, 80, and 120 microg/kg) doses of rFVIIa on correction of PT and the time to achieve hemostasis in cirrhotic patients with coagulopathy who are undergoing laparoscopic liver biopsy.\n Seventy-one patients (parts I and II) with advanced liver disease (Child-Turcotte B or C), platelet count > or =60,000/mm3, and PT in the range of 3-15 seconds above normal were included in the study. Efficacy endpoints were normalization of PT and time to hemostasis.\n PT was corrected to normal levels (<13.1 seconds) in the majority of patients. The duration of normalization of PT was longer in patients treated with higher doses of rFVIIa. Forty-eight (74%) of 65 patients (part II) achieved hemostasis within 10 minutes. No correlation between the time to hemostasis and duration of correction of PT was observed. None of the patients required operative intervention or transfusion of blood/blood products to control bleeding. One thrombotic event and one case of disseminated intravascular coagulation were reported, but both events were considered by the investigator as unlikely to be related to treatment with rFVIIa.\n The results of this study suggest that treatment with rFVIIa may offer benefit for patients with liver disease undergoing laparoscopic biopsy.", "Orthotopic liver transplantation (OLT) is affected by important alterations of hemostasis. The aim of this study was to evaluate the efficacy of recombinant factor VII activated (rFVIIa) to reduce intraoperative bleeding during OLT.\n Twenty OLT patients were assigned in double-blind way to a rFVIIa group or a control group. Inclusion criteria were hemoglobin > 8 g/dL: INR > 1,5 and fibrinogen > 100 mg/dL. We administered a single bouls of rFVIIa (40 microg/kg) or placebo. We determined INR, partial thromboplastin time, fibrinogen, ATIII, and blood cell counts. Blood products were administered as follows: 4 units of fresh frozen plasma when INR > 1.5, and 1 unit of RBC for Hb < 10 g/dL. The study ended 6 hours after the bolus.\n No thromboembolic events occurred. The INR was different between rFVIIa group and the controls at T0 (1.9 vs 1.6 P < .021) and during T1 (1.2 vs 1.6 P < .004). The total transfused red blood cells was 300 mL +/- 133 in rFVIIa group and 570 mL +/- 111 in control group (P < .017). The total fresh frozen plasma was 600 mL +/- 154 in rFVIIa group and 1400 mL +/- 187 in control group (P < .001). Total blood loss was greater in the control group than the rFVIIa group: 1140 mL +/- 112 vs 740 mL +/- 131 (P < .049).\n The use of rFVIIa during OLT can reduce the risk of bleeding during surgery. The literature has described cases who did not benefit from the treatment. An adequate cut-off of INR, allowed us to treat only patients at greater bleeding risk.", "Intracerebral hemorrhage is the least treatable form of stroke. We performed this phase 3 trial to confirm a previous study in which recombinant activated factor VII (rFVIIa) reduced growth of the hematoma and improved survival and functional outcomes.\n We randomly assigned 841 patients with intracerebral hemorrhage to receive placebo (268 patients), 20 microg of rFVIIa per kilogram of body weight (276 patients), or 80 microg of rFVIIa per kilogram (297 patients) within 4 hours after the onset of stroke. The primary end point was poor outcome, defined as severe disability or death according to the modified Rankin scale 90 days after the stroke.\n Treatment with 80 microg of rFVIIa per kilogram resulted in a significant reduction in growth in volume of the hemorrhage. The mean estimated increase in volume of the intracerebral hemorrhage at 24 hours was 26% in the placebo group, as compared with 18% in the group receiving 20 microg of rFVIIa per kilogram (P=0.09) and 11% in the group receiving 80 microg (P<0.001). The growth in volume of intracerebral hemorrhage was reduced by 2.6 ml (95% confidence interval [CI], -0.3 to 5.5; P=0.08) in the group receiving 20 microg of rFVIIa per kilogram and by 3.8 ml (95% CI, 0.9 to 6.7; P=0.009) in the group receiving 80 microg, as compared with the placebo group. Despite this reduction in bleeding, there was no significant difference among the three groups in the proportion of patients with poor clinical outcome (24% in the placebo group, 26% in the group receiving 20 microg of rFVIIa per kilogram, and 29% in the group receiving 80 microg). The overall frequency of thromboembolic serious adverse events was similar in the three groups; however, arterial events were more frequent in the group receiving 80 microg of rFVIIa than in the placebo group (9% vs. 4%, P=0.04).\n Hemostatic therapy with rFVIIa reduced growth of the hematoma but did not improve survival or functional outcome after intracerebral hemorrhage. (ClinicalTrials.gov number, NCT00127283 [ClinicalTrials.gov].).\n Copyright 2008 Massachusetts Medical Society.", "Traumatic coagulopathy contributes to early death by exsanguination and late death in multiple organ failure. Recombinant Factor VIIa (rFVIIa, NovoSeven) is a procoagulant that might limit bleeding and improve trauma outcomes.\n We performed a phase 3 randomized clinical trial evaluating efficacy and safety of rFVIIa as an adjunct to direct hemostasis in major trauma. We studied 573 patients (481 blunt and 92 penetrating) who bled 4 to 8 red blood cell (RBC) units within 12 hours of injury and were still bleeding despite strict damage control resuscitation and operative management. Patients were assigned to rFVIIa (200 μg/kg initially; 100 μg/kg at 1 hour and 3 hours) or placebo. Intensive care unit management was standardized using evidence-based trauma \"bundles\" with formal oversight of compliance. Primary outcome was 30-day mortality. Predefined secondary outcomes included blood products used. Safety was assessed through 90 days. Study powering was based on prior randomized controlled trials and large trauma center databases.\n Enrollment was terminated at 573 of 1502 planned patients because of unexpected low mortality prompted by futility analysis (10.8% vs. 27.5% planned/predicted) and difficulties consenting and enrolling sicker patients. Mortality was 11.0% (rFVIIa) versus 10.7% (placebo) (p = 0.93, blunt) and 18.2% (rFVIIa) versus 13.2% (placebo) (p = 0.40, penetrating). Blunt trauma rFVIIa patients received (mean ± SD) 7.8 ± 10.6 RBC units and 19.0 ± 27.1 total allogeneic units through 48 hours, and placebo patients received 9.1 ± 11.3 RBC units (p = 0.04) and 23.5 ± 28.0 total allogeneic units (p = 0.04). Thrombotic adverse events were similar across study cohorts.\n rFVIIa reduced blood product use but did not affect mortality compared with placebo. Modern evidence-based trauma lowers mortality, paradoxically making outcomes studies increasingly difficult.", "Blood loss is a common complication of cardiac surgery. Evidence suggests that recombinant activated factor VII (rFVIIa) can decrease intractable bleeding in patients after cardiac surgery. Our objective was to investigate the safety and possible benefits of rFVIIa in patients who bleed after cardiac surgery.\n In this phase II dose-escalation study, patients who had undergone cardiac surgery and were bleeding were randomized to receive placebo (n=68), 40 microg/kg rFVIIa (n=35), or 80 microg/kg rFVIIa (n=69). The primary end points were the number of patients suffering critical serious adverse events. Secondary end points included rates of reoperation, amount of blood loss, and transfusion of allogeneic blood. There were more critical serious adverse events in the rFVIIa groups. These differences did not reach statistical significance (placebo, 7%; 40 microg/kg, 14%; P=0.25; 80 microg/kg, 12%; P=0.43). After randomization, significantly fewer patients in the rFVIIa group underwent a reoperation as a result of bleeding (P=0.03) or required allogeneic transfusions (P=0.01).\n On the basis of this preliminary evidence, rFVIIa may be beneficial for treating bleeding after cardiac surgery, but caution should be applied and further clinical trials are required because there is an increase in the number of critical serious adverse events, including stroke, in those patients randomized to receive rFVIIa.", "Orthotopic liver transplantation (OLT) can be associated with excessive blood loss. As a result, there may be increased risk of adverse outcomes. Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve hemostasis in a variety of disorders; however, there has been a limited amount of research into its use in OLT. The purpose of this dose-finding study was to examine the efficacy and safety of rFVIIa in the reduction of bleeding in patients undergoing OLT. In this double-blind trial, patients with end-stage liver disease scheduled for OLT were randomized to 1 of 4 parallel study groups. They received a single intravenous bolus of rFVIIa (20, 40, or 80 microg/kg) or placebo prior to surgery. The primary assessment endpoint was the total number of red blood cell (RBC) units transfused perioperatively. Safety was evaluated by adverse events reported. Eighty-three comparable patients were randomized to receive study product, with 82 ultimately undergoing OLT. There were no significant differences in required RBC units between the placebo and rFVIIa study groups. The number of adverse events was comparable between study groups. In conclusion, rFVIIa has a good safety profile in patients undergoing OLT. However, the doses studied did not have any effect on the number of RBC transfusions required.", "Randomized, placebo-controlled, double-blind, multicenter, Phase IIa study.\n To assess the safety and efficacy of recombinant-activated Factor VII (rFVIIa) in major spinal surgery.\n Spinal fusion surgery can cause substantial blood loss and blood product transfusions. Recombinant FVIIa is approved for treatment of bleeding in patients with coagulation abnormalities and has been shown to reduce blood loss and transfusion requirements in surgery in patients with no underlying coagulopathy.\n Forty-nine patients undergoing fusion of 3 or more vertebral segments were randomized and treated on losing 10% of their estimated blood volume (with total expected surgical blood loss > or = 20%) and received 3 doses (2-hour intervals) of placebo (n = 13) or 30, 60, or 120 microg/kg rFVIIa (n = 12 per group). The primary endpoint was safety. A priori-defined efficacy endpoints included blood loss and transfusion requirements between placebo and each rFVIIa dose group, adjusted for surgery duration, number of segments fused, and estimated blood volume.\n Serious adverse events did not occur at any greater frequency in any of the treatment groups. One patient (3 x 30 microg/kg rFVIIa) with advanced cerebrovascular disease (undiagnosed, trial exclusion criterion) died 6 days after surgery due to an ischemic stroke. Mean blood loss was as follows: 2270 mL for placebo; 1909, 1262, and 1868 mL for 3 x 30, 3 x 60, and 3 x 120 microg/kg rFVIIa, respectively (differences not statistically significant). Mean adjusted surgical blood loss was as follows: 2536 mL for placebo; 1120, 400, and 823 mL for 3 x 30, 3 x 60, and 3 x 120 microg/kg rFVIIa, respectively (P < or = 0.001). Mean surgical transfusion volume was reduced by 27% to 50% with rFVIIa treatment (not significant). The mean adjusted surgical transfusion volume was reduced by 81% to 95% with rFVIIa treatment (P < or = 0.002).\n No safety concerns were indicated for the use of rFVIIa in patients at all doses tested; rFVIIa reduced adjusted blood loss and adjusted transfusions during spinal surgery.", "Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques. The authors conducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy.\n Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 microg/kg rFVIIa or placebo. Partial hepatectomy was performed according to local practice at the participating centers. Patients were monitored for 7 days after surgery. Key efficacy parameters were perioperative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities.\n The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26 of 63) in the 20-microg/kg group, and 25% (15 of 59) in the 80-microg/kg dose group (logistic regression model; P = 0.09). Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 ml with placebo, 1,354 ml with 20 microg/kg rFVIIa, and 1,036 ml with 80 microg/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 microg/kg rFVIIa, and 1,073 ml with 80 microg/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-microg/kg group, with a significant overall effect of treatment (P = 0.04).\n Recombinant factor VIIa dosing did not result in a statistically significant reduction in either the number of patients transfused or the volume of blood products administered. No safety issues were identified.", "Patients undergoing orthotopic liver transplantation (OLT) have excessive blood loss during surgery that requires blood transfusions, leading to increased postoperative morbidity and mortality. We studied the efficacy and safety of activated recombinant factor VII (rFVIIa) in reducing transfusion requirements in OLT. This multicenter, randomized, double-blind, placebo-controlled trial enrolled patients undergoing OLT because of cirrhosis (Child-Turcotte-Pugh class B or C). Patients received a repeated intravenous bolus regimen of rFVIIa 60 or 120 microg/kg or placebo. The primary efficacy endpoint was the total number of red blood cell (RBC) units transfused during the perioperative period. A total of 182 patients were analyzed for efficacy and 183 for safety. No significant effect of rFVIIa was observed on the number of RBC units transfused or intraoperative blood loss compared with the placebo group. A significantly higher number of patients in the rFVIIa study groups avoided RBC transfusion. Administration of rFVIIa but not placebo restored the preoperative prolonged prothrombin time to normal value during surgery. Patients receiving rFVIIa and placebo did not experience a significant difference in rate of thromboembolic events. Additionally, there was no statistically significant effect of rFVIIa treatment on hospitalization rate, total surgery time, and the proportion of patients undergoing retransplantation. In conclusion, use of rFVIIa during OLT significantly reduced the number of patients requiring RBC transfusion. There was no increase in thromboembolic events with rFVIIa administration compared with placebo.", "Hematoma growth occurs in 38% of intracerebral hemorrhage (ICH) patients scanned by computed tomography (CT) within 3 hours of onset. Activated recombinant factor VII (rFVIIa) promotes hemostasis at sites of vascular injury and may minimize hematoma growth after ICH.\n In this randomized, double-blind, placebo-controlled, dose-escalation trial, 48 subjects with ICH diagnosed within 3 hours of onset were treated with placebo (n=12) or rFVIIa (10, 20, 40, 80, 120, or 160 microg/kg; n=6 per group). The primary endpoint was the frequency of adverse events (AEs). Safety assessments included serial electrocardiography (ECG), troponin I and coagulation testing, lower extremity Doppler ultrasonography, and calculation of edema:ICH volume ratios.\n Mean age was 61 years (range, 30 to 93) and 57% were male. At admission, mean National Institutes of Health Stroke Scale (NIHSS) score was 14 (range, 1 to 26), median Glasgow Coma Scale score was 14 (range, 6 to 15), and mean ICH volume was 21 mL (range, 1 to 151). Mean time from onset to treatment was 181 minutes (range, 120 to 265). Twelve serious AEs occurred, including 5 deaths (mortality 11%). Six AEs were considered possibly treatment-related, including rash, vomiting, fever, ECG T-wave inversion, and 2 cases of deep vein thrombosis (placebo and 20-microg/kg groups). No myocardial ischemia, consumption coagulopathy, or dose-related increase in edema:ICH volume occurred.\n This small phase II trial evaluated a wide range of rFVIIa doses in acute ICH and raised no major safety concerns. Larger studies are justified to determine whether rFVIIa can safely and effectively limit ICH growth.", "A beneficial effect of recombinant activated factor VII (rFVIIa) in Child-Pugh class B and C patients with cirrhosis who have variceal bleeding has been suggested. This randomized controlled trial assessed the efficacy and safety of rFVIIa in patients with advanced cirrhosis and active variceal bleeding. At 31 hospitals in an emergency setting, 256 patients (Child-Pugh > 8; Child-Pugh B = 26%, C = 74%) were randomized equally to: placebo; 600 microg/kg rFVIIa (200 + 4x 100 microg/kg); or 300 microg/kg rFVIIa (200 + 100 microg/kg). Dosing was intravenous at 0, 2, 8, 14, and 20 hours after endoscopy, in addition to standard vasoactive, prophylactic antibiotic, and endoscopic treatment. The primary composite endpoint consisted of failure to control 24-hour bleeding, or failure to prevent rebleeding or death at day 5. Secondary endpoints included adverse events and 42-day mortality. Baseline characteristics were comparable between groups. Administration of rFVIIa had no significant effect on the composite endpoint compared with placebo (P = 0.37). There was no significant difference in 5-day mortality between groups; however, 42-day mortality was significantly lower with 600 microg/kg rFVIIa compared with placebo (odds ratio 0.31, 95% confidence interval = 0.13-0.74), and bleeding-related deaths were reduced from 12% (placebo) to 2% (600 microg/kg). A marked heterogeneity in the failure rate in all treatment groups was observed across participating centers. Adverse events, including overall thromboembolic events, were comparable between groups.\n Treatment with rFVIIa had no significant effect on the primary composite endpoint compared with placebo. Therefore, decision on the use of this hemostatic agent in acute variceal bleeding should be carefully considered, because results of this study do not support the routine use of rFVIIa in this setting. Adverse events were comparable across groups.", "Activated recombinant coagulation factor VII (rFVIIa) effectively prevents and controls bleeding in patients with coagulopathy. Data show that rFVIIa may reduce blood loss and eliminate the need for transfusion in patients with normal haemostasis undergoing major surgery. We assessed the efficacy of rFVIIa in patients with normal haemostasis undergoing repair surgery of major traumatic fracture of the pelvis or the pelvis and acetabulum, who were expected to have a large volume of blood loss.\n We performed a double-blind, randomized, placebo-controlled trial involving 48 patients undergoing major pelvic-acetabular surgery. Patients were randomized to receive an i.v. bolus injection of rFVIIa 90 microg kg(-1) or placebo as add-on therapy at the time of the first skin incision. All patients also received intraoperative salvaged red blood cells (RBC).\n There was no significant difference in the total volume of perioperative blood loss, the primary outcome variable, between the rFVIIa and placebo groups. In addition, there were no differences between the two groups in the total volume of blood components, including salvaged RBC transfused, number of patients requiring allogeneic blood components, total volume of fluids infused, total operating time, time taken after entry to the intensive care unit to reach normal body temperature and acid-base status, and time spent in hospital. No adverse events, in particular thromboembolic events, were reported in either group.\n In patients with normal haemostasis undergoing repair surgery of traumatic pelvic-acetabular fracture, the prophylactic use of rFVIIa does not decrease the volume of perioperative blood loss.", "Uncontrolled bleeding is a leading cause of death in trauma. Two randomized, placebo-controlled, double-blind trials (one in blunt trauma and one in penetrating trauma) were conducted simultaneously to evaluate the efficacy and safety of recombinant factor VIIa (rFVIIa) as adjunctive therapy for control of bleeding in patients with severe blunt or penetrating trauma.\n Severely bleeding trauma patients were randomized to rFVIIa (200, 100, and 100 microg/kg) or placebo in addition to standard treatment. The first dose followed transfusion of the eighth red blood cell (RBC) unit, with additional doses 1 and 3 hours later. The primary endpoint for bleeding control in patients alive at 48 hours was units of RBCs transfused within 48 hours of the first dose.\n Among 301 patients randomized, 143 blunt trauma patients and 134 penetrating trauma patients were eligible for analysis. In blunt trauma, RBC transfusion was significantly reduced with rFVIIa relative to placebo (estimated reduction of 2.6 RBC units, p = 0.02), and the need for massive transfusion (>20 units of RBCs) was reduced (14% vs. 33% of patients; p = 0.03). In penetrating trauma, similar analyses showed trends toward rFVIIa reducing RBC transfusion (estimated reduction of 1.0 RBC units, p = 0.10) and massive transfusion (7% vs. 19%; p = 0.08). Trends toward a reduction in mortality and critical complications were observed. Adverse events including thromboembolic events were evenly distributed between treatment groups.\n Recombinant FVIIa resulted in a significant reduction in RBC transfusion in severe blunt trauma. Similar trends were observed in penetrating trauma. The safety of rFVIIa was established in these trauma populations within the investigated dose range.", "We evaluated the efficacy and safety of recombinant activated factor VII (rFVIIa) in children aged < 18 years old with grade II or grade III Dengue hemorrhagic fever (DHF) who required blood component therapy for controlling bleeding episodes.\n Patients were randomized to the rFVIIa group or placebo group in a ratio of 2:1. rFVIIa or placebo (100 microg/kg body weight) was given by intravenous bolus injection. When bleeding was not effectively controlled, a second dose of rFVIIa or placebo (100 microg/kg) was given 30 min after the first dose.\n Nine and 16 patients received placebo and rFVIIa, respectively. The demographics, bleeding manifestations and grade of DHF were similar for the rFVIIa and placebo groups. Apart from petechiae and ecchymosis, one to four additional bleeding sites were found in each patient, including hematemesis (n = 15), epistaxis (n = 14), gum bleeding (n = 12), melena (n = 7), hypermenorrhea (n = 4), hematochezia (n = 2) and hematuria (n = 2). The mean total dose of rFVIIa (138.4 +/- 50.9 microg/kg) and placebo (145.4 +/- 53.7 microg/kg) were comparable. The efficacy of bleeding control at 2 h after the first dose was completely ceased (rFVIIa 75.0% versus placebo 44.4%), decreased (rFVIIa 18.7% versus placebo 11.2%), and unchanged or worsened (rFVIIa 6.3% versus placebo 44.4%). Some patients with active bleeding received platelet concentrates 3-12 h after the first dose of rFVIIa or placebo. The subsequent efficacy of bleeding control at 6, 12 and 24 h was comparable between the two groups. The cumulative use of red blood cells (rFVIIa 31.3% versus placebo 33.3%) and plasma (rFVIIa 25% versus placebo 22%) during the 24-h period was not significantly different between the two groups. In contrast, platelet concentrate requirement in the rFVIIa group (6.3%) was lower than the placebo (33.3%). No clinical evidence of thromboembolic complications or mortality as a result of bleeding was observed.\n rFVIIa appears to be a useful adjunctive treatment to blood component transfusion for controlling active bleeding in children with DHF especially when platelet concentrate is not readily available.", "Upper gastrointestinal bleeding (UGIB) is a severe and frequent complication of cirrhosis. Recombinant coagulation factor VIIa (rFVIIa) has been shown to correct the prolonged prothrombin time in patients with cirrhosis and UGIB. This trial aimed to determine efficacy and safety of rFVIIa in cirrhotic patients with variceal and nonvariceal UGIB.\n A total of 245 cirrhotic patients (Child-Pugh < 13; Child-Pugh A = 20%, B = 52%, C = 28%) with UGIB (variceal = 66%, nonvariceal = 29%, bleeding source unknown = 5%) were randomized equally to receive 8 doses of 100 microg/kg rFVIIa or placebo in addition to pharmacologic and endoscopic treatment. The primary end point was a composite including: (1) failure to control UGIB within 24 hours after first dose, or (2) failure to prevent rebleeding between 24 hours and day 5, or (3) death within 5 days.\n Baseline characteristics were similar between rFVIIa and placebo groups. rFVIIa showed no advantage over standard treatment in the whole trial population. Exploratory analyses, however, showed that rFVIIa significantly decreased the number of failures on the composite end point (P = 0.03) and the 24-hour bleeding control end point (P = 0.01) in the subgroup of Child-Pugh B and C variceal bleeders. There were no significant differences between rFVIIa and placebo groups in mortality (5- or 42-day) or incidence of adverse events including thromboembolic events.\n Although no overall effect of rFVIIa was observed, exploratory analyses in Child-Pugh B and C cirrhotic patients indicated that administration of rFVIIa significantly decreased the proportion of patients who failed to control variceal bleeding. Dosing with rFVIIa appeared safe. Further studies are needed to verify these findings." ]

[ "19596010", "18410774" ]

[ "Multicenter, randomized, placebo-controlled trial of amitriptyline in children with functional gastrointestinal disorders.", "Double-blind placebo-controlled trial of amitriptyline for the treatment of irritable bowel syndrome in adolescents." ]

[ "There are no prospective, multicenter, double-blind, placebo-controlled, randomized pharmacologic trials for the treatment of pain-predominant functional gastrointestinal disorders in children. The aim of this study was to evaluate the efficacy of amitriptyline in children with pain-predominant functional gastrointestinal disorders.\n In this multicenter placebo-controlled trial, children with irritable bowel syndrome, functional abdominal pain, or functional dyspepsia were randomized to 4 weeks of placebo or amitriptyline (10 mg/d, weight <35 kg; 20 mg/d, weight >35 kg). Assessment of gastrointestinal symptoms, psychological traits, and daily activities occurred before and after intervention. Pain was assessed daily with self-report diaries. The primary outcome was overall response to treatment (child's assessment of pain relief and sense of improvement). Secondary outcomes were effect on psychosocial traits and daily functioning.\n Ninety children were enrolled, and 83 completed the study (placebo, 40 children [30 girls]; drug, 43 children [35 girls]). A total of 63% of patients reported feeling better and 5% feeling worse in the amitriptyline arm compared with 57.5% feeling better and 2.5% feeling worse in the placebo arm (P = .63). Pain relief was excellent in 7% and good in 38% of children receiving placebo compared with excellent in 15% and good in 35% of children treated with amitriptyline (P = .85). Logistic regression analysis of those reporting excellent or good response versus fair, poor, or failed response showed no difference between amitriptyline and placebo (P = .83). Children who had more severe pain at baseline in both groups (P = .0065) had worse outcome. Amitriptyline reduced anxiety scores (P < .0001).\n Both amitriptyline and placebo were associated with excellent therapeutic response. There was no significant difference between amitriptyline and placebo after 4 weeks of treatment. Patients with mild to moderate intensity of pain responded better to treatment.", "To determine the efficacy of amitriptyline (AMI) in treating irritable bowel syndrome (IBS) in adolescents.\n Adolescents 12 to 18 years with newly diagnosed IBS were surveyed with a symptom checklist, pain rating scale, visual analog scale, and IBS quality of life (QOL) questionnaire. Subjects were randomized in a double-blinded fashion to receive AMI or placebo, and again completed surveys at 2, 6, 10, and 13 weeks.\n Thirty-three patients (24 female) were enrolled. Patients receiving AMI were more likely to experience improvement from baseline in overall QOL at 6, 10, and 13 weeks (P = .019, .004, and .013). Patients receiving AMI were also more likely to experience a reduction in IBS-associated diarrhea at 6 and 10 weeks (P = .029 for both), a reduction in periumbilical pain at 10 weeks (P = .018), and a reduction in right lower quadrant pain at 6, 10, and 13 weeks (P = .014, .039, and .004).\n AMI significantly improves overall QOL in adolescents with IBS and should be a therapeutic option for adolescents with this disorder." ]

[ "9519098", "10836281", "11032464", "9298518", "10200742", "9682999", "7802104", "9068769", "9696517", "7894879", "1973843", "7912819" ]

[ "One-year, low-dose neuroleptic study of in-patients with chronic schizophrenia characterised by persistent negative symptoms. Amisulpride v. haloperidol.", "Long-term safety and efficacy of amisulpride in subchronic or chronic schizophrenia. Amisulpride Study Group.", "Amisulpride has a superior benefit/risk profile to haloperidol in schizophrenia: results of a multicentre, double-blind study (the Amisulpride Study Group).", "Improvement of acute exacerbations of schizophrenia with amisulpride: a comparison with haloperidol. PROD-ASLP Study Group.", "Improvement of schizophrenic patients with primary negative symptoms treated with amisulpride. Amisulpride Study Group.", "Amisulpride versus flupentixol in schizophrenia with predominantly positive symptomatology -- a double-blind controlled study comparing a selective D2-like antagonist to a mixed D1-/D2-like antagonist. The Amisulpride Study Group.", "Improvement of some schizophrenic deficit symptoms with low doses of amisulpride.", "Amisulpride versus placebo in the medium-term treatment of the negative symptoms of schizophrenia.", "Amisulpride, and atypical antipsychotic, in the treatment of acute episodes of schizophrenia: a dose-ranging study vs. haloperidol. The Amisulpride Study Group.", "Treatment of negative symptoms in schizophrenia with amisulpride.", "Amisulpride versus haloperidol in treatment of schizophrenic patients--results of a double-blind study.", "Clinical, EEG mapping and psychometric studies in negative schizophrenia: comparative trials with amisulpride and fluphenazine." ]

[ "Amisulpride is a potent substituted benzamide antipsychotic drug claimed to improve the negative symptoms of schizophrenia, particularly at low dosage.\n Sixty long-term in-patients with schizophrenia and selected for predominant negative symptoms were randomised to receive either haloperidol or amisulpride. Over a year there was systematic dose reduction, as symptoms allowed.\n There were no significant differences between the treatment groups in the proportion receiving low-dose treatment, the control of positive symptoms, or ratings of social behaviour, side-effects or tardive dyskinesia. For negative symptoms, there were consistent but non-significant trends in favour of amisulpride. The amisulpride patients required significantly less anticholinergic medication.\n In chronically-hospitalised in-patients with schizophrenia characterised by persistent negative symptoms, amisulpride was a well-tolerated maintenance antipsychotic medication. The drug had only a limited effect in reducing negative symptoms, which were relatively stable, enduring phenomena in this sample, despite dosage reduction.", "Amisulpride is an atypical antipsychotic with selective affinity for dopamine D2/3 receptors. In this long-term, open, randomised, multicentre trial, patients with chronic or subchronic schizophrenia received amisulpride (n =370) or haloperidol (n = 118) for 12 months. Dosage regimens were flexible (amisulpride 200-800 mg/day, haloperidol 5-20 mg/day). Improvement in mean Brief Psychiatric Rating Scale total score was significantly greater for amisulpride than haloperidol (17.0 versus 12.8, P = 0.01). Positive symptoms (Positive and Negative Syndrome Scale [PANSS] positive) improved in a similar way in each group but amisulpride caused a significantly better improvement in negative symptoms (PANSS negative) (7.1 versus 3.7, P < 0.0001). Improvements in Global Assessment of Functioning (GAF) and Quality of Life Scale (QLS) scores were also significantly greater in the amisulpride group (GAF -20.1 versus -13.6, P = 0.001; QLS -0.64 versus -0.30, P = 0.02). Adverse events were mainly psychiatric in nature, and occurred with similar frequency in each group (amisulpride 254/370, 69%; haloperidol 82/118, 70%). Extrapyramidal symptoms were more frequent for haloperidol (48/118, 41% versus 96/370, 26% for amisulpride), leading to a greater requirement for antiparkinsonian medication (haloperidol 66/118, 56% versus amisulpride 118/370, 32%). Haloperidol significantly aggravated parkinsonism, akathisia and involuntary movement compared to amisulpride. The overall incidence of endocrine events was comparable between groups (4% for amisulpride, 3% for haloperidol). Maintenance of efficacy was comparable in both treatment groups; 59% of amisulpride patients and 55% of haloperidol patients improved after 1 month of therapy remained improved throughout the study period. Amisulpride is effective following flexible long-term administration and significantly improves social functioning and quality of life.", "In a multicentre, double-blind, flexible-dose study, 199 patients with paranoid schizophrenia or schizophreniform disorders received haloperidol (10-30 mg/d) or amisulpride (400-1200 mg/d) for four months. More patients in the haloperidol group withdrew prematurely (44% vs 26%; P = 0.0077) due to a higher incidence of adverse events. Amisulpride was at least as effective as haloperidol in reducing the Brief Psychiatric Rating Scale (BPRS) total score (-27.3 vs -21.9) (non-inferiority test; P < 0.001). The PANSS positive score improved to a similar extent in both groups whilst improvement in the PANSS negative score was significantly greater with amisulpride (-10.5 vs -7.2; P = 0.01). The percentage of responders on the Clinical Global Impression scale was also significantly greater with amisulpride (71% vs 47%; P < 0.001). Both the Quality of Life Scale (QLS) and the Functional Status Questionnaire (FSQ) improved to a significantly greater extent under amisulpride. Haloperidol was associated with a greater incidence in extrapyramidal symptoms and with a greater increase in the Simpson-Angus score than was seen with amisulpride (0.32 vs 0.02; P < 0.001). In conclusion, amisulpride is globally superior to haloperidol in the treatment of acute exacerbations of schizophrenia and significantly improves patients' quality of life and social adjustment.", "Amisulpride is a substituted benzamide with high selectivity for dopaminergic D2 and D3 receptors. This study compared 800 mg/day amisulpride and 20 mg/day haloperidol in patients with acute exacerbations of schizophrenia. This multicenter, double-blind trial involved 191 patients allocated, after a 1 to 7-day wash-out period, to amisulpride (n = 95) or haloperidol (n = 96) for 6 weeks. Improvement of mean BPRS total score was 48% for amisulpride and 38% for haloperidol (NS), whereas improvement in the Negative PANSS subscale was greater in the amisulpride group (37%) compared to haloperidol (24%) (P = 0.038). CGI scores showed a higher number of responders in the amisulpride (62%) than in the haloperidol group (44%) (P = 0.014). More extrapyramidal symptoms measured with the Simpson-Angus scale were provoked in the haloperidol group (P = 0.0009). Amisulpride is at least as effective as haloperidol in the treatment of acute exacerbations of schizophrenia, and is more effective in the treatment of negative symptoms whilst causing less parkinsonism.", "The goal of this placebo-controlled study was to evaluate the efficacy and safety of low doses of amisulpride, an atypical antipsychotic of the benzamide class with high affinity for D2 and D3 dopamine receptors, in the treatment of schizophrenic patients with predominantly primary negative symptoms.\n After completion of a 4-week washout period, schizophrenic patients with primary negative symptoms participated in a 12-week, multicenter double-blind trial of placebo (N = 83), amisulpride, 50 mg/day (N = 84), or amisulpride, 100 mg/day (N = 75). They were evaluated with the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms, the Brief Psychiatric Rating Scale, and the Montgomery-Asberg Depression Rating Scale.\n Both amisulpride treatment groups showed significantly greater improvement in negative symptoms than the placebo group. Positive symptom scores were low at baseline and changed minimally during the study, suggesting that the improvement in negative symptoms was independent of improvement in positive symptoms. The safety of amisulpride was comparable to that of placebo, and extrapyramidal symptoms were infrequent. Comparable efficacy and safety results were observed with either dose of amisulpride.\n These findings confirm and extend those of earlier placebo-controlled studies of low-dose amisulpride in the treatment of patients with predominantly negative symptoms of schizophrenia.", "The benzamide amisulpride (ASP) is a selective D2-like dopamine antagonist, while flupentixol (FPX), a thioxanthene, blocks D2-like, D1-like and 5-HT2 receptors. To evaluate efficacy and safety of ASP and to investigate the importance of an additional D1-like antagonism for antipsychotic effects and extrapyramidal tolerability, a randomized double-blind multi- center study versus FPX as reference drug was performed for 6 weeks in 132 patients suffering from acute schizophrenia (DSM-III-R) with predominant positive symptomatology. Doses were initially fixed (ASP: 1000 mg/day; FPX: 25 mg/day) but could be reduced by 40% in case of side effects (mean daily doses: ASP: 956 mg; FPX: 22.6 mg). Intention-to-treat evaluation demonstrated significant improvement under both medications. The difference between the mean BPRS decreases of both treatment groups was 5.6 points (95% CI: 0.55; 10.65) in favour of ASP. According to CGI, 62% of patients in either drug group were treatment responders. ANCOVA analysis showed that reductions of BPRS (ASP: -42%; FPX: -32%) and SAPS (ASP: -78%; FPX: -65%) were more pronounced under ASP. Due to adverse events, significantly fewer ASP patients (6%) were withdrawn from the study (FPX: 18%). Extrapyramidal tolerability was better in the ASP group, as demonstrated by smaller increases in the Simpson-Angus Scale, the AIMS, and the Barnes Akathisia Scale in ANCOVA analyses with dosage as covariate. ASP appears to be as effective as FPX with regard to antipsychotic effects on positive schizophrenic symptomatology, while extrapyramidal tolerability is better. These conclusions have to be drawn cautiously, as dosage effects on outcome parameters cannot be entirely ruled out. The present results question the notion that additional blockade of D1-like receptors may be necessary to achieve sufficient antipsychotic effects or to improve extrapyramidal tolerability.", "The authors assessed the effects on primary negative symptoms of low doses of amisulpride, a substituted benzamide neuroleptic with high affinity for D2 and D3 dopamine receptors.\n Young, drug-free schizophrenic patients with pure negative symptoms participated in a 6-week double-blind trial of placebo (N = 10) or low-dose amisulpride (N = 10). They were assessed with the Scale for the Assessment of Negative Symptoms.\n Amisulpride significantly improved negative symptoms. Improvement in avolition, attentional impairment, and retardation was significantly greater with amisulpride than with placebo.\n These findings suggest that some primary negative symptoms may be directly affected by low doses of benzamide neuroleptics.", "Amisulpride is a substituted benzamide with high selectivity for dopamine D2 and D3 receptors. The purpose of the study was to evaluate the effect of 100 mg amisulpride in patients with predominantly negative symptoms of schizophrenia.\n This was a multi-centre, randomised, parallel-group, double-blind study. Patients received either amisulpride (100 mg/day) or placebo over a six-month treatment period.\n A total of 141 patients were included, 69 received amisulpride, 72 placebo. Fifty-eight patients (41%) had received neuroleptic treatment prior to inclusion. The percentage of amisulpride patients completing the study (55%) was significantly higher than that with placebo (32%), and drop-out rates due to lack of efficacy were 27% with amisulpride and 47% with placebo. All efficacy assessments were statistically in favour of amisulpride compared with placebo. The overall incidence of extrapyramidal symptoms was comparable in both groups; only five patients started anti-Parkinsonian treatment during the study (one in the placebo and four in the amisulpride group).\n Amisulpride is effective in the medium-term treatment schizophrenic patients with predominantly negative symptoms.", "This 4-week, double-blind, randomized study was undertaken to determine the dose-response relationship of amisulpride in 319 patients with acute exacerbation of schizophrenia. Fixed doses of amisulpride (400, 800 and 1200 mg/day) and haloperidol (16 mg/day) were compared to amisulpride, 100 mg/day, as a potentially subtherapeutic dose. Efficacy data (BPRS total score and PANSS positive subscale) in the amisulpride groups generated a bell-shaped dose-response curve, with 400 mg/day and 800 mg/day being the most effective treatments for positive symptoms. Parkinsonism did not increase significantly between baseline and endpoint with amisulpride 400, 800 and 1200 mg/day compared to the amisulpride 100 mg/day group, whereas the difference was significant for haloperidol (P<0.05). It is concluded that amisulpride 400 mg and 800 mg/day is highly effective in treating the positive symptoms of schizophrenia, with less extrapyramidal side-effects than haloperidol 16 mg/day.", "The efficacy of low doses of certain neuroleptics in improving negative symptoms is still controversial. This study assessed the efficacy of amisulpride, a benzamide which increases dopaminergic transmission at low doses via presynaptic dopamine receptor blockade, on negative symptoms of schizophrenia.\n The study was designed as a parallel-group, double-blind, placebo-controlled trial. Patients had to fulfil DSM-III criteria for schizophrenia, Andreasen's criteria for negative schizophrenia, and to have a total score of at least 75 on the SANS; those treated with neuroleptics or antidepressants underwent a six-week placebo wash-out. One hundred and four in-patients were randomly assigned to amisulpride 100 mg/d, amisulpride 300 mg/d, or placebo for six weeks; 85 patients completed the study.\n Both amisulpride doses were significantly more effective than placebo on the primary evaluation criterion (SANS total score, MANOVA P < 0.02). No significant changes were found in positive symptoms or in extrapyramidal symptoms.\n Negative symptoms can be improved by low doses of amisulpride, favouring the hypothesis of dopaminergic hypofunction as one of the causes of negative symptoms.", "In a double-blind study, 41 schizophrenic patients (ICD, 9th rev.) were divided into two groups. With a flexible dose, twenty patients were treated with haloperidol, twenty-one with amisulpride. With respect to relevant criteria such as age, sex, length and degree of illness, the two groups were comparable. The study was conducted over 42 days. As early as within the first 14 days, both groups showed significant improvement with respect to their psychotic symptoms. When the two groups were compared on the basis of the BPRS subscore for the anxiety-depression syndrome, and the AMDP system subscores for the somatic-depressive syndrome and the hypochondriac syndrome, the amisulpride group showed significantly better results than the haloperidol group. The ratings on the EPS scales of Webster and Simpson revealed significantly fewer extrapyramidal side-effects in the amisulpride group. Psychotic symptoms were improved after both types of treatment. Amisulpride treatment showed better results with regard to depressive symptoms, and less tendency to generate extrapyramidal side-effects.", "Based on recent quantitative EEG findings of increased slow activity in negative schizophrenia indicating organicity, it was hypothesized that neuroleptics decreasing delta/theta activity should be beneficial for schizophrenics with predominantly negative symptoms. Thus, a double-blind, clinical, psychometric and neurophysiological study was carried out in 40 hospitalized patients with unproductive schizophrenia (mean age: 31 years; ICD diagnoses: 295.0, 295.1 and 295.6) who were treated randomly either with the benzamide amisulpride (AMI; n = 19) or low doses of fluphenazine (FLU; n = 21). In the first 2 weeks the daily doses were 50 mg AMI or 2 mg FLU, respectively, from the third week on up to the sixth week 100 mg AMI and 4 mg FLU. Clinical evaluations, psychometry and EEG mapping were performed on day 1 (hours 0 and 4--acute effect), on day 14 (hour 0--subacute effect) and on day 42 (hours 0 and 4--chronic and superimposed effects). Three AMI patients discontinued therapy prematurely because of productive symptoms (days 14, 28 and 35), while in the FLU group 2 patients dropped out due to depressive symptoms (days 21, 28), 1 due to productive symptoms (day 35), 1 due to ineffectiveness (day 28), and 1 because of an akinetic crisis (day 6). Statistical evaluation demonstrated a significant improvement in the AMDP apathy and Andreasen SANS score in both groups with the patients remaining severely ill as rated by the CGI. FLU-treated patients needed significantly more anticholinergic medication than the AMI-treated group. Psychometric evaluation showed in regard to the noopsyche significant improvement after subacute, chronic and superimposed AMI, while FLU-treated patients showed significant improvement only after subacute treatment. AMI was significantly superior to FLU at the hours 0 and 4 of day 42. The thymopsyche improved after subacute, chronic and superimposed administration of both compounds with a significant superiority of AMI on days 14 and 42 (4 h postdrug). EEG mapping showed a decrease of delta/theta and increase of beta activity as well as an acceleration of the centroid after acute and superimposed AMI on day 42 as compared with baseline; FLU patients exhibited a decrease of delta/theta activity and an acceleration of the total centroid too, while alpha activity was augmented and beta activity tended to be reduced. Our study demonstrated that, in addition to the new benzamide AMI, FLU in low doses may also be regarded as a neuroleptic with activating properties and may be utilized in the treatment of schizophrenics with predominantly negative symptoms." ]

[ "10359738", "15273454", "9015001" ]

[ "Assessment of permanent dual-chamber pacing as a treatment for drug-refractory symptomatic patients with obstructive hypertrophic cardiomyopathy. A randomized, double-blind, crossover study (M-PATHY).", "Doppler evaluation of the descending aorta in patients with hypertrophic cardiomyopathy: potential for assessing the functional significance of outflow tract gradients and for optimizing pacemaker function.", "Dual-chamber pacing for hypertrophic cardiomyopathy: a randomized, double-blind, crossover trial." ]

[ "Dual-chamber pacing (DDD) has been proposed as a treatment alternative to surgery for severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), based largely on uncontrolled studies.\n This prospective, multicenter trial assessed pacing in 48 symptomatic HCM patients with >/=50 mm Hg basal gradient, refractory to drug therapy. Patients were randomized to 3 months each of DDD pacing and pacing backup (AAI-30) in a double-blind, crossover study design, followed by an uncontrolled and unblinded 6-month pacing trial. With randomization, no significant differences were evident between pacing and no pacing for subjective or objective measures of symptoms or exercise capacity, including NYHA functional class, quality of life score, treadmill exercise time or peak oxygen consumption. After 6 additional months of unblinded pacing, functional class and quality of life score were improved compared with baseline (P<0.01), but peak oxygen consumption was unchanged. Outflow gradient decreased 40%, 82+/-32 mm Hg to 48+/-32 mm Hg (P<0. 001), and was reduced in 57% of patients but showed no change or an increase in 43%. At 12 months, 6 individual patients (12%) showed improved functional capacity; each was 65 to 75 years of age. Left ventricular wall thicknesses in the overall study group showed no remodeling between baseline (22+/-5 mm) and 12 months (21+/-5 mm; P=NS).\n (1) Pacing cannot be regarded as a primary treatment for obstructive HCM; (2) with randomization, perceived symptomatic improvement was most consistent with a substantial placebo effect; (3) longer, uncontrolled pacing periods were associated with some subjective benefit but unaccompanied by objective improvement in cardiovascular performance and should be interpreted cautiously; (4) modest reduction in outflow gradient was achieved in most patients; and (5) a small subset (12%) >/= 65 years of age showed a clinical response, suggesting that DDD pacing could be a therapeutic option for some elderly patients.", "We evaluated whether analysis of aortic flow could be useful for determining the functional significance of left ventricular outflow gradients and for optimizing pacing therapy in patients with hypertrophic cardiomyopathy (HOCM).\n Doppler echocardiography was performed in 32 patients with HOCM. Eleven patients with pacemakers (PPM) also underwent treadmill and quality-of-life (QOL) testing in a randomized crossover trial (1 month of backup pacing (AAI at 30 beats per minute), 1 month with an atrioventricular interval (AVI) of 30 ms (DDD30), and 1 month with an \"optimized\" AVI (DDDop) that maximized the descending aortic Doppler velocity time integral.\n Patients with HOCM displayed a notch in the aortic Doppler flow profile. The location of the notch in systole corresponded with the development of the peak left ventricular outflow gradient. Aortic flow after the notch was variable ranging from 6-48% of the total flow. In patients with pacemakers, improved response to pacing was noted in those patients that developed the notch early in systole and had subsequent attenuation of aortic flow. Optimizing the AVI was associated with improved exercise tolerance (AAI: 4.6 +/- 2.3 min., DDD30: 5.5 +/- 2.2 min., and DDDop: 7.7 +/- 2.5 min.; p < 0.05) and improved QOL.\n Patients with HOCM have a notch in their aortic Doppler flow profile. The location of the notch correlates with the development of the peak left ventricular outflow gradient and flow after the notch is variable. Patients with an early notch and attenuated flow after the notch appear to have the greatest response to pacing therapy.", "In a double-blind, randomized, crossover trial we sought to evaluate the effect of dual-chamber pacing in patients with severe symptoms of hypertrophic obstructive cardiomyopathy.\n Recently, several cohort trials showed that implantation of a dual-chamber pacemaker in patients with severely symptomatic hypertrophic obstructive cardiomyopathy can relieve symptoms and decrease the severity of the left ventricular outflow tract gradient. However, the outcome of dual-chamber pacing has not been compared with that of standard therapy in a randomized, double-blind trial.\n Twenty-one patients with severely symptomatic hypertrophic obstructive cardiomyopathy were entered into this trial after baseline studies consisting of Minnesota quality-of-life assessment, two-dimensional and Doppler echocardiography and cardiopulmonary exercise tests. Nineteen patients completed the protocol and underwent double-blind randomization to either DDD pacing for 3 months followed by backup AAI pacing for 3 months, or the same study arms in reverse order.\n Left ventricular outflow tract gradient decreased significantly to 55 +/- 38 mm Hg after DDD pacing compared with the baseline gradient of 76 +/- 61 mm Hg (p < 0.05) and the gradient of 83 +/- 59 mm Hg after AAI pacing (p < 0.05). Quality-of-life score and exercise duration were significantly improved from the baseline state after the DDD arm but were not significantly different between the DDD arm and the backup AAI arm. Peak oxygen consumption did not significantly differ among the three periods. Overall, 63% of patients had symptomatic improvement during the DDD arm, but 42% also had symptomatic improvement during the AAI backup arm. In addition, 31% had no change and 5% had deterioration of symptoms during the DDD pacing arm.\n Dual-chamber pacing may relieve symptoms and decrease gradient in patients with hypertrophic obstructive cardiomyopathy. In some patients, however, symptoms do not change or even become worse with dual-chamber pacing. Subjective symptomatic improvement can also occur from implantation of the pacemaker without its hemodynamic benefit, suggesting the role of a placebo effect. Long-term follow-up of a large number of patients in randomized trials is necessary before dual-chamber pacing can be recommended for all patients with severely symptomatic hypertrophic obstructive cardiomyopathy." ]