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Interim Analysis (interim + analysis)
Selected AbstractsHP37 PROGNOSTIC FACTORS IN OESOPHAGEAL CANCER: NUMBER OF LYMPH NODES AND EXTRACAPSULAR LYMPH NODE INVASION , AN INTERIM ANALYSISANZ JOURNAL OF SURGERY, Issue 2007S. K. Thompson Purpose Controversy exists over the 2nd edition of the TNM staging system introduced by the American Joint Committee in Cancer in 1988, and revised in 2002. Prognostic pathological factors such as the number of positive lymph nodes and any extracapsular lymph node invasion may refine this current staging system and optimize patient treatment. Methodology All patients who underwent surgical resection for oesophageal cancer were identified in a prospectively-maintained database. Patients without invasive adenocarcinoma or squamous cell cancer were excluded. Pathology slides were reviewed by a single pathologist. Survival data was calculated using Kaplan-Meier curves, and prognostic factors were examined using the log rank test. Results 235 surgical specimens met inclusion criteria, and 95 specimens have been reviewed so far. The 5-yr overall survival rate was 43% (median 31.4 months). Subdividing pN-stage into 1,2 positive nodes and >2 positive nodes showed significant differences in 5-yr survival between both groups: 41% vs. 6.0%, respectively (P = 0.0003). Similarly, including absence and presence of extracapsular lymph node invasion into our pathology review showed significant differences in 5-yr survival: 40% vs. 7.8%, respectively (P < 0.01). A negative circumferential margin, and the absence of both vascular and perineural invasion were also found to significantly improve survival rates. Conclusions The number and characteristics of metastatic invasion of lymph nodes should be included in current oesophageal cancer staging systems. Clinicians will then have more accurate prognostic information, and treatment can be better tailored to patients' needs. [source] Interim Analysis and Sample Size ReassessmentBIOMETRICS, Issue 4 2000Martin Posch Summary. This article deals with sample size reassessment for adaptive two-stage designs based on conditional power arguments utilizing the variability observed at the first stage. Fisher's product test for the p -values from the disjoint samples at the two stages is considered in detail for the comparison of the means of two normal populations. We show that stopping rules allowing for the early acceptance of the null hypothesis that are optimal with respect to the average sample size may lead to a severe decrease of the overall power if the sample size is a priori underestimated. This problem can be overcome by choosing designs with low probabilities of early acceptance or by midtrial adaptations of the early acceptance boundary using the variability observed in the first stage. This modified procedure is negligibly anticonservative and preserves the power. [source] Vigabatrin and Epilepsy: Lessons LearnedEPILEPSIA, Issue 7 2007John M. Wild Summary:,Purpose: The risk factors for visual field loss attributable to vigabatrin (VAVFL) are equivocal. This multinational, prospective, observational study aimed to clarify the principal/major factors for VAVFL. Methods: Interim analysis of three groups with refractory partial epilepsy, stratified by age (8,12 years; >12 years) and exposure to vigabatrin (VGB). Group I comprised participants treated with VGB for ,6 months, Group II participants previously treated with VGB for ,6 months who had discontinued the drug for ,6 months and Group III those never treated with VGB. Perimetry was undertaken at least every six months, for up to 36 months; results were evaluated masked to drug exposure. Results: Based upon 563 participants in the locked data set, 432 yielded one or more Conclusive visual field examinations. For Group I, the frequency of VAVFL at the last Conclusive examination was 10/32 (31.2%) for those aged 8,12 years and 52/125 (41.6%) for those aged >12 years. For Group II, the proportions were 4/39 (10.3%) and 31/129 (24.0%). No cases resembling VAVFL manifested in Group III. VAVFL was associated with duration of VGB therapy (Odds ratio [OR] 14.2; 95% CI 5.0 to 40.5); mean dose of VGB (OR 8.5; 95% CI 2.2 to 33.2); and male gender (OR 2.1; 95% CI 1.2 to 3.7). VAVFL was more common with static than kinetic perimetry (OR 2.3, 95% CI 1.3 to 4.2). Conclusions: The therapeutic benefit of VGB is counteracted by the progressive accrual of the risk of VAVFL with continued exposure and with increase in mean dose. [source] Role of Chronic Infection and Inflammation in the Gastrointestinal Tract in the Etiology and Pathogenesis of Idiopathic ParkinsonismHELICOBACTER, Issue 4 2005Part 2: Response of Facets of Clinical Idiopathic Parkinsonism to Helicobacter pylori Eradication. ABSTRACT Background., Links between etiology/pathogenesis of neuropsychiatric disease and infection are increasingly recognized. Aim., Proof-of-principle that infection contributes to idiopathic parkinsonism. Methods., Randomized, double-blind, placebo-controlled efficacy study of proven Helicobacter pylori eradication on the time course of facets of parkinsonism. Intervention was 1 week's triple eradication therapy/placebos. Routine deblinding at 1 year (those still infected received open-active), with follow-up to 5 years post-eradication. Primary outcome was mean stride length at free-walking speed, sample size 56 for a difference, active vs. placebo, of 3/4 (between-subject standard deviation). Recruitment of subjects with idiopathic parkinsonism and H. pylori infection was stopped at 31, because of marked deterioration with eradication failure. Interim analysis was made in the 20 who had reached deblinding, seven of whom were receiving antiparkinsonian medication (long- t1/2, evenly spaced) which remained unchanged. Results., Improvement in stride-length, on active (n = 9) vs. placebo (11), exceeded size of effect on which the sample size was calculated when analyzed on intention-to-treat basis (p = .02), and on protocol analysis of six weekly assessments, including (p = .02) and excluding (p = .05) those on antiparkinsonian medication. Active eradication (blind or open) failed in 4/20, in whom B-lymphocyte count was lower. Their mean time course was: for stride-length, ,243 (95% CI ,427, ,60) vs. 45 (,10, 100) mm/year in the remainder (p = .001); for the ratio, torque to extend to flex relaxed arm, 349 (146, 718) vs. 58 (27, 96)%/ year (p < .001); and for independently rated, visual-analog scale of stance,walk videos (worst,best per individual , 0,100 mm), ,64 vs. ,3 mm from anterior and ,50 vs. 11 lateral (p = .004 and .02). Conclusions., Interim analysis points to a direct or surrogate (not necessarily unique) role of a particular infection in the pathogenesis of parkinsonism. With eradication failure, bolus release of antigen from killed bacteria could aggravate an effect of ongoing infection. [source] Early stopping by using stochastic curtailment in a three-arm sequential trialJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES C (APPLIED STATISTICS), Issue 2 2003Denis Heng-Yan Leung Summary. Interim analysis is important in a large clinical trial for ethical and cost considerations. Sometimes, an interim analysis needs to be performed at an earlier than planned time point. In that case, methods using stochastic curtailment are useful in examining the data for early stopping while controlling the inflation of type I and type II errors. We consider a three-arm randomized study of treatments to reduce perioperative blood loss following major surgery. Owing to slow accrual, an unplanned interim analysis was required by the study team to determine whether the study should be continued. We distinguish two different cases: when all treatments are under direct comparison and when one of the treatments is a control. We used simulations to study the operating characteristics of five different stochastic curtailment methods. We also considered the influence of timing of the interim analyses on the type I error and power of the test. We found that the type I error and power between the different methods can be quite different. The analysis for the perioperative blood loss trial was carried out at approximately a quarter of the planned sample size. We found that there is little evidence that the active treatments are better than a placebo and recommended closure of the trial. [source] Latest news and product developmentsPRESCRIBER, Issue 9 2008Article first published online: 21 MAY 200 Dabigatran launched Dabigatran (Pradaxa), an orally active direct thrombin inhibitor, has been introduced for the prophylaxis of venous thromboembolism in patients undergoing elective total hip or knee replacement. Treatment is initiated within four hours of surgery and continued for 10 days after knee replacement and 28-35 days after hip replacement. Dabigatran has been shown to be as effective and well tolerated as enoxaparin (Clexane). The launch was widely publicised in the lay media; the charity Lifeblood claimed it could help prevent tens of thousands of deaths. NICE is preparing a technology appraisal of the new agent but it has not announced a publication date. Loop diuretics may increase bone loss Continuous use of a loop diuretic appears to double the rate of bone loss in men compared with nonusers, an observational study suggests (Ann Intern Med 2008;168: 735-40). Up to five years' follow-up of 3269 men aged over 65 revealed that the mean rate of bone loss in the hip among those who did not use a loop diuretic was 0.33 per cent compared with 0.78 per cent among users and 0.58 per cent in those who had intermittently used a loop diuretic. Use of these agents should be included as a risk factor for fractures, the authors suggest. Rosuvastatin not for heart failure patients? Prescribers should pause before using rosuvastatin (Crestor). in patients with heart failure and ischaemic heart disease, the National Prescribing Centre (NPC). says. Commenting on the CORONA trial (N Engl J Med 2008; published online 5 Nov 2007; 10.1056/NEJMoa 0706201)., which found no reduction in cardiovascular events or mortality in older patients with systolic heart failure despite a reduction in LDL-C, the NPC says GPs should still consider evidence-based statins such as simvastatin in this patient group. The reason for the outcome of CORONA is unclear but the NPC points out that not all statins affect mortality equally. Rimonabant CV benefits sustained Two-year follow-up of the RIO-Europe trial has shown that the benefits of rimonabant (Acomplia). on weight loss and cardiovascular risk factors are sustained with continuing treatment (Eur Heart J 2008; published online doi: 10.1093/ eurheartj/ehn076). In addition to a dietary deficit of 600kcal per day, rimonabant 20mg per day achieved greater mean weight loss (5.5 vs 1.2kg). and improvements in waist circumference, HDL-cholesterol, triglycerides, fasting glucose and insulin levels, insulin resistance, and metabolic syndrome prevalence compared with placebo. Many patients discontinued treatment (placebo 42 per cent, rimonabant 45 per cent). but, although psychiatric events were more common with rimonabant during the first year, there was little difference in patients remaining in the second year. Early glatiramer cuts MS progression risk Early treatment with glatiramer acetate (Copaxone). appears to reduce the risk of progression to multiple sclerosis (MS), according to a study presented at the 60th Annual Meeting of the American Academy of Neurology in Chicago. Interim analysis of the PreCISE trial showed that, in patients with a single episode and MRI suggestive of MS, glatiramer was associated with a lower incidence of progression to a second episode of MS compared with placebo (25 vs 43 per cent). The placebo arm of the trial has now been stopped. NRT before quitting Beginning nicotine replacement therapy (NRT) before stopping smoking may double the six-month success rate compared with beginning treatment on the scheduled quit day, a meta-analysis suggests (Addiction 2008;103: 557-63). The analysis of four trials involving 755 participants found that starting NRT two to four weeks before the agreed quit date was twice as likely as the conventional strategy to achieve abstinence after six weeks and six months. Copyright © 2008 Wiley Interface Ltd [source] Early stopping by using stochastic curtailment in a three-arm sequential trialJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES C (APPLIED STATISTICS), Issue 2 2003Denis Heng-Yan Leung Summary. Interim analysis is important in a large clinical trial for ethical and cost considerations. Sometimes, an interim analysis needs to be performed at an earlier than planned time point. In that case, methods using stochastic curtailment are useful in examining the data for early stopping while controlling the inflation of type I and type II errors. We consider a three-arm randomized study of treatments to reduce perioperative blood loss following major surgery. Owing to slow accrual, an unplanned interim analysis was required by the study team to determine whether the study should be continued. We distinguish two different cases: when all treatments are under direct comparison and when one of the treatments is a control. We used simulations to study the operating characteristics of five different stochastic curtailment methods. We also considered the influence of timing of the interim analyses on the type I error and power of the test. We found that the type I error and power between the different methods can be quite different. The analysis for the perioperative blood loss trial was carried out at approximately a quarter of the planned sample size. We found that there is little evidence that the active treatments are better than a placebo and recommended closure of the trial. [source] Two-Stage Group Sequential Robust Tests in Family-Based Association Studies: Controlling Type I ErrorANNALS OF HUMAN GENETICS, Issue 4 2008Lihan K. Yan Summary In family-based association studies, an optimal test statistic with asymptotic normal distribution is available when the underlying genetic model is known (e.g., recessive, additive, multiplicative, or dominant). In practice, however, genetic models for many complex diseases are usually unknown. Using a single test statistic optimal for one genetic model may lose substantial power when the model is mis-specified. When a family of genetic models is scientifically plausible, the maximum of several tests, each optimal for a specific genetic model, is robust against the model mis-specification. This robust test is preferred over a single optimal test. Recently, cost-effective group sequential approaches have been introduced to genetic studies. The group sequential approach allows interim analyses and has been applied to many test statistics, but not to the maximum statistic. When the group sequential method is applied, type I error should be controlled. We propose and compare several approaches of controlling type I error rates when group sequential analysis is conducted with the maximum test for family-based candidate-gene association studies. For a two-stage group sequential robust procedure with a single interim analysis, two critical values for the maximum tests are provided based on a given alpha spending function to control the desired overall type I error. [source] Alpha-dihydroergocryptine in the treatment of de novo parkinsonian patients: results ofa multicentre, randomized, double-blind, placebo-controlled studyACTA NEUROLOGICA SCANDINAVICA, Issue 6 2000B. Bergamasco Introduction, A multicentre, randomized, double-blind, placebo-controlled, parallel group study was carried out in 123 patients suffering from never treated (de novo) idiopathic Parkinson's disease (PD). The aim of the study was to confirm the efficiency and safety of ,-dihydroergocryptine (,-DHEC) given as monotherapy in the symptomatic treatment of PD. The total score of the Unified Parkinson's Disease Rating Scale (UPDRS) was identified as the efficacy target variable. Patients and methods, Sixty-two patients (32 males, 30 females, mean age±SD 64±10) were randomized to ,-dihydroergocryptine and 61 (30 males, 31 females, mean age 63.8±9.1) to placebo. According to the experimental design, a 18-month double-blind phase vs placebo was followed. Two interim analyses were planned both at the 3rd and 12th month of treatment, in order to avoid continuation on placebo, if clear differences between groups were found (stopping criterium: nominal significance level equal to 0.022 in the analysis of the target variable). Analysis of variance was performed both on the per protocol (PP) and intent-to-treat (ITT) sample. Results, The results on the first interim analysis showed significant differences between treatment groups of the UPDRS total score both in the ITT (115 patients, ,-DHEC: No. 56; placebo: No. 59; P=0.019) and PP (96 patients, ,-DHEC: No. 46; placebo: No. 50; P=0.001) sample, why the trial was stopped. At the time of stopping the trial, 73 patients (,-DHEC: No. 37; placebo: No. 36) had reached the 6-month observation visit; the analysis carried out on this subset of patients confirmed the efficacy of ,-dihydroergocryptine in early PD and the correctness of the decision to stop. The incidence of adverse drug reactions (ADR) did not differ between ,-dihydroergocryptine and placebo recipients, gastrointestinal complaints being the most frequent. Conclusion, The results indicate that ,-dihydroergocryptine is safe and effective in improving symptoms of de novo parkinsonian patients. [source] Persistence and Improvement of Nasolabial Fold Correction with Nonanimal-Stabilized Hyaluronic Acid 100,000 Gel Particles/mL Filler on Two Retreatment Schedules: Results up to 18 Months on Two Retreatment SchedulesDERMATOLOGIC SURGERY, Issue 2008RHODA S. NARINS MD BACKGROUND Nonanimal-stabilized hyaluronic acid (NASHA) fillers are frequently used for facial soft tissue augmentation. Their long-term efficacy and the effects of different retreatment schedules are not well established. OBJECTIVE This is an 18-month interim analysis of a 30-month study to evaluate the efficacy and persistence of NASHA 100,000 gel particles/mL filler with two different retreatment schedules. METHODS This multicenter, randomized, evaluator-blinded study enrolled 75 patients with moderate to severe nasolabial folds. Patients were randomized to retreatment of one nasolabial fold at 4.5 months and the contralateral fold at 9 months after correction of both folds at the initial visit. RESULTS Wrinkle Severity Rating Scale scores improved significantly (p<.001) from baseline, with mean improvements ranging from 1.1 to 1.7 grades. Almost all patients (97%) responded satisfactorily, and the efficacy of the retreatment schedules did not differ significantly. Adverse events, primarily swelling and bruising, occurred in 33% of patients; none were serious. CONCLUSION The improvements seen after initial treatment with NASHA 100,000 gel particles/mL filler persisted for up to 18 months with one retreatment. The response was equivalent for retreatment at 4.5 and 9 months. [source] Fifty-two-week efficacy and safety of vildagliptin vs. glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapyDIABETES OBESITY & METABOLISM, Issue 2 2009E. Ferrannini Aim:, To examine the efficacy and safety of vildagliptin vs. glimepiride as add-on therapy to metformin in patients with type 2 diabetes mellitus in a 52-week interim analysis of a large, randomized, double-blind, multicentre study. The primary objective was to demonstrate non-inferiority of vildagliptin vs. glimepiride in glycosylated haemoglobin (HbA1c) reduction at week 52. Methods:, Patients inadequately controlled on metformin monotherapy (HbA1c 6.5,8.5%) and receiving a stable dose of metformin (mean dose 1898 mg/day; mean duration of use 36 months) were randomized 1:1 to receive vildagliptin (50 mg twice daily, n = 1396) or glimepiride (titrated up to 6 mg/day; mean dose 4.5 mg/day, n = 1393). Results:, Non-inferiority of vildagliptin was demonstrated (97.5% confidence interval 0.02%, 0.16%) with a mean (SE) change from baseline HbA1c (7.3% in both groups) to week 52 endpoint of ,0.44% (0.02%) with vildagliptin and ,0.53% (0.02%) with glimepiride. Although a similar proportion of patients reached a target HbA1c level of <7% with vildagliptin and glimepiride (54.1 and 55.5%, respectively), a greater proportion of patients reached this target without hypoglycaemia in the vildagliptin group (50.9 vs. 44.3%; p < 0.01). Fasting plasma glucose (FPG) reductions were comparable between groups (mean [SE] ,1.01 [0.06] mmol/l and ,1.14 [0.06] mmol/l respectively). Vildagliptin significantly reduced body weight relative to glimepiride (mean [SE] change from baseline ,0.23 [0.11] kg; between-group difference ,1.79 kg; p < 0.001) and resulted in a 10-fold lower incidence of hypoglycaemia than glimepiride (1.7 vs. 16.2% of patients presenting at least one hypoglycaemic event; 39 vs. 554 hypoglycaemic events, p < 0.01). No severe hypoglycaemia occurred with vildagliptin compared with 10 episodes with glimepiride (p < 0.01), and no patient in the vildagliptin group discontinued because of hypoglycaemia compared with 11 patients in the glimepiride group. The incidence of adverse events (AEs), serious AEs and adjudicated cardiovascular events was 74.5, 7.1 and 0.9%, respectively, in patients receiving vildagliptin, and 81.1, 9.5 and 1.6%, respectively, in patients receiving glimepiride. Conclusions:, When metformin alone fails to maintain sufficient glycaemic control, the addition of vildagliptin provides comparable efficacy to that of glimepiride after 52 weeks and displays a favourable AE profile, with no weight gain and a significant reduction in hypoglycaemia compared with glimepiride. [source] Psychological effects of prevention: do participants of a type 2 diabetes prevention program experience increased mental distress?DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2009Katrin E. Giel Abstract Objective To evaluate the mental health outcome of a lifestyle intervention for the prevention of type 2 diabetes and to exclude possible harmful psychological effects. Background There is little empirical data on potential harmful effects of prevention programs. However, information, education, diagnostic procedures, phenotyping and risk assessment may cause or intensify psychological distress such as anxiety, depression or somatization in vulnerable individuals. Methods The Tuebingen Lifestyle Intervention Program (TULIP) for the prevention of type 2 diabetes has assessed mental health outcome in the participants after 9 months of program participation using the Symptom Checklist-90-R (SCL-90-R). The 24-months lifestyle intervention TULIP comprises regular exercise and changes in nutrition and assesses both, a broad range of somatic parameters as well as psychometric variables. For an interim analysis of psychological outcome, complete data sets of the SCL-90-R assessed at baseline and after 9 months of intervention were available for 195 participants (125 females, 70 males; age: 46.1 ± 10.6 years). Data on somatization, anxiety, depression and overall psychological distress were compared to baseline levels. Results SCL-90-R scores of the TULIP-participants did not significantly differ from the German healthy reference population. Compared to baseline, a significant decrease in SCL-90-R scores was found for anxiety, depression and overall psychological distress at re-assessment after 9 months. Conclusion The interim analysis on mental health outcome of a type 2 diabetes prevention program comprising extensive phenotyping and risk assessment rules out adverse psychological effects, suggesting rather beneficial changes concerning symptoms of anxiety, depression and overall psychological distress. Copyright © 2009 John Wiley & Sons, Ltd. [source] Exhaled Nitric Oxide Levels during Acute Asthma ExacerbationACADEMIC EMERGENCY MEDICINE, Issue 7 2005Michelle Gill MD Abstract Objectives: Fractional exhaled nitric oxide (FENO) has been shown in laboratory settings and trials of patients with stable asthma to correlate with the degree of airway inflammation. The authors hypothesized that the technique of measuring FENO would be reproducible in the setting of acute asthma in the emergency department (ED) and that the FENO results during ED visits would potentially predict disposition, predict relapse following discharge, and correlate with the National Institutes of Health (NIH) asthma severity scale and peak expiratory flow measurements. Methods: The authors prospectively measured FENO in a convenience sample of ED patients with acute exacerbations of asthma, both at the earliest possible opportunity and then one hour later. Each assessment point included triplicate measurements to assess reproducibility. The authors also performed spirometry and classified asthma severity using the NIH asthma severity scale. Discharged patients were contacted in 72 hours to determine whether their asthma had relapsed. Results: The authors discontinued the trial (n= 53) after a planned interim analysis demonstrated reproducibility (coefficient of variation, 15%) substantially worse than our a priori threshold for precision (4%). There was no association between FENO response and corresponding changes in spirometry or clinical scores. Areas under the receiver operating characteristic curves for the prediction of hospitalization and relapse were poor (0.579 and 0.713, respectively). Conclusions: FENO measurements in ED patients with acute asthma exacerbations were poorly reproducible and did not correlate with standard measures of asthma severity. These results suggest that using existing technology, FENO is not a useful marker for assessing severity, response to treatment, or disposition of acute asthmatic patients in the ED. [source] An aging Interventions Testing Program: study design and interim reportAGING CELL, Issue 4 2007Richard A. Miller Summary The National Institute on Aging's Interventions Testing Program (ITP) has developed a plan to evaluate agents that are considered plausible candidates for delaying rates of aging. Key features include: (i) use of genetically heterogeneous mice (a standardized four-way cross), (ii) replication at three test sites (the Jackson Laboratory, TJL; University of Michigan, UM; and University of Texas, UT), (iii) sufficient statistical power to detect 10% changes in lifespan, (iv) tests for age-dependent changes in T cell subsets and physical activity, and (v) an annual solicitation for collaborators who wish to suggest new interventions for evaluation. Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen (NFP), 4-OH-,-phenyl-N-tert-butyl nitrone (4-OH-PBN), or nordihydroguiaretic acid (NDGA). An interim analysis was conducted using survival data available on the date at which at least 50% of the male control mice had died at each test site. Survival of control males was significantly higher, at the interim time-point, at UM than at UT or TJL; all three sites had similar survival of control females. Males in the NDGA group had significantly improved survival (P = 0.0004), with significant effects noted at TJL (P < 0.01) and UT (P < 0.04). None of the other agents altered survival, although there was a suggestion (P = 0.07) of a beneficial effect of aspirin in males. More data will be needed to determine if any of these compounds can extend maximal lifespan, but the current data show that NDGA reduces early life mortality risks in genetically heterogeneous mice at multiple test sites. [source] Early stopping by using stochastic curtailment in a three-arm sequential trialJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES C (APPLIED STATISTICS), Issue 2 2003Denis Heng-Yan Leung Summary. Interim analysis is important in a large clinical trial for ethical and cost considerations. Sometimes, an interim analysis needs to be performed at an earlier than planned time point. In that case, methods using stochastic curtailment are useful in examining the data for early stopping while controlling the inflation of type I and type II errors. We consider a three-arm randomized study of treatments to reduce perioperative blood loss following major surgery. Owing to slow accrual, an unplanned interim analysis was required by the study team to determine whether the study should be continued. We distinguish two different cases: when all treatments are under direct comparison and when one of the treatments is a control. We used simulations to study the operating characteristics of five different stochastic curtailment methods. We also considered the influence of timing of the interim analyses on the type I error and power of the test. We found that the type I error and power between the different methods can be quite different. The analysis for the perioperative blood loss trial was carried out at approximately a quarter of the planned sample size. We found that there is little evidence that the active treatments are better than a placebo and recommended closure of the trial. [source] Corticosteroid-free immunosuppression with daclizumab in HCV+ liver transplant recipients: 1-year interim results of the HCV-3 study,LIVER TRANSPLANTATION, Issue 11 2007Goran B.G. Klintmalm This work is a 1-yr interim analysis of a prospective, randomized, multicenter trial evaluating the effect of corticosteroid-free immunosuppression on hepatitis C virus,positive (HCV+) liver transplant recipients following liver transplantation (LT). Patients received tacrolimus and corticosteroids (Arm 1; n = 80); tacrolimus, corticosteroids, and mycophenolate mofetil (MMF) (Arm 2; n = 79); or daclizumab induction, tacrolimus, and MMF (Arm 3; n = 153). At 1 yr, 64.1%, 63.4%, and 69.4% of patients achieved the composite primary endpoint of freedom from rejection, freedom from HCV recurrence, and freedom from treatment failure, respectively. Excellent patient and graft survival did not differ significantly among treatment arms. Freedom from HCV recurrence at 1 yr was 61.8 ± 6.2%, 60.1 ± 6.1%, and 67.0 ± 4.3% in Arms 1, 2, and 3, respectively (P = not significant). Freedom from rejection was significantly higher in Arm 3 compared to Arm 1 (93.0 ± 2.2% vs. 81.9 ± 4.4%; P = 0.011). Multivariate analysis identified acute rejection (hazard ratio = 2.692; P = 0.001) and donor age (hazard ratio = 1.015; P = 0.001) as significant risk factors for HCV recurrence. HCV recurrence was not influenced by recipient demographics, HCV genotype, or immunosuppression. In conclusion, these results suggest that a corticosteroid-free regimen of tacrolimus and MMF following daclizumab induction is safe and effective in HCV+ liver transplant recipients. Liver Transpl 13:1521,1531, 2007. © 2007 AASLD. [source] Unfavourable effects of colchicine in combination with interferon-, in the treatment of chronic hepatitis CALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2000M. Angelico Background: The prognosis of chronic hepatitis depends on the progression of hepatic fibrosis. Aim: To investigate whether the antifibrotic drug colchicine, in combination with interferon-, has a role in the treatment of chronic hepatitis C. Methods: Sixty-five HCV,RNA positive patients with chronic hepatitis were randomized to receive interferon-,, 6 MU t.i.w. for 6 months followed by 3 MU t.i.w. for further 6 months, with or without the adjunct of colchicine, 1 mg o.d., 6 days a week, for 3 years. We report an interim analysis after the first 18 months. Results: Thirty-four patients received interferon-, and 31 received interferon-, and colchicine. The two groups were comparable for baseline data, including HCV,RNA levels, genotypes and histological grading/staging. Drop-outs and side-effects were similar. The proportion of patients who achieved alanine transaminase normalization or undetectable HCV,RNA at month 6 was higher in the interferon-, (68% and 47%, respectively) than in the interferon-, plus colchicine group (32% and 23%, P=0.004 and P=0.04, respectively). End-of-treatment biochemical and virological response occurred in 41% and 29% of the interferon-, and 19% and 10% of the combination group, respectively (P=0.05 and P=0.05). Sustained biochemical response occurred in 26% of the interferon-, and 6% of the interferon-, plus colchicine group (P=0.03), corresponding percentages of sustained HCV,RNA loss being 21% and 3% (P=0.04). Conclusions: The combination of colchicine and interferon-, worsens the effectiveness of interferon-, alone in HCV chronic hepatitis. These alarming findings prompted us to interrupt the trial at this stage. [source] A "cure" for Parkinson's disease: Can neuroprotection be proven with current trial designs?MOVEMENT DISORDERS, Issue 5 2004Carl E. Clarke BSc Abstract Current medical and surgical therapies for Parkinson's disease provide symptomatic control of motor impairments rather than slowing or halting the progression of the disease. Previous clinical trials examining drugs such as dopamine agonists and selegiline for neuroprotective effects used "surrogate" outcomes, including clinical measures (rating scales, time to require levodopa), neuroimaging techniques (,-CIT single photon emission computed tomography; fluorodopa positron emission tomography), and mortality tracking. These studies failed to provide conclusive results because of design faults such as failing to control for symptomatic effects, small sample size, and not accounting for the possible effects of drugs on radionuclide tracer handling. Lessons must be learned from these failed neuroprotection trials. This review summarises the problems with previous neuroprotection studies and makes recommendations for future trial design. It is concluded that the primary outcome of explanatory trials should continue to be clinical measures such as the Unified Parkinson's Disease Rating Scale (UPDRS). It should be assumed that all agents have a symptomatic effect, which necessitates evaluation after a prolonged drug washout period. To achieve the evaluation after a prolonged drug washout period more effectively, trials must be performed in early disease and over a short period (6,12 months) so that symptomatic therapy is not required. To achieve adequate statistical power, these trials will need to include thousands of patients. Radionuclide imaging can only be used in such trials after considerable methodological work has been performed to establish its validity and reliability. To be affordable, such large explanatory trials need more streamlined designs with fewer hospital visits, fewer outcome measures, and rationalised safety monitoring. The clinical effectiveness of promising compounds from explanatory trials will need to be established in large long-term pragmatic trials using outcome measures such as quality of life, cost-effectiveness, and mortality. Such pragmatic trials could be continuations of the explanatory trials: after the primary outcome of the explanatory study (e.g., UPDRS) has been reported in an interim analysis, the trial could be continued for a further 5 to 10 years to report on quality of life and health economics outcomes. © 2004 Movement Disorder Society [source] (647) Evaluation of the Long-Term Efficacy and Safety of Transdermal Fentanyl in the Treatment of Noncancer Pain: The Interim AnalysisPAIN MEDICINE, Issue 2 2000Article first published online: 25 DEC 200 Authors: K Milligan, South Cleveland Hospital, L Haazen and L Bijnens, Janssen Research Foundation Aim of Investigation: To document long-term efficacy and safety of transdermal (TTS) fentanyl for the management of noncancer pain. Methods: The study was an open-label, international, multi-center, phase III trial in 532 patients (mean age 51.5 years) with a median pain duration of 6 years. Two hundred sixty-two patients (50%) had neuropathic pain and 367 (70%) had predominantly somatic, nociceptive pain. TTS-fentanyl was started at an equi-analgesic dose to the pretrial opioid, and given for 12 months. Main outcome measures were weekly assessment of pain control, global treatment satisfaction and quality of life scores. Results: At interim analysis, 120 patients had completed the trial, 211 were continuing treatment, and 201 patients had discontinued. The mean dose of TTS-fentanyl increased from 48 ,g/h to 105 ,g/h over 12 months, with most increases occurring in the first months. During treatment the number of subjects reporting very good, good, or moderate pain control remained stable at 65% (range 61% to 75%). Global satisfaction (very good or good) was also stable at 42% (range 38% to 46%). Eighty-six percent of patients reported preference for TTS-fentanyl over their previous treatment, stating the main reason as better pain relief. SF-36 scores improved from baseline for physical pain and physical summary measurements. The most frequently occurring adverse events were nausea (28%), sonmolence (17%), constipation (15%), vomiting (15%), and increased sweating (14%). Conclusions: Long-term treatment with TTS-fentanyl provides a stable degree of pain control in the majority of patients with moderate-to-severe noncancer pain. It was preferred by the majority of subjects to their previous medication and favorably improved their quality of life. Acknowledgments: Supported by the Janssen Research Foundation. [source] An interim analysis of a cohort study on the preoperative anxiety and postoperative behavioural changes in children having repeat anaestheticsPEDIATRIC ANESTHESIA, Issue 9 2002A. Watson Introduction Anxiety in the preoperative period and at induction of anaesthesia in children is associated with disturbances in postoperative behaviour (1,4). There is little work looking at the effects of repeat anaesthetic procedures on anxiety and subsequent postoperative behaviour disturbances. The aim of this study was to see if the effect of repeat anaesthetics was cumulative on postoperative behavioural problems and whether repeated anaesthetics provoke increasing anxiety. We investigated factors that may identify children who are susceptible to behavioural changes following repeat anaesthetics. We present an interim analysis of data on 8 patients as part of a long-term cohort study on 40 children with retinoblastoma who have required repeat anaesthetics for assessment and treatment of their condition. Method Approval for this study was granted by the East London and City Health Authority ethics committee. 40 patients are being recruited and being followed over a two year period. All children have retinoblastoma and are between the ages of 18 months to 4 years. The anaesthetic technique was not standardised but details of it were collected. Data collected were demographic details of child (age, sex, weight, ASA grade, siblings, stressful events in the last 3 months, recent immunisations, number of previous anaesthetics, problems with previous general anaesthetics, medical history of children, temperament of child using the EASI scoring system (4); demographic data of parents (age, parental education, family members affected, baseline measure of parental anxiety using State trait anxiety inventory (STAI). Anxiety on entry into the anaesthetic room and at induction was measured by the modified Yale preoperative anxiety scale (mYPAS), cooperation of the child at induction was measured by the Induction compliance checklist (ICC). Anxiety of the parent after induction was measured by the STAI score. Behaviour was measured at 1 day, 1 week, 1 month and 4 months after each procedure by means of the post hospital behaviour score (PHBQ) (5). A comparison with preoperative behaviour was made and data is presented of the percentage of children with new negative behavioural problems. A detailed analysis of the types of behaviour change was noted. anova for repeat measures with multiple dependent measures was used to analyse data on child anxiety and postoperative behavioural problems. Results Eight patients have had 3 separate anaesthetics over one and a half years. These have been at 4 monthly intervals. There was no significant increase in anxiety levels with repeat anaesthetics. The median mYPAS score at induction were 100 for all 3 anaesthetics. (P = 0.41). The type of behavioural change was variable and demonstrated no trend. No patient was identified as being prone to behavioural changes after every anaesthetic. Patients who displayed new negative behavioural problems would have them after any anaesthetic with no obvious cumulative effect with each repeat anaesthetic. Conclusions Our patients had maximum anxiety scores at induction, so the mYPAS scoring system is not sensitive enough to show that repeat anaesthetics provoke increasing anxiety. There is a very random pattern to behavioural disturbances after repeat anaesthetics with no evidence that negative behavioural changes are compounded with repeated anaesthetics. Collection of complete data from the remaining 32 patients may yield some trends regarding behavioural disturbances but our use of the mYPAS to measure anxiety in this very anxious population is unlikely to be helpful. [source] Latest news and product developmentsPRESCRIBER, Issue 14 2007Article first published online: 19 OCT 200 Studies suggest risk of bone loss with SSRIs Two cross-sectional studies have suggested the SSRI antidepressants may be associated with an increased risk of bone loss (Arch Intern Med 2007;167:1240,5 &1246,51). In 2722 older women (mean age 79) living in the community who were participating in the Study of Osteoporotic Fractures cohort study, use of SSRIs was associated with a significant increase in the rate of loss of hip bone density compared with nonusers(0.82 vs 0.47 per cent per year). The rate of loss among women taking a tricyclic antidepressant was also 0.47 per cent per year. Excluding women with more severe depression did not alter the findings. In 5995 men aged 65 or older taking an SSRI in another study, mean bone density was 3.9 per cent lower at the hip and 5.9 per cent lower in the lumbar spine compared with no use of antidepressants. Use of a tricyclic antidepressant or trazodone was not associated with increased bone loss. The authors comment that the degree of bone loss is comparable with that associated with corticosteroids. Serotonin transporters have been identified in osteoblasts and osteocytes. Risk of rare birth defects with SSRIs Two US case-control studies have found qualified evidence that use of SSRIs during the first trimester may be associated with a small increase in the risk of rare neonatal defects (N Engl J Med 2007;356:2675,83 & 2684,92). The Slone Epidemiology Center Birth Defects Study identified 9849 infants with birth defects and 5860 without and found no significant association between SSRI use overall and defects previously attributed to SSRIs (craniosynostosis, omphalocele or heart defects). There was some evidence that sertraline and paroxetine may cause specific defects, but this was based on few cases and the absolute risk remained low. The National Birth Defects Prevention Study identified 9622 infants with major birth defects and 4092 controls. There was no significant association with heart defects but the odds of anencephaly, craniosynostosis and omphalocele were each significantly increased by a factor of 2,3. The authors say the absolute risk remains small and their findings require confirmation. UK data do not support MI link with rosiglitazone An interim analysis of a UK clinical trial of rosiglitazone (Avandia) has found no evidence that it is associated with an increased risk of myocardial infarction (N Eng J Med 2007;357:28,38). A US meta-analysis (N Engl J Med 2007;356:2457,71) recently suggested that the odds of an MI or cardiovascular (CV) death in patients taking rosiglitazone were increased by 40,60 per cent compared with controls. The UK analysis of an ongoing nonblinded trial comparing rosiglitazone plus a sulphonylurea or metformin with sulphonylurea/metformin found no significant differences in the risk of MI or CV death. The risk of heart failure was doubled in patients taking rosiglitazone. The authors comment that, with a mean follow-up of 3.75 years, they had too few data to reach a conclusive finding. Switch piroxicam users to another NSAID The European Medicines Agency has advised prescribers to switch patients who are taking oral piroxicam to another NSAID. The advice follows a reappraisal of the safety of piroxicam when the 2006 review of all nonselective NSAIDs suggested it may be associated with increased risks of GI adverse effects and serious skin reactions. The advice does not apply to topical formulations. Piroxicam should not be prescribed for acute conditions and should not be first-choice for osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. The maximum dose should be 20mg per day and treatment should be reviewed after 14 days. The MHRA states there is no need for urgent action; long-term treatment should be reviewed at the next routine appointment. OTC azithromycin? The MHRA is consulting on a request by a pharmaceutical company to reschedule azithromycin to pharmacy-only status for the treatment of known or suspected Chlamydia trachomatis infection in individuals aged 16 years or older. The applicant envisages supplies being made only when a nucleic acid amplification test (NAAT) is positive. Responses should be submitted to the MHRA (www.mhra.gov.uk) by 2 August. Computers can reduce prescribing errors Computerised prescribing reduces by two-thirds the rate of medication errors associated with handwritten prescriptions, a new review has found (Health Services Research 2007; online doi:10.1111/j.1475,6773. 2007.00751.x). There was some evidence that the risk of all errors, dose errors and adverse effects were reduced by computerisation. The greatest impact was seen in settings with very high error rates (>12 per cent) associated with handwritten prescriptions. However, the studies included produced heterogeneous results and the reduction in errors in prescribing for children was not statistically significant. Furthermore, computerisation did not reduce the rate of prescribing the wrong drug. Echinacea works for colds, new study finds The herbal remedy Echinacea does reduce the risk of catching a cold, according to a new metaanalysis (Lancet Infect Dis 2007;7:473,80). In 2006, a Cochrane review found insufficient evidence to support the benefits claimed for Echinacea. The new study, which additionally included experimentally-induced infections among the 14 trials analysed, found that Echinacea reduced the odds of catching a cold by about half and reduced the average duration of a cold by 1.4 days. Though inconclusive, the possibility of publication bias and heterogeneity between the trials could not be excluded. HRT may reduce cardiovascular risk after all A subgroup analysis of the Women's Health Initiative (WHI) suggests that HRT may reduce the risk of coronary heart disease if started soon after the menopause (N Engl J Med 2007;356:2591,602). The main analysis of WHI showed no cardiovascular benefit for HRT, a finding attributed to the relatively old mean age of participants (59). In the new analysis of 1064 women aged 50,59, HRT use was associated with a significant reduction in coronary artery calcification compared with nonuse, with greater effect associated with greater adherence. Reducing BP key to avoiding heart failure An angiotensin,II receptor blocker (ARB) is no better than other antihypertensives at avoiding the development of heart failure in individuals with hypertension, say US investigators (Lancet 2007;369:2079,87). Drugs that affect the renin-angiotensin system can reduce ventricular hypertrophy and may therefore prevent the development of heart failure in patients with hypertension. This study found similar improvements in diastolic function in 384 patients with hypertension and left ventricular dysfunction randomised to valsartan (Diovan) or placebo in addition to standard antihypertensive treatment for 38 weeks. The authors conclude that blood pressure reduction, not choice of drug, is the most important factor. Copyright © 2007 Wiley Interface Ltd [source] Two-Stage Group Sequential Robust Tests in Family-Based Association Studies: Controlling Type I ErrorANNALS OF HUMAN GENETICS, Issue 4 2008Lihan K. Yan Summary In family-based association studies, an optimal test statistic with asymptotic normal distribution is available when the underlying genetic model is known (e.g., recessive, additive, multiplicative, or dominant). In practice, however, genetic models for many complex diseases are usually unknown. Using a single test statistic optimal for one genetic model may lose substantial power when the model is mis-specified. When a family of genetic models is scientifically plausible, the maximum of several tests, each optimal for a specific genetic model, is robust against the model mis-specification. This robust test is preferred over a single optimal test. Recently, cost-effective group sequential approaches have been introduced to genetic studies. The group sequential approach allows interim analyses and has been applied to many test statistics, but not to the maximum statistic. When the group sequential method is applied, type I error should be controlled. We propose and compare several approaches of controlling type I error rates when group sequential analysis is conducted with the maximum test for family-based candidate-gene association studies. For a two-stage group sequential robust procedure with a single interim analysis, two critical values for the maximum tests are provided based on a given alpha spending function to control the desired overall type I error. [source] Optimal Spending Functions for Asymmetric Group Sequential DesignsBIOMETRICAL JOURNAL, Issue 3 2007Keaven M. Anderson Abstract We present optimized group sequential designs where testing of a single parameter , is of interest. We require specification of a loss function and of a prior distribution for ,. For the examples presented, we pre-specify Type I and II error rates and minimize the expected sample size over the prior distribution for ,. Minimizing the square of sample size rather than the sample size is found to produce designs with slightly less aggressive interim stopping rules and smaller maximum sample sizes with essentially identical expected sample size. We compare optimal designs using Hwang-Shih-DeCani and Kim-DeMets spending functions to fully optimized designs not restricted by a spending function family. In the examples selected, we also examine when there might be substantial benefit gained by adding an interim analysis. Finally, we provide specific optimal asymmetric spending function designs that should be generally useful and simply applied when a design with minimal expected sample size is desired. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] A Comparison of Procedures for Adaptive Choice of Location Tests in Flexible Two-Stage DesignsBIOMETRICAL JOURNAL, Issue 3 2003Tim Friede Abstract Although linear rank statistics for the two-sample problem are distribution free tests, their power depends on the distribution of the data. In the planning phase of an experiment, researchers are often uncertain about the shape of this distribution and so the choice of test statistic for the analysis and the determination of the required sample size are based on vague information. Adaptive designs with interim analysis can potentially overcome both problems. And in particular, adaptive tests based on a selector statistic are a solution to the first. We investigate whether adaptive tests can be usefully implemented in flexible two-stage designs to gain power. In a simulation study, we compare several methods for choosing a test statistic for the second stage of an adaptive design based on interim data with the procedure that applies adaptive tests in both stages. We find that the latter is a sensible approach that leads to the best results in most situations considered here. The different methods are illustrated using a clinical trial example. [source] Sequential Tests for Noninferiority and SuperiorityBIOMETRICS, Issue 1 2003W. Brannath Summary. The problem of simultaneous sequential tests for noninferiority and superiority of a treatment, as compared to an active control, is considered in terms of continuous hierarchical families of one-sided null hypotheses, in the framework of group sequential and adaptive two-stage designs. The crucial point is that the decision boundaries for the individual null hypotheses may vary over the parameter space. This allows one to construct designs where, e.g., a rigid stopping criterion is chosen, rejecting or accepting all individual null hypotheses simultaneously. Another possibility is to use monitoring type stopping boundaries, which leave some flexibility to the experimenter: he can decide, at the interim analysis, whether he is satisfied with the noninferiority margin achieved at this stage, or wants to go for more at the second stage. In the case where he proceeds to the second stage, he may perform midtrial design modifications (e.g., reassess the sample size). The proposed approach allows one to "spend," e.g., less of , for an early proof of noninferiority than for an early proof of superiority, and is illustrated by typical examples. [source] Molecular markers and mortality in prostate cancerBJU INTERNATIONAL, Issue 6 2007John Concato OBJECTIVE To evaluate prognosis in prostate cancer by assessing the independent effect of selected molecular factors (e.g. markers of cell-cycle regulation), in addition to the effect of traditional clinical factors (e.g. anatomical stage, histological grade), in predicting long-term mortality among men newly diagnosed with prostate cancer. PATIENTS AND METHODS In a community-based population of 64 545 USA veterans aged ,,50 years and receiving ambulatory care during 1989,90 at nine Veterans Affairs (VA) medical centres in New England, 1274 had incident prostate cancer during 1991,95. We obtained the medical records and diagnostic tissue for these men, and then extracted demographic data and clinical information, and conducted immunohistochemical assays of molecular markers in biopsy tissue, as potential prognostic factors. In this interim analysis, data on 250 patients were analysed; the main outcome was overall mortality to 31 December 2003, providing 8,13 years of follow-up. RESULTS In 228 (91%) patients with available medical record and laboratory data, the median age was 72 years and the median prostate-specific antigen level was 10.4 ng/mL. In adjusted (multivariate) analyses that included traditional prognostic factors, bcl-2 staining (hazard ratio 2.14, 95% confidence interval 1.27,3.58, P = 0.004) and high microvessel density (1.76, 1.19,2.60; P = 0.005) had an independent effect on the outcome. CONCLUSIONS Bcl-2 and microvessel density are independent predictors of subsequent death among men with prostate cancer and might have a clinical role in assisting in deciding on treatment. [source] Randomized clinical trial of suture repair, polypropylene mesh or autodermal hernioplasty for incisional herniaBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 1 2002Dr M. Korenkov Background: Since conventional suture repair for incisional hernia is associated with high recurrence rates, alloplastic and autoplastic prosthetic techniques have been suggested. Methods: In a randomized trial, 160 patients with simple or complex hernias underwent either suture repair, autodermal skin graft or onlay polypropylene mesh repair. Suture repair was not done in complex hernias. This report concerns a planned interim analysis. Results: At mean follow-up of 16 months, there were 17 hernia recurrences that were distributed similarly between the surgical techniques. There were fewer infectious complications after suture repair (three of 33 patients) than after skin graft or mesh repair (seven of 39 and five of 28 for simple hernias; seven of 31 and ten of 29 respectively for complex hernias) (P not significant). The severity of infections after polypropylene mesh implantation prompted the trial committee to discontinue the study. No differences were noted in duration of stay in hospital and quality of life. However, pain was significantly more frequent after polypropylene mesh repair (pooled risk ratio 2·9 and 1·8 at 6 weeks and 1 year respectively). Conclusion: Suture repair was safe for small incisional hernias. Both autoplastic and alloplastic hernia repair yielded comparably low recurrence rates, but led to a high rate of wound infection. © 2002 British Journal of Surgery Society Ltd [source] Alpha-dihydroergocryptine in the treatment of de novo parkinsonian patients: results ofa multicentre, randomized, double-blind, placebo-controlled studyACTA NEUROLOGICA SCANDINAVICA, Issue 6 2000B. Bergamasco Introduction, A multicentre, randomized, double-blind, placebo-controlled, parallel group study was carried out in 123 patients suffering from never treated (de novo) idiopathic Parkinson's disease (PD). The aim of the study was to confirm the efficiency and safety of ,-dihydroergocryptine (,-DHEC) given as monotherapy in the symptomatic treatment of PD. The total score of the Unified Parkinson's Disease Rating Scale (UPDRS) was identified as the efficacy target variable. Patients and methods, Sixty-two patients (32 males, 30 females, mean age±SD 64±10) were randomized to ,-dihydroergocryptine and 61 (30 males, 31 females, mean age 63.8±9.1) to placebo. According to the experimental design, a 18-month double-blind phase vs placebo was followed. Two interim analyses were planned both at the 3rd and 12th month of treatment, in order to avoid continuation on placebo, if clear differences between groups were found (stopping criterium: nominal significance level equal to 0.022 in the analysis of the target variable). Analysis of variance was performed both on the per protocol (PP) and intent-to-treat (ITT) sample. Results, The results on the first interim analysis showed significant differences between treatment groups of the UPDRS total score both in the ITT (115 patients, ,-DHEC: No. 56; placebo: No. 59; P=0.019) and PP (96 patients, ,-DHEC: No. 46; placebo: No. 50; P=0.001) sample, why the trial was stopped. At the time of stopping the trial, 73 patients (,-DHEC: No. 37; placebo: No. 36) had reached the 6-month observation visit; the analysis carried out on this subset of patients confirmed the efficacy of ,-dihydroergocryptine in early PD and the correctness of the decision to stop. The incidence of adverse drug reactions (ADR) did not differ between ,-dihydroergocryptine and placebo recipients, gastrointestinal complaints being the most frequent. Conclusion, The results indicate that ,-dihydroergocryptine is safe and effective in improving symptoms of de novo parkinsonian patients. [source] 17 Our Patients, Our Residents, Their Case-Based Evidence: Development of an Intradepartmental Medical Education JournalACADEMIC EMERGENCY MEDICINE, Issue 2008Christopher Miller As clinical educators, we place a premium on teaching at the bedside. This academic medicine hallmark has many competitors in today's challenging emergency department environment. We therefore sought to complement bedside teaching with the creation of a monthly, case-based, best-evidence-practice, intra-departmental medical education journal. Residents were encouraged to annotate interesting cases during their shifts in a written log found in the emergency department. Monthly, a senior EM resident reviewed the cases and earmarked a select few for detailed review based on their potential educational merit. Comprehensive, evidence-based teaching summaries were presented in a case-report format (see attached examples). The completed manuscript was distributed electronically to staff and residents as a monthly medical education journal. Survey methodology performed at the conclusion of the publication's first year assessed its educational impact and estimated resources required for publication. 90% of residents reported reading the journal monthly, and 80% felt it was of high educational value. The mean preparation time was 16 hours per month. To assess reproducible and lasting didactic benefit, the journal was introduced at a second EM academic institution. To date, 19 issues at the primary site and 7 issues at the second have been published. Multi-institutional validation of its educational impact is ongoing, but interim analysis suggests continued success at both sites. [source] 2354: The range of waveform score of Ocular Response AnalyzerTM (ORA) in healthy subjects: interim analysisACTA OPHTHALMOLOGICA, Issue 2010M VANTOMME Purpose To assess the range of waveform score in IOP measurements with ocular response analyzer (ORA, Reichert) in healthy subjects. Methods Prospective study including both eyes of healthy subjects with no ocular pathology or previous refractive surgery. The IOP measurements with ORA from both eyes were performed. The inclusion criteria of the measurements were solely based on good waveforms by an experienced clinician. The waveform score of three measurements were included for statistical analysis. Other parameters including age, central corneal thickness (CCT) and axis length were also analysed to evaluate possible correlations. Spearman correlation coefficient was used to assess the correlation. Results To date, both eyes of 42 healthy subjects are included (Mean age: 46.6 ± 14.3 yrs, Axial length: 23.7 ± 1.1, CCT: 554 ± 34 µm). The mean waveform scores from the first IOP measurement were 4.2±2.3 and for the 2de and 3th respectively 4.2±1.9 and 4.2±2.1 (not significantly different). The mean waveform score of 252 signals (both eyes and 3 measurements) was 4.2±2.1 and ranged from 0.3 to 9.6. Considering the best signal value per patient, the mean of all best signal values was 5.5±2.0 and it ranged from 1.9 to 9.5. The lowest 10% of all the best signal value was<3. Conclusion The waveform score is a new parameter indicating the reliability of each measurement signal. The best signal value indicates the best measurements of each session (Not the mean of the measurements). To date, our results show that the lower 10% percentile is <3. This could suggest that all the measurements with waveform score lower than 3 should be discarded. [source] | |||||||||||||||||||||||||||||||