Discrepancies in autologous bone marrow stem cell trials and enhancement of ejection fraction (DAMASCENE): weighted regression and meta-analysis

Objective To investigate whether discrepancies in trials of use of bone marrow stem cells in patients with heart disease account for the variation in reported effect size in improvement of left ventricular function. Design Identification and counting of factual discrepancies in trial reports, and sample size weighted regression against therapeutic effect size. Meta-analysis of trials that provided sufficient information. Data sources PubMed and Embase from inception to April 2013. Eligibility for selecting studies Randomised controlled trials evaluating the effect of autologous bone marrow stem cells for heart disease on mean left ventricular ejection fraction. Results There were over 600 discrepancies in 133 reports from 49 trials. There was a significant association between the number of discrepancies and the reported increment in EF with bone marrow stem cell therapy (Spearman’s r=0.4, P=0.005). Trials with no discrepancies were a small minority (five trials) and showed a mean EF effect size of −0.4%. The 24 trials with 1-10 discrepancies showed a mean effect size of 2.1%. The 12 with 11-20 discrepancies showed a mean effect of size 3.0%. The three with 21-30 discrepancies showed a mean effect size of 5.7%. The high discrepancy group, comprising five trials with over 30 discrepancies each, showed a mean effect size of 7.7%. Conclusions Avoiding discrepancies is difficult but is important because discrepancy count is related to effect size. The mechanism is unknown but should be explored in the design of future trials because in the five trials without discrepancies the effect of bone marrow stem cell therapy on ejection fraction is zero

Electromagnetic Wave Theory and Remote Sensing

Contains reports on six research projects.Joint Services Electronics Program (Contract DAAG29-80-C-0104)National Science Foundation (Grant ENG78-23145)National Science Foundation (Grant ECS82-03390)Schlumberger-Doll Research CenterNational Aeronautics and Space Administration (Contract NAG 5-141)National Aeronautics and Space Administration (Contract NAS5-26861)National Aeronautics and Space Administration (Contract NAG5-270

Electromagnetic Wave Theory and Remote Sensing

Contains reports on seven research projects.Joint Services Electronics Program (Contract DAAG29-80-C-0104)National Science Foundation (Grant ENG 78-23145)Schlumberger-Doll Research CenterU.S. Air Force - Hanscom (Contract F19628-80-C-0052)National Aeronautics and Space Administration (Grant NAG5-16)Draper Laboratory (Contract DL-H-182642)National Aeornautics and Space Administration (Contract NAG5-141

Doppler assessment of aortic stenosis: a 25-operator study demonstrating why reading the peak velocity is superior to velocity time integral

Aims Measurements with superior reproducibility are useful clinically and research purposes. Previous reproducibility studies of Doppler assessment of aortic stenosis (AS) have compared only a pair of observers and have not explored the mechanism by which disagreement between operators occurs. Using custom-designed software which stored operators’ traces, we investigated the reproducibility of peak and velocity time integral (VTI) measurements across a much larger group of operators and explored the mechanisms by which disagreement arose. Methods and results Twenty-five observers reviewed continuous wave (CW) aortic valve (AV) and pulsed wave (PW) left ventricular outflow tract (LVOT) Doppler traces from 20 sequential cases of AS in random order. Each operator unknowingly measured each peak velocity and VTI twice. VTI tracings were stored for comparison. Measuring the peak is much more reproducible than VTI for both PW (coefficient of variation 10.1 vs. 18.0%; P < 0.001) and CW traces (coefficient of variation 4.0 vs. 10.2%; P < 0.001). VTI is inferior because the steep early and late parts of the envelope are difficult to trace reproducibly. Dimensionless index improves reproducibility because operators tended to consistently over-read or under-read on LVOT and AV traces from the same patient (coefficient of variation 9.3 vs. 17.1%; P < 0.001). Conclusion It is far more reproducible to measure the peak of a Doppler trace than the VTI, a strategy that reduces measurement variance by approximately six-fold. Peak measurements are superior to VTI because tracing the steep slopes in the early and late part of the VTI envelope is difficult to achieve reproducibly

Electromagnetic Wave Theory and Remote Sensing

Contains reports on seven research projects.Joint Services Electronics Program (Contract DAAG29-83-K-0003)National Science Foundation (Grant ECS82-03390)Schlumberger-Doll Research CenterNational Aeronautics and Space Administration (Contract NAG5-141)National Aeronautics and Space Administration (Contract NAS5-26861)National Aeronautics and Space Administration (Contract NAG5-270)U.S. Navy - Office of Naval Research (Contract N00014-83-K-0258

Electromagnetic Wave Theory and Remote Sensing

Contains reports on eight research projects.Joint Services Electronics Program (Contract DAAG29-83-K-0003)National Science Foundation (Grant ECS82-03390)Schlumberger-Doll Research CenterNational Aeronautics and Space Administration (Contract NAG5-141)National Aeronautics and Space Administration (Contract NAS5-26861)National Aeronautics and Space Administration (Contract NAG5-270)U.S. Navy - Office of Naval Research (Contract N00014-83-K-0258)International Business Machines, Inc

Neuraminidase inhibitors for preventing and treating influenza in children

Background: During epidemics, influenza attack rates in children may exceed 40%. Options for prevention and treatment currently include the neuraminidase inhibitors zanamivir and oseltamivir. Laninamivir octanoate, the prodrug of laninamivir, is currently being developed. Objectives: To assess the efficacy, safety and tolerability of neuraminidase inhibitors in the treatment and prevention of influenza in children. Search methods: For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1) which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to January week 2, 2011) and EMBASE (January 2010 to January 2011). Selection criteria: Double‐blind, randomised controlled trials (RCTs) comparing neuraminidase inhibitors with placebo or other antiviral drugs in children aged up to and including 12 years. We also included safety and tolerability data from other types of studies. Data collection and analysis: Four review authors selected studies, assessed study quality and extracted data for the current and previous versions of this review. We analysed data separately for oseltamivir versus placebo, zanamivir versus placebo and laninamivir octanoate versus oseltamivir. Main results: Six treatment trials involving 1906 children with clinical influenza and 450 children with influenza diagnosed on rapid near‐patient influenza testing were included. Of these 2356 children, 1255 had laboratory‐confirmed influenza. Three prophylaxis trials involving 863 children exposed to influenza were also included. In children with laboratory‐confirmed influenza oseltamivir reduced median duration of illness by 36 hours (26%, P < 0.001). One trial of oseltamivir in children with asthma who had laboratory‐confirmed influenza showed only a small reduction in illness duration (10.4 hours, 8%), which was not statistically significant (P = 0.542). Laninamivir octanoate 20 mg reduced symptom duration by 2.8 days (60%, P < 0.001) in children with oseltamivir‐resistant influenza A/H1N1. Zanamivir reduced median duration of illness by 1.3 days (24%, P < 0.001). Oseltamivir significantly reduced acute otitis media in children aged one to five years with laboratory‐confirmed influenza (risk difference (RD) ‐0.14, 95% confidence interval (CI) ‐0.24 to ‐0.04). Prophylaxis with either zanamivir or oseltamivir was associated with an 8% absolute reduction in developing influenza after the introduction of a case into a household (RD ‐0.08, 95% CI ‐0.12 to ‐0.05, P < 0.001). The adverse event profile of zanamivir was no worse than placebo but vomiting was more commonly associated with oseltamivir (number needed to harm = 17, 95% CI 10 to 34). The adverse event profiles of laninamivir octanoate and oseltamivir were similar. Authors' conclusions: Oseltamivir and zanamivir appear to have modest benefit in reducing duration of illness in children with influenza. However, our analysis was limited by small sample sizes and an inability to pool data from different studies. In addition, the inclusion of data from published trials only may have resulted in significant publication bias. Based on published trial data, oseltamivir reduces the incidence of acute otitis media in children aged one to five years but is associated with a significantly increased risk of vomiting. One study demonstrated that laninamivir octanoate was more effective than oseltamivir in shortening duration of illness in children with oseltamivir‐resistant influenza A/H1N1. The benefit of oseltamivir and zanamivir in preventing the transmission of influenza in households is modest and based on weak evidence. However, the clinical efficacy of neuraminidase inhibitors in 'at risk' children is still uncertain. Larger high‐quality trials are needed with sufficient power to determine the efficacy of neuraminidase inhibitors in preventing serious complications of influenza (such as pneumonia or hospital admission), particularly in 'at risk' groups

The Application of N-of-1 Treatment Trials in Schizophrenia: A Systematic Review

Background: Single patient or ‘n-of-1’ trials are a pragmatic method to achieve optimal, evidence-based treatments for individual patients. Such trials could be particularly valuable in chronic, heterogeneous, difficult to treat illnesses such as schizophrenia.Aim: We aimed to identify how often, and in what way, n-of-1 trials have been used in schizophrenia.Method: We performed a systematic search in the major electronic databases for studies adopting n-of-1 methodology in schizophrenia, published in English from the start of records until the end of January 2017. Results: We identified six studies meeting inclusion criteria. There was wide variability in study methodology and analysis. Each trial reported positive outcomes for their respective intervention, but all studies were at high risk of bias. Conclusions: In conclusion, n-of-1 trials are currently under-utilised in schizophrenia. Existing trials suggest the method is well tolerated and potentially effective in achieving optimal treatments for patients, but more standardised methods of design, execution and analysis are required in future trials.Declarations of interest: SML has received grants and personal fees from Janssen, and personal fees from Otsuka and Sunovion, in the past three years, outside the submitted work. The other authors have no conflicts of interest to declare