Objective: To delineate the temporal patterns of outcome and to determine the probability of seizure freedom with successive antiepileptic drug regimens in newly diagnosed epilepsy.Methods: Patients in whom epilepsy was diagnosed and the first antiepileptic drug prescribed between July 1, 1982, and April 1, 2006, were followed up until March 31, 2008. Outcomes were categorized into 4 patterns: A) early and sustained seizure freedom; B) delayed but sustained seizure freedom; C) fluctuation between periods of seizure freedom and relapse; and D) seizure freedom never attained. Probability of seizure freedom with successive drug regimens was compared. Seizure freedom was defined as no seizures for Ն1 year.Results: A total of 1,098 patients were included (median age 32 years, range 9-93). At the last clinic visit, 749 (68%) patients were seizure-free, 678 (62%) on monotherapy. Outcome pattern A was observed in 408 (37%), pattern B in 246 (22%), pattern C in 172 (16%), and pattern D in 272 (25%) patients. There was a higher probability of seizure freedom in patients receiving 1 compared to 2 drug regimens, and 2 compared to 3 regimens (p Ͻ 0.001). The difference was greater among patients with symptomatic or cryptogenic than with idiopathic epilepsy. Less than 2% of patients became seizure-free on subsequent regimens but a few did so on their sixth or seventh regimen. Conclusions:Most patients with newly diagnosed epilepsy had a constant course which could usually be predicted early. The chance of seizure freedom declined with successive drug regimens, most markedly from the first to the third and among patients with localization-related epilepsies. Neurology Seventy million people have epilepsy, with 34 -76 per 100,000 developing the condition every year.1 To formulate rational treatment plans, it is important to understand the different clinical courses and patterns of response to antiepileptic drugs (AEDs), ideally by following outcomes from the point of treatment initiation. Most studies conducted at specialist centers were limited by selection bias toward patients with chronic refractory epilepsy.2-5 The few reported cohorts of newly diagnosed patients tended to include only children 6,7 or focus on response over time irrespective of treatment status. 8 We have previously reported outcomes in adolescent and adult patients with newly diagnosed epilepsy.9,10 Over the ensuing years many new AEDs have become available, but their impact on the overall prognosis of epilepsy remains unclear. The main objectives of the present analysis were to delineate the temporal patterns of seizure outcome and to determine the probability of seizure freedom with successive regimens in an expanded cohort of 1,098 newly diagnosed patients, who were recruited between 1982 and 2006 and followed for up to 26 years. Most were referred by their primary care physicians with less than 10% by the hospital's accident and emergency department. The study population included the patients analyzed in our previous reports (n ϭ 470 and 890, ...

‘Will my study answer my research question?’ is the most fundamental question a researcher can ask when designing a study, yet when phrased in statistical terms – ‘What is the power of my study?’ or ‘How precise will my parameter estimate be?’ – few researchers in ecology and evolution (EE) try to answer it, despite the detrimental consequences of performing under- or over-powered research. We suggest that this reluctance is due in large part to the unsuitability of simple methods of power analysis (broadly defined as any attempt to quantify prospectively the ‘informativeness’ of a study) for the complex models commonly used in EE research. With the aim of encouraging the use of power analysis, we present simulation from generalized linear mixed models (GLMMs) as a flexible and accessible approach to power analysis that can account for random effects, overdispersion and diverse response distributions.We illustrate the benefits of simulation-based power analysis in two research scenarios: estimating the precision of a survey to estimate tick burdens on grouse chicks and estimating the power of a trial to compare the efficacy of insecticide-treated nets in malaria mosquito control. We provide a freely available R function, sim.glmm, for simulating from GLMMs.Analysis of simulated data revealed that the effects of accounting for realistic levels of random effects and overdispersion on power and precision estimates were substantial, with correspondingly severe implications for study design in the form of up to fivefold increases in sampling effort. We also show the utility of simulations for identifying scenarios where GLMM-fitting methods can perform poorly.These results illustrate the inadequacy of standard analytical power analysis methods and the flexibility of simulation-based power analysis for GLMMs. The wider use of these methods should contribute to improving the quality of study design in EE.

Aim Rectal cancer patients undergoing neoadjuvant chemoradiotherapy (NACRT) experience physical deterioration and reductions in their quality of life. This feasibility study assessed prehabilitation (a walking intervention) before, during and after NACRT to inform a definitive multi-centred randomized clinical trial (REx trial).Methods Patients planned for NACRT followed by potentially curative surgery were approached (August 2014-March 2016) (www.isrctn.com; 62859294). Prior to NACRT, baseline physical and psycho-social data were recorded using validated tools. Participants were randomized to either the intervention group (exercise counselling session followed by a 13-17 week telephone-guided walking programme) or a control group (standard care). Follow-up testing was undertaken 1-2 weeks before surgery. ResultsOf the 296 screened patients, 78 (26%) were eligible and 48 (61%) were recruited. N = 31 (65%) were men with a mean age of 65.9 years (range 33.7-82.6). Mean intervention duration was 14 weeks with 75% adherence. n = 40 (83%) completed follow-up testing.Both groups recorded reductions in daily walking but the reduction was less in the intervention group although not statistically significant. Participants reported high satisfaction and fidelity to trial procedures.Conclusion This study demonstrates that prehabilitation is feasible in rectal cancer patients undergoing NACRT. Good recruitment, adherence, retention and patient satisfaction rates support the development of a fully powered trial. The effects of the intervention on physical outcomes were promising.What does this paper add to the literature? This is the first study to show that performing prehabilitation in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy is feasible, safe and well tolerated by patients. With no reported interruption to each participant's planned clinical management, these findings support progression to a large powered multicentred trial.

Hagen, S. et al. (2014) Individualised pelvic floor muscle training in women with pelvic organ prolapse: a multicentre randomised controlled trial. Lancet, 383 (9919). pp. [796][797][798][799][800][801][802][803][804][805][806] Copyright © 2014 The Lancet Publishing Group A copy can be downloaded for personal non-commercial research or study, without prior permission or charge Content must not be changed in any way or reproduced in any format or medium without the formal permission of the copyright holder(s) Background Pelvic organ prolapse is common and is strongly associated with childbirth and increasing age. Women 8 with prolapse are often advised to do pelvic floor muscle exercises, but supporting evidence is limited. Our aim was to 9 establish if one--to--one individualised pelvic floor muscle training (PFMT) is effective in reducing prolapse symptoms. 11Methods A parallel--group multicentre randomised controlled trial (ISRCTN35911035) in female outpatients with 12 newly--diagnosed, symptomatic stage I, II or III prolapse, comparing five PFMT appointments over 16 weeks (n=225) 13 versus a lifestyle advice leaflet (n=222). Treatment allocation was by remote computer allocation using minimisation.14 Our primary endpoint was participants' self--report of prolapse symptoms at 12 months. Group assignment was 15 masked from outcome assessors. We compared outcomes between trial groups in an intention--to--treat analysis. The 16 cost of PFMT and savings on subsequent treatments were calculated to estimate cost--effectiveness. 18Findings Compared to the control group, the intervention group reported fewer prolapse symptoms at 12 months 19(mean difference between groups in change score 1. 27Interpretation One--to--one PFMT for prolapse is effective in improving prolapse symptoms. Longer--term benefits 28should be investigated, as should the effects in specific subgroups.

Models of the incubation period of anthrax are important to public health planners because they can be used to predict the delay before outbreaks are detected, the size of an outbreak and the duration of time that persons should remain on antibiotics to prevent disease. The difficulty is that there is little direct data about the incubation period in humans. The objective of this paper is to develop and apply models for the incubation period of anthrax. Mechanistic models that account for the biology of spore clearance and germination are developed based on a competing risks formulation. The models predict that the incubation period distribution depends critically on the rate that spores are cleared from the lung and to a lesser extent on the dose of inhaled spores. The models are used in a statistical analysis of data from an anthrax outbreak that occurred in Sverdlovsk, Russia. The analysis suggests that spores are cleared from the lung at a rate between 8 per cent per day and 14 per cent per day, which is in good agreement with experimental studies of animals. The analysis suggests that at low doses, the overall median incubation period time is about 10 days, which includes a median lag of about 2 days between spore germination and onset of symptoms. Male gender and younger ages were associated with longer incubation periods as was lower dose of inhaled spores.