Determining the sample size for a cluster-randomised trial: Bayesian hierarchical modelling of the ICC estimate

In common with many cluster-randomised trials, it was difficult to determine the appropriate sample size for the planned trial of the effectiveness of a systematic voiding programme for post-stroke incontinence due to the lack of a robust estimate of the intra-cluster correlation coefficient (ICC). One approach to overcome this problem is a method of combining ICC values in the Bayesian framework (Turner et al. 2005). We adopted this approach and used Bayesian hierarchical modelling to estimate the ICC

Hybrid sample size calculations for cluster randomised trials using assurance

Sample size determination for cluster randomised trials (CRTs) is challenging as it requires robust estimation of the intra-cluster correlation coefficient (ICC). Typically, the sample size is chosen to provide a certain level of power to reject the null hypothesis in a hypothesis test. This relies on the minimal clinically important difference (MCID) and estimates for the standard deviation, ICC and possibly the coefficient of variation of the cluster size. Varying these parameters can have a strong effect on the sample size. In particular, it is sensitive to small differences in the ICC. A relevant ICC estimate is often not available, or the available estimate is imprecise. If the ICC used is far from the unknown true value, this can lead to trials which are substantially over- or under-powered. We propose a hybrid approach using Bayesian assurance to find the sample size for a CRT with a frequentist analysis. Assurance is an alternative to power which incorporates uncertainty on parameters through a prior distribution. We suggest specifying prior distributions for the standard deviation, ICC and coefficient of variation of the cluster size, while still utilising the MCID. We illustrate the approach through the design of a CRT in post-stroke incontinence. We show assurance can be used to find a sample size based on an elicited prior distribution for the ICC, when a power calculation discards all information in the prior except a single point estimate. Results show that this approach can avoid misspecifying sample sizes when prior medians for the ICC are very similar but prior distributions exhibit quite different behaviour. Assurance provides an understanding of the probability of success of a trial given an MCID and can be used to produce sample sizes which are robust to parameter uncertainty. This is especially useful when there is difficulty obtaining reliable parameter estimates.Comment: 21 pages, 4 figures and 2 table

Bayesian Estimation of Heterogeneous Environments from Animal Movement Data

We describe a flexible class of stochastic models that aim to capture key features of realistic patterns of animal movements observed in radio‐tracking and global positioning system telemetry studies. In the model, movements are represented as a diffusion‐based process evolving differently in heterogeneous regions. In this article, we extend the process of inference for heterogeneous movement models to the case in which boundaries of habitat regions are unknown and need to be estimated. Data augmentation is used in reconstructing the partition of the heterogeneous environment. The augmentation helps to diminish the impact of uncertainty about when and where the animal crosses habitat boundaries, and allows the extraction of additional information from the given observations. The approach to inference is Bayesian, using Markov chain Monte Carlo methods, allowing us to estimate both the parameters of the diffusion processes and the unknown boundaries. The suggested methodology is illustrated on simulated data and applied to real movement data from a radio‐tracking experiment on ibex. Some model checking and model choice issues are also discussed

Students’ perceptions on their use of an EHR: pilot questionnaire study

Introduction Many clinical education programmes have not incorporated the use of the electronic health record (EHR) into their curriculum. It is important to incorporate technologies that will be used in real-world settings to better prepare students for clinical practice. Objectives To undertake a review of literature to identify a training evaluation framework; to conduct a self-completion survey, pretraining and post-training, to determine students’ perceptions on the benefit of using EHR training system. Setting Nursing School, University, North West England, UK; University Ethic Committee Approval Received. Participants Registered nurses undertaking a validated return to practice course; 24 participants for the first cohort who completed pretraining questionnaire and 23 for the second post-training cohort. Results The statistical results show that the students perceived that the training improved their capability in employing digital systems with statistically significant difference in the assessed preproficiency and post proficiency in the use of digital clinical systems (premedians and post medians are 2 and 5 on 10-point Likert scale, p=0.041). There was also an indication of an improvement in the knowledge of EHR systems although not statistically significant. Most students perceived it increased their knowledge on digital systems. Conclusion Students perceived an increase in proficiency with the EHR. There was evidence of improvement in confidence in the use of the EHR, but this confidence would be enhanced by additional use of the system. Some desire to increase confidence further and to develop knowledge of digital systems was expressed

Clinical and Epidemiologic Research Devising Two-Stage and Multistage Phase II Studies on Systemic Adjuvant Therapy for Uveal Melanoma

PURPOSE. Almost all uveal melanomas showing chromosome 3 loss (i.e., monosomy 3) are fatal. Randomized clinical trials are therefore needed to evaluate various systemic adjuvant therapies. Conventional trial designs require large numbers of patients, which are difficult to achieve in a rare disease. The aim of this study was to use existing data to estimate how sample size and study duration could be reduced by selecting high-risk patients and adopting multistage trial designs. METHODS. We identified 217 patients with a monosomy 3 melanoma exceeding 15 mm in basal diameter; these patients had a median survival of 3.27 years. Several trial designs comparing overall survival were explored for such a population. A power of 0.90 to detect a hazard ratio of 0.737 was set, and recruitment of 16 patients per month was assumed. RESULTS. A suitable single-stage study would require 960 patients and a duration of 76 months. A two-stage design with an interim analysis based on 852 patients after 53.3 months would have a 50% probability of stopping because no statistically significant treatment effect is seen. Encouraging but inconclusive results would require a further 108 patients and prolongation of the study to 77.2 months. A multistage design would have a 43% probability of stopping before 47 months having recruited 759 patients. CONCLUSIONS. Prospects for clinical studies of systemic adjuvant therapy for uveal melanoma are enhanced by multistage trial designs enrolling only high-risk patients. (Invest Ophthalmol Vis Sci. 2012;53:4986-4989

Repetitive Task Training for Improving Functional Ability After Stroke: A major update of a Cochrane Review

Repetitive task training (RTT) involves the active practice of task-specific motor activities and is a component of current therapy approaches in stroke rehabilitation

Length of labour in mothers and their daughters: A matched cohort study

Objective Physiological length of labour is highly variable and population norms have low sensitivity and specificity for individuals. The birth history of mothers may provide a basis for personalized assessment of labour progress in their nulliparous daughters. This study was designed to investigate the relationship between length of labour in nulliparous daughters and in their mother's first birth, as a basis for constructing individualised labour prediction models in future. Study design A mother-daughter matched cohort study was conducted in two Israeli maternity hospitals. Recruitment took place between September 2014 and June 2015 via antenatal clinics. Inclusion criteria were nulliparous daughters with singleton pregnancies at ≥32 weeks' gestation and mothers of included daughters who had a first birth in hospital prior to 1997. Data were collected prospectively for daughters by questionnaire and from electronic hospital records, and through retrospective recall questionnaires for mothers. Mother-daughter length of labour data were analysed using parametric and non-parametric tests and logistic regression. Length of labour was categorized as ≤10 h and >10 h. Other factors influencing daughters' length of labour were also examined. Results Data from 323 mother-daughter pairs were analysed. Univariate logistic regression analysis showed that daughters of mothers who were in active labour for more than 10 h showed increased likelihood of having a longer labour [OR1.91 (95 % CI 1.19, 3.05, P = 0.007)]. Controlling for infant gender increased the effect size [OR3.23 (95 % CI 1.55, 6.74, P = 0.002)]. Multivariable logistic regression indicated that mothers' length of labour [OR1.88 (95 % CI 1.12, 3.17)] and daughters' age [OR1.08 (95 % CI 1.02, 1.14)], weight gain in pregnancy [OR1.10 (95 % CI 1.04, 1.16)] and use of anesthesia, were statistically significant factors for daughters' length of labour, with sensitivity, specificity, and positive and negative predictive values of 74 %, 56 %, 66 %, and 64 %, respectively. Conclusions A strong positive association between mother and daughter lengths of labour was found. A model that includes length of labour in their mother's first birth might be useful for labour progress prediction for nulliparous women. Practitioners could inquire about maternal first birth patterns as an additional heuristic to guide practice and increase precision in the clinical management of nullipara women's labour and delivery

Genotypic distinctions of variability of biochemical composition of fruits of Vacciniaceae species under conditions of Belarus

Result of research of quantitative characteristics of biochemical composition of fruits of 30 taxons of 3 Vacciniaceae species (such as V. corymbosum L. (highbush blueberry), V. vitis-idaea L. (lingonberry) and Oxycoccus macrocarpus (Ait.) Pers. (cranberry)) inter-specific distinctions of a degree of stability of its separate components to complex influence of meteorological factors are revealed by 32 parameters (traits) describing the contents in fruits of some organic acids, carbohydrates, phenolic compounds, terpenoids and major mineral elements are presented. The cultivars possessing by the greatest and accordingly by the least levels of dependence on abiotic factors are identified

Micronutrient Status and Dietary Diversity of Women of Reproductive Age in Rural Pakistan

Consuming a diverse diet is essential to ensure an adequate intake of micronutrients. The aim of this study was to assess the nutritional status and dietary diversity of women of reproductive age (WRA) living in a marginalized community in rural Pakistan. Forty-seven WRA (35 ± 7 years old) who were not pregnant or lactating at enrollment, were recruited to participate in the study. Twenty-four-hour dietary recall interviews were conducted by the study nutritionist, and the data collected were used to create a minimum dietary diversity for women score (MDD-W) on five occasions during the monsoon and winter seasons (October to February). Nutritional status was assessed using anthropometry and biochemical markers of micronutrient status. Height and weight were used to determine body mass index (BMI), and mid-upper-arm circumference was measured. Plasma zinc, iron, and selenium concentrations were measured using inductively coupled mass spectrometry, and iron status was assessed using serum ferritin and blood hemoglobin concentrations. The mean (±SD) food group diversity score was 4 ± 1 with between 26% and 41% of participants achieving an MDD-W of 5. BMI was 27.2 ± 5.5 kg/m2 with 28% obese, 34% overweight, and 6% underweight. The prevalence of zinc deficiency, based on plasma zinc concentration, was 29.8%; 17% of the participants had low plasma selenium levels; 8.5% were iron deficient; and 2% were suffering from iron deficiency anemia. The findings indicate that the women living in this community consume a diet that has a low diversity, consistent with a diet low in micronutrients, and that zinc deficiency is prevalent. Public health interventions aimed at increasing the dietary diversity of WRA are needed to improve the micronutrient intake, particularly of zinc, in this population