Determining the sample size for a cluster-randomised trial using knowledge elicitation: Bayesian hierarchical modelling of the intracluster correlation coefficient.

BACKGROUND: The intracluster correlation coefficient is a key input parameter for sample size determination in cluster-randomised trials. Sample size is very sensitive to small differences in the intracluster correlation coefficient, so it is vital to have a robust intracluster correlation coefficient estimate. This is often problematic because either a relevant intracluster correlation coefficient estimate is not available or the available estimate is imprecise due to being based on small-scale studies with low numbers of clusters. Misspecification may lead to an underpowered or inefficiently large and potentially unethical trial. METHODS: We apply a Bayesian approach to produce an intracluster correlation coefficient estimate and hence propose sample size for a planned cluster-randomised trial of the effectiveness of a systematic voiding programme for post-stroke incontinence. A Bayesian hierarchical model is used to combine intracluster correlation coefficient estimates from other relevant trials making use of the wealth of intracluster correlation coefficient information available in published research. We employ knowledge elicitation process to assess the relevance of each intracluster correlation coefficient estimate to the planned trial setting. The team of expert reviewers assigned relevance weights to each study, and each outcome within the study, hence informing parameters of Bayesian modelling. To measure the performance of experts, agreement and reliability methods were applied. RESULTS: The 34 intracluster correlation coefficient estimates extracted from 16 previously published trials were combined in the Bayesian hierarchical model using aggregated relevance weights elicited from the experts. The intracluster correlation coefficients available from external sources were used to construct a posterior distribution of the targeted intracluster correlation coefficient which was summarised as a posterior median with a 95% credible interval informing researchers about the range of plausible sample size values. The estimated intracluster correlation coefficient determined a sample size of between 450 (25 clusters) and 480 (20 clusters), compared to 500-600 from a classical approach. The use of quantiles, and other parameters, from the estimated posterior distribution is illustrated and the impact on sample size described. CONCLUSION: Accounting for uncertainty in an unknown intracluster correlation coefficient, trials can be designed with a more robust sample size. The approach presented provides the possibility of incorporating intracluster correlation coefficients from various cluster-randomised trial settings which can differ from the planned study, with the difference being accounted for in the modelling. By using expert knowledge to elicit relevance weights and synthesising the externally available intracluster correlation coefficient estimates, information is used more efficiently than in a classical approach, where the intracluster correlation coefficient estimates tend to be less robust and overly conservative. The intracluster correlation coefficient estimate constructed is likely to produce a smaller sample size on average than the conventional strategy of choosing a conservative intracluster correlation coefficient estimate. This may therefore result in substantial time and resources savings.

Repetitive task training for improving functional ability after stroke.

BACKGROUND: Repetitive task training (RTT) involves the active practice of task-specific motor activities and is a component of current therapy approaches in stroke rehabilitation. OBJECTIVES: Primary objective: To determine if RTT improves upper limb function/reach and lower limb function/balance in adults after stroke. Secondary objectives: 1) To determine the effect of RTT on secondary outcome measures including activities of daily living, global motor function, quality of life/health status and adverse events. 2) To determine the factors that could influence primary and secondary outcome measures, including the effect of 'dose' of task practice; type of task (whole therapy, mixed or single task); timing of the intervention and type of intervention. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (4 March 2016); the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 5: 1 October 2006 to 24 June 2016); MEDLINE (1 October 2006 to 8 March 2016); Embase (1 October 2006 to 8 March 2016); CINAHL (2006 to 23 June 2016); AMED (2006 to 21 June 2016) and SPORTSDiscus (2006 to 21 June 2016). SELECTION CRITERIA: Randomised/quasi-randomised trials in adults after stroke, where the intervention was an active motor sequence performed repetitively within a single training session, aimed towards a clear functional goal. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts, extracted data and appraised trials. We determined the quality of evidence within each study and outcome group using the Cochrane 'Risk of bias' tool and GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria. We did not assess follow-up outcome data using GRADE. We contacted trial authors for additional information. MAIN RESULTS: We included 33 trials with 36 intervention-control pairs and 1853 participants. The risk of bias present in many studies was unclear due to poor reporting; the evidence has therefore been rated 'moderate' or 'low' when using the GRADE system. There is low-quality evidence that RTT improves arm function (standardised mean difference (SMD) 0.25, 95% confidence interval (CI) 0.01 to 0.49; 11 studies, number of participants analysed = 749), hand function (SMD 0.25, 95% CI 0.00 to 0.51; eight studies, number of participants analysed = 619), and lower limb functional measures (SMD 0.29, 95% CI 0.10 to 0.48; five trials, number of participants analysed = 419). There is moderate-quality evidence that RTT improves walking distance (mean difference (MD) 34.80, 95% CI 18.19 to 51.41; nine studies, number of participants analysed = 610) and functional ambulation (SMD 0.35, 95% CI 0.04 to 0.66; eight studies, number of participants analysed = 525). We found significant differences between groups for both upper-limb (SMD 0.92, 95% CI 0.58 to 1.26; three studies, number of participants analysed = 153) and lower-limb (SMD 0.34, 95% CI 0.16 to 0.52; eight studies, number of participants analysed = 471) outcomes up to six months post treatment but not after six months. Effects were not modified by intervention type, dosage of task practice or time since stroke for upper or lower limb. There was insufficient evidence to be certain about the risk of adverse events. AUTHORS' CONCLUSIONS: There is low- to moderate-quality evidence that RTT improves upper and lower limb function; improvements were sustained up to six months post treatment. Further research should focus on the type and amount of training, including ways of measuring the number of repetitions actually performed by participants. The definition of RTT will need revisiting prior to further updates of this review in order to ensure it remains clinically meaningful and distinguishable from other interventions.

Interventions to improve patient access to and utilisation of genetic and genomic counselling services.

This is the protocol for a review and there is no abstract. The objectives are as follows. PRIMARY OBJECTIVE: The primary objective is to assess the effectiveness of interventions to improve patient identification, access to and utilisation of genetic and genomic counselling services when compared to: No intervention;Usual or current practice; andOther active intervention. SECONDARY OBJECTIVE: The secondary objective is to explore the resource use and costs associated with interventions aimed at improving patient identification, access to and utilisation of genetic and genomic counselling services from studies meeting the eligibility criteria. We will report on factors that may explain variation in the effectiveness of interventions aimed at improving patient identification, access to and utilisation of genetic and genomic counselling services from studies meeting the eligibility criteria. Another secondary objective is to explore how interventions which target improved patient identification, access to and utilisation of genetic and genomic counselling services affect the subsequent appropriate use of health services for the prevention or early detection of disease. It is also possible that the genetic counselling interaction itself will contribute to the possible use of preventative services.

Comparing factors associated with overall satisfaction for different forms of remote breastfeeding support in the UK.

BACKGROUND: Remote forms of breastfeeding support, such as helplines and social media, offer a flexible and convenient form of support to offer help at critical points, e.g., when the risk of breastfeeding cessation is high. Currently, there is little known about who accesses different forms of remote breastfeeding support and what factors impact overall satisfaction. As part of an evaluation of the UK National Breastfeeding Helpline (NBH) (which offers breastfeeding support via a helpline and online media), we aimed to (a) understand who accesses different forms of NBH support, and (b) identify key factors associated with overall satisfaction for helpline and online media support. METHODS: All service users who contacted the NBH between November 2021 and March 2022 were invited to participate in the evaluation via an online survey. Survey questions explored the type and timing of support, reasons for the contact, attitudes towards the help and support received, impact of the support on breastfeeding experiences and demographic factors. Chi-squared and Mann-Whitney tests explored variations in who accessed the helpline or online media. Multiple linear regression models were fitted to explore the factors related to the service users' 'overall satisfaction'. The quantitive data were combined with qualitative comments into descriptive themes. RESULTS: Overall, online media users were significantly more likely to be younger, White, multiparous, less educated and have English as a first language compared to those who contact the helpline. Similar factors that significantly influenced overall satisfaction for both support models were the service being easy to access, receiving helpful information that met expectations, resolving breastfeeding issues, and feeling reassured and more confident. Significant factors for the helpline were callers feeling understood and more knowledgeable about breastfeeding following the call, being able to put into practice the information provided, feeling encouraged to continue breastfeeding, feeling that the volunteer gave the support that was needed, and seeking out additional support. CONCLUSIONS: Online and helpline forms of breastfeeding support suit different demographics and call purposes. While optimal breastfeeding support needs to be accessible, flexible and instrumental, helpline users need real-time relational support to deal with more complex challenges.

Systematic voiding programme in adults with urinary incontinence following acute stroke: the ICONS-II RCT.

BACKGROUND: Urinary incontinence affects around half of stroke survivors in the acute phase, and it often presents as a new problem after stroke or, if pre-existing, worsens significantly, adding to the disability and helplessness caused by neurological deficits. New management programmes after stroke are needed to address urinary incontinence early and effectively. OBJECTIVE: The Identifying Continence OptioNs after Stroke (ICONS)-II trial aimed to evaluate the clinical effectiveness and cost-effectiveness of a systematic voiding programme for urinary incontinence after stroke in hospital. DESIGN: This was a pragmatic, multicentre, individual-patient-randomised (1 : 1), parallel-group trial with an internal pilot. SETTING: Eighteen NHS stroke services with stroke units took part. PARTICIPANTS: Participants were adult men and women with acute stroke and urinary incontinence, including those with cognitive impairment. INTERVENTION: Participants were randomised to the intervention, a systematic voiding programme, or to usual care. The systematic voiding programme comprised assessment, behavioural interventions (bladder training or prompted voiding) and review. The assessment included evaluation of the need for and possible removal of an indwelling urinary catheter. The intervention began within 24 hours of recruitment and continued until discharge from the stroke unit. MAIN OUTCOME MEASURES: The primary outcome measure was severity of urinary incontinence (measured using the International Consultation on Incontinence Questionnaire) at 3 months post randomisation. Secondary outcome measures were taken at 3 and 6 months after randomisation and on discharge from the stroke unit. They included severity of urinary incontinence (at discharge and at 6 months), urinary symptoms, number of urinary tract infections, number of days indwelling urinary catheter was in situ, functional independence, quality of life, falls, mortality rate and costs. The trial statistician remained blinded until clinical effectiveness analysis was complete. RESULTS: The planned sample size was 1024 participants, with 512 allocated to each of the intervention and the usual-care groups. The internal pilot did not meet the target for recruitment and was extended to March 2020, with changes made to address low recruitment. The trial was paused in March 2020 because of COVID-19, and was later stopped, at which point 157 participants had been randomised (intervention, n = 79; usual care, n = 78). There were major issues with attrition, with 45% of the primary outcome data missing: 56% of the intervention group data and 35% of the usual-care group data. In terms of the primary outcome, patients allocated to the intervention group had a lower score for severity of urinary incontinence (higher scores indicate greater severity in urinary incontinence) than those allocated to the usual-care group, with means (standard deviations) of 8.1 (7.4) and 9.1 (7.8), respectively. LIMITATIONS: The trial was unable to recruit sufficient participants and had very high attrition, which resulted in seriously underpowered results. CONCLUSIONS: The internal pilot did not meet its target for recruitment and, despite recruitment subsequently being more promising, it was concluded that the trial was not feasible owing to the combined problems of poor recruitment, poor retention and COVID-19. The intervention group had a slightly lower score for severity of urinary incontinence at 3 months post randomisation, but this result should be interpreted with caution. FUTURE WORK: Further studies to assess the effectiveness of an intervention starting in or continuing into the community are required. TRIAL REGISTRATION: This trial is registered as ISRCTN14005026. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 31. See the NIHR Journals Library website for further project information.

Urinary incontinence affects around half of stroke survivors. It causes embarrassment and distress, affecting patients' ability to take part in rehabilitation. It also has a major impact on families and may determine whether or not patients are able to return home. Finding the underlying cause and addressing it can prevent, cure or reduce problems. Doing this in a systematic way for everyone with incontinence problems as early as possible after the stroke, while they are still in hospital, may work best. We also wanted to avoid using catheters in the bladder to drain the urine away, as these are often unnecessary and can cause urinary tract infections. This study aimed to test whether or not continence problems and the use of urinary catheters could be reduced if everyone with incontinence was fully assessed and given the right management and support early after hospital admission. We also wanted to find out if the benefits outweighed the costs. We planned to involve 1024 men and women with incontinence from 18 stroke units in the study, with 512 people receiving the intervention and 512 receiving usual care. However, the trial was paused because of COVID-19, at which time only 157 participants had been recruited. When we were thinking about restarting the study and looked at its progress, we found that not enough people had agreed to take part and, of those who had agreed, many had not returned their outcome questionnaires. This indicated that the trial was not feasible and should not restart. We could not make any firm conclusions about whether or not the intervention worked, as not enough people were involved. We found that stays in hospital after stroke are shorter than they were in the past. This suggests that future studies investigating ways of treating incontinence should consider interventions with management and support for incontinence that continue after patients leave the hospital.

Biofortified Wheat Increases Dietary Zinc Intake: A Randomised Controlled Efficacy Study of Zincol-2016 in Rural Pakistan.

A new variety of zinc biofortified wheat (Zincol-2016) was released in Pakistan in 2016. The primary aim of this study was to examine the effects of consuming Zincol-2016 wheat flour on biochemical and functional markers of zinc status in a population with widespread zinc deficiency. An individually-randomised, double-blind, placebo-controlled cross over design was used. Fifty households were recruited to participate in the study, with each household included at least one woman of reproductive age (16-49 years) who was neither pregnant nor breast feeding or currently taking nutritional supplements. All households were provided with control flour for an initial 2-week baseline period, followed by the intervention period where households were randomly allocated in a 1:1 ratio to receive biofortified flour (group A; n = 25) and control flour (group B; n = 25) for 8-weeks, then switched to the alternate flour for 8-weeks. The trial has been registered with the ISRCTN (https://www.isrctn.com), ID ISRCTN83678069. The primary outcome measure was plasma zinc concentration, and the secondary outcome measures were plasma selenium and copper concentrations, plasma copper:zinc ratio and fatty acid desaturase and elongase activity indices. Nutrient intake was assessed using 24-h dietary recall interviews. Mineral concentrations in plasma were measured using inductively coupled plasma mass spectrometry and free fatty acids and sphingolipids by mass spectrometry. Linear Mixed Model regression and General Linear Model with repeated measures were used to analyse the outcomes. Based on an average flour consumption of 224 g/day, Zincol-2016 flour provided an additional daily zinc intake of between 3.0 and 6.0 mg for white and whole grain flour, respectively. No serious adverse events were reported. This resulted in significant, increase in plasma zinc concentration after 4 weeks [mean difference 41.5 µg/L, 95% CI (6.9-76.1), p = 0.02]. This was not present after 8 weeks (p = 0.6). There were no consistent significant effects of the intervention on fatty acid desaturase and elongase activity indices. Regular consumption of Zincol-2016 flour increased the daily zinc intake of women of reproductive age by 30-60%, however this was not associated with a sustained improvement in indices of zinc status.

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.

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.

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.

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.