Exploring awareness and prevalence of chronic viral hepatitis in a UK based Nepali population - lessons learned for future models in engaging migrant communities

Introduction The burden of chronic viral hepatitis (CVH) in the UK Nepali population is unknown. We aimed to determine knowledge of liver disease (LD) and prevalence of CVH in this community. Methods This was a mixed method (qualitative and quantitative) study guided by a multidisciplinary stakeholder group. Focus groups (FG) led by Nepali community leaders explored LD knowledge. Thereafter, a prospective community-based cohort study utilising dried-blood spot testing was conducted. Thematic analysis explored FG data with categorical data analysed with Excel and R Studio. Results FG data showed a lack of LD knowledge, with conflict between the roles of traditional and modern practices; 1,005 participants (525 male, 480 female) were tested for CVH, with a mean age of 63 years (range:19–86). Rates of CVH infection were low: 0.3% had current hepatitis B, with no active hepatitis C. Discussion Key drivers for enthusiastic participation were development of peer support networks and advisory groups to disseminate information, including hepatitis B vaccine recommendations

A framework of methodologies for designing new trials based on the power of updated evidence synthesis models, which include the new trial

The consideration of power of a clinical trial to detect the treatment effect is integral in the planning and designing stage of any trial. Recent research however argues that the power of the subsequent evidence synthesis model including the new trial should receive attention in the design stage of any new trial besides the power of the new trial in isolation. This thesis begins with a survey aiming to assess the extent of the use of previous evidence in the design stage of a new trial. The survey concludes that there is a lack of such use of previous evidence, particularly in determining the sample size of the new trial. The findings of the survey set the background and the context of the methodology developed in this thesis. The thesis aims to develop a simulation based methodological framework for designing new trials based on the power of the subsequent evidence synthesis model including the new trial, using several evidence synthesis models. The purpose of this methodology is to offer guidance to researchers in computing the sample size of a new trial on the basis that the new trial will eventually be a part of an evidence synthesis model. The variety of evidence synthesis methods includes standard meta-analysis methods, indirect comparison methods, mixed treatment comparison methods and meta-regression methods. This approach treats the pooled effect size of the initial evidence synthesis model to be the mean of the predictive distribution of the new trial. The predictive distribution of the new trial provides the distribution of an effect size of a new trial that is deemed sufficiently similar to the existing trials to be eligible for the synthesis. Under each evidence synthesis method, we develop various models to design new trials by varying the variance of the predictive distribution. The power of the new trial is shown to increase with increased variance in the predictive distribution. In contrast, the power of the updated evidence synthesis is shown to decrease with the increased variance of the predictive distribution. The new trials designed using fixed effects principles yield the lowest power. However, the updated evidence synthesis model including the new trial designed using the fixed effects principles shows the highest power. This is a common phenomenon noticed in all evidence synthesis methods explored. The framework also includes a component that develops a methodology to design new trials using Bayesian meta-analysis principles. The reasons for the differences found in power results of the Bayesian and frequentist approaches are investigated. The variance of the predictive distribution of a new trial clearly influences both the power of the new trial and the updated evidence synthesis. Trialists are advised to adapt the fixed effects method in designing new trials, whenever the assumption of a common true effect is possible. The Bayesian meta-analysis method developed here does not produce sufficient power in the updated meta-analysis and the methodology requires further refinements

Admission plasma potassium and length of hospital stay: a meta-analysis

Objective Hypokalaemia and hyperkalaemia (‘dyskalaemia’) are commonly seen in patients requiring emergency hospital admission. The adverse effect of dyskalaemia on mortality is well described but there are few data for the effect on hospital length of stay. We sought to determine the association of serum potassium concentration with in-hospital length of stay.Design Systematic review and meta-analysis.Data sources A structured search of MEDLINE, PubMed and SCOPUS databases to 19 March 2021.Eligibility criteria Observational cohort studies defining exposure of interest as serum potassium levels (at admission or within the first 72 hours) and with outcome of interest as length of hospital stay. Studies had to provide estimates of length of stay as a comparison between normokalaemia and defined ranges of hyperkalaemia or hypokalaemia.Data extraction and synthesis We identified 39 articles published to March 2021 that met the inclusion and exclusion criteria. Study selection, data extraction and quality assessment were carried out by two reviewers working independently and in duplicate, to assessed eligibility and risk of bias, and extract data from eligible studies. Random effects models were used to pool estimates across the included studies. Meta-analyses were performed using Cochrane-RevMan.Results Five studies were included in the meta-analysis. Compared with the reference group (3.5–5.0 mmol/L), the pooled raw differences of medians were 4.45 (95% CI 2.71 to 6.91), 1.99 (95% CI 0.03 to 3.94), 0.98 (95% CI 0.91 to 1.05), 1.51 (95% CI 1.03 to 2.0), 1 (95% CI 0.75 to 1.25) and 2.76 (95% CI 1.24 to 4.29) for patients with potassium levels of <2.5, 2.5 to <3.0, 3.0 to <3.5, <5 to 5.5, <5.5 to 6 and >6.0 mmol/L, respectively.Conclusion Hospital length of stay follows a U-shaped distribution, with duration of admission being twofold greater at the extremes of the potassium range

Systematic review and meta-analysis of the effects of iodine supplementation on thyroid function and child neurodevelopment in mildly-to-moderately iodine-deficient pregnant women

Background: Mild-to-moderate iodine deficiency, particularly in pregnancy, is prevalent; this is of concern as observational studies have shown negative associations with child neurodevelopment. Though neither the benefits nor the safety of iodine supplementation in pregnancy in areas of mild-to-moderate deficiency are well researched, such supplementation is increasingly being recommended by health authorities in a number of countries. Objective: By reviewing the most recent published data on the effects of iodine supplementation in mildly-to-moderately deficient pregnant women on maternal and infant thyroid function and child cognition, we aimed to determine whether the evidence was sufficient to support such recommendations in these areas. Design: A systematic review of randomised controlled trials (RCTs), non-RCT interventions and observational studies was conducted. To identify relevant papers we searched the PubMed and Embase databases. We defined mild-to-moderate iodine deficiency as a baseline, median, urinary iodine-concentration (UIC) of 50-149 µg/L. Eligible studies were included in meta-analyses. Results: In total, 37 publications were included – ten RCTs, four non-RCT interventions and 23 observational studies. Most studies showed no effect of iodine supplementation on maternal or infant thyroid-stimulating hormone and free-thyroxine. Most RCTs found that supplementation reduced maternal thyroglobulin and in three RCTs, it prevented or diminished the increase in maternal thyroid volume during pregnancy. Three RCTs addressed child neurodevelopment; only one was adequately-powered. Meta-analyses of two RCTs showed no effect on child cognitive [mean difference (MD) (95%CI): -0.18 (-1.22, 0.87)], language [MD (95%CI): 1.28 (-0.28, 2.83)] or motor scores [MD (95%CI): 0.28 (-1.10, 1.66)]. 4 Conclusions: There is insufficient good-quality evidence to support current recommendations for iodine supplementation in pregnancy in areas of mild-to-moderate deficiency. Well designed RCTs with child cognitive outcomes are needed in areas of moderate deficiency (median UIC<100 µg/L). The maternal intra-thyroidal iodine stores should be considered in future trials by including appropriate measures of pre-conceptional iodine intake

Investigating the efficiency of lung multi‐disciplinary team meetings—A mixed methods study of eight lung multi‐disciplinary teams

Abstract Background Multidisciplinary team meetings (MDTMs), where treatment recommendations are discussed and agreed, are fundamental to effective cancer care. The increasing volume and complexity of caseloads has led to the need to transform MDTM pathways to improve efficiency and allow sufficient time for discussion of complex cases. Understanding of current functioning and inefficiencies is required to inform such transformation. Methods A mixed‐methods observational study of all lung cancer MDTMs in one UK cancer network over 12 weeks (n = 8 MDTs, 96 MDT meetings). Data were collected on meeting attendance and on each discussed case using a validated MDT tool. Semi‐structured interviews were conducted with a range of MDT members and cancer service managers to gain understanding of perceived influences on the efficiency of MDTMs. Results In total, 1671 case discussions were observed. Models of MDT working, including referral and diagnostic pathway management, varied within the network. Attendance was quorate in only 21% of the observed MDTMs, most often lacking palliative care specialists. Over a third (37%) of observed cases were repeat discussions pre‐diagnosis. Treatment recommendations were agreed in 48% of case discussions but deferred for a quarter (24%) of discussed cases, most commonly due to awaiting results. Information about patients' fitness for treatment and/or performance status score was available for 60% of cases discussed overall (30%–75% by MDT). Interviews (n = 56) identified addressing clinical and administrative workforce shortages, less reliance on the MDTM for pre‐diagnostic decision‐making and better availability of key clinical information about patients discussed in the MDTM as factors critical to improved MDT function. Conclusions Inefficiencies were prevalent in all MDTMs; improvements would require an individualised approach due to the variation in ways of working. Local, regional and national support is needed for lung MDTs to develop their diagnostic workforce and facilities, and clinical and administrative resource

Prognostication in Advanced Cancer by Combining Actigraphy-Derived Rest-Activity and Sleep Parameters with Routine Clinical Data: An Exploratory Machine Learning Study

Survival prediction is integral to oncology and palliative care, yet robust prognostic models remain elusive. We assessed the feasibility of combining actigraphy, sleep diary data, and routine clinical parameters to prognosticate. Fifty adult outpatients with advanced cancer and estimated prognosis of ® (wrist actigraph) for 8 days, and complete a sleep diary. Univariate and regularised multivariate regression methods were used to identify predictors from 66 variables and construct predictive models of survival. A total of 49 patients completed the study, and 34 patients died within 1 year. Forty-two patients had disrupted rest-activity rhythms (dichotomy index (I p < 0.0001). Predictors associated with increased survival time were: time of awakening sleep efficiency, subjective sleep quality, clinician’s estimate of survival and global health status score, and haemoglobin. A shorter survival time was associated with self-reported sleep disturbance, neutrophil count, serum urea, creatinine, and C-reactive protein. Applying machine learning to actigraphy and sleep data combined with routine clinical data is a promising approach for the development of prognostic tools

A Double-Blind, Randomized, Placebo-Controlled Pilot Study examining an Oxygen Nanobubble Beverage for 16.1-km Time Trial and Repeated Sprint Cycling Performance

There is growing interest of ergogenic aids that deliver supplemental oxygen during exercise and recovery, however, breathing supplemental oxygen via specialist facemasks is often not feasible. Therefore, this study investigated the effect of an oxygen-nanobubble beverage during submaximal and repeated sprint cycling. In a double-blind, randomized, placebo-controlled study, 10 male cyclists (peak aerobic capacity, 56.9 ± 6.1 mL·kg−1·min−1; maximal aerobic power, 385 ± 25 W) completed submaximal or maximal exercise after consuming an oxygen-nanobubble (O2) or placebo (PLA) beverage. Submaximal trials comprised 30-min of steady-state cycling at 60% peak aerobic capacity and 16.1-km time-trial (TT). Maximal trials involved 4 × 30 s Wingate tests interspersed by 4-min recovery. Time-to-completion during the 16.1-km TT was 2.4% faster after O2 compared with PLA (95% CI = 0.7–4.0%, p = 0.010, d = 0.41). Average power for the 16.1-km TT was 4.1% higher for O2 vs. PLA (95% CI = 2.1–7.3%, p = 0.006, d = 0.28). Average peak power during the repeated Wingate tests increased by 7.1% for O2 compared with PLA (p = 0.002, d = 0.58). An oxygen-nanobubble beverage improves performance during submaximal and repeated sprint cycling, therefore may provide a practical and effective ergogenic aid for competitive cyclists.</p