A systematic review identifying common data items in neonatal trials and assessing their completeness in routinely recorded United Kingdom national neonatal data

Background We aimed to test whether a common set of key data items reported across high impact neonatal clinical trials could be identified, and to quantify their completeness in routinely recorded United Kingdom neonatal data held in the National Neonatal Research Database (NNRD). Methods We systematically reviewed neonatal clinical trials published in four high impact medical journals over 10 years (2006-2015) and extracted baseline characteristics, stratification items, and potential confounders used to adjust primary outcomes. Completeness was examined using data held in the NNRD for identified data items, for infants admitted to neonatal units in 2015. The NNRD is a repository of routinely recorded data extracted from neonatal Electronic Patient Records (EPR) of all admissions to National Health Service (NHS) Neonatal Units in England, Wales and Scotland. We defined missing data as an empty field or an implausible value. We reported common data items as frequencies and percentages alongside percentages of completeness. Results We identified 44 studies involving 32,095 infants and 126 data items. Fourteen data items were reported by more than 20% of studies (table 2). Gestational age (95%), sex (93%) and birth weight (91%) were the most common baseline data items. The completeness of data in the NNRD was high for these data with greater than 90% completeness found for 9 of the 14 most common items. Conclusion High impact neonatal clinical trials share common data items. In the United Kingdom, these items can be obtained at a high level of completeness from routinely recorded data held in the NNRD. The feasibility and efficiency using routinely recorded EPR data, such as that held in the NNRD, for clinical trials, rather than collecting these items anew, should be examined

Severity of obesity and management of hypertension, hypercholesterolaemia and smoking in primary care: population-based cohort study

Obesity and obesity-associated cardiovascular risk are increasing worldwide. This study aimed to determine how different levels of obesity are associated with the management of smoking, hypertension and hypercholesterolaemia in primary care. We conducted a cohort study of adults aged 30–100 years in England, sampled from the primary care electronic health records in the Clinical Practice Research Datalink. Prevalence, treatment and control were estimated for each risk factor by body mass index (BMI) category. Adjusted odds ratios (AOR) were estimated, allowing for age, gender, comorbidity and socioeconomic status, with normal weight as reference category. Data were analysed for 247 653 patients including 153 308 (62%) with BMI recorded, of whom 46 149 (30%) were obese. Participants were classified into simple (29 257), severe (11 059) and morbid obesity (5833) categories. Smoking declined with the increasing BMI category, but smoking cessation treatment increased. Age-standardised hypertension prevalence was twice as high in morbid obesity (men 78.6%; women 66.0%) compared with normal weight (men 37.3%; women 29.4%). Hypertension treatment was more frequent (AOR 1.75, 1.59–1.92) but hypertension control less frequent (AOR 0.63, 0.59–0.69) in morbid obesity, with similar findings for severe obesity. Hypercholesterolaemia was more frequent in morbid obesity (men 48.2%; women 36.3%) than normal weight (men 25.0%; women 20.0%). Lipid lowering therapy was more frequent in morbid obesity (AOR 1.83, 1.61–2.07) as was cholesterol control (AOR 1.19, 1.06–1.34). Increasing obesity category is associated with elevated risks from hypertension and hypercholesterolaemia. Inadequate hypertension control in obesity emerges as an important target for future interventions

Adjusting for verification bias in diagnostic accuracy measures when comparing multiple screening 2 tests - an application to the IP1-PROSTAGRAM study

Introduction Novel screening tests used to detect a target condition are compared against either a reference standard or other existing screening methods. However, as it is not always possible to apply the reference standard on the whole population under study, verification bias is introduced. Statistical methods exist to adjust estimates to account for this bias. We extend common methods to adjust for verification bias when multiple tests are compared to a reference standard using data from a prospective double blind screening study for prostate cancer. Methods Begg and Greenes method and multiple imputation are extended to include the results of multiple screening tests which determine condition verification status. These two methods are compared to the complete case analysis using the IP1-PROSTAGRAM study data. IP1-PROSTAGRAM used a paired84 cohort double-blind design to evaluate the use of imaging as alternative tests to screen for prostate 85 cancer, compared to a blood test called prostate specific antigen (PSA). Participants with positive imaging (index) and/or PSA (control) underwent a prostate biopsy (reference). Results When comparing complete case results to Begg and Greenes and methods of multiple imputation there is a statistically significant increase in the specificity estimates for all screening tests. Sensitivity estimates remained similar across the methods, with completely overlapping 95% confidence intervals. Negative predictive value (NPV) estimates were higher when adjusting for verification bias, compared to complete case analysis, even though the 95% confidence intervals overlap. Positive predictive value (PPV) estimates were similar across all methods. Conclusion Statistical methods are required to adjust for verification bias in accuracy estimates of screening tests. Expanding Begg and Greenes method to include multiple screening tests can be computationally intensive, hence multiple imputation is recommended, especially as it can be modified for low prevalence of the target condition

Screening for type 2 diabetes is feasible, acceptable, but associated with increased short-term anxiety: A randomised controlled trial in British general practice

Background To assess the feasibility and uptake of a diabetes screening programme; to examine the effects of invitation to diabetes screening on anxiety, self-rated health and illness perceptions. Methods Randomised controlled trial in two general practices in Cambridgeshire. Individuals aged 40–69 without known diabetes were identified as being at high risk of having undiagnosed type 2 diabetes using patient records and a validated risk score (n = 1,280). 355 individuals were randomised in a 2 to 1 ratio into non-invited (n = 238) and invited (n = 116) groups. A stepwise screening programme confirmed the presence or absence of diabetes. Six weeks after the last contact (either test or invitation), a questionnaire was sent to all participants, including non-attenders and those who were not originally invited. Outcome measures included attendance, anxiety (short-form Spielberger State Anxiety Inventory-STAI), self-rated health and diabetes illness perceptions. Results 95 people (82% of those invited) attended for the initial capillary blood test. Six individuals were diagnosed with diabetes. Invited participants were more anxious than those not invited (37.6 vs. 34.1 STAI, p-value = 0.015), and those diagnosed with diabetes were considerably more anxious than those classified free of diabetes (46.7 vs. 37.0 STAI, p-value = 0.031). Non-attenders had a higher mean treatment control sub-scale (3.87 vs. 3.56, p-value = 0.016) and a lower mean emotional representation sub-scale (1.81 vs. 2.68, p-value = 0.001) than attenders. No differences in the other five illness perception sub-scales or self-rated health were found. Conclusion Screening for type 2 diabetes in primary care is feasible but may be associated with higher levels of short-term anxiety among invited compared with non-invited participants. Trial registration ISRCTN9917549

A systematic review of randomised controlled trials in rheumatoid arthritis: the reporting and handling of missing data in composite outcomes

Background Most reported outcome measures in rheumatoid arthritis (RA) trials are composite, whose components comprise single measures that are combined into one outcome. The aims of this review were to assess the range of missing data rates in primary composite outcomes and to document the current practice for handling and reporting missing data in published RA trials compared to the Consolidated Standards of Reporting Trials (CONSORT) recommendations. Methods A systematic search for randomised controlled trials was conducted for RA trials published between 2008 and 2013 in four rheumatology and four high impact general medical journals. Results A total of 51 trials with a composite primary outcome were identified, of which 38 (75 %) used the binary American College of Rheumatology responder index and 13 (25 %) used the Disease Activity Score for 28 joints (DAS28). Forty-four trials (86 %) reported on an intention-to-treat analysis population, while 7 trials (14 %) analysed according to a modified intention-to-treat population. Missing data rates for the primary composite outcome ranged from 2–53 % and were above 30 % in 9 trials, 20–30 % in 11 trials, 10–20 % in 18 trials and below 10 % in 13 trials. Thirty-eight trials (75 %) used non-responder imputation and 10 (20 %) used last observation carried forward to impute missing composite outcome data at the primary time point. The rate of dropout was on average 61 % times higher in the placebo group compared to the treatment group in the 34 placebo controlled trials (relative rate 1.61, 95 % CI: 1.29, 2.02). Thirty-seven trials (73 %) did not report the use of sensitivity analyses to assess the handling of missing data in the primary analysis as recommended by CONSORT guidelines. Conclusions This review highlights an improvement in rheumatology trial practice since the revision of CONSORT guidelines, in terms of power calculation and participant’s flow diagram. However, there is a need to improve the handling and reporting of missing composite outcome data and their components in RA trials. In particular, sensitivity analyses need to be more widely used in RA trials because imputation is widespread and generally uses single imputation methods, and in this area the missing data rates are commonly differentially higher in the placebo group

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Mortality of Care Home Residents and Community-Dwelling Controls During the COVID-19 Pandemic in 2020: Matched Cohort Study

Objective:This study aimed to estimate and compare mortality of care home residents, and matched community-dwelling controls, during the COVID-19 pandemic from primary care electronic health records in England. Design: Matched cohort study. Setting and Participants: Family practices in England in the Clinical Practice Research Datalink Aurum database. There were 83,627 care home residents in 2020, with 26,923 deaths; 80,730 (97%) were matched on age, sex, and family practice with 300,445 community-dwelling adults. Methods: All-cause mortality was evaluated and adjusted rate ratios by negative binomial regression were adjusted for age, sex, number of long-term conditions, frailty category, region, calendar month or week, and clustering by family practice. Results:Underlying mortality of care home residents was higher than community controls (adjusted rate ratio 5.59, 95% confidence interval 5.23‒5.99, P < .001). During April 2020, there was a net increase in mortality of care home residents over that of controls. The mortality rate of care home residents was 27.2 deaths per 1000 patients per week, compared with 2.31 per 1000 for controls. Excess deaths for care home residents, above that predicted from pre-pandemic years, peaked between April 13 and 19 (men, 27.7, 95% confidence interval 25.1‒30.3; women, 17.4, 15.9‒18.8 per 1000 per week). Compared with care home residents, long-term conditions and frailty were differentially associated with greater mortality in community-dwelling controls. Conclusions and Implications: Individual-patient data from primary care electronic health records may be used to estimate mortality in care home residents. Mortality is substantially higher than for community-dwelling comparators and showed a disproportionate increase in the first wave of the COVID-19 pandemic. Care home residents require particular protection during periods of high infectious disease transmission

Nutritional labelling for healthier food or non-alcoholic drink purchasing and consumption

Background Nutritional labelling is advocated as a means to promote healthier food purchasing and consumption, including lower energy intake. Internationally, many different nutritional labelling schemes have been introduced. There is no consensus on whether such labelling is effective in promoting healthier behaviour. Objectives To assess the impact of nutritional labelling for food and non-alcoholic drinks on purchasing and consumption of healthier items. Our secondary objective was to explore possible effect moderators of nutritional labelling on purchasing and consumption. Search methods We searched 13 electronic databases including CENTRAL, MEDLINE and Embase to 26 April 2017. We also handsearched references and citations and sought unpublished studies through websites and trials registries. Selection criteria Eligible studies: were randomised or quasi-randomised controlled trials (RCTs/Q-RCTs), controlled before-and-after studies, or interrupted time series (ITS) studies; compared a labelled product (with information on nutrients or energy) with the same product without a nutritional label; assessed objectively measured purchasing or consumption of foods or non-alcoholic drinks in real-world or laboratory settings. Data collection and analysis Two authors independently selected studies for inclusion and extracted study data. We applied the Cochrane 'Risk of bias' tool and GRADE to assess the quality of evidence. We pooled studies that evaluated similar interventions and outcomes using a random-effects meta-analysis, and we synthesised data from other studies in a narrative summary. Main results We included 28 studies, comprising 17 RCTs, 5 Q-RCTs and 6 ITS studies. Most (21/28) took place in the USA, and 19 took place in university settings, 14 of which mainly involved university students or staff. Most (20/28) studies assessed the impact of labelling on menus or menu boards, or nutritional labelling placed on, or adjacent to, a range of foods or drinks from which participants could choose. Eight studies provided participants with only one labelled food or drink option (in which labelling was present on a container or packaging, adjacent to the food or on a display board) and measured the amount consumed. The most frequently assessed labelling type was energy (i.e. calorie) information (12/28). Eleven studies assessed the impact of nutritional labelling on purchasing food or drink options in real-world settings, including purchases from vending machines (one cluster-RCT), grocery stores (one ITS), or restaurants, cafeterias or coffee shops (three RCTs, one Q-RCT and five ITS). Findings on vending machines and grocery stores were not interpretable, and were rated as very low quality. A meta-analysis of the three RCTs, all of which assessed energy labelling on menus in restaurants, demonstrated a statistically significant reduction of 47 kcal in energy purchased (MD −46.72 kcal, 95% CI −78.35, −15.10, N = 1877). Assuming an average meal of 600 kcal, energy labelling on menus would reduce energy purchased per meal by 7.8% (95% CI 2.5% to 13.1%). The quality of the evidence for these three studies was rated as low, so our confidence in the effect estimate is limited and may change with further studies. Of the remaining six studies, only two (both ITS studies involving energy labels on menus or menus boards in a coffee shop or cafeteria) were at low risk of bias, and their results support the meta-analysis. The results of the other four studies which were conducted in a restaurant, cafeterias (2 studies) or a coffee shop, were not clearly reported and were at high risk of bias. Seventeen studies assessed the impact of nutritional labels on consumption in artificial settings or scenarios (henceforth referred to as laboratory studies or settings). Of these, eight (all RCTs) assessed the effect of labels on menus or placed on a range of food options. A meta-analysis of these studies did not conclusively demonstrate a reduction in energy consumed during a meal (MD −50 kcal, 95% CI −104.41, 3.88, N = 1705). We rated the quality of the evidence as low, so our confidence in the effect estimate is limited and may change with further studies. Six laboratory studies (four RCTs and two Q-RCTs) assessed the impact of labelling a single food or drink option (such as chocolate, pasta or soft drinks) on energy consumed during a snack or meal. A meta-analysis of these studies did not demonstrate a statistically significant difference in energy (kcal) consumed (SMD 0.05, 95% CI −0.17 to 0.27, N = 732). However, the confidence intervals were wide, suggesting uncertainty in the true effect size. We rated the quality of the evidence as low, so our confidence in the effect estimate is limited and may change with further studies. There was no evidence that nutritional labelling had the unintended harm of increasing energy purchased or consumed. Indirect evidence came from five laboratory studies that involved mislabelling single nutrient content (i.e. placing low energy or low fat labels on high-energy foods) during a snack or meal. A meta-analysis of these studies did not demonstrate a statistically significant increase in energy (kcal) consumed (SMD 0.19, 95% CI −0.14to 0.51, N = 718). The effect was small and the confidence intervals wide, suggesting uncertainty in the true effect size. We rated the quality of the evidence from these studies as very low, providing very little confidence in the effect estimate. Authors' conclusions Findings from a small body of low-quality evidence suggest that nutritional labelling comprising energy information on menus may reduce energy purchased in restaurants. The evidence assessing the impact on consumption of energy information on menus or on a range of food options in laboratory settings suggests a similar effect to that observed for purchasing, although the evidence is less definite and also of low quality. Accordingly, and in the absence of observed harms, we tentatively suggest that nutritional labelling on menus in restaurants could be used as part of a wider set of measures to tackle obesity. Additional high-quality research in real-world settings is needed to enable more certain conclusions. Further high-quality research is also needed to address the dearth of evidence from grocery stores and vending machines and to assess potential moderators of the intervention effect, including socioeconomic status

The impact of communicating genetic risks of disease on risk-reducing health behaviour: systematic review with meta-analysis.

OBJECTIVE: To assess the impact of communicating DNA based disease risk estimates on risk-reducing health behaviours and motivation to engage in such behaviours. DESIGN: Systematic review with meta-analysis, using Cochrane methods. DATA SOURCES: Medline, Embase, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials up to 25 February 2015. Backward and forward citation searches were also conducted. STUDY SELECTION: Randomised and quasi-randomised controlled trials involving adults in which one group received personalised DNA based estimates of disease risk for conditions where risk could be reduced by behaviour change. Eligible studies included a measure of risk-reducing behaviour. RESULTS: We examined 10,515 abstracts and included 18 studies that reported on seven behavioural outcomes, including smoking cessation (six studies; n=2663), diet (seven studies; n=1784), and physical activity (six studies; n=1704). Meta-analysis revealed no significant effects of communicating DNA based risk estimates on smoking cessation (odds ratio 0.92, 95% confidence interval 0.63 to 1.35, P=0.67), diet (standardised mean difference 0.12, 95% confidence interval -0.00 to 0.24, P=0.05), or physical activity (standardised mean difference -0.03, 95% confidence interval -0.13 to 0.08, P=0.62). There were also no effects on any other behaviours (alcohol use, medication use, sun protection behaviours, and attendance at screening or behavioural support programmes) or on motivation to change behaviour, and no adverse effects, such as depression and anxiety. Subgroup analyses provided no clear evidence that communication of a risk-conferring genotype affected behaviour more than communication of the absence of such a genotype. However, studies were predominantly at high or unclear risk of bias, and evidence was typically of low quality. CONCLUSIONS: Expectations that communicating DNA based risk estimates changes behaviour is not supported by existing evidence. These results do not support use of genetic testing or the search for risk-conferring gene variants for common complex diseases on the basis that they motivate risk-reducing behaviour. SYSTEMATIC REVIEW REGISTRATION: This is a revised and updated version of a Cochrane review from 2010, adding 11 studies to the seven previously identified