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ObjectiveTo identify what dimensions of socioeconomic position (SEP) are most closely associated with childhood obesity in Finland, leveraging population-wide data among the whole child population aged 2–17 years in Finland.DesignRegistry-based study.SettingData from several administrative registries linked on individual level covering the whole of Finland were used. Data on height and weight measurements in 2018 were obtained from the Register of Primary Health Care visits and data on sociodemographic and socioeconomic indicators (2014–2018) from Statistics Finland.ParticipantsChildren aged 2–17 years with valid height and weight measurements performed at the child health clinic or school healthcare in 2018 (final n=194 423).Main outcome measuresObesity was defined according to WHO Growth Reference curves. Sociodemographic and socioeconomic indicators were linked on individual level for adults (both parents) who lived in the same household (42 predictors). Boosted regression model was used to analyse the contribution of SEP to obesity.ResultsFrom socioeconomic indicators, annual household income (12.6%) and mother and father’s educational level (12.6% and 8.1%, respectively) had the highest relative influence on obesity risk. The relative influence of a child’s sex was 7.7%.ConclusionsThe parents’ SEP was inversely associated with obesity among the offspring. A remarkable number of objective SEP indicators were analysed with parents’ education and household income finally being the indicators most strongly associated with obesity among children. In future research, more attention should be paid to reliable and objective ways of measuring educational status and income rather than on developing new SEP indicators. Administrative registries with information on both healthcare and socioeconomic indicators can in future provide better opportunities to assess the influence of SEP on various health risks.

ObjectiveThe Brazilian state of Paraná has suffered from COVID-19 effects, understanding predictors of increased mortality in health system interventions prevent hospitalisation of patients. We selected the best models to evaluate the association of death with demographic characteristics, symptoms and comorbidities based on three levels of clinical severity for COVID-19: non-hospitalised, hospitalised non-ICU ward and ICU ward.DesignCross-sectional survey using binomial mixed models.SettingCOVID-19-positive cases diagnosed by reverse transcription–PCR of municipalities located in Paraná State.PatientsCases of anonymous datasets of electronic medical records from 1 April 2020 to 31 December 2020.Primary and secondary outcome measuresThe best prediction factors were chosen based on criteria after a stepwise analysis using multicollinearity measure, lower Akaike information criterion and goodness-of-fit χ2tests from univariate to multivariate contexts.ResultsMale sex was associated with increased mortality among non-hospitalised patients (OR 1.76, 95% CI 1.47 to 2.11) and non-ICU patients (OR 1.22, 95% CI 1.05 to 1.43) for symptoms and for comorbidities (OR 1.89, 95% CI 1.59 to 2.25, and OR 1.30, 95% CI 1.11 to 1.52, respectively). Higher mortality occurred in patients older than 35 years in non-hospitalised (for symptoms: OR 4.05, 95% CI 1.55 to 10.54; and for comorbidities: OR 3.00, 95% CI 1.24 to 7.27) and in hospitalised over 40 years (for symptoms: OR 2.72, 95% CI 1.08 to 6.87; and for comorbidities: OR 2.66, 95% CI 1.22 to 5.79). Dyspnoea was associated with increased mortality in non-hospitalised (OR 4.14, 95% CI 3.45 to 4.96), non-ICU (OR 2.41, 95% CI 2.04 to 2.84) and ICU (OR 1.38, 95% CI 1.10 to 1.72) patients. Neurological disorders (OR 2.16, 95% CI 1.35 to 3.46), neoplastic (OR 3.22, 95% CI 1.75 to 5.93) and kidney diseases (OR 2.13, 95% CI 1.36 to 3.35) showed the majority of increased mortality for ICU as well in the three levels of severity jointly with heart disease, diabetes and CPOD.ConclusionsThese findings highlight the importance of the predictor’s assessment for the implementation of public healthcare policy in response to the COVID-19 pandemic, mainly to understand how non-pharmaceutical measures could mitigate the virus impact over the population.

ObjectivesMultidisciplinary teams in cancer care are increasingly using information and communication technology (ICT), hospital health information system (HIS) functionalities and ICT-driven care components. We aimed to explore the use of these tools in multidisciplinary team meetings (MTMs) and to identify the critical challenges posed by their adoption based on the perspective of professionals representatives from European scientific societies.DesignThis qualitative study used discussion of cases and focus group technique to generate data. Thematic analysis was applied.SettingHealthcare professionals working in a multidisciplinary cancer care environment.ParticipantsSelection of informants was carried out by European scientific societies in accordance with professionals’ degree of experience in adopting the implementation of ICT and from different health systems.ResultsProfessionals representatives of 9 European scientific societies were involved. Up to 10 ICTs, HIS functionalities and care components are embedded in the informational and decision-making processes along three stages of MTMs. ICTs play a key role in opening MTMs to other institutions (eg, by means of molecular tumour boards) and information types (eg, patient-reported outcome measures), and in contributing to the internal efficiency of teams. While ICTs and care components have their own challenges, the information technology context is characterised by the massive generation of unstructured data, the lack of interoperability between systems from different hospitals and HIS that are conceived to store and classify information rather than to work with it.ConclusionsThe emergence of an MTM model that is better integrated in the wider health system context and incorporates inputs from patients and support systems make traditional meetings more dynamic and interconnected. Although these changes signal a second transition in the development process of multidisciplinary teams, they occur in a context marked by clear gaps between the information and management needs of MTMs and the adequacy of current HIS.

BackgroundDeaths from COVID-19 have exceeded 1.8 million globally (January 2020). We examined trends in markers of neonatal care before and during the pandemic at two tertiary neonatal units in Zimbabwe and Malawi.MethodsWe analysed data collected prospectively via the NeoTree app at Sally Mugabe Central Hospital (SMCH), Zimbabwe, and Kamuzu Central Hospital (KCH), Malawi. Neonates admitted from 1 June 2019 to 25 September 2020 were included. We modelled the impact of the first cases of COVID-19 (Zimbabwe: 20 March 2020; Malawi: 3 April 2020) on number of admissions, gestational age and birth weight, source of admission referrals, prevalence of neonatal encephalopathy, and overall mortality.FindingsThe study included 3,450 neonates at SMCH and 3,350 neonates at KCH. Admission numbers at SMCH did not initially change after the first case of COVID-19 but fell by 48% during a nurses’ strike (Relative risk (RR) 0·52, 95%CI 0·40-0·68, p < 0·002). At KCH, admissions dropped by 42% (RR 0·58; 95%CI 0·48-0·70; p < 0·001) soon after the first case of COVID-19. At KCH, gestational age and birth weight decreased slightly (1 week, 300 grams), outside referrals dropped by 28%, and there was a slight weekly increase in mortality. No changes in these outcomes were found at SMCH.InterpretationThe indirect impacts of COVID-19 are context-specific. While this study provides vital evidence to inform health providers and policy makers, national data are required to ascertain the true impacts of the pandemic on newborn health.FundingInternational Child Health Group, Wellcome Trust.RESEARCH IN CONTEXTEvidence before this studyWe searched PubMed for evidence of the indirect impact of the COVID-19 pandemic on neonatal care in low-income settings using the search terms neonat*ornewborn, andCOVID-19orSARS-CoV 2orcoronavirus, and the Cochrane low and middle income country (LMIC) filters, with no language limits between 01.10.2019 and 21.11.20. While there has been a decrease in global neonatal mortality rates, the smaller improvements seen in low-income settings are threatened by the direct and indirect impact of the COVID-19 pandemic. A modelling study of this threat predicted between 250000-1.1 million extra neonatal deaths as a result of decreased service provision and access in LMICs. A webinar and survey of frontline maternal/newborn healthcare workers in >60 countries reported a decline in both service attendance and in quality of service across the ante-, peri- and post-natal journey. Reporting fear of attending services, and difficulty in access, and a decrease in service quality due to exacerbation of existing service weaknesses, confusion over guidelines and understaffing. Similar findings were reported in a survey of healthcare workers providing childhood and maternal vaccines in LMICs. One study to date has reported data from Nepal describing an increase in stillbirths and neonatal deaths, with institutional deliveries nearly halved during lockdown.Added value of this studyTo our knowledge, this is the first and only study in Sub-Saharan Africa describing the impact of COVID-19 pandemic on health service access and outcomes for newborns in two countries. We analysed data from the digital quality improvement and data collection tool, the NeoTree, to carry out an interrupted time series analysis of newborn admission rates, gestational age, birth weight, diagnosis of hypoxic ischaemic encephalopathy and mortality from two large hospitals in Malawi and Zimbabwe (n∼7000 babies). We found that the indirect impacts of COVID-19 were context-specific. In Sally Mugabe Central Hospital, Zimbabwe, initial resilience was demonstrated in that there was no evidence of change in mortality, birth weight or gestational age. In comparison, at Kamuzu Central Hospital, Malawi, soon after the first case of COVID-19, the data revealed a fall in admissions (by 42%), gestational age (1 week), birth weight (300 grams), and outside referrals (by 28%), and there was a slight weekly increase in mortality (2%). In the Zimbabwean hospital, admission numbers did not initially change after the first case of COVID-19 but fell by 48% during a nurses’ strike, which in itself was in response to challenges exacerbated by the pandemic.Implications of all the available evidenceOur data confirms the reports from frontline healthcare workers of a perceived decline in neonatal service access and provision in LMICs. Digital routine healthcare data capture enabled rapid profiling of indirect impacts of COVID-19 on newborn care and outcomes in two tertiary referral hospitals, Malawi and Zimbabwe. While a decrease in service access was seen in both countries, the impacts on care provided and outcome differed by national context. Health systems strengthening, for example digital data capture, may assist in planning context-specific mitigation efforts.

IntroductionIt is unknown if a temporary break in long-term immune-suppressive treatment after vaccination against COVID-19 improves vaccine response. The objective of this study was to evaluate if a 2-week interruption in low-dose weekly methotrexate treatment after SARS-CoV-2 vaccine boosters enhances the immune response compared with continuing treatment in adults with autoimmune inflammatory conditions.Methods and analysisAn open-label, pragmatic, prospective, parallel group, randomised controlled superiority trial with internal feasibility assessment and nested mechanistic substudy will be conducted in rheumatology and dermatology clinics in approximately 25 UK hospitals. The sample size is 560, randomised 1:1 to intervention and usual care arms. The main outcome measure is anti-spike receptor-binding domain (RBD) antibody level, collected at prebooster (baseline), 4 weeks (primary outcome) and 12 weeks (secondary outcome) post booster vaccination. Other secondary outcome measures are patient global assessments of disease activity, disease flares and their treatment, EuroQol 5- dimention 5-level (EQ-5D-5L), self-reported adherence with advice to interrupt or continue methotrexate, neutralising antibody titre against SARS-CoV-2 (mechanistic substudy) and oral methotrexate biochemical adherence (mechanistic substudy). Analysis of B-cell memory and T-cell responses at baseline and weeks 4 and 12 will be investigated subject to obtaining additional funding. The principal analysis will be performed on the groups as randomised (ie, intention to treat). The difference between the study arms in anti-spike RBD antibody level will be estimated using mixed effects model, allowing for repeated measures clustered within participants. The models will be adjusted for randomisation factors and prior SARS-CoV-2 infection status.Ethics and disseminationThis study was approved by the Leeds West Research Ethics Committee and Health Research Authority (REC reference: 21/HRA/3483, IRAS 303827). Participants will be required to give written informed consent before taking part in the trial. Dissemination will be via peer review publications, newsletters and conferences. Results will be communicated to policymakers.Trial registration numberISRCTN11442263.

ObjectivesWe sought to investigate if duplicate faecal immunochemical testing (FIT) sampling improves the negative and positive predictive value of patients thought to be at risk of colorectal cancer (CRC). Specifically, we aimed to investigate whether the proportion of FIT-negative CRC missed by a single FIT test in symptomatic patients could be reduced by duplicate FIT testing.DesignA retrospective service evaluation cohort study of the diagnostic accuracy of duplicate FIT testing.SettingPatients referred from primary care with suspected CRC to four secondary care trusts in North-West England.Participants28 622 patients over 18-years-old with lower gastrointestinal symptoms suggestive of CRC who completed two FIT samples.Primary and secondary outcome measuresThe performance of duplicate FIT for detecting CRC at a threshold of 10 µgHb/g.ResultsThe sensitivity if either test was >10 µgHb/g was 0.978 (0.955–0.989), specificity was 0.662 (0.657–0.668), positive predictive value 0.031 (0.028–0.035) and negative predictive value 1.00 (0.999–1.00). Despite two-thirds of patients (18952) being negative following two tests, at this threshold only seven CRC were missed over a 26-month period. All seven patients had other high-risk features which should have prompted investigation.ConclusionsThis study suggests that in routine NHS practice, a duplicate FIT sample strategy together with clinical evaluation for evidence of anaemia and weight loss is superior to a single FIT sample alone and would allow symptomatic patients to be managed in primary care without the need for urgent referral to secondary care for urgent colonic imaging.

ObjectivesTo investigate alcohol use recording in people with newly diagnosed depression in English primary care and individual characteristics associated with the recording of alcohol use.DesignA population-based cross-sectional study.SettingPrimary care data from English practices contributing to the UK Clinical Practice Research Datalink.ParticipantsWe included adults (18+ years) diagnosed with depression between 1 January 2011 and 1 January 2017 without previous antidepressant use and at least 1 year of registration before diagnosis.Primary and secondary outcome measuresWe described the proportion of individuals with alcohol use and level of alcohol use recorded at four time points (the date of depression diagnosis, 3 months before or after depression diagnosis, 12 months before or after depression diagnosis and any point pre or postdepression diagnosis). We used logistic regression to investigate individual characteristics associated with alcohol use recording in the 3 months before or after depression diagnosis.ResultsWe identified 36 424 adults with depression. 538 (2%) had alcohol use recorded in the 3 months before or after depression diagnosis using formal validated methods such as the Alcohol Use Disorders Identification Test and its abbreviated versions. At each time point, most individuals with alcohol use recorded were low risk drinkers. Alcohol use recording in the 3 months before or after depression diagnosis was associated with male sex (OR=1.38, 95% CI 1.29 to 1.48) and several other individual-level factors.ConclusionsOur study shows low levels of alcohol use recording in the 3 months before or after depression diagnosis. Levels of alcohol use recording varied depending on individual characteristics. Incentivised recording of alcohol use will increase completeness, which could improve clinical management and reduce missed opportunities for care in people with depression.

BackgroundScarlet fever incidence has risen steeply in recent years, and is associated with wider outbreaks of severe Group A Streptococcal infections. Yet, few studies of its epidemiology, clinical features, and management have been undertaken in the antibiotic era.AimTo characterize symptomatology, management, and consequences of scarlet fever and identify associations with delayed diagnosis.Design/SettingCross-sectional study of children with scarlet fever in London, 2018-2019.Methodsonline survey of parents/guardians of children with scarlet fever identified by Health Protection Teams, recording demographics, symptoms, care-seeking, and management; logistic regression for factors associated with delayed diagnosis; Cox’s regression for consequences of delayed diagnosis.ResultsResponses represented 412 cases in a period with 6828 notifications for children 0-14 years old, and 410 school/nursery outbreaks. 70% first sought care from general practice, and 31% had multiple consultations. For 28%, scarlet fever was not considered at first consultation: in these cases, symptoms were frequently attributed to viral infection (60%, 64/106). Delay in diagnosis beyond first consultation occurred more frequently among children aged 5+ who presented with sore throat (odds ratio 2.8 vs. 5+ without sore throat; 95%CI 1.3-5.8; P=0.006). On average, cases with delayed diagnosis took one day longer to return to baseline activities, and required one additional day off school versus those diagnosed at first consultation.ConclusionsIn assessing children with fever, rash, and sore throat, practitioners should be alert to the possibility of scarlet fever: it is frequently missed at first consultation, and prompt recognition speeds clinical recovery and public health management.How this fits in [4 sentences summarising key messages of background and findings]-In the five years leading up to the pandemic lockdown of 2020, scarlet fever incidence rose markedly in England and Wales, prompting this investigation of cases in London 2018-2019.-Prompt recognition of the disease by carers and clinicians can direct timely antibiotic therapy, limit transmission in the household and community, and direct the identification and control of outbreaks.-In this study, delayed diagnosis was more likely to occur among older children presenting with sore throat—perhaps reflecting a lower index of suspicion in this age group.-Cases with delayed diagnosis took longer to return to normal activities, and required more time off from school than those diagnosed at the first consultation.

ObjectivesObstructive sleep apnoea (OSA) is a heavily underdiagnosed condition, which can lead to significant multimorbidity. Underdiagnosis is often secondary to limitations in existing diagnostic methods. We conducted a diagnostic accuracy and usability study, to evaluate the efficacy of a novel, low-cost, small, wearable medical device, AcuPebble_SA100, for automated diagnosis of OSA in the home environment.SettingsPatients were recruited to a standard OSA diagnostic pathway in an UK hospital. They were trained on the use of type-III-cardiorespiratory polygraphy, which they took to use at home. They were also given AcuPebble_SA100; but they were not trained on how to use it.Participants182 consecutive patients had been referred for OSA diagnosis in which 150 successfully completed the study.Primary outcome measuresEfficacy of AcuPebble_SA100 for automated diagnosis of moderate–severe-OSA against cardiorespiratory polygraphy (sensitivity/specificity/likelihood ratios/predictive values) and validation of usability by patients themselves in their home environment.ResultsAfter returning the systems, two expert clinicians, blinded to AcuPebble_SA100’s output, manually scored the cardiorespiratory polygraphy signals to reach a diagnosis. AcuPebble_SA100 generated automated diagnosis corresponding to four, typically followed, diagnostic criteria: Apnoea Hypopnoea Index (AHI) using 3% as criteria for oxygen desaturation; Oxygen Desaturation Index (ODI) for 3% and 4% desaturation criteria and AHI using 4% as desaturation criteria. In all cases, AcuPebble_SA100 matched the experts’ diagnosis with positive and negative likelihood ratios over 10 and below 0.1, respectively. Comparing against the current American Academy of Sleep Medicine’s AHI-based criteria demonstrated 95.33% accuracy (95% CI (90·62% to 98·10%)), 96.84% specificity (95% CI (91·05% to 99·34%)), 92.73% sensitivity (95% CI (82·41% to 97·98%)), 94.4% positive-predictive value (95% CI (84·78% to 98·11%)) and 95.83% negative-predictive value (95% CI (89·94% to 98·34%)). All patients used AcuPebble_SA100 correctly. Over 97% reported a strong preference for AcuPebble_SA100 over cardiorespiratory polygraphy.ConclusionsThese results validate the efficacy of AcuPebble_SA100 as an automated diagnosis alternative to cardiorespiratory polygraphy; also demonstrating that AcuPebble_SA100 can be used by patients without requiring human training/assistance. This opens the doors for more efficient patient pathways for OSA diagnosis.Trial registration numberNCT03544086; ClinicalTrials.gov.

ObjectivesThis study aimed to investigate the presence of perceived stressors, psychological safety and teamwork in healthcare professionals. As the timeframe for this study spanned the first wave of the COVID-19 pandemic, data were captured demonstrating the impact of the pandemic on these factors.DesignQualitative interview study.SettingAll staff working within the emergency and critical care departments of one National Health Service Trust in London, UK.ParticipantsForty-nine participants were recruited using a purposive sampling technique and interviewed when the first wave of the COVID-19 pandemic had subsided.Main outcome measuresEvaluation of changes in perceived stressors, psychological safety and teamwork in individuals working during the COVID-19 pandemic.ResultsThe thematic analysis relating to a participant’s lived experiences while working during COVID-19 led to the construction of five key themes, including ‘psychological effects’ and ‘changes in team dynamics’. Several psychological effects were described, including the presence of psychological distress and insights into the aetiology of moral injury. There was marked heterogeneity in participants’ response to COVID-19, particularly with respect to changes in team dynamics and the perception of a psychologically safe environment. Descriptions of improved team cohesiveness and camaraderie contrasted with stories of new barriers, notably due to the high workload and the impact of personal protective equipment. Building on these themes, a map of key changes arising due to the pandemic was developed, highlighting potential opportunities to provide targeted support.ConclusionsWorking on the front line of a pandemic can have significant implications for healthcare workers, putting them at risk of psychological distress and moral injury, as well as affecting team dynamics. There is striking heterogeneity in the manifestation of these challenges. Team leaders can use the themes and qualitative data from this study to help identify areas for management focus and individual and team support.

ObjectivesStudies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644

ObjectivesThe COVID-19 pandemic instigated multiple societal and healthcare interventions with potential to affect perinatal practice. We evaluated population-level changes in preterm and full-term admissions to neonatal units, care processes and outcomes.DesignObservational cohort study using the UK National Neonatal Research Database.SettingEngland and Wales.ParticipantsAdmissions to National Health Service neonatal units from 2012 to 2020.Main outcome measuresAdmissions by gestational age, ethnicity and Index of Multiple Deprivation, and key care processes and outcomes.MethodsWe calculated differences in numbers and rates between April and June 2020 (spring), the first 3 months of national lockdown (COVID-19 period), and December 2019–February 2020 (winter), prior to introduction of mitigation measures, and compared them with the corresponding differences in the previous 7 years. We considered the COVID-19 period highly unusual if the spring–winter difference was smaller or larger than all previous corresponding differences, and calculated the level of confidence in this conclusion.ResultsMarked fluctuations occurred in all measures over the 8 years with several highly unusual changes during the COVID-19 period. Total admissions fell, having risen over all previous years (COVID-19 difference: −1492; previous 7-year difference range: +100, +1617; pConclusionsOur findings indicate substantial changes occurred in care pathways and clinical thresholds, with disproportionate effects on black ethnic groups, during the immediate COVID-19 period, and raise the intriguing possibility that non-healthcare interventions may reduce extremely preterm births.

ObjectiveWhile the trend in smoking prevalence is decreasing worldwide, the number of male tobacco smokers is growing in Africa. This study compares the cigarette market in eight sub-Saharan African countries. This includes examining cigarette prices, pricing differentials, pack sizes and affordability at national and subnational levels.Design and settingA cross-sectional data analysis using data from the Data on Alcohol and Tobacco in Africa (DATA) Project. The DATA Project was centrally coordinated by project supervisors following a standardised protocol. University students were recruited to conduct data collection and a total of 22 347 retail cigarette price data points collected between June and August 2018 were analysed (including Botswana, Ethiopia, Lesotho, Namibia, Nigeria, South Africa, Zambia and Zimbabwe). Prices were converted to US$ and standardised to the price of a 20-cigarette pack.ResultsThis research found large price differentials within provinces/states, with the gap between medium and minimum prices per 20-cigarette pack exceeding 50% of the medium price in 18 out of 24 provinces/states. Single cigarettes were widely available, especially in Lesotho and Ethiopia. Results of multivariable regression suggest prices (per 20-cigarette pack) were lower for cigarettes sold in packs than single sticks (−US$0.27, 95% CI: −US$0.39 to −US$0.23) and lower in less populated areas (−US$0.28 in rural compared with urban settings, 95% CI: −US$0.41 to −US$0.15). Availability of cheaper single cigarettes (lower per unit price than packed cigarettes) were identified for Lesotho and South Africa.ConclusionsThese findings identify a varied picture in cigarette pricing in studied countries and suggest measures to tackle pricing differentials and availability of single sticks are warranted. These measures should counteract the potential health consequences of the increasing penetration of tobacco industry in these sub-Saharan African countries.

ObjectiveTo summarise the literature on frequent attendances to hospital emergency departments (EDs) and describe sociodemographic and clinical characteristics of children who attend EDs frequently.SettingHospital EDs.ParticipantsChildren Primary outcome measuresOutcomes measures were defined separately in each study, and were predominantly the number of ED attendances per year.ResultsWe included 21 studies representing 6 513 627 children. Between 0.3% and 75% of all paediatric ED users were frequent users. Most studies defined four or more visits per year as a ‘frequent ED’ usage. Children who were frequent ED users were more likely to be less than 5 years old. In the USA, patients with public insurance were more likely to be frequent attenders. Frequent ED users more likely to be frequent users of primary care and have long-term conditions; the most common diagnoses were infections and gastroenteritis.ConclusionsThe review included a wide range of information across various health systems, however, children who were frequent ED users have some universal characteristics in common. Policies to reduce frequent attendance might usefully focus on preschool children and supporting primary care in responding to primary care oriented conditions.

ObjectivesThe steroid hormone vitamin D has roles in immunomodulation and bone health. Insufficiency is associated with susceptibility to respiratory infections. We report 25-hydroxy vitamin D (25(OH)D) measurements in hospitalised people with COVID-19 and influenza A and in survivors of critical illness to test the hypotheses that vitamin D insufficiency scales with illness severity and persists in survivors.DesignCross-sectional study.Setting and participantsPlasma was obtained from 295 hospitalised people with COVID-19 (International Severe Acute Respiratory and emerging Infections Consortium (ISARIC)/WHO Clinical Characterization Protocol for Severe Emerging Infections UK study), 93 with influenza A (Mechanisms of Severe Acute Influenza Consortium (MOSAIC) study, during the 2009–2010 H1N1 pandemic) and 139 survivors of non-selected critical illness (prior to the COVID-19 pandemic). Total 25(OH)D was measured by liquid chromatography-tandem mass spectrometry. Free 25(OH)D was measured by ELISA in COVID-19 samples.Outcome measuresReceipt of invasive mechanical ventilation (IMV) and in-hospital mortality.ResultsVitamin D insufficiency (total 25(OH)D 25–50 nmol/L) and deficiency (ConclusionsVitamin D deficiency/insufficiency was present in majority of hospitalised patients with COVID-19 or influenza A and correlated with severity and persisted in critical illness survivors at concentrations expected to disrupt bone metabolism. These findings support early supplementation trials to determine if insufficiency is causal in progression to severe disease, and investigation of longer-term bone health outcomes.

IntroductionPulmonary rehabilitation (PR), an exercise and education programme for people with chronic lung disease, aims to improve exercise capacity, breathlessness and quality of life. Most evidence to support PR is from trials that use specialist exercise equipment, for example, treadmills (PR-gym). However, a significant proportion of programmes do not have access to specialist equipment with training completed with minimal exercise equipment (PR-min). There is a paucity of robust literature examining the efficacy of supervised, centre-based PR-min. We aim to determine whether an 8-week supervised, centre-based PR-min programme is non-inferior to a standard 8-week supervised, centre-based PR-gym programme in terms of exercise capacity and health outcomes for patients with chronic lung disease.Methods and analysisParallel, two-group, assessor-blinded and statistician-blinded, non-inferiority randomised trial. 436 participants will be randomised using minimisation at the individual level with a 1:1 allocation to PR-min (intervention) or PR-gym (control). Assessment will take place pre-PR (visit 1), post-PR (visit 2) and 12 months following visit 1 (visit 3). Exercise capacity (incremental shuttle walk test), dyspnoea (Chronic Respiratory Questionnaire (CRQ)-Dyspnoea), health-related quality of life (CRQ), frailty (Short Physical Performance Battery), muscle strength (isometric quadriceps maximum voluntary contraction), patient satisfaction (Global Rating of Change Questionnaire), health economic as well as safety and trial process data will be measured. The primary outcome is change in exercise capacity between visit 1 and visit 2. Two sample t-tests on an intention to treat basis will be used to estimate the difference in mean primary and secondary outcomes between patients randomised to PR-gym and PR-min.Ethics and disseminationLondon-Camden and Kings Cross Research Ethics Committee and Health Research Authority have approved the study (18/LO/0315). Results will be submitted for publication in peer-reviewed journals, presented at international conferences, disseminated through social media, patient and public routes and directly shared with stakeholders.Trial registration numberISRCTN16196765.

IntroductionIn recent years, there has been increasing interest in the use of spirometry for the assessment of small airways obstruction (SAO) driven by the idea that these changes occur prior to development of established obstructive lung disease. Maximal mid-expiratory and distal flow rates have been widely used despite a lack of agreement regarding parameter selection or definition of an abnormal result. We aim to provide evidence from population-based studies, describing the different parameters, definitions of normal range and the resulting impact on prevalence estimates for SAO. Summarising this evidence is important to inform development of future studies in this area.Methods and analysisA systematic review of population-based studies will be conducted. MEDLINE, Web of Science and Google Scholar will be searched from database inception to May 2021. Primary outcomes will include the spirometry parameter used to define SAO, and the definition of an abnormal result. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed for study selection. Study methods will be assessed using the Newcastle-Ottawa scale and the Grading of Recommendations Assessment, Development and Evaluation working group methodology. Narrative synthesis will be conducted for all included studies. Meta-analysis will also be conducted for prevalence estimates and associated risk factors where data quality and availability allow. Random effects models will be used to conduct the meta-analysis and I2 statistics will be used to assess heterogeneity across studies. Where appropriate subgroup analysis will be conducted to explore heterogeneity.Ethics and disseminationThere is no requirement for ethical approval for this project. Findings will be disseminated via peer-reviewed publications and other formats, for example, conferences, congresses or symposia.PROSPERO registration numberCRD42021250206.

IntroductionIn non-elderly adults, aortic valve replacement (AVR) with conventional prostheses yield poor long-term outcomes. Recent publications suggest a benefit of the Ross procedure over conventional AVR and highlight the need for high-quality randomised controlled trial (RCTs) on the optimal AVR. We have initiated a pilot trial assess two feasibility criteria and one assumption: (1) evaluate the capacity to enrol six patients per centre per year in at least five international centre, (2) validate greater than 90% compliance with allocation and (3) to validate the proportion of mechanical (≥65%) vs biological (≤35%) valves in the conventional arm.Methods and analysisRoss for Valve replacement In AduLts (REVIVAL) is a multinational, expertise-based RCT in adults aged 18–60 years undergoing AVR, comparing the Ross procedure versus one of the alternative approaches (mechanical vs stented or stentless bioprosthesis). The feasibility objectives will be assessed after randomising 60 patients; we will then make a decision regarding whether to expand the trial with the current protocol. We will ultimately examine the impact of the Ross procedure as compared with conventional AVR in non-elderly adults on survival free of valve-related life-threatening complications (major bleeding, systemic thromboembolism, valve thrombosis and valve reoperation) over the duration of follow-up. The objectives of the pilot trial will be analysed using descriptive statistics. In the full trial, the intention-to-treat principle will guide all primary analyses. A time-to-event analysis will be performed and Kaplan-Meier survival curves with comparison between groups using a log rank test will be presented.Ethics and disseminationREVIVAL will answer whether non-elderly adults benefit from the Ross procedure over conventional valve replacement. The final results at major meetings, journals, regional seminars, hospital rounds and via the Reducing Global Perioperative Risk Multimedia Resource Centre.Trial registration numberClinicalTrials.gov Identifier: NCT03798782Protocol versionJanuary 29, 2019 (Final Version 1.0)

ObjectiveTo describe the discrimination and calibration of clinical prediction models, identify characteristics that contribute to better predictions and investigate predictors that are associated with unplanned hospital readmissions.DesignSystematic review and meta-analysis.Data sourceMedline, EMBASE, ICTPR (for study protocols) and Web of Science (for conference proceedings) were searched up to 25 August 2020.Eligibility criteria for selecting studiesStudies were eligible if they reported on (1) hospitalised adult patients with acute heart disease; (2) a clinical presentation of prediction models with c-statistic; (3) unplanned hospital readmission within 6 months.Primary and secondary outcome measuresModel discrimination for unplanned hospital readmission within 6 months measured using concordance (c) statistics and model calibration. Meta-regression and subgroup analyses were performed to investigate predefined sources of heterogeneity. Outcome measures from models reported in multiple independent cohorts and similarly defined risk predictors were pooled.ResultsSixty studies describing 81 models were included: 43 models were newly developed, and 38 were externally validated. Included populations were mainly patients with heart failure (HF) (n=29). The average age ranged between 56.5 and 84 years. The incidence of readmission ranged from 3% to 43%. Risk of bias (RoB) was high in almost all studies. The c-statistic was 0.8 in 5 models. The study population, data source and number of predictors were significant moderators for the discrimination. Calibration was reported for 27 models. Only the GRACE (Global Registration of Acute Coronary Events) score had adequate discrimination in independent cohorts (0.78, 95% CI 0.63 to 0.86). Eighteen predictors were pooled.ConclusionSome promising models require updating and validation before use in clinical practice. The lack of independent validation studies, high RoB and low consistency in measured predictors limit their applicability.PROSPERO registration numberCRD42020159839.

International audience; Download PDFPDFNeurologyProtocolPatient-reportedimpact of myasthenia gravis in the real world: protocol for a digital observational study (MyRealWorld MG) Sonia Berrih-Aknin1, Kristl G Claeys2,3, Nancy Law4, Renato Mantegazza5,6, Hiroyuki Murai7, Francesco Saccà8, Sarah Dewilde9, Mathieu F Janssen10, http://orcid.org/0000-0001-7208-1303Emma Bagshaw11, Hara Kousoulakou11, Mark Larkin11, Jon Beauchamp12, Trevor Leighton12, Sandra Paci12 INSERM, Institute of Myology, Center of Research in Myology, Sorbonne Université, Paris, France Department of Neurology, University Hospitals Leuven, Leuven, Belgium Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, Leuven, Belgium Myasthenia Gravis Foundation of America Inc, Westborough, Massachusetts, USA Fondazione IRCCS, Istituto Nazionale Neurologico Carlo Besta, Milan, Italy Associazione Italiana Miastenia e Malattie Immunodegenerative, Milan, Italy Department of Neurology, International University of Health and Welfare, Narita, Japan DNSRO Department, University of Naples Federico II, Naples, Italy Services in Health Economics, Brussels, Belgium Section Medical Psychology and Psychotherapy, Department of Psychiatry, Erasmus MC, Rotterdam, Netherlands Vitaccess Limited, London, UK argenx BV, Ghent, BelgiumIntroduction Myasthenia gravis (MG) is a rare, chronic, autoimmune disease, mediated by immunoglobulin G antibodies, which causes debilitating muscle weakness. As with most rare diseases, there is little patient-reported data with which to understand and address patient needs. This study explores the impact of MG in the real world from the patient perspective.Methods and analysis This is a 2-year prospective, observational, digital, longitudinal study of adults with MG, resident in the following countries: the USA, Japan, Germany, France, the UK, Italy, Spain, Canada and Belgium. The planned sample size is 2000. Recruitment will be community based, via patient advocacy groups, social media and word of mouth. Participants will use a smartphone application (app) to check eligibility, provide consent and contribute data. Planned data entry is as follows: (1) personal profile on enrollment—covering demographics, MG characteristics and previous care; (2) monthly event tracker—current treatments, healthcare visits, treatment-related adverse events, productivity losses; (3) monthly selection of validated generic and disease-specific patient-reported outcomes instruments: EQ-5D-5L, Myasthenia Gravis Activities of Daily Living, Myasthenia Gravis Quality of Life 15-item revised scale, Hospital Anxiety and Depression Scale and Health Utilities Index III. Analyses are planned for when the study has been running in most countries for approximately 6, 12, 18 and 24 months.Ethics and dissemination The study protocol has been reviewed and granted ethics approval by Salus IRB for participants resident in the following countries: Germany, the UK and the US. Local ethics approval is being sought for the following study countries: Belgium, Canada, France, Italy, Japan and Spain. Study results will be communicated to the public and participants via conference presentations and journal publications, as well as regular email, social media and in-application communication.

Objectives Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) have a major impact on mortality worldwide. Although effective treatments are available for both HBV and HCV infection

IntroductionMany people with HIV report both distress and pain. The relationship between distress and pain is bidirectional, but the mechanisms by which distress exacerbates pain are unclear. The inflammatory response to challenge (inflammatory reactivity, IR) may be a partial mediator, given that neuroimmune interactions provide a substrate for IR to also influence neurological reactivity and, thus, pain-related neural signalling. This prospective, observational, case–control study will characterise the relationships between distress, IR, pain-related signalling as captured by induced secondary hyperalgesia (SH), and pain, in people with HIV who report persistent pain (PP) (cases) or no pain (controls).Methods and analysisOne hundred people with suppressed HIV, reporting either PP or no pain, will be assessed two or four times over 6 months. The primary outcomes are distress (Hopkins 25-item symptom checklist), IR (multiplex assay after LPS challenge), and PP (Brief Pain Inventory), assessed at the baseline timepoint, although each will also be assessed at follow-up time points. Induced SH will be assessed in a subsample of 60 participants (baseline timepoint only). To test the hypothesis that IR partly mediates the relationship between distress and pain, mediation analysis will use the baseline data from the PP group to estimate direct and indirect contributions of distress and IR to pain. To test the hypothesis that IR is positively associated with SH, data from the subsample will be analysed with generalised mixed effects models to estimate the association between IR and group membership, with SH as the dependent variable.Ethics and disseminationInformation obtained from this study will be published in peer-reviewed journals and presented at scientific meetings. The study has been approved by the Human Research Ethics Committee of the University of Cape Town (approval number: 764/2019) and the City of Cape Town (ref: 24699).Trial registration numberNCT04757987.

ObjectivesRandomised controlled trials conducted using cohorts and routinely collected data, including registries, electronic health records and administrative databases, are increasingly used in healthcare intervention research. A Consolidated Standards of Reporting Trials (CONSORT) statement extension for trials conducted using cohorts and routinely collected data (CONSORT-ROUTINE) has been developed with the goal of improving reporting quality. This article describes the processes and methods used to develop the extension and decisions made to arrive at the final checklist.MethodsThe development process involved five stages: (1) identification of the need for a reporting guideline and project launch; (2) conduct of a scoping review to identify possible modifications to CONSORT 2010 checklist items and possible new extension items; (3) a three-round modified Delphi study involving key stakeholders to gather feedback on the checklist; (4) a consensus meeting to finalise items to be included in the extension, followed by stakeholder piloting of the checklist; and (5) publication, dissemination and implementation of the final checklist.Results27 items were initially developed and rated in Delphi round 1, 13 items were rated in round 2 and 11 items were rated in round 3. Response rates for the Delphi study were 92 of 125 (74%) invited participants in round 1, 77 of 92 (84%) round 1 completers in round 2 and 62 of 77 (81%) round 2 completers in round 3. Twenty-seven members of the project team representing a variety of stakeholder groups attended the in-person consensus meeting. The final checklist includes five new items and eight modified items. The extension Explanation & Elaboration document further clarifies aspects that are important to report.ConclusionUptake of CONSORT-ROUTINE and accompanying Explanation & Elaboration document will improve conduct of trials, as well as the transparency and completeness of reporting of trials conducted using cohorts and routinely collected data.

ObjectiveTo determine whether assessment tools for non-randomised studies (NRS) address critical elements that influence the validity of NRS findings for comparative safety and effectiveness of medications.DesignSystematic review and Delphi survey.Data sourcesWe searched PubMed, Embase, Google, bibliographies of reviews and websites of influential organisations from inception to November 2019. In parallel, we conducted a Delphi survey among the International Society for Pharmacoepidemiology Comparative Effectiveness Research Special Interest Group to identify key methodological challenges for NRS of medications. We created a framework consisting of the reported methodological challenges to evaluate the selected NRS tools.Study selectionChecklists or scales assessing NRS.Data extractionTwo reviewers extracted general information and content data related to the prespecified framework.ResultsOf 44 tools reviewed, 48% (n=21) assess multiple NRS designs, while other tools specifically addressed case–control (n=12, 27%) or cohort studies (n=11, 25%) only. Response rate to the Delphi survey was 73% (35 out of 48 content experts), and a consensus was reached in only two rounds. Most tools evaluated methods for selecting study participants (n=43, 98%), although only one addressed selection bias due to depletion of susceptibles (2%). Many tools addressed the measurement of exposure and outcome (n=40, 91%), and measurement and control for confounders (n=40, 91%). Most tools have at least one item/question on design-specific sources of bias (n=40, 91%), but only a few investigate reverse causation (n=8, 18%), detection bias (n=4, 9%), time-related bias (n=3, 7%), lack of new-user design (n=2, 5%) or active comparator design (n=0). Few tools address the appropriateness of statistical analyses (n=15, 34%), methods for assessing internal (n=15, 34%) or external validity (n=11, 25%) and statistical uncertainty in the findings (n=21, 48%). None of the reviewed tools investigated all the methodological domains and subdomains.ConclusionsThe acknowledgement of major design-specific sources of bias (eg, lack of new-user design, lack of active comparator design, time-related bias, depletion of susceptibles, reverse causation) and statistical assessment of internal and external validity is currently not sufficiently addressed in most of the existing tools. These critical elements should be integrated to systematically investigate the validity of NRS on comparative safety and effectiveness of medications.Systematic review protocol and registrationhttps://osf.io/es65q.

ObjectivesTo determine the impact of the first lockdown in the Netherlands’ measures during the COVID-19 pandemic on the number and type of trauma-related injuries presenting to the emergency department (ED).DesignA single-centre retrospective cohort study.SettingA level 2 trauma centre in Breda, The Netherlands.ParticipantsAll patients with trauma seen at the ED between 11 March and 10 May 2020 (the first Dutch lockdown period) were included in this study. Comparable groups were generated for 2019 and 2018.Main outcome measuresPrimary outcomes were the total number of patients with trauma admitted to the ED and the trauma mechanism. Secondary outcomes were triage categories, time of ED visit, trauma severity (Injury Severity Score (ISS) >12), anatomical region of injury and treatment.ResultsA total of 4674 patients were included in this study. During the first months of the COVID-19 pandemic, there was a decrease of 32% in traumatic injuries at the ED (n=1182) compared with the previous years 2019 (n=1717) and 2018 (n=1775) (p12. The amount of patients admitted for emergency surgery was significantly higher (14.6% vs 9.4%; 8.6%, pConclusionsMeasures taken in the COVID-19 outbreak result in a predictable decrease in the total number of patients with trauma, especially sports-related trauma. Although the trauma burden on the emergency room appears to be lower, more people have been admitted for trauma surgery, possibly due to increased throughput in the operating theatres.

Background: Process evaluations provide insight into how interventions are delivered across varying contexts and why interventions work in some contexts and not in others. This manuscript outlines the detailed protocol for a process evaluation embedded in a cluster randomised trial of a digital depression prevention intervention delivered to secondary school students (The Future Proofing Study). The purpose of this manuscript is to describe the methods that will be used to capture process evaluation data within this trial. Methods: A mixed methods design will be used for this process evaluation with data collected in the intervention arm of the Future Proofing Study. Data collection methods will include semi-structured interviews with school staff members and study facilitators, automatically collected intervention usage and completion data, and participant questionnaires (completed by school staff, school counsellors, study facilitators, and school students). Information will be collected about: i) how the intervention was implemented in schools, including fidelity; ii) school contextual factors and their association with intervention reach (including completion), uptake and acceptability; iii) how school staff, study facilitators, and students and responded to delivering or completing the intervention. How these factors relate to trial effectiveness outcomes will also be assessed. Overall synthesis of the data will provide school cluster-level and individual-level process outcomes. Discussion: This process evaluation provides a detailed description of how to embed a process evaluation into a trial of a complex intervention in schools. It will provide important information about the Future Proofing Study from the perspectives of key groups necessary for implementation – school-teachers, school counsellors and other school staff, as well as study facilitators and students. An understanding of school contextual factors that hinder or facilitate intervention reach and uptake will be provided. Results will also contextualise the trial findings with respect to how the intervention may have worked in some schools but not in others. Furthermore, this process evaluation will inform the development of a model for rolling out digital interventions for the prevention of mental illness across the school sector. Trial Registration: The randomised controlled trial has been prospectively registered: ACTRN12619000855123. Registered 31 May 2019, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377664&isReview=trueContributions to the Literature· Process evaluations are critical for understanding how interventions are delivered in real world contexts but are rarely embedded in randomised controlled trials or detailed in prospective protocols. · This protocol is the first to illustrate how to embed a process evaluation into a school-based trial of a digital depression prevention intervention, including the use of flexible and pragmatic quantitative and qualitative data collection methods with key stakeholders. · School context factors will be rigorously assessed and analysed for contribution to intervention reach and completion, uptake of study processes, and clinical outcomes. · Study outcomes will guide sustainability efforts in the delivery of digital depression prevention interventions in schools.

Introduction: Approximately 60,000 (9/100) infants are born into water annually in the UK and this is likely to increase. Case reports identified infants with water inhalation or sepsis following birth in water and there is a concern that women giving birth in water may sustain more complex perineal trauma. There have not been studies large enough to show whether waterbirth increases these poor outcomes. The POOL Study [ISRCTN 13315580] plans to answer the question about the safety of waterbirths among women who are classified appropriate for midwifery-led intrapartum care. Methods and Analysis: A cohort study with a nested qualitative component. Objectives will be answered; using retrospective and prospective data captured in electronic NHS maternity and neonatal systems. The qualitative component aims to explore factors influencing pool-use and waterbirth; data will be gathered via discussion groups, interviews and case studies of maternity units. Ethics and Disseminations: The protocol has been approved by NHS Wales Research Ethics Committee (18/WA/0291) the transfer of identifiable data has been approved by Health Research Authority Confidentiality Advisory Group (18CAG0153). Study findings and innovative methodology will be disseminated through peer-reviewed journals, conferences and events. Results will be of interest to the general public, clinical and policy stakeholders in the UK and will be disseminated accordingly. Strengths and Limitations of the Study: • Using large retrospective and prospective datasets concomitantly provides six years’ data over a three-year study period. • Ability to look at all neonatal outcomes and treatments across the wide geographical range and number of units. • Using existing, routine data enhanced by prospective data to investigate the safety of waterbirth across a range of outcomes. • Data collected will only represent users of Wellbeing-Software’s EuroKing® maternity software system. • Allocation is not random, so unmeasured confounding is possible.

ObjectivesExamine longitudinal associations between modes of travel to school and adiposity.SettingThe UK.Participants8432 children surveyed at ages 7, 11 and 14 years from the UK Millennium Cohort Study.Primary and secondary outcomesObjective percentage body fat and body mass index (BMI). Transport mode was categorised as private motorised transport, public transport and active transport (walking or cycling). Socioeconomic position (SEP) was measured by household income group and occupational social class. We adjusted analyses for changes in the country of UK, frequency of eating breakfast, self-reported growth spurts, hours of screen time and days per week of moderate-to-vigorous physical activity. Longitudinal (panel) regression models adjusting for individual fixed effects examined associations in changes in mode of travel to school and adiposity, controlling for both time-varying and time-invariant potential confounders. Interaction tests and stratified analyses investigated differences by markers of SEP.ResultsAt age 14 years, 26.1% of children (2198) reported using private motorised transport, 35.3% (2979) used public transport and 38.6% (3255) used active transport to get to school. 36.6% (3083) of children changed mode two times between the three waves and 50.7% (4279) changed once. Compared with continuing to use private transport, switching to active transport was associated with a lower BMI (−0.21 kg/m2, 95% CI −0.31 to −0.10) and body fat (−0.55%, 95% CI −0.80% to −0.31%). Switching to public transport was associated with lower percentage body fat (−0.43%, 95% CI −0.75% to −0.12%), but associations with BMI did not reach statistical significance (−0.13 kg/m2, 95% CI −0.26 to 0.01). Interaction tests showed a trend for these effects to be stronger in more deprived groups, but these interactions did not reach statistical significance.ConclusionThis longitudinal study during a key life course period found switching to physically active forms of travel can have beneficial adiposity impacts; these associations may be more apparent for more disadvantaged children. Increasing active travel has potential to ameliorate inequalities.

ObjectivesPeriprosthetic fractures have considerable clinical implications for patients and financial implications for healthcare systems. This study aims to determine the burden of periprosthetic fractures of the lower and upper limbs in England and identify any factors associated with differences in treatment and outcome.DesignA national, observational study.SettingEngland.ParticipantsAll individuals admitted to hospital with periprosthetic fractures between 1 April 2015 and 31 December 2018.Primary and secondary outcome measuresMortality, length of stay, change in rate of admissions.MethodsWe analysed Hospital Episode Statistics data using the International Classification of Diseases 10th Revision code M96.6 (Fracture of bone following insertion of orthopaedic implant, joint prosthesis, or bone plate) to identify periprosthetic fractures recorded between April 2013 and December 2018. We determined the demographics, procedures performed, mortality rates and discharge destinations. Patient characteristics associated with having a procedure during the index admission were estimated using logistic regression. The annual rate of increase in admissions was estimated using Poisson regression.ResultsBetween 1 April 2015 and 31 December 2018, there were 13 565 patients who had 18 888 admissions (89.5% emergency) with M96.6 in the primary diagnosis field. There was a 13% year-on-year increase in admissions for periprosthetic fracture in England during that period. Older people, people living in deprived areas and those with heart failure or neurological disorders were less likely to receive an operation. 14.4% of patients did not return home after hospital discharge. The overall inpatient mortality was 4.3% and total 30-day mortality was 3.3%.ConclusionsThe clinical and operational burden of periprosthetic fractures is considerable and increasing rapidly. We suggest that the management of people with periprosthetic fractures should be undertaken and funded in a similar manner to that successfully employed for people sustaining hip fractures, using national standards and data collection to monitor and improve performance.

IntroductionRespiratory distress syndrome is a condition seen in preterm infants primarily due to surfactant insufficiency. European guidelines recommend the dose and method of surfactant administration. However, in routine practice, clinicians often use a ‘whole vial’ approach to surfactant dosing. The aim of this study is to assess whether in preterm infants of gestational age 36+6weeks+daysor less, a low first dose of surfactant (100–130 mg/kg) compared with a high first dose (170–200 mg/kg) affects survival with no mechanical ventilation on either on postnatal days 3 and 4, and other outcomes.Methods and analysisIn this prospective, observational study, we will use the National Neonatal Research Database as the main data source. We will obtain additional information describing the dose and method of surfactant administration through the neonatal EPR system. We will use propensity scores to form matched groups with low first dose and high first dose for comparison.Ethics and disseminationThis study was approved by the West Midlands—Black Country Research Ethics Committee (REC reference: 18/WM/0132; IRAS project ID: 237111). The results of the research will be made publicly available through presentations at local, national or international conferences and will be submitted for publication in a peer-reviewed journal.Trial registration numberNCT03808402.

ObjectiveTo assess the suitability of primary care vignettes in benchmarking the performance of online symptom checkersDesignObservational study using publicly available, free online symptom checkersParticipantsThree symptom checkers (Healthily, Ada and Babylon) that provided consultations in English. 139 standardized patient vignettes were compiled by RCGP. Three independent GPs interpreted the vignettes to arrive at a “Gold Standard” consisting of 3 dispositions and divided into one of three categories of triage urgency: (1) emergency care required, (2) primary care required and (3) self-care.Main outcome measuresSix professional non-medical and lay inputters simulated 2774 standardized patient evaluations using 3 online symptom checkers (OSC). We recorded when OSC provided a triage recommendation and whether it correctly recommended the appropriate triage recommendation across three categories of triage urgency (emergency care, primary care or self-care). We collected data on whether the solution appeared within the first 3 dispositions in each of the standards across 2774 standardized patient evaluations.ResultsWhen benchmarked against the Gold Standard, Healthily provided an appropriate triage recommendation 61.9% of the time compared to 45.3% and 42.4% of the time for Babylon and Ada respectively. There was poor agreement between OSC consultation outcome and Gold Standard dispositions. When compared to the Gold Standard, Healthily gave an unsafe “under-triage” recommendation 28.6% of the time overall across the three categories compared to 43.3% for Ada and 47.5% for Babylon (PConclusionsOSCs recommended ‘very unsafe’ triages only Strengths and limitations of this study139 independently created primary care vignettes covering 18 subcategories of primary care were used to benchmark the performance of three online symptom checkers using 2774 unique patient simulationsA gold standard for each primary care vignette was derived using GP roundtables and single blinded testingWe investigated the extent that different inputters using the same vignette and online symptom checker received differing consultation outcomes and triage recommendationsWe developed an accuracy matrix to objectively monitor online symptom checker consultation outcome and the safety of the triage recommendationLimitations included a different number of inputters to simulate patients across the three online symptom checkers tested

ObjectivesEarly switch from intravenous to oral therapy of bioequivalent drugs has major advantages but remains challenging. At our hospital, a basic clinical rule was designed to automatically alert the physician to review potential intravenous to oral switch (IVOS). A rather low acceptance rate was observed. In this study, we aimed to develop, validate and investigate the effect of more advanced clinical rules for IVOS, as part of a centralised pharmacist-led medication review service.Design and settingA quasi-experimental study was performed in a large teaching hospital in Belgium using an interrupted time series design.InterventionA definite set of 13 criteria for IVOS, focusing on the ability of oral absorption and type of infection, was obtained by literature search and validated by a multidisciplinary expert panel. Based on these criteria, we developed a clinical rule for paracetamol and one for ten bioequivalent antibiotics to identify patients with potentially inappropriate intravenous prescriptions (PIVs). Postintervention, the clinical rule alerts were reviewed by pharmacists, who provided recommendations to switch in case of eligibility.Primary and secondary outcome measuresA regression model was used to assess the impact of the intervention on the number of persistent PIVs between the preintervention and the postintervention period. The total number of recommendations, acceptance rate and financial impact were recorded for the 8-month postintervention period.ResultsAt baseline, a median number of 11 (range: 7–16) persistent PIVs per day was observed. After the intervention, the number reduced to 3 (range: 1–7) per day. The advanced IVOS clinical rules showed an immediate relative reduction of 79% (incidence rate ratio=0.21, 95% CI 0.13 to 0.32; pConclusionsWe showed the efficacy of advanced clinical rules combined with a pharmacist-led medication review for IVOS of bioequivalent drugs.

ObjectiveTo estimate the rate and type of downstream activities (DAs) after laboratory testing in primary care, with a specific focus on check-up laboratory panels, and to explore the effect of a clinical decision support system (CDSS) for laboratory ordering on these DAs.DesignCluster randomised clinical trial.Setting72 primary care practices in Belgium, with 272 general practitioners (GPs), randomly assigned to the intervention arm or the control arm.ParticipantsThe study included 10 270 lab panels from 9683 primary care patients (women 55.1%, mean age 56.5). All adult patients who consulted one of the participating GPs during the trial period and needed a laboratory exam were eligible for participation.InterventionsGPs in the intervention group used a CDSS integrated into their online laboratory ordering system, while GPs in the control arm used their lab ordering system as usual. The trial duration was 6 months, with another 6 months follow-up.Main outcome measuresThis publication reports on the exploratory outcome of DAs after an initial laboratory exam and the effect of the CDSS on these DAs.Results19.7% of all laboratory panels resulted in further diagnostic procedures (95% CI 18.9% to 20.5%) and 19% (95% CI 18.2% to 19.7%) in treatment changes. Check-up laboratory exams showed similar rates of DAs, with 17.5% (95% CI 13.8% to 21.2%) diagnostic DAs and 18.9% (95% CI 13.9% to 23.9%) treatment changes. Using the CDSS resulted in a significant reduction in downstream referrals (−2.4%; 95% CI −4.2% to −0.6%; p=0008), imaging and endoscopies (−0.9%; 95% CI −1.6% to −0.1%; p=0026) and treatment changes (−5.4%; 95% CI −9.5% to −1.2%; p=0.01).ConclusionThis is the largest study so far to examine DAs after laboratory testing. It shows that almost one in three laboratory exams leads to further DAs, even in check-up panels. Using a CDSS for laboratory orders may reduce the rate of some DAs.Trial registration numberNCT02950142.

ObjectivesTo investigate predictors of falls and fractures leading to hospitalisation in people with affective disorders.DesignCohort study.SettingThe South London and Maudsley National Health Service (NHS) Foundation Trust (SLaM) Biomedical Research Centre (BRC) Case Register.ParticipantsA large cohort of people with affective disorders (International Classification of Diseases- 10th version [ICD-10] codes F30–F34) diagnosed between January 2008 and March 2016 was assembled using data from the SLaM BRC Case Register.Primary and secondary outcome measuresFalls and fractures leading to hospitalisation were ascertained from linked national hospitalisation data. Multivariable Cox proportional hazards analyses were administrated to identify predictors of first falls and fractures.ResultsOf 36 101 people with affective disorders (mean age 44.4 years, 60.2% female), 816 (incidence rate 9.91 per 1000 person-years) and 1117 (incidence rate 11.92 per 1000 person-years) experienced either a fall or fracture, respectively. In multivariable analyses, older age, analgesic use, increased physical illness burden, previous hospital admission due to certain comorbid physical illnesses and increase in attendances to accident and emergency services following diagnosis were significant risk factors for both falls and fractures. Having a history of falls was a strong risk factor for recurrent falls, and a previous fracture was also associated with future fractures.ConclusionsOver a mean 5 years’ follow-up, approximately 8% of people with affective disorders were hospitalised with a fall or fracture. Several similar factors were found to predict risk of falls and fracture, for example, older age, comorbid physical disorders and analgesic use. Routine screening for bone mineral density and fall prevention programmes should be considered for this clinical group.

ObjectivesTo investigate prognostic factors for anxiety, depression and post-traumatic stress (PTS) symptoms 1 month after early pregnancy loss (EPL).DesignA prospective cohort study. Consecutive women were recruited, and demographic and clinical data were collected. Surveys containing the Hospital Anxiety and Depression Scale (HADS) and Post-traumatic Stress Diagnostic Scale (PDS) were emailed 1 month after a loss. Univariable logistic regression was performed to link factors with caseness of anxiety, depression or PTS according to screening measures.SettingEarly pregnancy units of three central London hospitals.Participants737/1116 eligible women with an EPL were recruited. 492 responded to HADS and 487 to PDS.Primary and secondary outcome measuresPrimary outcome is the area under the curve (AUC) to predict any psychological morbidity (defined as moderate/severe anxiety or depression, or meeting screening criteria for PTS) for each variable. Further outcomes are explained variation (R2) and p value for any morbidity, and AUC, explained variation, and p value for each morbidity separately.ResultsWomen who had a past diagnosis of a psychiatric condition were more likely to meet criteria for anxiety, depression or PTS (75% for current diagnosis vs 55% for past vs 30% for no diagnosis; AUC 0.61; R28.4%; p24.3%; p2≤0.9%).ConclusionsWomen with a history of mental health problems, or those with previous losses, may be at higher risk of psychological illness 1 month after pregnancy loss. However, prognostic ability was poor overall. All women should be considered at risk.

PurposeThe East London Health and Care Partnership (ELHCP) Data Repository was established to support commissioning decisions in London. This dataset comprises routine clinical data for the general practitioner (GP)-registered populations of two London boroughs, Tower Hamlets and City and Hackney, and provides a rich source of demographic, clinical and health service use data of relevance to clinicians, commissioners, researchers and policy makers. This paper describes the dataset in its current form, its representativeness and data completeness.ParticipantsThere were 351 749 and 344 511 members of the GP-registered population in the two boroughs, respectively, for the financial year 2017/2018. Demographic information and prevalence data were available for 9 mental health and 15 physical health conditions. Prevalence rates from the cohort were compared with local and national data. In order to illustrate the health service use data available in the dataset, emergency department use across mental health conditions was described. Information about data completeness was provided.Findings to dateThe ELHCP Data Repository provides a rich source of information about a relatively young, urban, ethnically diverse, population within areas of socioeconomic deprivation. Prevalence data were in line with local and national statistics with some exceptions. Physical health conditions were more common in those with mental health conditions, reflecting that comorbidities are the norm rather than the exception. This has implications for integrated care. Data completeness for risk factors (eg, blood pressure, cholesterol) was high in patients with long-term conditions.Future plansThe data are being further cleaned and evaluated using imputation, Bayesian and economic methods, principally focusing on specific cohorts, including type II diabetes, depression and personality disorder. Data continue to be collected for the foreseeable future to support commissioning decisions, which will also enable more long-term prospective analysis as data become available at the end of each financial year.

IntroductionNeonatal sepsis is responsible for significant morbidity and mortality worldwide. Diagnosis is often difficult due to non-specific clinical features and the unavailability of laboratory tests in many low-income and middle-income countries (LMICs). Clinical prediction models have the potential to improve diagnostic accuracy and rationalise antibiotic usage in neonatal units, which may result in reduced antimicrobial resistance and improved neonatal outcomes. In this paper, we outline our scoping review protocol to map the literature concerning clinical prediction models to diagnose neonatal sepsis. We aim to provide an overview of existing models and evidence underlying their use and compare prediction models between high-income countries and LMICs.Methods and analysisThe protocol was developed with reference to recommendations by the Joanna Briggs Institute. Searches will include six electronic databases (Ovid MEDLINE, Ovid Embase, Scopus, Web of Science, Global Index Medicus and the Cochrane Library) supplemented by hand searching of reference lists and citation analysis on included studies. No time period restrictions will be applied but only studies published in English or Spanish will be included. Screening and data extraction will be performed independently by two reviewers, with a third reviewer used to resolve conflicts. The results will be reported by narrative synthesis in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines.Ethics and disseminationThe nature of the scoping review methodology means that this study does not require ethical approval. Results will be disseminated through peer-reviewed publications and conference presentations, as well as through engagement with peers and relevant stakeholders.

ObjectivesUsing a standardised diagnostic and generic treatment path for breast cancer, and the molecular subtype perspective, we aim to measure the impact of several patient and disease characteristics on the overall treatment cost for patients. Additionally, we aim to generate insights into the drivers of cost variability within one medical domain.Design, setting and participantsWe conducted a retrospective study at a breast clinic in Belgium. We used 14 anonymous patient files for conducting our analysis.ResultsSignificant cost variations within each molecular subtype and across molecular subtypes were found. For the luminal A classification, the cost differential amounts to roughly 166%, with the greatest treatment cost amounting to US$29 780 relative to US$11 208 for a patient requiring fewer medical activities. The major driver for these cost variations relates to disease characteristics. For the luminal B classification, a cost difference of roughly 242% exists due to both disease-related and patient-related factors. The average treatment cost for triple negative patients amounted to US$26 923, this is considered to be a more aggressive type of cancer. The overall cost for HER2-enriched is driven by the inclusion of Herceptin, thus this subtype is impacted by disease characteristics. Cost variability across molecular classifications is impacted by the severity of the disease, thus disease-related factors are the major drivers of cost.ConclusionsGiven the cost challenge in healthcare, the need for greater cost transparency has become imperative. Through our analysis, we generate initial insights into the drivers of cost variability for breast cancer. We found evidence that disease characteristics such as severity and more aggressive cancer forms such as HER2-enriched and triple negative have a significant impact on treatment cost across the different subtypes. Similarly, patient factors such as age and presence of gene mutation contribute to differences in treatment cost variability within molecular subtypes.

IntroductionDiet is an important modifiable risk factor for many chronic diseases. Measurement of dietary intake usually relies on self-report, subject to multiple biases. There is a need to understand gender differences in the self-report of dietary intake and the implications of any differences in targeting nutrition interventions. Literature in this area is limited and it is currently unknown whether self-report dietary assessment methods are equally accurate for women and men. The aim of this systematic review is to determine whether there are differences by gender in reporting energy intake compared with a reference measure of total energy expenditure.Methods and analysisA comprehensive search of published original research studies will be performed in MEDLINE, Scopus, Web of Science, EMBASE, CINAHL and Cochrane library. Original research studies will be included if they were conducted in free-living/unhospitalised adults and included a measure for both women and men of (a) self-reported energy intake and (b) total energy expenditure by doubly labelled water. One author will conduct the electronic database searches, two authors will independently screen studies, conduct a quality appraisal of the included studies using standardised tools and extract data. If further information is needed, then study authors will be contacted. If appropriate, a random-effects meta-analysis will be conducted, with inverse probability weighting, to quantify differences in the mean difference in agreement between reported energy intake and measured energy expenditure between women and men, by self-report assessment method. Subgroup analyses will be conducted by participant factors, geographical factors and study quality.Ethics and disseminationAll data used will be from published primary research studies or deidentified results provided at the discretion of any study authors that we contact. We will submit our findings to a peer-reviewed scientific journal and will disseminate results through presentations at international scientific conferences.PROSPERO registration numberCRD42019131715.

Introduction Problematic benzodiazepine use is a global health issue. Although the adverse side effects of long-term use of benzodiazepines are well known, it remains difficult to implement interventions for discontinuation in primary care. Considering the success of blended care for the treatment of sleeping disorders and the support of substance use disorders, evidence suggests that a blended care approach, combining face-to-face consultations with the general practitioner with web-based self-learning by the patient, is beneficial for the discontinuation of chronic benzodiazepine use for primary insomnia in general practice. Therefore, the aim of this study is to evaluate the effectiveness of such an approach for the discontinuation of benzodiazepine and zolpidem, zopiclone and zaleplon drugs ((z-)BZD) use in the long term and evaluate the implementation process. Methods and analysis This study is a multicentre, pragmatic, cluster randomised controlled trial with 1200 patients, included by 120 general practitioners. Allocation to usual or blended care happens at the level of the general practice in a 1:1 ratio using a block randomisation system stratified per language. The study population consists of adult primary care patients who have been using (z-)BZD for primary insomnia on a daily basis for at least 6 months. Primary outcome measure is the proportion of patients that discontinued (z-)BZD at 12 months assessed by toxicological screening for (z-)BZD in urine. Secondary outcomes include discontinuation of (z-)BZD at 6 months, quality of life and the number of defined daily doses of (z-)BZD prescribed. Data will be collected using a study-specific online platform and analysed using the intention-to-treat approach. The process of implementing blended care will be evaluated in a nested study. Ethics and dissemination This trial was approved by the Ethics Committee for Research of UZ/KU Leuven (ref. S61194). Study results will be disseminated via open-access, peer-reviewed publications and conference presentations. Trial registration number NCT03937180., SCOPUS: ar.j, info:eu-repo/semantics/published

ObjectivesPrevious studies of women in their 20s and 30s have reported impaired autonomic function in women with polycystic ovary syndrome (PCOS). We aimed to study, for the first time, whether PCOS is associated with impaired cardiac autonomic function independent of metabolic and hormonal status in their late reproductive years.DesignA prospective Northern Finland Birth Cohort 1966 (NFBC1966) study including 5889 women born in 1966 and followed through the age of 46. At that age, n=3706/5123 women (72%) answered the postal questionnaires and n=3280/5123 women (64%) participated in the clinical examination.SettingGeneral community.ParticipantsThe sample included women presenting both irregular menses (oligomenorrhoea or amenorrhoea) and hirsutism at age 31 (n=125) or with formally diagnosed PCOS by age 46 (n=181) and women without PCOS symptoms or diagnosis (n=1577).Primary and secondary outcome measuresHeart rate variability parameters: the root mean square of successive R-R differences (rMSSD), spectral power densities (LF: low frequency and HF: high frequency) and baroreflex sensitivity (BRS).ResultsWe found that parasympathetic activity (assessed by rMSSD: 19.5 (12.4; 31.9) vs 24.3 (16.1; 34.8) ms, p=0.004 and HF: 172 (75; 399) vs 261 (112; 565) ms2, p=0.002) and BRS (6.13±3.12 vs 6.99±3.52 ms/mm Hg, p=0.036) were lower in women with PCOS compared with the controls. However, in the multivariate regression analysis, PCOS, body mass index and the free androgen index did not significantly associate with rMSSD, whereas blood pressure, insulin resistance and triglycerides did.ConclusionsWe report here for the first time that late reproductive-aged women with PCOS display impaired cardiac autonomic function manifested as decreased vagal activity. Metabolic status, rather than hyperandrogenaemia and PCOS per se, was the strongest contributing factor. Given the link between cardiac morbidity and impaired autonomic function, the findings underline the importance of screening and treating metabolic abnormalities early on in women with PCOS.

ObjectivesTo examine the association between the use of oral antibiotics and subsequent colorectal cancer risk.DesignMatched case–control study.SettingGeneral practice centres participating in the Integrated Computerised Network database in Flanders, Belgium.ParticipantsIn total, 1705 cases of colorectal cancer diagnosed between 01 January 2010 and 31 December 2015 were matched to 6749 controls by age, sex, comorbidity and general practice centre.Primary outcome measureThe association between the number of prescriptions for oral antibiotics and the incidence of colorectal cancer over a period of 1–10 years, estimated by a conditional logistic regression model.ResultsA significantly increased risk of colorectal cancer (OR 1.25, 95% CI 1.10 to 1.44) was found in subjects with one or more prescriptions compared with those with none after correction for diabetes mellitus. No dose-response relationship was found.ConclusionsThis study resulted in a modestly higher risk of having colorectal cancer diagnosed after antibiotic exposure. The main limitation was missing data on known risk factors, in particular smoking behaviour. This study did not allow us to examine the causality of the relationship, indicating the need of further investigation.

IntroductionThe predictive utility for incident tuberculosis (TB) of the purified protein derivative tuberculin skin test and region of difference 1 (RD1)-based interferon-gamma release assays (IGRA) is comparable; and either is recommended to test for latent TB infection (LTBI). Despite associated high costs of IGRA, sites participating in LTBI screening in many high-income settings pragmatically favour IGRA due to its higher specificity and simpler logistics. A new RD1-based skin test, C-Tb, could offer an acceptable and as accurate, cheaper alternative to IGRA. Evaluating the impact of C-Tb on process and patient-related outcomes would provide important information to help guide its use in LTBI testing strategies.Methods and analysisThis is a pragmatic multicentre, open-label, non-inferiority, randomised controlled trial. The trial will assess the initiation of LTBI treatment following a positive result of the randomised test as the primary outcome. Participants will be randomised to receive the C-Tb test (intervention) or IGRA (usual care, control) for initiation of treatment. We will enrol 1530 participants in England aged≥16 years who are eligible for LTBI testing and treatment according to UK guidance. In the C-Tb arm, skin induration will be assessed 2–3 days after intradermal injection and measured in millimetres of induration. Results of IGRA will be obtained in line with standard practice. Behavioural studies will explore people’s experiences, perspectives and preferences of LTBI testing and treatment. Economic analysis will estimate cost-effectiveness of changes to the diagnostic algorithm for LTBI. The protocol was developed with Patient and Public Involvement (PPI), which will continue throughout the trial.Ethics and disseminationEthics approval has been obtained from The NHS Health Research Authority (269485). We will share results of the trial in peer-reviewed journals and conferences.Trial registration numberEudraCT 2019-002592-34; ISRCTN17936038.

ObjectivesThe study aimed at identifying the determinants of adolescents’ access to healthcare services.SettingIntermediate and secondary schools across all 13 regions in the Kingdom of Saudi Arabia (KSA) from 2011 to 2012 through the Jeeluna national school-based survey.ParticipantsIntermediate and secondary school students participated in the study. A multistage, cluster, random sampling technique was used. Participants responded to a self-administered questionnaire that addressed several domains.Main outcome measureAdolescents’ perception of access to healthcare services.ResultsTwenty-five per cent of participants reported difficulty in accessing healthcare. Women, early (younger) adolescents and adolescents with three siblings were less likely to report difficulty in accessing healthcare than men, late (older) adolescents and those with fewer than three siblings. Adolescents from low-income families and those with either mental or physical illness were more likely to report difficulty in accessing healthcare than adolescents from higher income families and those without mental or physical illnesses.ConclusionsDisparities in access to care exist between certain subpopulations of adolescents. Efforts are needed to support enhancing access and making it more equitable. Training for healthcare professionals and targeted health policies are necessary to improve adolescents’ access to health services in the KSA.Trial registration numberRC08-092; King Abdullah International Medical Research Centre.

ObjectivesTo conduct an independent study investigating how adults perceive the usability and functionality of the ‘National Health Service (NHS) COVID-19’ application (app). This study aims to highlight strengths and provide recommendations to improve adoption of future contact tracing developments.DesignA 60-item, anonymous online questionnaire, disseminated through social media outlets and email lists by a team from Imperial College London.SettingEngland.ParticipantsConvenience sample of 1036 responses, from participants aged 18 years and above, between December 2020 and January 2021.Primary outcome measuresEvaluate the compliance and public attitude towards the ‘NHS COVID-19’ app regarding its functionality and features. This included whether participants’ expectations were met, and their thoughts on the app privacy and security. Furthermore, to distinguish how usability, perception, and adoption differed with varying demographics and user values.ResultsFair compliance with the app features was identified, meeting expectations of the 62.1% of participants who stated they downloaded it after weighted analysis. However, participants finding the interface challenging were less likely to read information in the app and had a lesser understanding of its functionality. Furthermore, little understanding regarding the app’s functionality and privacy concerns was a possible reason why users did not download it. A readability analysis of the text revealed information within the app was conveyed at a level that may be too complex for up to 43% of the UK population. The study highlighted issues related to the potential of false positives caused by the design choices in the ‘Check-In’ feature.ConclusionThis study showed that while the ‘NHS COVID-19’ app was viewed positively, there remained issues regarding participants’ perceived knowledge of app functionality, potentially affecting compliance. Therefore, we recommended improvements regarding the delivery and presentation of the app’s information, and highlighted the potential need for the ability to check out of venues to reduce the number of false positive contacts.

IntroductionThe mental health burden and treatment gap in South and Southeast Asia is high and significant. Capacity building of healthcare workers is essential to support programmes related to the detection and management of patients with mental health conditions. We aim to conduct a systematic review to summarise the research on educational, training and capacity-building interventions aimed at the healthcare workforce in detection and management of mental health conditions in South and Southeast Asia.ObjectiveTo synthesise evidence on (1) the types of educational and training interventions that have been used to improve the knowledge, skills and attitudes of healthcare workers in South and Southeast Asian countries in the detection and management of mental health conditions; (2) the effectiveness, including cost-effectiveness of the interventions; and (3) the enabling factors and barriers that influence the effectiveness of these interventions.Methods and analysisThis review will be conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. We will search six electronic databases: MEDLINE, EMBASE, PsycINFO, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and Global Health for empirical studies published from 1 January 2000 to 31 August 2020. Search results from each database will be combined and uploaded in Covidence library. Title, abstract and full-text screening, and data extraction of each included study will be performed by two independent reviewers. Disagreements between reviewers will be resolved by a third reviewer and study team. Quality of included studies will be assessed by the modified Cochrane Collaboration tool and ROBINS-I tool. Data will be synthesised and if a meta-analysis is not appropriate, a stepwise thematic analysis will be performed.Ethics and disseminationEthics approval is not required for this study. Findings will be disseminated through peer-reviewed publications, fact sheets, multimedia press briefings, conferences, seminars and symposia.PROSPERO registration numberCRD42020203955.

ObjectivesThe study aimed to compare candidate performance between traditional best-of-five single-best-answer (SBA) questions and very-short-answer (VSA) questions, in which candidates must generate their own answers of between one and five words. The primary objective was to determine if the mean positive cue rate for SBAs exceeded the null hypothesis guessing rate of 20%.DesignThis was a cross-sectional study undertaken in 2018.Setting20 medical schools in the UK.Participants1417 volunteer medical students preparing for their final undergraduate medicine examinations (total eligible population across all UK medical schools approximately 7500).InterventionsStudents completed a 50-question VSA test, followed immediately by the same test in SBA format, using a novel digital exam delivery platform which also facilitated rapid marking of VSAs.Main outcome measuresThe main outcome measure was the mean positive cue rate across SBAs: the percentage of students getting the SBA format of the question correct after getting the VSA format incorrect. Internal consistency, item discrimination and the pass rate using Cohen standard setting for VSAs and SBAs were also evaluated, and a cost analysis in terms of marking the VSA was performed.ResultsThe study was completed by 1417 students. Mean student scores were 21 percentage points higher for SBAs. The mean positive cue rate was 42.7% (95% CI 36.8% to 48.6%), one-sample t-test against ≤20%: t=7.53, pConclusionsSBA questions can give a false impression of students’ competence. VSAs appear to have greater authenticity and can provide useful information regarding students’ cognitive errors, helping to improve learning as well as assessment. Electronic delivery and marking of VSAs is feasible and cost-effective.

IntroductionA recently recognised form of chronic kidney disease (CKD) of unknown origin (CKDu) is afflicting communities, mostly in rural areas in several regions of the world. Prevalence studies are being conducted in a number of countries, using a standardised protocol, to estimate the distribution of estimated glomerular filtration rate (eGFR), and thus identify communities with a high prevalence of reduced glomerular filtration rate (GFR). In this paper, we propose a standardised minimum protocol for cohort studies in high-risk communities aimed at investigating the incidence of, and risk factors for, early kidney dysfunction.Methods and analysisThis generic cohort protocol provides the information to establish a prospective population-based cohort study in low-income settings with a high prevalence of CKDu. This involves a baseline survey that included key elements from the DEGREE survey (eg, using the previously published DEGREE methodology) of a population-representative sample, and subsequent follow-up visits in young adults (without a pre-existing diagnosis of CKD (eGFR2), proteinuria or risk factors for CKD at baseline) over several years. Each visit involves a core questionnaire, and collection and storage of biological samples. Local capacity to measure serum creatinine will be required so that immediate feedback on kidney function can be provided to participants. After completion of follow-up, repeat measures of creatinine should be conducted in a central laboratory, using reference standards traceable to isotope dilution mass spectrometry (IDMS) quality control material to quantify the main outcome of eGFR decline over time, alongside a description of the early evolution of disease and risk factors for eGFR decline.Ethics and disseminationEthical approval will be obtained by local researchers, and participants will provide informed consent before the study commences. Participants will typically receive feedback and advice on their laboratory results, and referral to a local health system where appropriate.

IntroductionSmoking prevalence continues to be high over the world and smoking-induced diseases impose a heavy burden on the medical care system. As believed by many researchers, a promising way to promote healthcare and well-being at low cost for the large vulnerable smoking population is through eHealth solutions by providing self-help information about smoking cessation. But in the absence of first-hand knowledge about smoking habits in daily life settings, systems built on these methods often fail to deliver proactive and tailored interventions for different users and situations over time, thus resulting in low efficacy. To fill the gap, an observational study has been developed on the theme of objective and non-biased monitoring of smoking habits in a longitudinal and ambulatory mode. This paper presents the study protocol. The primary objective of the study is to reveal the contextual and physiological pattern of different smoking behaviours using wearable sensors and mobile phones. The secondary objectives are to (1) analyse cue factors and contextual situations of smoking events; (2) describe smoking types with regard to users’ characteristics and (3) compare smoking types between and within subjects.Methods and analysesThis is an observational study aimed at reaching 100 participants. Inclusion criteria are adults aged between 18 and 65 years, current smoker and office worker. The primary outcome is a collection of a diverse and inclusive data set representing the daily smoking habits of the general smoking population from similar social context. Data analysation will revolve around our primary and secondary objectives. First, linear regression and linear mixed model will be used to estimate whether a factor or pattern have consistent (p valueEthics and disseminationThe study was designed together by an interdisciplinary group of researchers, including psychologist, psychiatrist, engineer and user involvement coordinator. The protocol was reviewed and approved by the ethical review board of UZ Leuven on 18 April 2016, with an approval number S60078. The study will allow us to characterise the types of smokers and triggering events. These findings will be disseminated through peer-reviewed articles.

ObjectiveTo evaluate the effects of drug interventions that may modify the progression of chronic kidney disease (CKD) in adults with CKD stages 3 and 4.DesignSystematic review and meta-analysis.MethodsSearching MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, International Clinical Trials Registry Platform, Health Technology Assessment, Science Citation Index, Social Sciences Citation Index, Conference Proceedings Citation Index and Clinical Trials Register, from March 1999 to July 2018, we identified randomised controlled trials (RCTs) of drugs for hypertension, lipid modification, glycaemic control and sodium bicarbonate, compared with placebo, no drug or a drug from another class, in ≥40 adults with CKD stages 3 and/or 4, with at least 2 years of follow-up and reporting renal function (primary outcome), proteinuria, adverse events, maintenance dialysis, transplantation, cardiovascular events, cardiovascular mortality or all-cause mortality. Two reviewers independently screened citations and extracted data. For continuous outcomes, we used the ratio of means (ROM) at the end of the trial in random-effects meta-analyses. We assessed methodological quality with the Cochrane Risk of Bias Tool and confidence in the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.ResultsWe included 35 RCTs and over 51 000 patients. Data were limited, and heterogeneity varied. Final renal function (estimated glomerular filtration rate) was 6% higher in those taking glycaemic control drugs (ROM 1.06, 95% CI 1.02 to 1.10, I2=0%, low GRADE confidence) and 4% higher in those taking lipid-modifying drugs (ROM 1.04, 95% CI 1.00 to 1.08, I2=88%, very low GRADE confidence). For RCTs of antihypertensive drugs, there were no significant differences in renal function. Treatment with lipid-modifying drugs led to a 36% reduction in cardiovascular disease and 26% reduction in all-cause mortality.ConclusionsGlycaemic control and lipid-modifying drugs may slow the progression of CKD, but we found no pooled evidence of benefit nor harm from antihypertensive drugs. However, given the data limitations, further research is needed to confirm these findings.PROSPERO registration numberCRD42015017501.