Trends in inequalities in avoidable hospitalisations across the COVID-19 pandemic: a cohort study of 23.5 million people in England.

OBJECTIVE: To determine whether periods of disruption were associated with increased 'avoidable' hospital admissions and wider social inequalities in England. DESIGN: Observational repeated cross-sectional study. SETTING: England (January 2019 to March 2022). PARTICIPANTS: With the approval of NHS England we used individual-level electronic health records from OpenSAFELY, which covered ~40% of general practices in England (mean monthly population size 23.5 million people). PRIMARY AND SECONDARY OUTCOME MEASURES: We estimated crude and directly age-standardised rates for potentially preventable unplanned hospital admissions: ambulatory care sensitive conditions and urgent emergency sensitive conditions. We considered how trends in these outcomes varied by three measures of social and spatial inequality: neighbourhood socioeconomic deprivation, ethnicity and geographical region. RESULTS: There were large declines in avoidable hospitalisations during the first national lockdown (March to May 2020). Trends increased post-lockdown but never reached 2019 levels. The exception to these trends was for vaccine-preventable ambulatory care sensitive admissions which remained low throughout 2020-2021. While trends were consistent by each measure of inequality, absolute levels of inequalities narrowed across levels of neighbourhood socioeconomic deprivation, Asian ethnicity (compared with white ethnicity) and geographical region (especially in northern regions). CONCLUSIONS: We found no evidence that periods of healthcare disruption from the COVID-19 pandemic resulted in more avoidable hospitalisations. Falling avoidable hospital admissions has coincided with declining inequalities most strongly by level of deprivation, but also for Asian ethnic groups and northern regions of England.

Impact of first UK COVID-19 lockdown on hospital admissions: Interrupted time series study of 32 million people.

Background: Uncontrolled infection and lockdown measures introduced in response have resulted in an unprecedented challenge for health systems internationally. Whether such unprecedented impact was due to lockdown itself and recedes when such measures are lifted is unclear. We assessed the short- and medium-term impacts of the first lockdown measures on hospital care for tracer non-COVID-19 conditions in England, Scotland and Wales across diseases, sexes, and socioeconomic and ethnic groups. Methods: We used OpenSAFELY (for England), EAVEII (Scotland), and SAIL Databank (Wales) to extract weekly hospital admission rates for cancer, cardiovascular and respiratory conditions (excluding COVID-19) from the pre-pandemic period until 25/10/2020 and conducted a controlled interrupted time series analysis. We undertook stratified analyses and assessed admission rates over seven months during which lockdown restrictions were gradually lifted. Findings: Our combined dataset included 32 million people who contributed over 74 million person-years. Admission rates for all three conditions fell by 34.2% (Confidence Interval (CI): -43.0, -25.3) in England, 20.9% (CI: -27.8, -14.1) in Scotland, and 24.7% (CI: -36.7, -12.7) in Wales, with falls across every stratum considered. In all three nations, cancer-related admissions fell the most while respiratory-related admissions fell the least (e.g., rates fell by 40.5% (CI: -47.4, -33.6), 21.9% (CI: -35.4, -8.4), and 19.0% (CI: -30.6, -7.4) in England for cancer, cardiovascular-related, and respiratory-related admissions respectively). Unscheduled admissions rates fell more in the most than the least deprived quintile across all three nations. Some ethnic minority groups experienced greater falls in admissions (e.g., in England, unscheduled admissions fell by 9.5% (CI: -20.2, 1.2) for Whites, but 44.3% (CI: -71.0, -17.6), 34.6% (CI: -63.8, -5.3), and 25.6% (CI: -45.0, -6.3) for Mixed, Other and Black ethnic groups respectively). Despite easing of restrictions, the overall admission rates remained lower in England, Scotland, and Wales by 20.8%, 21.6%, and 22.0%, respectively when compared to the same period (August-September) during the pre-pandemic years. This corresponds to a reduction of 26.2, 23.8 and 30.2 admissions per 100,000 people in England, Scotland, and Wales respectively. Interpretation: Hospital care for non-COVID diseases fell substantially across England, Scotland, and Wales during the first lockdown, with reductions persisting for at least six months. The most deprived and minority ethnic groups were impacted more severely. Funding: This work was funded by the Medical Research Council as part of the Lifelong Health and Wellbeing study as part of National Core Studies (MC_PC_20030). SVK acknowledges funding from the Medical Research Council (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17). EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE - The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. BG has received research funding from the NHS National Institute for Health Research (NIHR), the Wellcome Trust, Health Data Research UK, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme.

Secondary analyses to test the impact on inequalities and uptake of the schools-based human papillomavirus (HPV) vaccination programme by stage of implementation of a new consent policy in the south-west of England.

OBJECTIVES: To test the impact on inequalities and uptake of the schools-based human papillomavirus (HPV) vaccination programme by stage of implementation of a new policy providing additional opportunities to consent. SETTING: Two local authorities in the south-west of England. PARTICIPANTS: Young women (n=7129) routinely eligible for HPV vaccination aged 12-13 years during the intervention period (2017/2018 to 2018/2019 programme years). INTERVENTIONS: Local policy change that included additional opportunities to provide consent (parental verbal consent and adolescent self-consent). OUTCOMES: Secondary analyses of cross-sectional intervention data were undertaken to examine uptake by: (1) receipt of parental written consent forms and; (2) percentage of unvaccinated young women by stage of implementation. RESULTS: During the intervention period, 6341 (89.0%) eligible young women initiated the HPV vaccination series. Parental written consent forms were less likely to be returned where young women attended alternative education provider settings (p<0.001), belonged to non-white British ethnic groups (p<0.01) or more deprived quintiles (p<0.001). Implementation of parental verbal consent and adolescent self-consent reduced the percentage of unvaccinated young women from 21.3% to 16.5% (risk difference: 4.8%). The effect was greater for young women belonging to the most deprived compared with the least deprived quintile (risk difference: 7.4% vs 2.3%, p<0.001), and for young women classified as Unknown ethnic category compared with white British young women (6.7% vs 4.2%, p<0.001). No difference was found for non-white British young women (5.4%, p<0.21). CONCLUSIONS: Local policy change to consent procedures that allowed parents to consent verbally and adolescents to self-consent overcame some of the barriers to vaccination of young women belonging to families less likely to respond to paper-based methods of gaining consent and at greater risk of developing cervical cancer. TRIAL REGISTRATION NUMBER: 49 086 105.

Trauma-informed approaches to primary and community mental health care: protocol for a mixed-methods systematic review.

INTRODUCTION: Exposure to different types of psychological trauma may lead to a range of adverse effects on trauma survivors, including poor mental and physical health, economic, social and cognitive functioning outcomes. Trauma-informed (TI) approaches to care are defined as a service system grounded in and directed by an understanding of how trauma affects the survivors' neurological, biological, physiological and social development. TI service system involves training of all staff, service improvements and sometimes screening for trauma experiences. The UK started incorporating TI approaches into the National Health Service. While policies recommend it, the evidence base for TI approaches to healthcare is not well established. We aim to conduct a systematic review to synthesise evidence on TI approaches in primary and community mental healthcare globally. METHODS AND ANALYSIS: We will undertake a systematic search for primary studies in Medline, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Cochrane library, websites of organisations involved in the development and implementation of TI approaches in healthcare, and databases of thesis and dissertation. Included studies will be in English published between 1990 and February 2020. Two reviewers will independently perform study selection with data extraction and quality appraisal undertaken by one reviewer and checked for accuracy by a second reviewer. A results-based convergent synthesis will be conducted where quantitative (narratively) and qualitative (thematically) evidence will be analysed separately and then integrated using another method of synthesis. We set up a trauma survivor group and a professional group to consult throughout this review. ETHICS AND DISSEMINATION: There is no requirement for ethical approval for this systematic review as no empirical data will be collected. The findings will be disseminated through a peer-reviewed publication, scientific and practitioner conferences, and policy briefings targeted at local and national policy makers. PROSPERO REGISTRATION NUMBER: CRD42020164752.

Increasing uptake of hepatitis C virus infection case-finding, testing, and treatment in primary care: evaluation of the HepCATT (Hepatitis C Assessment Through to Treatment) trial.

BACKGROUND: Hepatitis C virus (HCV) infection is a key cause of liver disease but can be cured in more than 95% of patients. Around 70 000 people in England may have undiagnosed HCV infection and many more will not have been treated. Interventions to increase case-finding in primary care are likely to be cost-effective; however, evidence of effective interventions is lacking. The Hepatitis C Assessment Through to Treatment (HepCATT) trial assessed whether a complex intervention in primary care could increase case-finding, testing, and treatment of HCV. AIM: To investigate the feasibility and acceptability of the HepCATT intervention. DESIGN AND SETTING: A qualitative study with primary care practice staff from practices in the south west of England taking part in the HepCATT trial. METHOD: Semi-structured interviews were carried out with GPs, nurses, and practice staff to ascertain their views of the HepCATT intervention at least 1 month after implementing the intervention in their practice. Normalisation process theory, which outlines the social processes involved in intervention implementation, informed thematic data analysis. RESULTS: Participants appreciated the HepCATT intervention for increasing knowledge and awareness of HCV. Although some initial technical difficulties were reported, participants saw the benefits of using the audit tool to systematically identify patients with HCV infection risk factors and found it straightforward to use. Participants valued the opportunity to discuss HCV testing with patients, especially those who may not have been previously aware of HCV risk. Future implementation should consider fully integrating software systems and additional resources to screen patient lists and conduct tests. CONCLUSION: When supported by a complex intervention, primary care can play a crucial role in identifying and caring for patients with HCV infection, to help stem the HCV epidemic, and prevent HCV-related illness.

Cost effectiveness of an intervention to increase uptake of hepatitis C virus testing and treatment (HepCATT): cluster randomised controlled trial in primary care.

OBJECTIVE: To evaluate the effectiveness and cost effectiveness of a complex intervention in primary care that aims to increase uptake of hepatitis C virus (HCV) case finding and treatment. DESIGN: Pragmatic, two armed, practice level, cluster randomised controlled trial and economic evaluation. SETTING AND PARTICIPANTS: 45 general practices in South West England (22 randomised to intervention and 23 to control arm). Outcome data were collected from all intervention practices and 21/23 control practices. Total number of flagged patients was 24 473 (about 5% of practice list). INTERVENTION: Electronic algorithm and flag on practice systems identifying patients with HCV risk markers (such as history of opioid dependence or HCV tests with no evidence of referral to hepatology), staff educational training in HCV, and practice posters/leaflets to increase patients' awareness. Flagged patients were invited by letter for an HCV test (with one follow-up) and had on-screen pop-ups to encourage opportunistic testing. The intervention lasted one year, with practices recruited April to December 2016. MAIN OUTCOME MEASURES: Primary outcome: uptake of HCV testing. SECONDARY OUTCOMES: number of positive HCV tests and yield (proportion HCV positive); HCV treatment assessment at hepatology; cost effectiveness. RESULTS: Baseline HCV testing of flagged patients (six months before study start) was 608/13 097 (4.6%) in intervention practices and 380/11 376 (3.3%) in control practices. During the study 2071 (16%) of flagged patients in the intervention practices and 1163 (10%) in control practices were tested for HCV: overall intervention effect as an adjusted rate ratio of 1.59 (95% confidence interval 1.21 to 2.08; P<0.001). HCV antibodies were detected in 129 patients from intervention practices and 51 patients from control practices (adjusted rate ratio 2.24, 1.47 to 3.42) with weak evidence of an increase in yield (6.2% v 4.4%; adjusted risk ratio 1.40, 0.99 to 1.95). Referral and assessment increased in intervention practices compared with control practices (adjusted rate ratio 5.78, 1.6 to 21.6) with a risk difference of 1.3 per 1000 and a "number needed to help" of one extra HCV diagnosis, referral, and assessment per 792 (95% confidence interval 558 to 1883) patients flagged. The average cost of HCV case finding was £4.03 (95% confidence interval £2.27 to £5.80) per at risk patient and £3165 per additional patient assessed at hepatology. The incremental cost effectiveness ratio was £6212 per quality adjusted life year (QALY), with 92.5% probability of being below £20 000 per QALY. CONCLUSION: HepCATT had a modest impact but is a low cost intervention that merits optimisation and implementation as part of an NHS strategy to increase HCV testing and treatment. TRIAL REGISTRATION: ISRCTN61788850.

Investigating the effectiveness and cost-effectiveness of FITNET-NHS (Fatigue In Teenagers on the interNET in the NHS) compared to activity management to treat paediatric chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME): amendment to the published protocol.

The FITNET-NHS Trial is a UK, national, trial investigating whether an online cognitive behavioural therapy program (FITNET-NHS) for treating chronic fatigue syndrome/ME in adolescents is clinically effective and cost-effective in the NHS. At the time of writing (September 2019), the trial was recruiting participants. This article presents an update to the planned sample size and data collection duration previously published within the trial protocol. TRIAL REGISTRATION: ISRCTN, ID: 18020851. Registered 8 April 2016.

Socio-demographic patterns in hospital admissions and accident and emergency attendances among young people using linkage to NHS Hospital Episode Statistics: results from the Avon Longitudinal Study of Parents and Children.

BACKGROUND: In England emergency hospital admissions among children are increasing and the under 25s are the most frequent attenders of A&E departments. Children of lower socio-economic status (SES) have poorer health outcomes and higher hospital admission rates. NHS Hospital Episode Statistics (HES) are increasingly being used for research but lack detailed data on individual characteristics such as SES. We report the results of an Avon Longitudinal Study of Parents and Children (ALSPAC) study that linked the data of 3,189 consenting participants to HES. We describe rates of hospital admission, emergency readmissions, and A&E attendances and examine socio-demographic correlates of these. METHODS: Subjects were singletons and twins enrolled in ALSPAC who had provided consent for linkage to their health records by the study cut-off date (31.02.12). Linkage was carried out by the Health and Social Care Information Centre (now NHS Digital). We examined rates of admissions between birth and age 20 and A&E attendances between 14 and 20 years. Socio-demographic information collected in ALSPAC questionnaires during pregnancy were used to examine factors associated with admissions, emergency readmissions (an emergency admission within 30 days of discharge) and A&E attendances. RESULTS: Excluding birth records, we found at least one admission for 1,792/3,189 (56.2%) participants and 4,305 admissions in total. Admission rates were highest in the first year of life. Among males, admissions declined until about age 5 and then remained relatively stable; conversely, among females, they increased sharply from the age of 15. ICD 10 chapters for diseases of the digestive system and injury and poisoning accounted for the largest proportions of admissions (15.8 and 14.5%, respectively). Tooth decay was the highest single cause of admission for those aged 5-9 years. Overall, 1,518/3,189 (47.6%) of participants attended A&E at least once, with a total of 3,613 attendances between age 14 and 20 years. Individuals from more deprived backgrounds had higher rates of admissions, readmissions and A&E attendances. CONCLUSIONS: Linkage between cohort studies such as ALSPAC and HES data provides unique opportunities for detailed insights into socio-demographic and other determinants of hospital activity, which can inform secondary care demand management in the NHS.

Childhood Risk Factors for Heavy Episodic Alcohol Use and Alcohol Problems in Late Adolescence: A Marginal Structural Model Analysis.

OBJECTIVE: This study seeks to clarify the nature of the association between five well-studied late childhood predictors and alcohol-related behaviors in adolescence. METHOD: We examined, in 7,168 subjects from the Avon Longitudinal Study of Parents and Children (ALSPAC), using linear probability and marginal structural models, the association between parental alcohol problems, peer group deviance, antisocial behavior, and low parental monitoring, and sensation seeking assessed at multiple times from ages 12.5 to 18 years and heavy episodic drinking and alcohol problems at ages 16.5, 17.5, and 20 years. RESULTS: Based on the pattern of the attenuation in the association with heavy episodic drinking and alcohol problems from the linear probability to marginal structural models, our five factors were divisible into three groups. For parental alcohol problems, no substantial attenuation was seen. For peer group deviance and antisocial behavior, the associations in the marginal structural models were modestly attenuated (10%-20%). By contrast, for low parental monitoring and sensation seeking, moderate attenuations of 41% and 35%, respectively, were observed. CONCLUSIONS: Our results are consistent with the hypothesis that all or nearly all of the association between parental alcohol problems and heavy episodic drinking and alcohol problems in mid to late adolescence is causal. For peer group deviance and antisocial behavior, the large majority of the associations appear to be causal, but confounding influences are also present. However, for low parental monitoring and sensation seeking, our findings suggest that a substantial proportion of the observed association with alcohol outcomes reflects confounding rather than causal influences.

Adult psychosocial outcomes of men and women who were looked-after or adopted as children: prospective observational study.

OBJECTIVE: To investigate whether men and women who were looked-after (in public care) or adopted as children are at increased risk of adverse psychological and social outcomes in adulthood. DESIGN, SETTING: Prospective observational study using the Avon Longitudinal Study of Parents and Children, which recruited pregnant women and their male partners in and around Bristol, UK in the early 1990s. PARTICIPANTS: 8775 women and 3654 men who completed questionnaires at recruitment (mean age: women 29; men 32) and 5 years later. EXPOSURE: Childhood public care status: looked-after; adopted; not looked-after or adopted (reference group). OUTCOMES: Substance use (alcohol, cannabis, tobacco) prepregnancy and 5 years later; if ever had addiction; anxiety and depression during pregnancy and 5 years later; if ever had mental health problem; social support during pregnancy; criminal conviction. RESULTS: For women, 2.7% were adopted and 1.8% had been looked-after; for men, 2.4% and 1.4%, respectively. The looked-after group reported the poorest outcomes overall, but this was not a universal pattern, and there were gender differences. Smoking rates were high for both the looked-after (men 47%, women 58%) and adopted (men 44%, women 40%) groups relative to the reference group (both 28%). The looked-after group were at increased risk of a high depression score (men: 26% vs 11%, OR 2.9 (95% CI 1.5 to 5.6); women: 24% vs 9%, 3.4 (2.2 to 5.0)). A high anxiety score was reported by 10% of the reference women, compared with 26% of those looked-after (3.0 (2.0 to 4.5)) and 17% of those adopted (1.8 (1.2 to 2.6)). Looked-after men and women reported the lowest social support, while criminal convictions and addiction were highest for looked-after men. Adjustment for adult socioeconomic position generally attenuated associations for the looked-after group. CONCLUSIONS: The needs of those who experience public care as children persist into adulthood. Health and social care providers should recognise this.

Investigating the effectiveness and cost-effectiveness of FITNET-NHS (Fatigue In Teenagers on the interNET in the NHS) compared to Activity Management to treat paediatric chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME): protocol for a randomised controlled trial.

BACKGROUND: Paediatric chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a relatively common and disabling condition. The National Institute for Health and Clinical Excellence (NICE) recommends Cognitive Behavioural Therapy (CBT) as a treatment option for paediatric CFS/ME because there is good evidence that it is effective. Despite this, most young people in the UK are unable to access local specialist CBT for CFS/ME. A randomised controlled trial (RCT) showed FITNET was effective in the Netherlands but we do not know if it is effective in the National Health Service (NHS) or if it is cost-effective. This trial will investigate whether FITNET-NHS is clinically effective and cost-effective in the NHS. METHODS: Seven hundred and thirty-four paediatric patients (aged 11-17 years) with CFS/ ME will be randomised (1:1) to receive either FITNET-NHS (online CBT) or Activity Management (delivered via video call). The internal pilot study will use integrated qualitative methods to examine the feasibility of recruitment and the acceptability of treatment. The full trial will assess whether FITNET-NHS is clinically effective and cost-effective. The primary outcome is disability at 6 months, measured using the SF-36-PFS (Physical Function Scale) questionnaire. Cost-effectiveness is measured via cost-utility analysis from an NHS perspective. Secondary subgroup analysis will investigate the effectiveness of FITNET-NHS in those with co-morbid mood disorders. DISCUSSION: If FITNET-NHS is found to be feasible and acceptable (internal pilot) and effective and cost-effective (full trial), its provision by the NHS has the potential to deliver substantial health gains for the large number of young people suffering from CFS/ME but unable to access treatment because there is no local specialist service. This trial will provide further evidence evaluating the delivery of online CBT to young people with chronic conditions. TRIAL REGISTRATION: ISRCTN registry, registration number: ISRCTN18020851 . Registered on 4 August 2016.

Effectiveness and cost-effectiveness of serum B-type natriuretic peptide testing and monitoring in patients with heart failure in primary and secondary care: an evidence synthesis, cohort study and cost-effectiveness model.

BACKGROUND: Heart failure (HF) affects around 500,000 people in the UK. HF medications are frequently underprescribed and B-type natriuretic peptide (BNP)-guided therapy may help to optimise treatment. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of BNP-guided therapy compared with symptom-guided therapy in HF patients. DESIGN: Systematic review, cohort study and cost-effectiveness model. SETTING: A literature review and usual care in the NHS. PARTICIPANTS: (a) HF patients in randomised controlled trials (RCTs) of BNP-guided therapy; and (b) patients having usual care for HF in the NHS. INTERVENTIONS: Systematic review: BNP-guided therapy or symptom-guided therapy in primary or secondary care. Cohort study: BNP monitored (≥ 6 months' follow-up and three or more BNP tests and two or more tests per year), BNP tested (≥ 1 tests but not BNP monitored) or never tested. Cost-effectiveness model: BNP-guided therapy in specialist clinics. MAIN OUTCOME MEASURES: Mortality, hospital admission (all cause and HF related) and adverse events; and quality-adjusted life-years (QALYs) for the cost-effectiveness model. DATA SOURCES: Systematic review: Individual participant or aggregate data from eligible RCTs. Cohort study: The Clinical Practice Research Datalink, Hospital Episode Statistics and National Heart Failure Audit (NHFA). REVIEW METHODS: A systematic literature search (five databases, trial registries, grey literature and reference lists of publications) for published and unpublished RCTs. RESULTS: Five RCTs contributed individual participant data (IPD) and eight RCTs contributed aggregate data (1536 participants were randomised to BNP-guided therapy and 1538 participants were randomised to symptom-guided therapy). For all-cause mortality, the hazard ratio (HR) for BNP-guided therapy was 0.87 [95% confidence interval (CI) 0.73 to 1.04]. Patients who were aged < 75 years or who had heart failure with a reduced ejection fraction (HFrEF) received the most benefit [interactions (p = 0.03): < 75 years vs. ≥ 75 years: HR 0.70 (95% CI 0.53 to 0.92) vs. 1.07 (95% CI 0.84 to 1.37); HFrEF vs. heart failure with a preserved ejection fraction (HFpEF): HR 0.83 (95% CI 0.68 to 1.01) vs. 1.33 (95% CI 0.83 to 2.11)]. In the cohort study, incident HF patients (1 April 2005-31 March 2013) were never tested (n = 13,632), BNP tested (n = 3392) or BNP monitored (n = 71). Median survival was 5 years; all-cause mortality was 141.5 out of 1000 person-years (95% CI 138.5 to 144.6 person-years). All-cause mortality and hospital admission rate were highest in the BNP-monitored group, and median survival among 130,433 NHFA patients (1 January 2007-1 March 2013) was 2.2 years. The admission rate was 1.1 patients per year (interquartile range 0.5-3.5 patients). In the cost-effectiveness model, in patients aged < 75 years with HFrEF or HFpEF, BNP-guided therapy improves median survival (7.98 vs. 6.46 years) with a small QALY gain (5.68 vs. 5.02) but higher lifetime costs (£64,777 vs. £58,139). BNP-guided therapy is cost-effective at a threshold of £20,000 per QALY. LIMITATIONS: The limitations of the trial were a lack of IPD for most RCTs and heterogeneous interventions; the inability to identify BNP monitoring confidently, to determine medication doses or to distinguish between HFrEF and HFpEF; the use of a simplified two-state Markov model; a focus on health service costs and a paucity of data on HFpEF patients aged < 75 years and HFrEF patients aged ≥ 75 years. CONCLUSIONS: The efficacy of BNP-guided therapy in specialist HF clinics is uncertain. If efficacious, it would be cost-effective for patients aged < 75 years with HFrEF. The evidence reviewed may not apply in the UK because care is delivered differently. FUTURE WORK: Identify an optimal BNP-monitoring strategy and how to optimise HF management in accordance with guidelines; update the IPD meta-analysis to include the Guiding Evidence Based Therapy Using Biomarker Intensified Treatment (GUIDE-IT) RCT; collect routine long-term outcome data for completed and ongoing RCTs. TRIAL REGISTRATION: Current Controlled Trials ISRCTN37248047 and PROSPERO CRD42013005335. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 40. See the NIHR Journals Library website for further project information. The British Heart Foundation paid for Chris A Rogers' and Maria Pufulete's time contributing to the study. Syed Mohiuddin's time is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care West at University Hospitals Bristol NHS Foundation Trust. Rachel Maishman contributed to the study when she was in receipt of a NIHR Methodology Research Fellowship.

Assessment of rates of recanting and hair testing as a biological measure of drug use in a general population sample of young people.

AIMS: We investigate the extent of and factors associated with denial of previously reported cannabis and other illicit drug use, and assess the potential of hair testing for measuring substance use in general population samples. DESIGN: Birth cohort study. SETTING: United Kingdom, 1991-present. PARTICIPANTS: A total of 3643 participants who provided hair and self-report measures of cannabis and other illicit drug use in the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 18 years. MEASUREMENTS: Denial of ever use of cannabis and other illicit drugs at age 18 following previously reported use. Positive hair drug tests for cannabis and other illicit drugs, and expected numbers of false positives and false negatives based on expected sensitivity and specificity. FINDINGS: Cannabis and other illicit drug use was reported by 1223 and 393 individuals, respectively, before age 18 years. Of these 176 (14.4%) and 99 (25.2%), respectively, denied use at age 18. Denial of cannabis use decreased with the reporting of other substances and antisocial behaviour. Cannabis and other illicit drug use at age 18 was reported by 547 (22.5%) and 203 (8.4%) individuals, respectively. Of these, 111 (20.3%) and 13 (6.4%) were hair-positive for cannabis and other illicit drugs, respectively. Based on hair testing for cannabis use we expect 0 [95% confidence interval (CI) = 0-169] false positives and 394 (95% CI = 323-449) false negatives compared to observed 362 potential false positives and 436 potential false negatives based on self-report. In hair-positive individuals, reporting the use of other substances and antisocial behaviour decreased the odds of a negative self-report. CONCLUSIONS: Hair analysis provides an unreliable marker of substance use in general population samples. People who report more frequent substance use before age 18 are less likely to later deny previous substance use at age 18 than people who report occasional use.

Model-based cost-effectiveness analysis of B-type natriuretic peptide-guided care in patients with heart failure.

OBJECTIVE: Monitoring B-type natriuretic peptide (BNP) to guide pharmacotherapy might improve survival in patients with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). However, the cost-effectiveness of BNP-guided care is uncertain and guidelines do not uniformly recommend it. We assessed the cost-effectiveness of BNP-guided care in patient subgroups defined by age and ejection fraction. METHODS: We used a Markov model with a 3-month cycle length to estimate the lifetime health service costs, quality-adjusted life years (QALYs) and incremental net monetary benefits (iNMBs) of BNP-guided versus clinically guided care in 3 patient subgroups: (1) HFrEF patients <75 years; (2) HFpEF patients <75 years; and (3) HFrEF patients ≥75 years. There is no evidence of benefit in patients with HFpEF aged ≥75 years. We used individual patient data meta-analyses and linked primary care, hospital and mortality data to inform the key model parameters. We performed probabilistic analysis to assess the uncertainty in model results. RESULTS: In younger patients (<75 years) with HFrEF, the mean QALYs (5.57 vs 5.02) and costs (£63 527 vs £58 139) were higher with BNP-guided care. At the willingness-to-pay threshold of £20 000 per QALY, the positive iNMB (£5424 (95% CI £987 to £9469)) indicates that BNP-guided care is cost-effective in this subgroup. The evidence of cost-effectiveness of BNP-guided care is less strong for younger patients with HFpEF (£3155 (-£10 307 to £11 613)) and older patients (≥75 years) with HFrEF (£2267 (-£1524 to £6074)). BNP-guided care remained cost-effective in the sensitivity analyses, albeit the results were sensitive to assumptions on its sustained effect. CONCLUSIONS: We found strong evidence that BNP-guided care is a cost-effective alternative to clinically guided care in younger patients with HFrEF. It is potentially cost-effective in younger patients with HFpEF and older patients with HFrEF, but more evidence is required, particularly with respect to the frequency, duration and BNP target for monitoring. Cost-effectiveness results from trials in specialist settings cannot be generalised to primary care.

Hepatitis C - Assessment to Treatment Trial (HepCATT) in primary care: study protocol for a cluster randomised controlled trial.

BACKGROUND: Public Health England (PHE) estimates that there are upwards of 160,000 individuals in England and Wales with chronic hepatitis C virus (HCV) infection, but until now only around 100,000 laboratory diagnoses have been reported to PHE and of these 28,000 have been treated. Targeted case-finding in primary care is estimated to be cost-effective; however, there has been no robust randomised controlled trial evidence available of specific interventions. Therefore, this study aims to develop and conduct a complex intervention within primary care and to evaluate this approach using a cluster randomised controlled trial. METHODS/DESIGN: A total of 46 general practices in South West England will be randomised in a 1:1 ratio to receive either a complex intervention comprising: educational training on HCV for the practice; poster and leaflet display in the practice waiting rooms to raise awareness and encourage opportunistic testing; a HCV risk prediction algorithm based on information on possible risk markers in the electronic patient record run using Audit + software (BMJ Informatica). The audit will then be used to recall and offer patients a HCV test. Control practices will follow usual care. The effectiveness of the intervention will be measured by comparing number and rates of HCV testing, the number and proportion of patients testing positive, onward referral, rates of specialist assessment and treatment in control and intervention practices. Intervention costs and health service utilisation will be recorded to estimate the NHS cost per new HCV diagnosis and new HCV patient initiating treatment. Longer-term cost-effectiveness of the intervention in improving quality-adjusted life years (QALYs) will be extrapolated using a pre-existing dynamic health economic model. Patients' and health care workers' experiences and acceptability of the intervention will be explored through semi-structured qualitative interviews. DISCUSSION: This trial has the potential to make an important impact on patient care and will provide high-quality evidence to help general practitioners make important decisions on HCV testing and onward referral. If found to be effective and cost-effective the intervention is readily scalable and can be used to support the implementation of NICE recommendations on HCV case-finding. TRIAL REGISTRATION: ISRCTN61788850 . Registered on 24 April 2015; Protocol Version: 2.0, 22 May 2015.

A randomised controlled trial comparing opt-in and opt-out home visits for tracing lost participants in a prospective birth cohort study.

BACKGROUND: Attrition is an important problem in cohort studies. Tracing cohort members who have moved or otherwise lost contact with the study is vital. There is some debate about the acceptability and relative effectiveness of opt-in versus opt-out methods of contacting cohort members to re-engage them in this context. We conducted a randomised controlled trial to compare the two approaches in terms of effectiveness (tracing to confirm address and consenting to continue in the study), cost-effectiveness and acceptability. METHODS: Participants in this trial were individuals (young people and mothers) recruited to the Avon Longitudinal Study of Parents and Children (ALSPAC), who had not engaged with the study in the previous 5 years and for whom mail had been returned from their last known address. The sampling frame was restricted to those for whom database searching led to a potential new address being found in the Bristol area. 300 participants were randomly selected and assigned using stratified randomisation to the opt-in or opt-out arm. A tailored letter was sent to the potential new address, either asking participants to opt in to a home visit, or giving them the option to opt out of a home visit. Fieldworkers from Ipsos MORI conducted home visits to confirm address details. RESULTS: The proportion who were traced was higher in the opt-out arm (77/150 = 51 %) than the opt-in arm (6/150 = 4 %), as was the proportion who consented to continue in ALSPAC (46/150 = 31 % v 4/150 = 3 %). The mean cost per participant was £8.14 in the opt-in arm and £71.93 in the opt-out arm. There was no evidence of a difference in acceptability between the opt-in and opt-out approaches. CONCLUSION: Since the opt-in approach yielded very low response rates, and there were no differences in terms of acceptability, we conclude that the opt-out approach is the most effective method of tracing disengaged study members. The gains made in contacting participants must be weighed against the increase in cost using this methodology.

Adolescent cannabis and tobacco use and educational outcomes at age 16: birth cohort study.

AIMS: To investigate the relationship between cannabis and tobacco use by age 15 and subsequent educational outcomes. DESIGN: Birth cohort study. SETTING: England. PARTICIPANTS: The sample was drawn from the Avon Longitudinal Study of Parents and Children; a core sample of 1155 individuals had complete information on all the variables. MEASUREMENTS: The main exposures were cannabis and tobacco use at age 15 assessed in clinic by computer-assisted questionnaire and serum cotinine. The main outcomes were performance in standardized assessments at 16 [Key Stage 4, General Certificate of Secondary Education (GCSE)] in English and mathematics (mean scores), completion of five or more assessments at grade C level or higher and leaving school having achieved no qualifications. Analyses were sequentially adjusted for multiple covariates using a hierarchical approach. Covariates considered were: maternal substance use (ever tobacco or cannabis use, alcohol use above recommended limits); life course socio-economic position (family occupational class, maternal education, family income); child sex; month and year of birth; child educational attainment prior to age 11 (Key Stage 2); child substance use (tobacco, alcohol and cannabis) prior to age 15 and child conduct disorder. FINDINGS: In fully adjusted models both cannabis and tobacco use at age 15 were associated with subsequent adverse educational outcomes. In general, the dose-response effect seen was consistent across all educational outcomes assessed. Weekly cannabis use was associated negatively with English GCSE results [grade point difference (GPD), -5.93, 95% confidence interval (CI) = -8.34, -3.53] and with mathematics GCSE results (GPD, -6.91, 95% CI = -9.92, -3.89). Daily tobacco smoking was associated negatively with English GCSE (GPD, -11.90, 95% CI = -13.47, -10.33) and with mathematics GCSE (GPD, -16.72, 95% CI = -18.57, -14.86). The greatest attenuation of these effects was seen on adjustment for other substance use and conduct disorder. Following adjustment, tobacco appeared to have a consistently stronger effect than cannabis. CONCLUSIONS: Both cannabis and tobacco use in adolescence are associated strongly with subsequent adverse educational outcomes. Given the non-specific patterns of association seen and the attenuation of estimates on adjustment, it is possible that these effects arise through non-causal mechanisms, although a causal explanation cannot be discounted. © 2015 Society for the Study of Addiction.

Social factors associated with readiness for sexual activity in adolescents: a population-based cohort study.

Various factors are associated with sexual activity in adolescence and it is important to identify those that promote healthy and adaptive romantic and sexual development. The objectives of this study were to describe rates of early sexual intercourse (before 16 years) and sexual readiness in adolescence and to assess the extent to which these were social patterned. We prospectively studied nearly 5,000 15-year-olds from the Avon Longitudinal Study of Parents and Children, a UK birth cohort. Between 2006 and 2008, female and male participants answered a computer assisted interview about romantic and sexual behaviors in the last year. Predictors of sexual intercourse and readiness for sexual intercourse were examined across a range of sociodemographic measures. Overall, 17.7% (95% CI 16.7%, 18.9%) of participants reported having had sexual intercourse in the last year, with more girls than boys reporting sexual experience (risk ratio 1.30, 95% CI 1.15, 1.47). Of these, one-third of both male and female were classed as unready because they were unwilling, lacking in autonomy, felt regret or had not used contraception. There was strong evidence of social patterning for sexual activity with higher rates for young people from poorer homes, with lower social class, and with younger, less educated mothers. In contrast, among 860 young people who had had sexual intercourse, there was no clear evidence of associations between social factors and sexual readiness. The lack of social patterning in sexual readiness supports the provision of comprehensive education to develop life skills for adolescents across all social groups.