Data Resource Profile: Clinical Practice Research Datalink (CPRD).

The Clinical Practice Research Datalink (CPRD) is an ongoing primary care database of anonymised medical records from general practitioners, with coverage of over 11.3 million patients from 674 practices in the UK. With 4.4 million active (alive, currently registered) patients meeting quality criteria, approximately 6.9% of the UK population are included and patients are broadly representative of the UK general population in terms of age, sex and ethnicity. General practitioners are the gatekeepers of primary care and specialist referrals in the UK. The CPRD primary care database is therefore a rich source of health data for research, including data on demographics, symptoms, tests, diagnoses, therapies, health-related behaviours and referrals to secondary care. For over half of patients, linkage with datasets from secondary care, disease-specific cohorts and mortality records enhance the range of data available for research. The CPRD is very widely used internationally for epidemiological research and has been used to produce over 1000 research studies, published in peer-reviewed journals across a broad range of health outcomes. However, researchers must be aware of the complexity of routinely collected electronic health records, including ways to manage variable completeness, misclassification and development of disease definitions for research.LS is supported by a Wellcome Trust Senior Research Fellowship in Clinical Science grant number 098504/Z/12/Z

Towards an evidence‐base for student wellbeing and mental health : definitions, developmental transitions and data sets

Against a background of huge changes in the world of university and college students since the turn of the millennium, together with a multitude of reports on student mental health/wellbeing, this article argues that the field of student mental health is hampered by the imprecise use of terms, a rush to action by universities in the absence of a robust evidence‐base, and a lack of overall coordination and collaboration in the collection and use of data. In response, we argue for clearer and more consistent use of definitions of, as well as differentiations between, student wellbeing and mental health, for a longitudinal approach to the student body that captures their developmental transitions to and through university, and a strategic and systematic approach to the use of bona fide measures in the collection of data on wellbeing and on the process of outcomes in embedded university counselling services. Such a coordinated approach will provide the necessary evidence‐base upon which to develop and deliver appropriate support and interventions to underpin and enhance the quality of students’ lives and learning while at university or college

Cancer Pharmacogenomics and Pharmacoepidemiology: Setting a Research Agenda to Accelerate Translation

Recent advances in genomic research have demonstrated a substantial role for genomic factors in predicting response to cancer therapies. Researchers in the fields of cancer pharmacogenomics and pharmacoepidemiology seek to understand why individuals respond differently to drug therapy, in terms of both adverse effects and treatment efficacy. To identify research priorities as well as the resources and infrastructure needed to advance these fields, the National Cancer Institute (NCI) sponsored a workshop titled “Cancer Pharmacogenomics: Setting a Research Agenda to Accelerate Translation” on July 21, 2009, in Bethesda, MD. In this commentary, we summarize and discuss five science-based recommendations and four infrastructure-based recommendations that were identified as a result of discussions held during this workshop. Key recommendations include 1) supporting the routine collection of germline and tumor biospecimens in NCI-sponsored clinical trials and in some observational and population-based studies; 2) incorporating pharmacogenomic markers into clinical trials; 3) addressing the ethical, legal, social, and biospecimen- and data-sharing implications of pharmacogenomic and pharmacoepidemiologic research; and 4) establishing partnerships across NCI, with other federal agencies, and with industry. Together, these recommendations will facilitate the discovery and validation of clinical, sociodemographic, lifestyle, and genomic markers related to cancer treatment response and adverse events, and they will improve both the speed and efficiency by which new pharmacogenomic and pharmacoepidemiologic information is translated into clinical practice

A Comparative Analysis of Competency Frameworks for Youth Workers in the Out-of-School Time Field

Research suggests that the quality of out-of-school time (OST) programs is related to positive youth outcomes and skilled staff are a critical component of high quality programming. This descriptive case study of competency frameworks for youth workers in the OST field demonstrates how experts and practitioners characterize a skilled youth worker. A comparative analysis of 11 competency frameworks is conducted to identify a set of common core competencies. A set of 12 competency areas that are shared by existing frameworks used in the OST field are identified. The age of youth being served, descriptions of mastery for each competency area, an emphasis on developing mid-level managers, and incorporating research emerge as factors that should be addressed in future competency frameworks

Molecular testing for Lynch syndrome in people with colorectal cancer: systematic reviews and economic evaluation

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Inherited mutations in deoxyribonucleic acid (DNA) mismatch repair (MMR) genes lead to an increased risk of colorectal cancer (CRC), gynaecological cancers and other cancers, known as Lynch syndrome (LS). Risk-reducing interventions can be offered to individuals with known LS-causing mutations. The mutations can be identified by comprehensive testing of the MMR genes, but this would be prohibitively expensive in the general population. Tumour-based tests - microsatellite instability (MSI) and MMR immunohistochemistry (IHC) - are used in CRC patients to identify individuals at high risk of LS for genetic testing. MLH1 (MutL homologue 1) promoter methylation and BRAF V600E testing can be conducted on tumour material to rule out certain sporadic cancers. OBJECTIVES: To investigate whether testing for LS in CRC patients using MSI or IHC (with or without MLH1 promoter methylation testing and BRAF V600E testing) is clinically effective (in terms of identifying Lynch syndrome and improving outcomes for patients) and represents a cost-effective use of NHS resources. REVIEW METHODS: Systematic reviews were conducted of the published literature on diagnostic test accuracy studies of MSI and/or IHC testing for LS, end-to-end studies of screening for LS in CRC patients and economic evaluations of screening for LS in CRC patients. A model-based economic evaluation was conducted to extrapolate long-term outcomes from the results of the diagnostic test accuracy review. The model was extended from a model previously developed by the authors. RESULTS: Ten studies were identified that evaluated the diagnostic test accuracy of MSI and/or IHC testing for identifying LS in CRC patients. For MSI testing, sensitivity ranged from 66.7% to 100.0% and specificity ranged from 61.1% to 92.5%. For IHC, sensitivity ranged from 80.8% to 100.0% and specificity ranged from 80.5% to 91.9%. When tumours showing low levels of MSI were treated as a positive result, the sensitivity of MSI testing increased but specificity fell. No end-to-end studies of screening for LS in CRC patients were identified. Nine economic evaluations of screening for LS in CRC were identified. None of the included studies fully matched the decision problem and hence a new economic evaluation was required. The base-case results in the economic evaluation suggest that screening for LS in CRC patients using IHC, BRAF V600E and MLH1 promoter methylation testing would be cost-effective at a threshold of £20,000 per quality-adjusted life-year (QALY). The incremental cost-effectiveness ratio for this strategy was £11,008 per QALY compared with no screening. Screening without tumour tests is not predicted to be cost-effective. LIMITATIONS: Most of the diagnostic test accuracy studies identified were rated as having a risk of bias or were conducted in unrepresentative samples. There was no direct evidence that screening improves long-term outcomes. No probabilistic sensitivity analysis was conducted. CONCLUSIONS: Systematic review evidence suggests that MSI- and IHC-based testing can be used to identify LS in CRC patients, although there was heterogeneity in the methods used in the studies identified and the results of the studies. There was no high-quality empirical evidence that screening improves long-term outcomes and so an evidence linkage approach using modelling was necessary. Key determinants of whether or not screening is cost-effective are the accuracy of tumour-based tests, CRC risk without surveillance, the number of relatives identified for cascade testing, colonoscopic surveillance effectiveness and the acceptance of genetic testing. Future work should investigate screening for more causes of hereditary CRC and screening for LS in endometrial cancer patients. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016033879. FUNDING: The National Institute for Health Research Health Technology Assessment programme.Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Researc

Bronchiolitis of Infancy Discharge Study (BIDS):a multicentre, parallel-group, double-blind, randomised controlled, equivalence trial with economic evaluation

Background: There are no randomised trials of peripheral capillary oxygen saturation (SpO2) targets in acute respiratory infection. Two national guidelines recommended different targets for the management of acute viral bronchiolitis. Objectives: To compare the American Academy of Pediatrics guideline target of SpO2 ≥ 90% with the Scottish Intercollegiate Guidelines Network target of SpO2 ≥ 94%. Design: A multicentre, parallel-group, double-blind, randomised controlled, equivalence trial with economic evaluation. Setting: Eight paediatric hospital departments in the UK. Participants: Infants > 6 weeks and ≤ 12 months of age (corrected for prematurity) with physician-diagnosed bronchiolitis admitted to hospital from a paediatric emergency assessment area. Follow-up for 6 months by standardised telephone contacts. Intervention: Infants were randomised to a target oxygen saturation of ≥ 94% (standard care) or ≥ 90% (modified care) displayed by a pulse saturation oximeter (Masimo Corporation Limited, CA, USA). Routine care: All infants received routine care in addition to the study intervention. Infants were eligible for discharge when they exhibited a SpO2 of ≥ 94% in room air for 4 hours including a period of sleep and were also feeding adequately (≥ 75% usual volume). Primary outcome: A total of 615 infants were recruited, of whom 308 were allocated to the standard care group and 307 to the modified care group. The primary outcome was time to cough resolution. There was equivalence at the prespecified variance of ± 2 days [time to cough resolution: standard care group, 15 days; modified care group, 15 days; median difference 1 day (benefit modified), 95% confidence interval (CI) –1 to 2 days]. Secondary results: Return to adequate feeding occurred sooner in infants in the modified care group than in those in the standard care group (19.5 vs. 24.1 hours). This difference was non-equivalent [median difference 2.7 hours (95% CI –0.3 to 7.0 hours) versus prespecified ± 4 hours; post-hoc hazard ratio 1.22 (95% CI 1.04 to 1.44 (p-value = 0.015)]. Parent perspective of the time taken to return to normal was not equivalent, being 12 days in the standard care group compared with 11 days in the modified care group [median difference 1.0 day (95% CI 0.0 to 3.0 days) versus prespecified ± 2 days; post-hoc hazard ratio 1.19 (95% CI 1.00 to 1.41); p-value = 0.043]. At 28 days, SpO2 was equivalent [mean difference 0.11% (95% CI –0.35% to 0.57%), within the 1% prespecified]. The modified care group (55.6%) required oxygen less than the standard care group (73.1%), and for a shorter period (5.7 hours vs. 27.6 hours). Infants in the modified care group were fit for discharge (30.2 hours vs. 44.2 hours, hazard ratio 1.46, 95% CI 1.23 to 1.73; p-value < 0.001) and were discharged (40.9 hours vs. 50.9 hours; hazard ratio 1.28, 95% CI 1.06 to 1.50; p-value < 0.003) sooner than those in the standard care group. There were 35 serious adverse events in the standard care group, compared with 25 in the modified care group. Eight infants in the standard care group and 12 in the modified care group were admitted to a high-dependency unit. By 28 days, 23 infants had been readmitted to hospital in the standard care group and 12 infants in the modified care group. Parents of infants in the modified care group did not experience higher levels of anxiety and, by 14 days, had lost 28% fewer hours to usual activities. NHS costs were £290 lower in the modified care group than in the standard care group, with additional societal costs also being lower in the modified care group. Conclusions: Management of infants to a SpO2 target of ≥ 90% is as clinically effective as ≥ 94%, gives rise to no additional safety concerns, and appears to be cost-effective. Future work could focus on the safety and effectiveness of using intermittent oxygen saturation monitoring in secondary care, and to consider what are safe and effective oxygen saturation targets for children with bronchiolitis managed in primary care. Trial registration: This trial is registered as ISRCTN28405428. Funding: This project was funded by the NIHR Health Technology Assessment programme. Masimo Corporation Limited, CA, USA, kindly provided oxygen saturation monitors with standard and altered algorithms