The RECORD reporting guidelines: meeting the methodological and ethical demands of transparency in research using routinely-collected health data.

Routinely-collected health data (RCD) are now used for a wide range of studies, including observational studies, comparative effectiveness research, diagnostics, studies of adverse effects, and predictive analytics. At the same time, limitations inherent in using data collected without specific a priori research questions are increasingly recognized. There is also a growing awareness of the suboptimal quality of reports presenting research based on RCD. This has created a perfect storm of increased interest and use of RCD for research, together with inadequate reporting of the strengths and weaknesses of these data resources. The REporting of studies Conducted using Observational Routinely-collected Data (RECORD) statement was developed to address these limitations and to help researchers using RCD to meet their ethical obligations of complete and accurate reporting, as well as improve the utility of research conducted using RCD. The RECORD statement has been endorsed by more than 15 journals, including Clinical Epidemiology. This journal now recommends that authors submit the RECORD checklist together with any manuscript reporting on research using RCD

Effectiveness of herpes zoster vaccination in an older United Kingdom population.

BACKGROUND: Vaccination against herpes zoster was introduced in the United Kingdom in 2013 for individuals aged 70 years, with a phased catch-up campaign for 71-79 year olds. Vaccine introduction has resulted in a marked fall in incident herpes zoster and in post-herpetic neuralgia (PHN), but formal evaluation of vaccine effectiveness is needed. METHODS: In a population-based cohort study of older individuals born between 1933 and 1946, we used linked UK anonymised primary care health records for the first three years of the vaccination programme (01/09/2013-31/08/2016) and multivariable Poisson regression to obtain incidence rates and vaccine effectiveness (VE) against zoster and PHN. RESULTS: Among 516,547 individuals, 21% were vaccinated. Incidence of zoster was 3.15/1000 person-years in vaccinees and 8.80/1000 person-years in unvaccinated individuals. After adjustment, VE was 64% (95%CI = 60-68%) against incident zoster and 81% (95%CI = 61-91%) against PHN, with very similar VE estimates in the routine and catch-up cohorts. VE against zoster was lower in those with a previous history of zoster: 47% (95%CI = 31-58%) versus 64% (95%CI = 60-68%) in those without previous zoster. There was evidence of waning VE over time, from 69% (95%CI = 65-74%) in the first year after vaccination to 45% (95%CI = 29-57%) by the third year. CONCLUSION: This first formal assessment of VE in the UK zoster vaccination programme demonstrates good effectiveness of zoster vaccine, and very good protection against PHN. The findings provide evidence that VE is similar across the age groups targeted for vaccination in the UK, and on duration of protection of the vaccine in public health use. The study provides key information for decision-makers about the future direction of UK zoster vaccination programme, indicating that the live zoster vaccine may be more cost-effective than estimated previously. It also supports efforts to communicate the benefits of zoster vaccination to address the declining coverage observed across the UK

Lansoprazole use and tuberculosis incidence in the United Kingdom Clinical Practice Research Datalink: A population based cohort.

BACKGROUND: Recent in vitro and animal studies have found the proton pump inhibitor (PPI) lansoprazole to be highly active against Mycobacterium tuberculosis. Omeprazole and pantoprazole have no activity. There is no evidence that, in clinical practice, lansoprazole can treat or prevent incident tuberculosis (TB) disease. METHODS AND FINDINGS: We studied a cohort of new users of lansoprazole, omeprazole, or pantoprazole from the United Kingdom Clinical Practice Research Datalink to determine whether lansoprazole users have a lower incidence of TB disease than omeprazole or pantoprazole users. Negative control outcomes of myocardial infarction (MI) and herpes zoster were also studied. Multivariable Cox proportional hazards regression was used to adjust for potential confounding by a wide range of factors. We identified 527,364 lansoprazole initiators and 923,500 omeprazole or pantoprazole initiators. Lansoprazole users had a lower rate of TB disease (n = 86; 10.0 cases per 100,000 person years; 95% confidence interval 8.1-12.4) than omeprazole or pantoprazole users (n = 193; 15.3 cases per 100,000 person years; 95% confidence interval 13.3-17.7), with an adjusted hazard ratio (HR) of 0.68 (0.52-0.89). No association was found with MI (adjusted HR 1.04; 95% confidence interval 1.00-1.08) or herpes zoster (adjusted HR 1.03; 95% confidence interval 1.00-1.06). Limitations of this study are that we could not determine whether TB disease was due to reactivation of latent infection or a result of recent transmission, nor could we determine whether lansoprazole would have a beneficial effect if given to people presenting with TB disease. CONCLUSIONS: In this study, use of the commonly prescribed and cheaply available PPI lansoprazole was associated with reduced incidence of TB disease. Given the serious problem of drug resistance and the adverse side effect profiles of many TB drugs, further investigation of lansoprazole as a potential antituberculosis agent is warranted

Distribution of vitamin D status in the UK: a cross-sectional analysis of UK Biobank.

OBJECTIVE: No recent large studies have described the distribution of vitamin D status in the UK. Understanding the epidemiology of vitamin D deficiency is important to inform targeted public health recommendations. This study aimed to investigate the distribution of factors associated with serum vitamin D status in a large national cohort. DESIGN: A cross-sectional study. SETTING: The UK Biobank, a prospective cohort study following the health and well-being of middle-aged and older adults recruited between 2006 and 2010. PARTICIPANTS: A total of 449 943 participants aged 40-69 years with measured serum vitamin D status were eligible for the analysis. Participants completed a questionnaire about sex, age, ethnic background, vitamin D supplementation, smoking, drinking and socioeconomic status. PRIMARY AND SECONDARY OUTCOME MEASURES: We investigated the distribution of serum vitamin D status and the association between demographic factors and vitamin D deficiency or insufficiency. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D level <25 nmol/L. Multivariable logistic regression was used to assess the association between demographic factors and vitamin D status. RESULTS: Asian (n=4297/8000, 53.7%) and black (n=2459/7046, 34.9%) participants had a higher proportion of vitamin D deficiency than white participants (n=50 920/422 907, 12%). During spring and winter, the proportion of vitamin D deficiency was higher across the UK and higher in the north than in the south. Male sex, abnormal body mass index, non-white ethnic backgrounds, smoking and being more socioeconomically deprived were associated with higher odds of vitamin D deficiency. Increasing age, taking vitamin D supplements and drinking alcohol were associated with lower odds of deficiency. CONCLUSIONS: Vitamin D status varied among different ethnic groups and by season and geographical area within the UK. Taking supplements was associated with a lower risk of vitamin D deficiency. These findings support the vitamin D supplementation recommendations of Public Health England

Validation of treatment escalation as a definition of atopic eczema flares.

BACKGROUND: Atopic eczema (AE) is a chronic disease with flares and remissions. Long-term control of AE flares has been identified as a core outcome domain for AE trials. However, it is unclear how flares should be defined and measured. OBJECTIVE: To validate two concepts of AE flares based on daily reports of topical medication use: (i) escalation of treatment and (ii) days of topical anti-inflammatory medication use (topical corticosteroids and/or calcineurin inhibitors). METHODS: Data from two published AE studies (studies A (n=336) and B (n=60)) were analysed separately. Validity and feasibility of flare definitions were assessed using daily global bother (scale 0 to 10) as the reference standard. Intra-class correlations were reported for continuous variables, and odds ratios and area under the receiver operator characteristic (ROC) curve for binary outcome measures. RESULTS: Good agreement was found between both AE flare definitions and change in global bother: area under the ROC curve for treatment escalation of 0.70 and 0.73 in studies A and B respectively, and area under the ROC curve of 0.69 for topical anti-inflammatory medication use (Study A only). Significant positive relationships were found between validated severity scales (POEM, SASSAD, TIS) and the duration of AE flares occurring in the previous week - POEM and SASSAD rose by half a point for each unit increase in number of days in flare. Smaller increases were observed on the TIS scale. Completeness of daily diaries was 95% for Study A and 60% for Study B over 16 weeks). CONCLUSION: Both definitions were good proxy indicators of AE flares. We found no evidence that 'escalation of treatment' was a better measure of AE flares than 'use of topical anti-inflammatory medications'. Capturing disease flares in AE trials through daily recording of medication use is feasible and appears to be a good indicator of long-term control. TRIAL REGISTRATION: Current Controlled Trials ISRCTN71423189 (Study A)

Long-term oral prednisolone exposure in primary care for bullous pemphigoid: population-based study

Background: Oral prednisolone is the mainstay treatment for bullous pemphigoid, an autoimmune blistering skin disorder affecting older people. Treatment with moderate-to-high doses is often initiated in secondary care, but then continued in primary care. Aim: To describe long-term oral prednisolone prescribing in UK primary care for adults with bullous pemphigoid from 1998 to 2017. Design and setting: A prospective cohort study using routinely collected data from the Clinical Practice Research Datalink, a primary care database containing the healthcare records for over 17 million people in the UK. Method: Oral prednisolone exposure was characterised in terms of the proportion of individuals with incident bullous pemphigoid prescribed oral prednisolone following their diagnosis, and the duration and dose of prednisolone. Results: In total, 2312 (69.6%) of 3322 people with bullous pemphigoid were prescribed oral prednisolone in primary care. The median duration of exposure was 10.6 months (interquartile range [IQR] 3.4–24.0). Of prednisolone users, 71.5% were continuously exposed for >3 months, 39.7% for >1 year, 14.7% for >3 years, 5.0% for >5 years, and 1.7% for >10 years. The median cumulative dose was 2974 mg (IQR 1059–6456). Maximum daily doses were ≥10 mg/day in 74.4% of prednisolone users, ≥20 mg/day in 40.7%, ≥30 mg/day in 18.2%, ≥40 mg/day in 6.6%, ≥50 mg/day in 3.8%, and ≥60 mg/day in 1.9%. Conclusion: A high proportion of people with incident bullous pemphigoid are treated with oral prednisolone in UK primary care. Action is required by primary and second care services to encourage use of steroid-sparing alternatives and, where switching is not possible, ensure prophylactic treatments and proactive monitoring of potential side effects are in place

Validation study of bullous pemphigoid and pemphigus vulgaris recording in routinely collected electronic primary healthcare records in England.

OBJECTIVES The validity of bullous pemphigoid and pemphigus vulgaris recording in routinely collected healthcare data in the UK is unknown. We assessed the positive predictive value (PPV) for bullous pemphigoid and pemphigus vulgaris primary care Read codes in the Clinical Practice Research Datalink (CPRD) using linked inpatient data (Hospital Episode Statistics (HES)) as the diagnostic benchmark. SETTING:Adult participants with bullous pemphigoid or pemphigus vulgaris registered with HES-linked general practices in England between January 1998 and December 2017. Code-based algorithms were used to identify patients from the CPRD and extract their benchmark blistering disease diagnosis from HES. PRIMARY OUTCOME MEASURE The PPVs of Read codes for bullous pemphigoid and pemphigus vulgaris. RESULTS:Of 2468 incident cases of bullous pemphigoid and 431 of pemphigus vulgaris, 797 (32.3%) and 85 (19.7%) patients, respectively, had a hospitalisation record for a blistering disease. The PPV for bullous pemphigoid Read codes was 93.2% (95% CI 91.3% to 94.8%). Of the bullous pemphigoid cases, 3.0% had an HES diagnosis of pemphigus vulgaris and 3.8% of another blistering disease. The PPV for pemphigus vulgaris Read codes was 58.5% (95% CI 48.0% to 68.9%). Of the pemphigus vulgaris cases, 24.7% had an HES diagnosis of bullous pemphigoid and 16.5% of another blistering disease. CONCLUSIONS:The CPRD can be used to study bullous pemphigoid, but recording of pemphigus vulgaris needs to improve in primary care

The epidemiology of atopic dermatitis in older adults: A population-based study in the United Kingdom

Background Atopic dermatitis is known to be common among children, but there are few studies examining the epidemiology across the life course. In particular, there is a paucity of data on atopic dermatitis among older adults. Objective To evaluate participant characteristics, patterns of disease activity and severity, and calendar trends in older adult atopic dermatitis in comparison to other age groups in a large population-based cohort. Methods This was a cohort study of 9,154,936 individuals aged 0-99 years registered in The Health Improvement Network, a database comprised of electronic health records from general practices in the United Kingdom between 1994 and 2013. Atopic dermatitis was defined by a previously validated algorithm using a combination of at least one recorded atopic dermatitis diagnostic code in primary care and two atopic dermatitis therapies recorded on separate days. Cross-sectional analyses of disease prevalence were conducted at each age. Logistic mixed effect regression models were used to identify predictors of prevalent disease over time among children (0-17 years), adults (18-74 years), and older adults (75-99 years). Results Physician-diagnosed atopic dermatitis was identified in 894,454 individuals with the following proportions in each age group: 18.3% of children, 7.7% of adults, and 11.6% of older adults. Additionally, atopic dermatitis prevalence increased across the 2-decade period (beta from linear regression test for trend in the change in proportion per year = 0.005, p = 0.044). In older adults, atopic dermatitis was 27% less common among females (adjusted OR 0.73, 95% CI 0.70-0.76) and was more likely to be active (59.7%, 95% CI 59.5-59.9%) and of higher severity (mean annual percentage with moderate and severe disease: 31.8% and 3.0%, respectively) than in other age groups. Conclusion In a large population-based cohort, the prevalence of physician-diagnosed atopic dermatitis has increased throughout adulthood and was most common among males age 75 years and above. Compared to children ages 0-17 and adults ages 18-74, older adult atopic dermatitis was more active and severe. Because the prevalence of atopic dermatitis among older adults has increased over time, additional characterization of disease triggers and mechanisms and targeted treatment recommendations are needed for this population

Long-term oral prednisolone exposure in primary care for bullous pemphigoid: population-based study

Background Oral prednisolone is the mainstay treatment for bullous pemphigoid, an autoimmune blistering skin disorder affecting older people. Treatment with moderate-to-high doses is often initiated in secondary care, but then continued in primary care. Aim To describe long-term oral prednisolone prescribing in UK primary care for adults with bullous pemphigoid from 1998 to 2017. Design and setting A prospective cohort study using routinely collected data from the Clinical Practice Research Datalink, a primary care database containing the healthcare records for over 17 million people in the UK. Method Oral prednisolone exposure was characterised in terms of the proportion of individuals with incident bullous pemphigoid prescribed oral prednisolone following their diagnosis, and the duration and dose of prednisolone. Results In total, 2312 (69.6%) of 3322 people with bullous pemphigoid were prescribed oral prednisolone in primary care. The median duration of exposure was 10.6 months (interquartile range [IQR] 3.4-24.0). Of prednisolone users, 71.5% were continuously exposed for >3 months, 39.7% for >1 year, 14.7% for >3 years, 5.0% for >5 years, and 1.7% for >10 years. The median cumulative dose was 2974 mg (IQR 1059-6456). Maximum daily doses were ≥10 mg/day in 74.4% of prednisolone users, ≥20 mg/day in 40.7%, ≥30 mg/day in 18.2%, ≥40 mg/day in 6.6%, ≥50 mg/day in 3.8%, and ≥60 mg/day in 1.9%. Conclusion A high proportion of people with incident bullous pemphigoid are treated with oral prednisolone in UK primary care. Action is required by primary and second care services to encourage use of steroid-sparing alternatives and, where switching is not possible, ensure prophylactic treatments and proactive monitoring of potential side effects are in place

Quantifying possible bias in clinical and epidemiological studies with quantitative bias analysis: common approaches and limitations

Bias in epidemiological studies can adversely affect the validity of study findings. Sensitivity analyses, known as quantitative bias analyses, are available to quantify potential residual bias arising from measurement error, confounding, and selection into the study. Effective application of these methods benefits from the input of multiple parties including clinicians, epidemiologists, and statisticians. This article provides an overview of a few common methods to facilitate both the use of these methods and critical interpretation of applications in the published literature. Examples are given to describe and illustrate methods of quantitative bias analysis. This article also outlines considerations to be made when choosing between methods and discusses the limitations of quantitative bias analysis