Harriet Forbes

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.

Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults

Summary Background High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers. Methods With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects. Findings 5·24 million individuals were included; 166 955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m2 increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56–1·69; p<0·0001), gallbladder (1·31, 1·12–1·52; p<0·0001), kidney (1·25, 1·17–1·33; p<0·0001), cervix (1·10, 1·03–1·17; p=0·00035), thyroid (1·09, 1·00–1·19; p=0·0088), and leukaemia (1·09, 1·05–1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12–1·27), colon (1·10, 1·07–1·13), ovarian (1·09, 1.04–1.14), and postmenopausal breast cancers (1·05, 1·03–1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95–1·00; premenopausal breast cancer 0·89, 0·86–0·92) and in never-smokers (prostate 0·96, 0·93–0·99; premenopausal breast cancer 0·89, 0·85–0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93–1·05; oral cavity 1·07, 0·91–1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m2 population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI. Interpretation BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups. Funding National Institute for Health Research, Wellcome Trust, and Medical Research Council.

Quantification of risk factors for herpes zoster: population based case-control study

Objectives To quantify the effects of possible risk factors for herpes zoster at different ages. Design Case-control study. Setting UK Clinical Practice Research Datalink primary care data. Participants 144 959 adults diagnosed with zoster between 2000 and 2011; 549 336 age, sex, and practice matched controls. Main outcome measures Conditional logistic regression was used to generate adjusted odds ratios to estimate the strength of association of each potential risk factor with zoster and assess effect modification by age. Results The median age of the cases and controls was 62 years. Factors associated with increased risk of zoster included rheumatoid arthritis (3111 (2.1%) v 8029 (1.5%); adjusted odds ratio 1.46, 99% confidence interval 1.38 to 1.55), inflammatory bowel disease (1851 (1.3%) v 5118 (0.9%); 1.36, 1.26 to 1.46), chronic obstructive pulmonary disease (6815 (4.7%) v 20 201 (3.7%); 1.32, 1.27 to 1.37), asthma (10 243 (7.1%) v 31 865 (5.8%); 1.21, 1.17 to 1.25), chronic kidney disease (8724 (6.0%) v 29 437 (5.4%); 1.14, 1.09 to 1.18), and depression (6830 (4.7%) v 22 052 (4.0%); 1.15, 1.10 to 1.20). Type 1, but not type 2, diabetes showed some association with zoster (adjusted odds ratio 1.27, 1.07 to 1.50). The relative effects of many assessed risk factors were larger in younger patients. Patients with severely immunosuppressive conditions were at greatest risk of zoster—for example, patients with lymphoma (adjusted odds ratio 3.90, 3.21 to 4.74) and myeloma (2.16, 1.84 to 2.53), who are not eligible for zoster vaccination. Conclusions A range of conditions were associated with increased risk of zoster. In general, the increased risk was proportionally greater in younger age groups. Current vaccines are contraindicated in people at the greatest risk of zoster, highlighting the need for alternative risk reduction strategies in these groups.

Validation of chronic obstructive pulmonary disease recording in the Clinical Practice Research Datalink (CPRD-GOLD)

Objectives The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known. We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database. Setting 951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012. Individuals were selected for ≥1 of 8 algorithms to identify people with COPD. General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested. All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard. Primary outcome measure The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed. Results 951 questionnaires were sent and 738 (78%) returned. After quality control, 696 (73.2%) patients were included in the final analysis. All four algorithms including a specific COPD diagnostic code performed well. Using a diagnostic code alone, the PPV was 86.5% (77.5–92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7–94.5%) but reduced case numbers by 10%. Algorithms without specific diagnostic codes had low PPVs (range 12.2–44.4%). Conclusions Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes. Requiring spirometry or COPD medications only marginally improved accuracy. The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004.

A systematic review and meta-analysis of risk factors for postherpetic neuralgia.

Abstract Patients with herpes zoster can develop persistent pain after rash healing, a complication known as postherpetic neuralgia. By preventing zoster through vaccination, the risk of this common complication is reduced. We searched MEDLINE and Embase for studies assessing risk factors for postherpetic neuralgia, with a view to informing vaccination policy. Nineteen prospective studies were identified. Meta-analysis showed significant increases in the risk of postherpetic neuralgia with clinical features of acute zoster including prodromal pain (summary rate ratio 2.29, 95% confidence interval: 1.42-3.69), severe acute pain (2.23, 1.71-2.92), severe rash (2.63, 1.89-3.66), and ophthalmic involvement (2.51, 1.29-4.86). Older age was significantly associated with postherpetic neuralgia; for individual studies, relative risk estimates per 10-year increase ranged from 1.22 to 3.11. Evidence for differences by gender was conflicting, with considerable between-study heterogeneity. A proportion of studies reported an increased risk of postherpetic neuralgia with severe immunosuppression (studies, n = 3/5) and diabetes mellitus (n = 1/4). Systemic lupus erythematosus, recent trauma, and personality disorder symptoms were associated with postherpetic neuralgia in single studies. No evidence of higher postherpetic neuralgia risk was found with depression (n = 4) or cancer (n = 5). Our review confirms a number of clinical features of acute zoster are risk factors for postherpetic neuralgia. It has also identified a range of possible vaccine-targetable risk factors for postherpetic neuralgia; yet aside from age-associated risks, evidence regarding risk factors to inform zoster vaccination policy is currently limited.

Early Service leavers: a study of the factors associated with premature separation from the UK Armed Forces and the mental health of those that leave early

BACKGROUND Approximately 18,000 personnel leave the UK Armed Forces annually. Those leaving before completing the minimum term of their contracts are called early Service leavers (ESLs). This study aims to identify characteristics associated with being an ESL, and compare the post-discharge mental health of ESLs and other Service leavers (non-ESLs). METHOD A cross-sectional study used data on ex-Serving UK Armed Forces personnel. ESLs were personnel leaving before completing their 3-4.5 years minimum Service contracts and were compared with non-ESLs. Multivariable logistic regression was used to estimate odds ratios and 95% confidence intervals for the associations between Service leaving status with socio-demographics, military characteristics and mental health outcomes. RESULTS Of 845 Service leavers, 80 (9.5%) were ESLs. Being an ESL was associated with younger age, female sex, not being in a relationship, lower rank, serving in the Army and with a trend of reporting higher levels of childhood adversity, but not with deployment to Iraq. ESLs were at an increased risk of probable post-traumatic stress disorder (PTSD), common mental disorders, fatigue and multiple physical symptoms, but not alcohol misuse. CONCLUSIONS The study suggests that operational Service is not a factor causing personnel to become an ESL. Current mental health problems were more commonly reported among ESLs than other Service leavers. There may be a need to target interventions to ESLs on leaving Service to smooth their transition to civilian life and prevent the negative mental health outcomes experienced by ESLs further down the line.

Representativeness and optimal use of body mass index (BMI) in the UK Clinical Practice Research Datalink (CPRD)

Objectives To assess the completeness and representativeness of body mass index (BMI) data in the Clinical Practice Research Datalink (CPRD), and determine an optimal strategy for their use. Design Descriptive study. Setting Electronic healthcare records from primary care. Participants A million patient random sample from the UK CPRD primary care database, aged ≥16 years. Primary and secondary outcome measures BMI completeness in CPRD was evaluated by age, sex and calendar period. CPRD-based summary BMI statistics for each calendar year (2003–2010) were age-standardised and sex-standardised and compared with equivalent statistics from the Health Survey for England (HSE). Results BMI completeness increased over calendar time from 37% in 1990–1994 to 77% in 2005–2011, was higher among females and increased with age. When BMI at specific time points was assigned based on the most recent record, calendar–year-specific mean BMI statistics underestimated equivalent HSE statistics by 0.75–1.1 kg/m2. Restriction to those with a recent (≤3 years) BMI resulted in mean BMI estimates closer to HSE (≤0.28 kg/m2 underestimation), but excluded up to 47% of patients. An alternative strategy of imputing up-to-date BMI based on modelled changes in BMI over time since the last available record also led to mean BMI estimates that were close to HSE (≤0.37 kg/m2 underestimation). Conclusions Completeness of BMI in CPRD increased over time and varied by age and sex. At a given point in time, a large proportion of the most recent BMIs are unlikely to reflect current BMI; consequent BMI misclassification might be reduced by employing model-based imputation of current BMI.

Quantification of risk factors for postherpetic neuralgia in herpes zoster patients: A cohort study

Objective: To investigate risk factors for postherpetic neuralgia, the neuropathic pain that commonly follows herpes zoster. Methods: Using primary care data from the Clinical Practice Research Datalink, we fitted multivariable logistic regression models to investigate potential risk factors for postherpetic neuralgia (defined as pain ≥90 days after zoster, based on diagnostic or prescription codes), including demographic characteristics, comorbidities, and characteristics of the acute zoster episode. We also assessed whether the effects were modified by antiviral use. Results: Of 119,413 zoster patients, 6,956 (5.8%) developed postherpetic neuralgia. Postherpetic neuralgia risk rose steeply with age, most sharply between 50 and 79 years (adjusted odds ratio [OR] for a 10-year increase, 1.70, 99% confidence interval 1.63–1.78). Postherpetic neuralgia risk was higher in women (6.3% vs 5.1% in men: OR 1.19, 1.10–1.27) and those with severely immunosuppressive conditions, including leukemia (13.7%: 2.07, 1.08–3.96) and lymphoma (12.7%: 2.45, 1.53–3.92); autoimmune conditions, including rheumatoid arthritis (9.1%: 1.20, 0.99–1.46); and other comorbidities, including asthma and diabetes. Current and ex-smokers, as well as underweight and obese individuals, were at increased risk of postherpetic neuralgia. Antiviral use was not associated with postherpetic neuralgia (OR 1.04, 0.97–1.11). However, the increased risk associated with severe immunosuppression appeared less pronounced in patients given antivirals. Conclusions: Postherpetic neuralgia risk was increased for a number of patient characteristics and comorbidities, notably with age and among those with severe immunosuppression. As zoster vaccination is contraindicated for patients with severe immunosuppression, strategies to prevent zoster in these patients, which could include the new subunit zoster vaccine, are an increasing priority.

The impact of the conflicts of Iraq and Afghanistan: a UK perspective.

Abstract Concerns about the mental health of military personnel deployed to Iraq and Afghanistan has led to a new generation of research. This review is an examination of the UK literature on the mental health consequences of deployment of armed forces personnel to Iraq and Afghanistan. As yet, deployment to Iraq or Afghanistan has not been associated with a general increase in mental health problems for the UK Armed Forces. However, research has highlighted certain problems that continue to need to be addressed. Whilst, the rate of post-traumatic stress disorder (PTSD) is low in the UK Armed Forces (1.6–6%), deployment to Iraq or Afghanistan is associated with an increased risk of PTSD for reserve personnel. In contrast to PTSD, the rate of alcohol misuse is high in the UK Armed Forces (between 16–20%), and has been associated with deployment to Iraq or Afghanistan for regular personnel. As the UK military engagement in Afghanistan continues and more personnel are deployed, the demand for help from military health services, the NHS and the service charities will increase.

What are the effects of having an illness or injury whilst deployed on post deployment mental health? A population based record linkage study of UK army personnel who have served in Iraq or Afghanistan.

BackgroundThe negative impact of sustaining an injury on a military deployment on subsequent mental health is well-documented, however, the relationship between having an illness on a military operation and subsequent mental health is unknown.MethodsPopulation based study, linking routinely collected data of attendances at emergency departments in military hospitals in Iraq and Afghanistan [Operational Emergency Department Attendance Register (OpEDAR)], with data on 3896 UK Army personnel who participated in a military health study between 2007 and 2009 and deployed to Iraq or Afghanistan between 2003 to 2009.ResultsIn total, 13.8% (531/3896) of participants had an event recorded on OpEDAR during deployment; 2.3% (89/3884) were medically evacuated. As expected, those medically evacuated for an injury were at increased risk of post deployment probable PTSD (odds ratio 4.27, 95% confidence interval 1.80-10.12). Less expected was that being medically evacuated for an illness was also associated with a similarly increased risk of probable PTSD (4.39, 1.60-12.07) and common mental disorders (2.79, 1.41-5.51). There was no association between having an OpEDAR event and alcohol misuse. Having an injury caused by hostile action was associated with increased risk of probable PTSD compared to those with a non-hostile injury (3.88, 1.15 to 13.06).ConclusionsPersonnel sustaining illnesses on deployment are just as, if not more, at risk of having subsequent mental health problems as personnel who have sustained an injury. Monitoring of mental health problems should consider those with illnesses as well as physical injuries.