Scientific
publications

OBJECTIVE: Irregular menstrual cycles are associated with increased cardiovascular mortality. Polycystic ovary syndrome (PCOS) is characterized by androgen excess and irregular menses; androgens are drivers of increased metabolic risk in women with PCOS. Combined oral contraceptive pills (COCPs) are used in PCOS both for cycle regulation and to reduce the biologically active androgen fraction. We examined COCP use and risk of dysglycemia (prediabetes and type 2 diabetes) in women with PCOS. RESEARCH DESIGN AND METHODS: Using a large U.K. primary care database (The Health Improvement Network [THIN]; 3.7 million patients from 787 practices), we carried out a retrospective population-based cohort study to determine dysglycemia risk (64,051 women with PCOS and 123,545 matched control subjects), as well as a nested pharmacoepidemiological case-control study to investigate COCP use in relation to dysglycemia risk (2,407 women with PCOS with [case subjects] and without [control subjects] a diagnosis of dysglycemia during follow-up). Cox models were used to estimate the unadjusted and adjusted hazard ratio, and conditional logistic regression was used to obtain adjusted odds ratios (aORs). RESULTS: The adjusted hazard ratio for dysglycemia in women with PCOS was 1.87 (95% CI 1.78-1.97, < 0.001; adjustment for age, social deprivation, BMI, ethnicity, and smoking), with increased rates of dysglycemia in all BMI subgroups. Women with PCOS and COCP use had a reduced dysglycemia risk (aOR 0.72, 95% CI 0.59-0.87). CONCLUSIONS: In this study, limited by its retrospective nature and the use of routinely collected electronic general practice record data, which does not allow for exclusion of the impact of prescription-by-indication bias, women with PCOS exposed to COCPs had a reduced risk of dysglycemia across all BMI subgroups. Future prospective studies should be considered for further understanding of these observations and potential causality.

BACKGROUND: Parkinson's disease (PD) is associated with increased mortality, but little is known about changes over time, and relationship to disease progression. OBJECTIVES: To explore how PD mortality rates have changed over time and their relationship to disease duration and demographics using a large population-based cohort in the UK. METHODS: We included individuals aged 50+ years with a first recording of PD diagnosis and at least two prescriptions of any antiparkinsonian drug actively registered within a general practice from 2006 to 2016 and up to six frequency-matched controls from The Health Improvement Network (THIN) database. We estimated adjusted mortality rates using multivariable Poisson regression. RESULTS: A total of 10,104 people with a diagnosis of PD and 55,664 people without PD were included. Overall, PD was associated with slightly increased mortality compared to non-PD controls (adjusted mortality rate ratio: 1.14; 95% CI: 1.03 to 1.19). Adjusted mortality rates per 1000 person-years at risk for people with PD approximately doubled in the 5 years following diagnosis from 43 (95% CI: 38 to 48) to 75 (95% CI: 64 to 85). Following adjustments for age, gender, and time since diagnosis, mortality rates between 2007 and 2016 declined more slowly for people with PD (2% per year; 95% CI: 0%-4%) compared to people without PD (5% per year; 95% CI: 3%-6%). CONCLUSIONS: Whilst mortality in PD is only slightly increased overall, it gradually increases with advancing disease. There has been a decline in mortality in PD over time, but this decrease was less pronounced than that in the general population. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

PURPOSE: The purpose of this study was to develop and validate a prediction model for 90-day mortality following a total knee replacement (TKR). TKR is a safe and cost-effective surgical procedure for treating severe knee osteoarthritis (OA). Although complications following surgery are rare, prediction tools could help identify high-risk patients who could be targeted with preventative interventions. The aim was to develop and validate a simple model to help inform treatment choices. METHODS: A mortality prediction model for knee OA patients following TKR was developed and externally validated using a US claims database and a UK general practice database. The target population consisted of patients undergoing a primary TKR for knee OA, aged ≥ 40 years and registered for ≥ 1 year before surgery. LASSO logistic regression models were developed for post-operative (90-day) mortality. A second mortality model was developed with a reduced feature set to increase interpretability and usability. RESULTS: A total of 193,615 patients were included, with 40,950 in The Health Improvement Network (THIN) database and 152,665 in Optum. The full model predicting 90-day mortality yielded AUROC of 0.78 when trained in OPTUM and 0.70 when externally validated on THIN. The 12 variable model achieved internal AUROC of 0.77 and external AUROC of 0.71 in THIN. CONCLUSIONS: A simple prediction model based on sex, age, and 10 comorbidities that can identify patients at high risk of short-term mortality following TKR was developed that demonstrated good, robust performance. The 12-feature mortality model is easily implemented and the performance suggests it could be used to inform evidence based shared decision-making prior to surgery and targeting prophylaxis for those at high risk. LEVEL OF EVIDENCE: III.

Intimate partner violence (IPV) is a global public health issue with a variety of ill health consequences associated with exposure. Due to the stimulation of chronic stress and inflammatory pathways, childhood abuse has been associated with the subsequent development of functional syndromes such as fibromyalgia and chronic fatigue syndrome (CFS). Although IPV in women appears to elicit similar biochemical responses, this association has not been tested thoroughly in IPV survivors. These functional syndromes are complex in etiology and any indication of their risk factors would benefit health care professionals managing this population. Therefore, we aimed to investigate the association between exposure to IPV with functional syndromes: fibromyalgia and CFS. We conducted a retrospective open cohort study using "The Heath Improvement Network" database between January 1, 1995 and December 1, 2017. A total of 18,547 women who were exposed to IPV were each matched by age to four controls who were not exposed ( = 74,188). The main outcome measures were the risk of developing fibromyalgia and CFS. These were presented as adjusted incidence rate ratios (aIRR) with 95% confidence intervals (CIs). We found that 97 women in the exposed group developed fibromyalgia (incidence rate [IR] = 1.63 per 1,000 person-years) compared to 239 women in the unexposed group (IR = 0.83 per 1,000 person-years). Following adjustment, this translated to an IRR of 1.73 (95% CI = [1.36, 2.22]). Similarly, 19 women developed CFS in the exposed group (IR = 0.32 per 1,000 person-years), compared to 53 in the unexposed group (0.18 per 1,000 person-years), which translates to an aIRR of 1.92 (95% CI = [1.11, 3.33]). Therefore, we have identified an association between a history of IPV in women and the development of these functional syndromes, which may provide more information to inform the biopsychosocial pathway precipitating the development of fibromyalgia and CFS.

BACKGROUND: Faecal calprotectin (FC) testing to detect inflammatory bowel disease (IBD) was recommended for use in UK general practice in 2013. The actual use of FC testing following the national recommendations is unknown. AIM: To characterise the use of FC testing for IBD in UK general practice. DESIGN AND SETTING: A retrospective cohort study of routine electronic patient records from The Health Improvement Network database from UK general practice. METHOD: The study included 6 965 853 adult patients (aged ≥18 years), between 2006 and 2016. FC test uptake, the patients tested, and patient management following testing were characterised. RESULTS: A total of 17 027 patients had 19 840 FC tests recorded. The mean age of tested patients was 44.2 years. The first FC tests were documented in 2009. FC test use was still increasing in 2016. By 2016, 66.8% ( = 493/738) of practices had started FC testing. About one-fifth (20.7%, = 1253/6051) of tests were carried out in patients aged ≥60 years. Only 7.8% ( = 473/6051) of the FC test records were preceded by symptoms eligible for FC testing. Only 3.1% ( = 1720/55 477) of patients with eligible symptoms have received FC testing since the national recommendations were published. There was only a small number of patients with symptoms, FC test, and a IBD diagnosis. In total, 71.3% ( = 1416/1987) of patients with a positive and 47.7% ( = 1337/2805) with a negative FC test were referred or further investigated. CONCLUSION: Uptake of FC testing in clinical practice has been slow and inconsistent. The indication of non-compliance with national recommendations may suggest that these recommendations lack applicability to the general practice context.

INTRODUCTION: While the etiopathogenesis of functional gastrointestinal disorders (FGIDs) is not completely understood, alterations of the intestinal microbiome have been observed. Antibiotics can induce dysbiosis, but whether antibiotics are a risk factor for the onset of FGIDs is uncertain. Antibiotics have been reported as both a risk factor for new onset FGID but also as a therapy for existing FGID. This study aimed to estimate the fraction of cases where antibiotics provoked the onset of FGID. METHOD: Electronic medical records were obtained from general practices (primary care) in the United Kingdom. Dates of antibiotic prescription (AP) were compared with first date of FGID diagnosis and contrasted across three prevalent FGIDs and controls without gastrointestinal disorders. RESULTS: There were 10,926 GI healthy controls, 4326 IBS alone, 3477 FD alone, 340 chronic constipation and 4402 with overlap of multiple conditions. Both the prevalence of AP and rate were higher in FGID patients and increased with diagnosis of multiple FGIDs. 7%-14% of FGID patients were prescribed their first recorded antibiotic in the 12 months prior to their first FGID diagnosis and 20%-33% were prescribed an antibiotic in the same period. Differences between FGID groups were not accounted for by social deprivation and only rate of AP was moderated by social deprivation. In contrast, only 5%-10% of patients ever had a gastrointestinal infection recorded and only 1.5%-3.5% prior to their first FGID diagnosis. CONCLUSION: These data indicate that antibiotics are prescribed prior to FGID diagnosis in a significant minority of care-seeking FGID patients, opening the potential for this medication to contribute to the pathophysiology. APs appears to mostly be for non-gastrointestinal conditions.

OBJECTIVE: A regional 'Be Clear on Cancer' (BCoC) campaign developed by Public Health England aimed to promote public awareness of key abdominal cancer symptoms in people aged 50 years and over. METHODS: Data were analysed for metrics at different stages in the patient care pathway including public awareness, GP attendance and referrals, to cancer diagnosis. RESULTS: There was significantly higher recognition of the BCoC abdominal campaign in the campaign region compared to the control area (Post Campaign/Control, n = 401/406; 35% vs. 24%, p < 0.05). The campaign significantly improved knowledge of 'bloating' as a symptom (p = 0.03) compared to pre-campaign levels. GP attendances for abdominal symptoms increased significantly by 5.8% (p = 0. 03), although the actual increase per practice was small (average 16.8 visits per week in 2016 to 17.7 in 2017). Urgent GP referrals for suspected abdominal cancer increased by 7.6%, compared to a non-significant change (0.05%) in the control area. For specific abdominal cancers, the number diagnosed were similar to or higher than the median in the campaign area but not in the control area in people aged 50 and over: colorectal (additional n = 61 cancers), pancreatic (additional n = 102) and stomach cancers (additional n = 17). CONCLUSIONS: This campaign had a modest impact on public awareness of abdominal cancer symptoms, GP attendances and cancers diagnosed.

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.

BACKGROUND AND AIMS: The effect of major depression and antidepressant use on patient survival in chronic liver disease is unknown. We evaluated the impact of major depressive disorder (MDD) and antidepressants on survival among patients with alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). METHODS: The Health Improvement Network database, the largest medical database in the United Kingdom, was used to identify incident ALD (n = 4148) and NAFLD (n = 19 053) in patients between 1986 and 2017. Our primary outcome was development of decompensated cirrhosis or death. MDD and each class of antidepressants were assessed in multivariate Cox proportional hazards models as time-varying covariates. Models were adjusted for age, sex, socio-economic status and comorbidities. RESULTS: MDD rate was higher among patients with ALD (22.8%) compared to those with NAFLD (16.1%), P < .01. Antidepressant usage was common in patients with ALD (47.4%) and NAFLD (40.8%). After adjusting for covariates, MDD (adjusted hazard ratio [AHR]: 0.80, 95% CI: 0.63-1.02 for NAFLD; and AHR 1.01, 0.88-1.15 for ALD) was not associated with improved decompensated cirrhosis-free survival. The antidepressant mirtazapine was associated with worse decompensated cirrhosis-free survival among NAFLD (AHR 2.16, 95% CI: 1.32-3.52) and ALD (AHR 1.53, 1.09-2.15) cohorts. Similarly, mirtazapine was associated with mortality in both cohorts. CONCLUSIONS: MDD was not associated with worse outcomes for ALD or NAFLD. Mirtazapine was associated with an increased risk of decompensated cirrhosis or death, which was not observed with other antidepressants. Prospective studies are warranted to confirm these findings.

OBJECTIVES: There is still a large unmet need for novel osteoarthritis (OA) treatments that could provide clinically important effects on long-term pain relief (≥12 months). We examined the relation of bariatric surgery along with weight loss to analgesic prescription and all-cause mortality among individuals with OA. METHODS: We conducted a cohort study among individuals with OA using The Health Improvement Network. We compared the rate of no analgesic prescription ≥12 consecutive months and the risk of all-cause mortality using inverse probability weighting Cox-proportional hazard models and the difference in number of analgesic prescriptions (non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in the 50 , 75 and 90 percentiles using quantile regression model between bariatric and non-bariatric cohorts. RESULTS: Included were 588,494 individuals (694 had bariatric surgery). Compared with non-bariatric group, the rate of no analgesic prescription ≥12 consecutive months was higher (HR = 1.23, 95% CI: 1.08-1.38) in bariatric surgery group, and the number of analgesic prescriptions was lower in the 75 (44 vs 58) and 90 (74 vs 106) percentiles during a mean follow-up of 4.3 years. All-cause mortality in bariatric surgery group was lower than comparison group (HR = 0.46, 95% CI: 0.41-0.51). CONCLUSION: This study presents the first evidence that bariatric surgery was associated with decreased long-term analgesic prescription and decreased all-cause mortality among individuals with OA. However, our findings may be overestimated owing to intractable confounding by indication for bariatric surgery; thus, future studies (e.g., clinical trials) are warranted.