Association between disease activity and risk of serious infections in subjects with rheumatoid arthritis treated with etanercept or disease-modifying anti-rheumatic drugs.

OBJECTIVES: To determine the risk of serious infection in patients with rheumatoid arthritis (RA) receiving etanercept (ETN) or disease-modifying anti-rheumatic drugs (DMARDs) and to identify factors that predict a higher risk. METHODS: Five-year data from the British Society of Rheumatology Biologics Register (BSRBR), a prospective observational study of patients with active RA treated with ETN, were used. These data were compared with a cohort of patients receiving DMARDs with active RA. RESULTS: Total follow-up was 19,964 patient-years (py; ETN, 14,381 py; DMARDs, 5583 py). Over the study period, 651 first-recorded serious infections were reported (ETN, 469 [39.9 per 1000 py]; DMARDs, 182 [35.0 per 1000 py]). Overall the risk of serious infection was similar for the 2 treatments; however, in the first 6 months of treatment the hazard ratio (HR) was higher in the ETN than the DMARD group (1.979; p=0.015). A linear association was observed between the serious infection rate and disease-activity score in 28 joints (DAS28) in patients from each treatment group and overall (DAS28 <4, 27.1 per 1000 py; DAS28 ≥8, 64.4 per 1000 py; 7.5% increase in serious infection for each unit increase of DAS28 score at baseline). In a time-dependent analysis, a DAS28 change of 1 unit during follow-up predicted a 27% increase in serious infection rates. CONCLUSIONS: No significant increase in the risk of serious infection was observed with ETN versus DMARDs over the 5-year study; a linear relationship existed between the serious infection rate and disease activity, as measured by DAS28.

Women With Polycystic Ovary Syndrome Have an Increased Risk of Major Cardiovascular Events: a Population Study.

CONTEXT: The effects of polycystic ovary syndrome (PCOS) on cardiovascular morbidity and mortality are unclear. OBJECTIVE: This work aims to establish the relative risk of myocardial infarction (MI), stroke, angina, revascularization, and cardiovascular mortality for women with PCOS. METHODS: Data were extracted from the Clinical Practice Research Datalink Aurum database. Patients with PCOS were matched to controls (1:1) by age, body mass index (BMI) category, and primary care practice. The primary outcome was the time to major adverse cardiovascular event (MACE); a composite end point incorporating MI, stroke, angina, revascularization and cardiovascular mortality. Secondary outcomes were the individual MACE end points. RESULTS: Of 219 034 individuals with a diagnosis of PCOS, 174 660 (79.7%) met the eligibility criteria and were matched. Crude rates of the composite end point, MI, stroke, angina, revascularization, and cardiovascular mortality were respectively 82.7, 22.7, 27.4, 32.8, 10.5, and 6.97 per 100 000 patient-years for cases, and 64.3, 15.9, 25.7, 19.8, 7.13, and 7.75 per 100 000 patient-years for controls. In adjusted Cox proportional hazard models (CPHMs), the hazard ratios (HRs) were 1.26 (95% CI, 1.13-1.41), 1.38 (95% CI, 1.11-1.72), 1.60 (95% CI, 1.32-1.94), and 1.50 (95% CI, 1.08-2.07) for the composite outcome, MI, angina, and revascularization, respectively. In a time-dependent CPHM, weight gain (HR 1.01; 1.00-1.01), prior type 2 diabetes mellitus (T2DM) (HR 2.40; 1.76-3.30), and social deprivation (HR 1.53; 1.11-2.11) increased risk of progression to the composite end point. CONCLUSION: The risk of incident MI, angina, and revascularization is increased in young women with PCOS. Weight and T2DM are potentially modifiable risk factors amenable to intervention.

Polycystic Ovary Syndrome Is Associated With Adverse Mental Health and Neurodevelopmental Outcomes.

Context: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and subfertility, but the effects on mental health and child neurodevelopment are unclear. Objectives: To determine if (1) there is an association between PCOS and psychiatric outcomes and (2) whether rates of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are higher in children of mothers with PCOS. Design: Data were extracted from the Clinical Practice Research Datalink. Patients with PCOS were matched to two control sets (1:1) by age, body mass index, and primary care practice. Control set 2 was additionally matched on prior mental health status. Primary outcomes were the incidence of depression, anxiety, and bipolar disorder. Secondary outcomes were the prevalence of ADHD or ASD in the children. Results: Eligible patients (16,986) were identified; 16,938 and 16,355 were matched to control sets 1 and 2, respectively. Compared with control set 1, baseline prevalence was 23.1% vs 19.3% for depression, 11.5% vs 9.3% for anxiety, and 3.2% vs 1.5% for bipolar disorder (P < 0.001). The hazard ratio for time to each endpoint was 1.26 (95% confidence interval 1.19 to 1.32), 1.20 (1.11 to 1.29), and 1.21 (1.03 to 1.42) for set 1 and 1.38 (1.30 to 1.45), 1.39 (1.29 to 1.51), and 1.44 (1.21 to 1.71) for set 2. The odds ratios for ASD and ADHD in children were 1.54 (1.12 to 2.11) and 1.64 (1.16 to 2.33) for set 1 and 1.76 (1.27 to 2.46) and 1.34 (0.96 to 1.89) for set 2. Conclusions: PCOS is associated with psychiatric morbidity and increased risk of ADHD and ASD in their children. Screening for mental health disorders should be considered during assessment.

Contemporary Reproductive Outcomes for Patients With Polycystic Ovary Syndrome: A Retrospective Observational Study.

CONTEXT: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility and may be associated with adverse pregnancy and neonatal outcomes. However, it is difficult to establish how much of this risk is due to PCOS and how much to obesity. OBJECTIVE: This study aimed to determine the effect of PCOS upon fertility, pregnancy, and neonatal outcomes. DESIGN AND SETTING: Data were extracted from the Clinical Practice Research Datalink (CPRD), a longitudinal anonymized primary care research database in the United Kingdom. Patients with a diagnosis of PCOS were matched to controls (1:2) by age (±1 y), body mass index (± 3 U), and CPRD practice. Standardized fertility ratios before and after diagnosis (index date) were calculated. Rates of miscarriage, pre-eclampsia, gestational diabetes, premature delivery, delivery method, and neonatal outcomes were compared. RESULTS: Nine thousand sixty-eight women with PCOS matched study criteria. Prior to index date the standardized fertility ratio for patients with PCOS was 0.80 (95% confidence interval, 0.77­0.83); following index date it was 1.16 (1.12­1.20). The adjusted odds ratios (95% CI) for miscarriage (1.70; 1.56­1.84), pre-eclampsia (1.32; 1.16­1.49), gestational diabetes (1.41; 1.2­1.66), and premature delivery (1.25; 1.1­1.43) were all increased compared with controls. Of PCOS births, 27.7% were by Caesarean section compared with 23.7% of controls (1.13; 1.05­1.21). Infants born to mothers with PCOS had an increased risk of neonatal jaundice (1.20; 1.03­1.39) and respiratory complications (1.20; 1.06­1.37). CONCLUSIONS: PCOS is associated with subfertility but fertility rates are restored to those of the background population following diagnosis. Pregnancy complications and adverse neonatal outcomes are more prevalent for women with PCOS independently of obesity.

Evaluation of adverse outcome in young women with polycystic ovary syndrome versus matched, reference controls: a retrospective, observational study.

CONTEXT: Polycystic ovary syndrome (PCOS) is associated with insulin resistance, hyperandrogenism, and dyslipidemia, but the effects of these disturbances on long-term health are not fully understood. AIM: Our aim was to determine the relative risk of type 2 diabetes, cancer, large-vessel disease (LVD), and all-cause mortality for women diagnosed with PCOS. DESIGN: Data were extracted from the General Practice Research Database, a longitudinal, anonymized research database derived from nearly 600 primary-care practices in the United Kingdom. Patients with a diagnosis of PCOS between 1990 and 2010 were selected. Patients were matched to two sets of controls. The first set was matched according to primary-care practice and age, and the second was also matched on body mass index. Primary outcome was first incident record of diabetes. Crude rates for diabetes were presented, and time to diabetes was analyzed using Cox proportional hazard models. Secondary outcomes (cancer, LVD, and mortality) were also modeled. RESULTS: Of 53,303 identified with a diagnosis of PCOS, 21,740 (40.8%) met the eligibility criteria. Median follow-up was 4.7 yr (interquartile range = 2.0-8.6 yr) in those with PCOS and 5.8 yr (2.7-9.6) in the reference group. Crude rates of diabetes were 5.7 and 1.7 per 1000 patient-years for cases and controls, respectively. The corresponding adjusted hazard ratio was 3.015 (95% confidence interval = 2.733-3.327). Of cases matched by body mass index, crude rates of diabetes were 4.7 and 2.4 per 1000 patient-years, respectively. The corresponding adjusted hazard ratio was 1.752 (1.514-2.028). No significant difference in BMI-adjusted risk was evident for cancer, LVD, or all-cause mortality. CONCLUSIONS: During this follow-up period, women with PCOS were not at increased risk of LVD, cancer, or death, but they had increased risk of type 2 diabetes.

The impact of the overactive bladder on health-related utility and quality of life.

OBJECTIVE: To evaluate the impact of the overactive bladder (OAB) on quality of life and health-related utility. PATIENTS AND METHODS: In a study conducted in Cardiff and Vale NHS Trust, patients were identified from an academic urology unit inpatient database for admissions and sent a postal survey. The survey pack comprised questionnaires on demography, urological functioning, health utility (EQ5D(index)), and health-related quality of life (Short Form-36, SF36). Respondents were classified according to general urinary status, frequency, urgency, and stress incontinence. RESULTS: Of 2193 surveys dispatched, 609 (27.8%) were returned; of these patients, 52% had incontinence, of whom 83% had both frequency and urgency, and 60% stress incontinence. Patients with stress incontinence reported a mean (sd) EQ5D(index) of 0.578 (0.331), compared to 0.714 (0.281) for all other patients (P < 0.001). From the SF36, respondents scored lowest in the role physical domain and highest in the mental domain, with mean scores of 33.8 and 72.1, respectively. Multivariate analysis of SF36 and EQ5D(index) scores, controlling for age, gender and body mass index, showed that incontinence was associated with a notable reduction in the EQ5D(index) and SF36 scores across all domains. CONCLUSION: This study showed a significant reduction in quality of life for all patient groups with OAB; in particular, stress incontinence had the greatest impact.