The risk of acute infections in new users of antidepressants: An observational cohort study.

BACKGROUND: Preclinical studies suggested that drugs that functionally inhibit acid sphingomyelinase (FIASMA)may enhance immune cell longevity and potentially offer protection against infections. Many antidepressants have shown FIASMA activity. METHODS: We conducted a cohort study using primary-care data from the UK-based Clinical Practice Research Datalink (2000-2021). We assessed the association of composite diagnosed acute infections in new users of fluoxetine, sertraline, paroxetine, or venlafaxine aged 18-80 years compared to citalopram. We compared SARS-CoV-2 infections between groups in a secondary analysis. We estimated incidence rates (IR) and IR ratios (IRR) of acute infections in four pairwise comparisons using negative binomial regression. We applied propensity score (PS) fine stratification to control for confounding. RESULTS: In the PS-weighted cohorts, we included 353,138 fluoxetine, 222,463 sertraline, 69,963 paroxetine, 32,608 venlafaxine, and between 515,996 and 516,583 new citalopram users. PS-weighted IRs ranged between 76.8 acute infections /1000 person-years (py) (sertraline) and 98.9 infections/1000 py (citalopram). We observed PS-weighted IRRs around unity for paroxetine (0.97, 95 % CI, 0.95-1.00), fluoxetine (0.94, 95 % CI, 0.92-0.95), and venlafaxine (0.90, 95 % CI, 0.87-0.94) vs citalopram. Reduced IRR for sertraline vs citalopram (0.84, 95 % CI, 0.82-0.85), became null within subgroups by cohort entry date. In the analysis of SARS-CoV-2 infection, no statistically relevant risk reduction was seen. LIMITATIONS: Analysis not limited to patients with diagnosed depression, possible underestimation of infection incidence, and unclear FIASMA activity of citalopram. CONCLUSIONS: Fluoxetine, sertraline, paroxetine, and venlafaxine were not associated with a reduced risk of acute infection when compared with the presumably weak FIASMA citalopram.

Risk of skin cancer in new users of thiazides and thiazide-like diuretics: a cohort study using an active comparator group.

BACKGROUND: Case-control studies report a dose-dependent increased risk of skin cancer in users of hydrochlorothiazide (HCTZ) vs. nonusers. The degree to which other thiazides and thiazide-like diuretics (TZs) are associated with skin cancer is less certain. OBJECTIVES: To assess the risk of skin cancer in new users of different TZs compared with new users of calcium channel blockers (CCBs). METHODS: We conducted a cohort study using a UK primary-care database (1998-2017), including 271 154 new TZ users [87·6% bendroflumethiazide (BFT), 5·8% indapamide and 3·6% HCTZ] and 275 263 CCB users. The outcomes were basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and cutaneous malignant melanoma (CMM). We estimated incidence rates (IRs) and IR ratios (IRRs) in short-term (< 20 prescriptions) and long-term (≥ 20 prescriptions) users of TZs and CCBs using negative binomial regression, and calculated rate differences (RDs) for selected results. We used fine stratification on the propensity score (PS) to control for 23 baseline covariates. RESULTS: Long-term use of HCTZ increased absolute and relative risks of SCC [PS-weighted IRR 1·95; 95% confidence interval (CI) 1·87-2·02; RD per 100 000 person-years 87.4], but not of BCC or CMM. Long-term use of indapamide was associated with an increased incidence of CMM (IRR 1·43; 95% CI 1·35-1·50). BFT was not meaningfully associated with the risk of any type of skin cancer. CONCLUSIONS: Our results corroborate the previously reported increased risk of SCC (but not of BCC or CMM) for long-term use of HCTZ. BFT may be a safer alternative for patients at increased risk of skin cancer.

Infections in patients diagnosed with multiple sclerosis: A multi-database study.

BACKGROUND: Recent data on the rates of infections among patients with multiple sclerosis (MS) are sparse. The objective of this study was to quantify incidence of infections in patients with MS compared with a matched sample of patients without MS (non-MS). METHODS: This study was conducted in two separate electronic medical databases: the United States Department of Defense (US-DOD) military health care system and the United Kingdom's Clinical Practice Research Datalink GOLD (UK-CPRD). We identified patients with a first recorded diagnosis of MS between 2001 and 2016 (UK-CPRD) or 2004 and 2017 (US-DOD) and matched non-MS patients. We identified infections recorded after the MS diagnosis date (or the matched date in non-MS patients) and calculated incidence rates (IRs) and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) by infection site and type. RESULTS: Relative to non-MS patients, MS patients had higher rates of any infection (US-DOD IRR 1.76; 95% CI 1.72-1.80 and UK-CPRD IRR 1.25; 95% CI 1.21-1.29) and a two-fold higher rate of hospitalized infections (US-DOD IRR 2.43; 95% CI 2.23-2.63 and UK-CPRD IRR 2.00; 95% CI 1.84-2.17). IRs of any infection were higher in females compared with males in both MS and non-MS patients, while IRs of hospitalized infections were similar between sexes in both MS and non-MS patients. The IR of first urinary tract or kidney infection was nearly two-fold higher in MS compared with non-MS patients (US-DOD IRR 1.88; 95% CI 1.81-1.95 and UK-CPRD IRR 1.97; 95% CI 1.86-2.09) with higher rates in females compared with males. IRs for any opportunistic infection, candidiasis and any herpes virus were increased between 20 and 52% among MS patients compared with non-MS patients. IRs of meningitis, tuberculosis, hepatitis B and C were all low. CONCLUSION: MS patients have an increased risk of infection, notably infections of the renal tract, and a two-fold increased risk of hospitalized infections compared with non-MS patients.

Hyperlipidaemia and incident osteoarthritis of the hand: a population-based case-control study.

OBJECTIVE: Preclinical evidence suggests that increased cholesterol levels might be involved in the pathophysiology of osteoarthritis of the hand (HOA), but evidence from observational studies remains scarce. We aimed to analyse the association between hyperlipidaemia and incident HOA. DESIGN: We conducted a matched (1:1) case-control study using the UK-based Clinical Practice Research Datalink (CPRD). Cases were patients aged 30-89 years with an incident diagnosis of HOA between 1995 and 2014. In multivariable conditional logistic regression analyses, we calculated odds ratios (OR) for incident HOA in patients with hyperlipidaemia, categorized by gender, age, previous duration of hyperlipidaemia, and recent statin treatment. RESULTS: Among 19,590 cases and 19,590 controls, we observed an increased risk of HOA in patients with hyperlipidaemia (OR 1.37, 95% confidence intervals (CI) 1.28-1.47), when compared to patients without hyperlipidaemia. Thus, of all HOA cases in our study population, 3.6% may have been attributable to the presence of hyperlipidaemia (population attributable risk). Most patients with HOA were elderly, but the strength of the association between HOA and hyperlipidaemia inversely correlated with increasing age, with the highest OR of 1.72 (95% CI 1.24-2.38) in patients aged 29-49 years. Categorization by previous hyperlipidaemia duration, as well as sub-classification of patients with hyperlipidaemia into those with and without recent statin use did not meaningfully change the effect estimate. CONCLUSIONS: Our results suggest that hyperlipidaemia may be an independent risk factor for new onset HOA.

Antibiotic use during pregnancy and asthma in preschool children: the influence of confounding.

BACKGROUND: A recent study suggested that early-life intestinal microbiota may play an important role in the development of childhood asthma, indicating that antibiotics taken during early life or in late pregnancy may be associated with childhood asthma. OBJECTIVE: This study aims to assess the association between prenatal antibiotic use and asthma in preschool children using data from the prescription database IADB.nl. To assess the influence of potential confounding, we conducted both a case-sibling and a case-control study and compared the results. METHODS: We conducted a case-sibling study in which 1228 children with asthma were compared to 1228 siblings without asthma, using data from the prescription database IADB.nl. In addition, a case-control study was conducted. Asthma in preschool children was defined as ≥ 3 prescriptions for anti-asthma medication within a year before the fifth birthday. Conditional logistic regression was used to estimate crude and adjusted odds ratios (aORs). RESULTS: In both the case-sibling and case-control analysis, the use of antibiotics in the third trimester of pregnancy was associated with an increased risk of asthma in preschool children (aOR 1.37; 95% CI 1.02-1.83 and aOR 1.40; 95% CI 1.15-1.47). Time-trend analyses showed that results were not influenced by a time trend in antibiotic exposure. A significant association between exposure to antibiotics in any trimester of pregnancy and the development of asthma in preschool children was observed in the case-control analysis only (aOR 1.46; 95% CI 1.34-1.59). CONCLUSION: Antibiotic use in the third trimester of pregnancy was associated with a small increased risk of asthma in preschool children. This association was robust to time-invariant confounding or exposure time trends, further supporting the important role for early-life intestinal microbiota in the development of childhood asthma.

Type II diabetes mellitus and incident osteoarthritis of the hand: a population-based case-control analysis.

OBJECTIVES: Emerging evidence suggests that diabetes may be a risk factor for osteoarthritis (OA). However, previous results on the association between diabetes and all OA were conflicting. We aimed to comprehensively analyse the association between type II diabetes mellitus (T2DM) and osteoarthritis of the hand (HOA) specifically. METHODS: We conducted a matched (1:1) case-control study using the UK-based Clinical Practice Research Datalink (CPRD) of cases aged 30-90 years with an incident diagnosis of HOA from 1995 to 2013. In multivariable conditional logistic regression analyses, we calculated odds ratios (OR) for incident HOA in patients with T2DM, categorized by T2DM severity (HbA1C), duration, and pharmacological treatment. We further performed sensitivity analyses in patients with and without other metabolic diseases (hypertension (HT), hyperlipidaemia (HL), obesity). RESULTS: Among 13,500 cases and 13,500 controls, we observed no statistically significant association between T2DM and HOA (OR 0.95, 95% confidence interval (CI) 0.87-1.04), regardless of T2DM severity, duration, or pharmacological treatment. Having HT did not change the OR. Although we observed slightly increased ORs in overweight T2DM patients with co-occurring HL with or without coexisting HT, none of these ORs were statistically significant. CONCLUSIONS: Our results provide evidence that T2DM is not an independent risk factor for HOA. Concurrence of T2DM with HT, HL, and/or obesity did not change this association significantly.

Intrauterine device use and the risk of pre-eclampsia: a case-control study.

OBJECTIVE: To determine the association between intrauterine device (IUD) use, timing of removal prior to pregnancy, and the risk of pre-eclampsia. DESIGN: A case-control study within the Clinical Practice Research Datalink, UK. SETTING: Medical record database in the UK. SAMPLE: Cases of pre-eclampsia (n = 2744) were identified among pregnancies resulting in singleton deliveries from 1993 to 2010. Four controls, or pregnancies unaffected by pre-eclampsia, were matched to each case on maternal age, general practice, and year of delivery. METHODS: Data on IUD use were obtained from patient records. The odds ratios (ORs) for the association between IUD and pre-eclampsia were adjusted for covariates identified a priori, and analyses were stratified by BMI and number of prior deliveries. MAIN OUTCOME MEASURES: Odds ratios (95% confidence intervals, 95% CIs) of pre-eclampsia in pregnancies among women with a history of IUD use, compared with women without a history of IUD use. RESULTS: Prior IUD use was associated with a reduced risk of pre-eclampsia (OR 0.76; 95% CI 0.58-0.98). The timing of removal in relation to the start of pregnancy showed an inverse association, with shorter intervals associated with a larger decrease in risk of pre-eclampsia. IUD removal within a year prior to pregnancy had an OR of 0.68 (95% CI 0.46-1.00). Among women with a prior delivery, the association between IUD use and pre-eclampsia was null. CONCLUSIONS: Intrauterine device use is associated with a small decreased risk of pre-eclampsia, specifically if removed within the year prior to conception. TWEETABLE ABSTRACT: A case-control study of pregnancies in the UK suggests a reduced risk of pre-eclampsia for former IUD users.

Trends in incidence and medical resource utilisation in patients with chronic lymphocytic leukaemia: insights from the UK Clinical Practice Research Datalink (CPRD).

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in European adults. We aimed to evaluate time trends in CLL incidence and medical resource utilisation of CLL patients in the UK. We conducted a retrospective, observational cohort analysis using the UK Clinical Practice Research Datalink (CPRD) comprising mainly primary care data. We included adult patients with newly diagnosed CLL between January 2000 and June 2012. Descriptive and trend analyses of CLL incidence and medical resource utilisation were performed. A total of 2576 patients with CLL met the eligibility criteria. At diagnosis, the majority of patients (71.7 %) were above 65 years of age. The European age-standardised CLL incidence rate in the CPRD was 6.2/100,000 (95 % confidence interval [CI] 6.0, 6.5/100,000) person-years. There was no statistically significant increase over time. The CLL patients had on average 74.6 general practitioner visits during a median follow-up of 3.3 years. Between 2000 and 2012, the average number of recorded hospitalisations and referrals per year corrected for duration of follow-up significantly (p < 0.001) increased by 8.1 % (95 % CI 6.8 %, 9.3 %) and 16.4 % (95 % CI 15.4 %, 17.3 %), respectively. Referrals and hospitalisations in the second year compared to the first year following the CLL diagnosis significantly decreased. CLL incidence rates in the CPRD were stable over the period from 2000 to 2012. Medical resource utilisation in UK primary care was well documented, but further research is needed to describe secondary and tertiary care medical resource utilisation e.g. chemotherapy administration, which is inadequately captured in the CPRD.

Previously diagnosed influenza infections and the risk of developing epilepsy.

Several epidemiological studies suggest a possible involvement of viral infection in the development of epilepsy. While recent research from in vitro studies increasingly supports the role of herpes simplex virus type 1 (HSV-1) in the pathogenesis of epilepsy, little is known about the role of other viral infections such as influenza. Using data from the Clinical Practice Research Datalink (CPRD), we conducted a matched case-control analysis to assess the association between GP-diagnosed influenza infections and the risk of developing an incident diagnosis of epilepsy. During the study period 11 244 incident epilepsy cases and 44 976 matched control patients were identified. Prior exposure to influenza was reported in 7·5% of epilepsy cases and 6·7% of controls [adjusted odds ratio (aOR) 1·12, 95% confidence interval (CI) 1·03-1·22]. Prior history of 'complicated influenza', i.e. influenza associated with a possible super-infection, was associated with a slightly increased epilepsy risk (aOR 1·64, 95% CI 1·10-2·46), particularly if recorded within the 2 months preceding the epilepsy diagnosis (aOR 6·03, 95% CI 1·10-33·2). Our findings suggest that prior influenza exposure does not appear to materially alter the risk of developing epilepsy. By contrast, influenza episodes accompanied by complications were associated with a slightly increased epilepsy risk.

Metformin and the risk of head and neck cancer: a case-control analysis.

AIMS: Metformin use has been associated with a decreased risk of some cancers, although data on head and neck cancer (HNC) are scarce. We explored the relation between the use of antidiabetic drugs and the risk of HNC. METHODS: We conducted a case-control analysis in the UK-based Clinical Practice Research Datalink (CPRD) of people with incident HNC between 1995 and 2013 below the age of 90 years. Six controls per case were matched on age, sex, calendar time, general practice and number of years of active history in the CPRD prior to the index date. Other potential confounders including body mass index (BMI), smoking, alcohol consumption and comorbidities were also evaluated. The final analyses were adjusted for BMI, smoking and diabetes mellitus (or diabetes duration in a sensitivity analysis). Results are presented as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Use of metformin was neither associated with a statistically significant altered risk of HNC overall (1-29 prescriptions: adjusted OR 0.87, 95% CI 0.61-1.24 and ≥ 30 prescriptions adjusted OR 0.80, 95% CI 0.53-1.22), nor was long-term use of sulphonylureas (adjusted OR 0.87, 95% CI 0.59-1.30), or any insulin use (adjusted OR 0.92, 95% CI 0.63-1.35). However, we found a (statistically non-significant) decreased risk of laryngeal cancer associated with long-term metformin use (adjusted OR 0.41, 95% CI 0.17-1.03). CONCLUSIONS: In this population-based study, the use of antidiabetic drugs was not associated with a materially altered risk of HNC. Our data suggest a protective effect of long-term metformin use for laryngeal cancer.

Mortality of patients with multiple sclerosis: a cohort study in UK primary care.

We aimed to estimate rates, causes and risk factors of all-cause mortality in a large population-based cohort of multiple sclerosis (MS) patients compared with patients without MS. Using data from the UK General Practice Research Database, we identified MS cases diagnosed during 2001-2006 and validated using patients' original records where possible. We also included MS cases during 1993-2000 identified and validated in an earlier study. Cases were matched to up to ten referents without MS by age, sex, index date (date of first MS diagnosis for cases and equivalent reference date for controls), general practice and length of medical history before first MS diagnosis. Patients were followed up to identify deaths; hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox-proportional regression. MS patients (N = 1,822) had a significantly increased risk of all-cause mortality compared with referents (N = 18,211); adjusted HR 1.7 (95 % CI 1.4-2.1). Compared with referents, female MS patients had a higher but not significantly different HR for death than males; adjusted HR 1.86 (95 % CI 1.46-2.38) vs. HR 1.31 (95 % CI 0.93-1.84), respectively. The most commonly recorded cause of death in MS patients was 'MS' (41 %), with a higher proportion recorded among younger patients. A significantly higher proportion of referents than MS patients had cancer recorded as cause of death (40 vs. 19 %). Patients with MS have a significant 1.7-fold increased risk of all-cause mortality compared with the general population. MS is the most commonly recorded cause of death among MS patients.

Epidemiology of basal cell carcinoma in the United Kingdom: incidence, lifestyle factors, and comorbidities.

BACKGROUND: Little is known about the epidemiology of basal cell carcinoma (BCC). METHODS: Using the Clinical Practice Research Datalink, we calculated annual incidence rates. In a case-control analysis, we examined lifestyle factors and comorbidities. RESULTS: Incidence rose significantly between 2000 and 2011. Basal cell carcinoma risk was increased in alcohol drinkers (slightly) and immunocompromised patients, but reduced in smokers and individuals with abnormal weight. CONCLUSIONS: Basal cell carcinoma places a growing public health burden. Lifestyle factors do not play a major role in pathogenesis, but immunosuppression is important.

Incidence of and risk factors for severe hypoglycaemia in treated type 2 diabetes mellitus patients in the UK--a nested case-control analysis.

AIMS: To assess incidence rates (IRs) of and identify risk factors for incident severe hypoglycaemia in patients with type 2 diabetes newly treated with antidiabetic drugs. METHODS: Using the UK-based General Practice Research Database, we performed a retrospective cohort study between 1994 and 2011 and a nested case-control analysis. Ten controls from the population at risk were matched to each case with a recorded severe hypoglycaemia during follow-up on general practice, years of history in the database and calendar time. Using multivariate conditional logistic regression analyses, we adjusted for potential confounders. RESULTS: Of 130,761 patients with newly treated type 2 diabetes (mean age 61.7 ± 13.0 years), 690 (0.5%) had an incident episode of severe hypoglycaemia recorded [estimated IR 11.97 (95% confidence interval, CI, 11.11-12.90) per 10,000 person-years (PYs)]. The IR was markedly higher in insulin users [49.64 (95% CI, 44.08-55.89) per 10,000 PYs] than in patients not using insulin [8.03 (95% CI, 7.30-8.84) per 10,000 PYs]. Based on results of the nested case-control analysis increasing age [≥ 75 vs. 20-59 years; adjusted odds ratio (OR), 2.27; 95% CI, 1.65-3.12], cognitive impairment/dementia (adjusted OR, 2.00; 95% CI, 1.37-2.91), renal failure (adjusted OR, 1.34; 95% CI, 1.04-1.71), current use of sulphonylureas (adjusted OR, 4.45; 95% CI, 3.53-5.60) and current insulin use (adjusted OR, 11.83; 95% CI, 9.00-15.54) were all associated with an increased risk of severe hypoglycaemia. CONCLUSIONS: Severe hypoglycaemia was recorded in 12 cases per 10,000 PYs. Risk factors for severe hypoglycaemia included increasing age, renal failure, cognitive impairment/dementia, and current use of insulin or sulphonylureas.

Antihypertensive drugs and the risk of incident rosacea.

BACKGROUND: Despite scarce evidence, use of calcium channel blockers is discouraged in patients with rosacea, whereas beta-blockers are recommended as an off-label treatment for erythematotelangiectatic rosacea. OBJECTIVES: To study the association of the use of calcium channel blockers, beta-blockers and other antihypertensive drugs with incident rosacea. METHODS: We conducted a matched case-control study of antihypertensive drugs and incident rosacea, using the U.K.-based General Practice Research Database. Cases had an incident diagnosis of rosacea recorded between 1995 and 2009. Each case was matched to one control on age, sex, general practice and years of history on the database before the index date. Drug use was stratified by timing (≤ or > 180 days before the index date) and duration (number of prescriptions) of drug exposure, in a multivariate conditional logistic regression model. RESULTS: Among 53 927 cases and 53 927 controls, we observed odds ratios (ORs) around unity for calcium channel blockers across all strata, with a slightly decreased OR of 0·77 (95% CI 0·69-0·86) for current users of dihydropyridine calcium channel blockers with ≥ 40 prescriptions. Among beta-blockers, atenolol and bisoprolol yielded slightly decreased ORs across all exposure strata, whereas propranolol revealed ORs around 1·0, irrespective of timing and duration of exposure. Neither angiotensin-converting-enzyme inhibitors nor angiotensin receptor blockers altered the relative rosacea risk. CONCLUSIONS: Our data contradict the prevailing notion that calcium channel blockers increase the risk of rosacea. Beta-blocker use was associated with a slightly decreased risk of rosacea, but the effect may be somewhat stronger in patients with erythematotelangiectatic rosacea.

Prenatal exposure to acid-suppressive drugs and the risk of allergic diseases in the offspring: a cohort study.

BACKGROUND: Recent studies reported increased risks for the development of asthma in children after prenatal exposure to acid-suppressive drugs. As a result of common pathogenesis, associations could also be present for other allergic diseases. METHODS: Using the prescription database IADB.nl, we conducted a cohort study amongst 33 536 children in the Netherlands, with a maximum follow-up of 8 years. Maternal exposure was defined as ≥1 dispensed prescription for proton pump inhibitors (PPIs) and/or Histamine 2-antagonists (H2As) during pregnancy. Children were considered to have a drug-treated allergic disease if they received either ≥2 prescriptions for dermal (atopic dermatitis), inhaled (asthma) or nasal (allergic rhinitis) steroids within a 12-month period. Clustered Cox proportional hazard regression was used to estimate crude and adjusted hazard ratios (aHR) with 95% confidence intervals (95% CI). RESULTS: The aHR for the development of any allergic disease was 1.37 (95% CI: 1.14-1.66) for children exposed to PPIs or H2As. Prenatal exposure to PPIs and/or H2As was associated with atopic dermatitis, asthma and allergic rhinitis with aHRs of 1.32 (95% CI 1.06-1.64), 1.57 (95% CI 1.20-2.05) and 2.40 (95% CI 1.42-4.04), respectively. The aHR for the development of two or more (aHR 2.13 95% CI: 1.43-3.19) and three allergic diseases (aHR 5.18 95% CI: 2.16-12.42) were even more elevated after prenatal exposure to PPIs or H2As. CONCLUSION: Prenatal exposure to PPIs and H2As appeared associated with an increased risk for the development of atopic dermatitis, asthma and allergic rhinitis in the offspring, especially with the development of multiple allergic diseases. Because our study has limitations inherent to observational studies, prospective studies are now warranted to confirm our findings.

The association between psychiatric diseases, psychotropic drugs and the risk of incident rosacea.

BACKGROUND: Psychological conditions, such as traumatic events or stress, have been discussed controversially as aetiological factors for rosacea. OBJECTIVES: To assess the association between diagnosed depression, other affective disorders or schizophrenia and subsequent incident rosacea. We further aimed at evaluating the possible role of various psychotropic drugs within this association. METHODS: We conducted a matched case-control study of psychiatric diseases and incident rosacea, stratified by exposure to various psychotropic drugs, using the UK-based General Practice Research Database. Cases had a first diagnosis of rosacea recorded between 1995 and 2009. Each case was matched to one control on age, sex, general practice and years of history on the database. RESULTS: A history of depression or other affective disorders was not associated with an increased risk of developing rosacea; lithium was the only antidepressant drug that significantly altered this association. Current long-term use of lithium was associated with a decreased odds ratio (OR) of 0·58 [95% confidence interval (CI) 0·38-0·88] among people without a schizophrenia diagnosis (with or without affective disorders), compared with people not exposed to lithium. Patients with diagnosed schizophrenia revealed a decreased rosacea risk (OR 0·71, 95% CI 0·60-0·91), independent of antipsychotic drug use. CONCLUSIONS: Depression or other affective disorders were not associated with incident rosacea, whereas patients with schizophrenia were at a decreased risk of this skin disease in our study population. The materially decreased risk of rosacea among people with chronic lithium exposure may lead to new insights into the pathomechanism of rosacea.

Rosiglitazone use and post-discontinuation glycaemic control in two European countries, 2000-2010.

OBJECTIVES: To evaluate the impact of risk minimisation policies on the use of rosiglitazone-containing products and on glycaemic control among patients in Denmark and the UK. DESIGN, SETTING AND PARTICIPANTS: We used population-based data from the Aarhus University Prescription Database (AUPD) in northern Denmark and from the General Practice Research Database (GPRD) in the UK. MAIN OUTCOME MEASURES: We examined the use of rosiglitazone during its entire period of availability on the European market (2000-2010) and evaluated changes in the glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels among patients discontinuing this drug. RESULTS: During 2000-2010, 2321 patients with records in AUPD used rosiglitazone in northern Denmark and 25 428 patients with records in GPRD used it in the UK. The proportion of rosiglitazone users among all users of oral hypoglycaemic agents peaked at 4% in AUPD and at 15% in GPRD in May 2007, the month of publication of a meta-analysis showing increased cardiovascular morbidity associated with rosiglitazone use. 12 months after discontinuation of rosiglitazone-containing products, the mean change in HbA1c was -0.16% (95% CI -3.4% to 3.1%) in northern Denmark and -0.17% (95% CI -0.21% to 0.13%) in the UK. The corresponding mean changes in FPG were 0.01 mmol/L (95% CI -7.3 to 7.3 mmol/L) and 0.03 mmol/L (95% CI -0.22 to 0.28 mmol/L). CONCLUSIONS: Publication of evidence concerning the potential cardiovascular risks of rosiglitazone was associated with an irreversible decline in the use of rosiglitazone-containing products in Denmark and the UK. The mean changes in HbA1c and FPG after drug discontinuation were slight.

A study on the epidemiology of rosacea in the U.K.

BACKGROUND: Rosacea is a chronic facial skin disease of unclear origin. Epidemiological data are scarce and controversial, with reported prevalences ranging from 0·09% to 22%. To our knowledge, incidence rates have not been quantified before. OBJECTIVES: In this observational study we quantified incidence rates of diagnosed rosacea in the U.K. and described demographic characteristics and the prevalence of ocular symptoms in patients with rosacea. We compared lifestyle factors such as smoking and alcohol consumption between patients with rosacea and controls. METHODS: Using the U.K.-based General Practice Research Database, we identified patients with an incident diagnosis of rosacea between 1995 and 2009 and matched them (1:1) to rosacea-free control patients. We assessed person-time of all patients at risk and assessed incidence rates of rosacea, stratified by age, sex, year of diagnosis and region. RESULTS: We identified 60,042 rosacea cases and 60,042 controls (61·5% women). The overall incidence rate for diagnosed rosacea in the U.K. was 1·65 per 1000 person-years. Rosacea was diagnosed in some 80% of cases after the age of 30 years. Ocular symptoms were recorded in 20·8% of cases at the index date. We observed a significantly reduced relative risk of developing rosacea among current smokers (odds ratio 0·64, 95% confidence interval 0·62-0·67). Alcohol consumption was associated with a marginal risk increase. CONCLUSIONS: We quantified incidence rates and characteristics of patients with rosacea diagnosed in clinical practice in a large epidemiological study using primary care data from the U.K. Smoking was associated with a substantially reduced risk of developing rosacea.

NSAID use and risk of Parkinson disease: a population-based case-control study.

BACKGROUND: Previous epidemiologic studies have produced inconsistent findings regarding the association between the use of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of Parkinson disease (PD). METHODS: We conducted a case-control analysis using the General Practice Research Database. Cases (≥40 years) had a new diagnosis of PD between 1994 and 2009. We matched four controls to each PD case on age, sex, general practice, and index date. Use of NSAIDs, aspirin, and acetaminophen was stratified by exposure timing and duration for both cases and controls. We calculated odds ratios (OR) using conditional logistic regression. For additional analyses, the index date was brought backward 1, 2, and 3 years, respectively. RESULTS: We identified 4026 cases with an incident idiopathic PD diagnosis and 15,969 matched controls. Compared with patients without any previous prescription for NSAIDs, those with prior use had no increased risk of a PD diagnosis (OR 1.07, 95% CI 0.99-1.16). Long-term use (≥15 prescriptions) was associated with a slightly lower PD risk (adjusted OR 0.94, 95% CI 0.83-1.07). The relative PD risks of the use of aspirin or acetaminophen were not materially higher (PD risk of long-term use: adjusted ORs 1.16, 95% CI 1.03-1.30 and 1.15, 95% CI 1.02-1.30, respectively) compared with those for non-users. The risk estimate diminished toward the null in subsequent analyses with shifted index dates. CONCLUSION: In this large observational study with data from the UK primary care, the long-term use of NSAIDs, aspirin, or acetaminophen was not associated with a substantially altered risk of developing PD.