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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives Use of postmenopausal hormone replacement therapy (HRT) has been associated with an elevated risk of gynecological cancers. There is evidence that the effect differs with the type of hormone used. Dydrogesterone is pharmacologically very similar to progesterone. Methods We used the UK-based General Practice Research Database (GPRD) to conduct a follow-up study with a nested case–control analysis. We assessed and compared the risk of developing breast, ovarian, endometrial/uterine or cervical cancer in estradiol/dydrogesterone (E/D) users, users of other HRT, or non-users of HRT. Results The breast cancer incidence rates were 2.41 (95% confidence interval (CI) 1.81–3.15), 3.28 (95% CI 3.01–3.55) and 3.16 (95% CI 2.92–3.42) per 1000 person-years for E/D users, users of other HRT or non-users, respectively. In a direct comparison, the breast cancer risk for E/D users was lower than for users of other HRT (odds ratio 0.76, 95% CI 0.56–1.05). The incidence rates of other gynecological cancers were similar or also slightly lower for E/D users than for users of other HRT. Conclusion This study provides evidence that the risk of developing gynecological cancers with E/D use of several months to a few years is similar to the risks of developing gynecological cancer without HRT or use of other HRT. [ABSTRACT FROM AUTHOR]

Background Use of postmenopausal hormone replacement therapy (HRT) used to be promoted to reduce the risk of ischemic cardiovascular diseases, a concept which has been challenged by results of the large Women's Health Initiative trial in users of estrogen and progestin. It is postulated that the type of progestin used in HRT affects the cardiovascular risk. Methods We used the UK-based General Practice Research Database to conduct a follow-up study with a nested case-control analysis. We assessed and compared the risk of developing myocardial infarction, thrombotic stroke or venous thromboembolism in estradiol/dydrogesterone users, users of other HRT, or non-users of HRT. Results The incidence rates of myocardial infarction, thrombotic stroke and venous thromboembolism in estradiol/dydrogesterone users were 0.40 (95% confidence interval (CI) 0.18-0.76), 0.27 (95% CI 0.10-0.58) and 0.31 (95% CI 0.13-0.64) per 1000 person-years, respectively. As compared to non-users of HRT, the adjusted relative risk estimates (odds ratios) in the nested case-control analysis for estradiol/dydrogesterone users or users of other HRT were 1.06 (95% CI 0.48-2.36) and 1.12 (95% CI 0.84-1.51) for myocardial infarction, 0.50 (95% CI 0.21-1.22) and 1.18 (95% CI 0.94-1.48) for thrombotic stroke, and 0.84 (95% CI 0.37-1.92) and 1.42 (95% CI 1.10-1.82) for venous thromboembolism, respectively. Conclusion The study provides evidence that estradiol/dydrogesterone use of several months to a few years is not associated with a higher risk of cardiovascular events than use of other HRT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Non-motor symptoms are not widely recognized in patients with Parkinson disease (PD). We sought to assess the incidence rate as well as the risk of depression in newly diagnosed patients with PD and to compare it to PD-free controls. We conducted a population-based follow-up study with a nested case-control analysis based on data from the UK-based General Practice Research Database (GPRD). We included PD patients ≥ aged 40 years with a first PD diagnosis between 1994 and 2005, and a matched comparison group free of PD. We assessed incidence rates (IRs) and relative risk estimates (odds ratios [ORs] with 95% confidence intervals [CI]). The IR of depression in newly diagnosed PD in the UK community was 26.0 (95% CI 22.9-29.5) per 1000 person-years. The risk of developing depression was increased almost twofold in patients with PD when compared to patients without PD (adj. OR 1.89; 95% CI 1.49-2.40). The increased relative risk was most pronounced in women and in individuals 40-69 years of age. Long-term users of levodopa had an increased depression risk when compared to short-term users. Patients with PD are at an approximately twofold increased risk of being diagnosed with depression compared to the PD-free population. [ABSTRACT FROM AUTHOR]

Background Systemic inflammation may increase the risk for cardiovascular diseases in patients with psoriasis, but data on this risk in patients with early psoriasis are scarce. Objectives To assess and compare the risk of developing incident myocardial infarction (MI), stroke or transient ischaemic attack (TIA) between an inception cohort of patients with psoriasis and a psoriasis-free population. Methods We conducted an inception cohort study with a nested case–control analysis within the U.K.-based General Practice Research Database. The study population encompassed 36 702 patients with a first-time recorded diagnosis of psoriasis 1994–2005, matched 1 : 1 to psoriasis-free patients. We assessed crude incidence rates (IRs) and applied conditional logistic regression to obtain odds ratios (ORs) with 95% confidence intervals (CIs). Results Overall, the IRs of MI ( n = 449), stroke ( n = 535) and TIA ( n = 402) were similar among patients with or without psoriasis. However, the adjusted OR of developing MI for patients with psoriasis aged < 60 years was 1·66 (95% CI 1·03–2·66) compared with patients without psoriasis, while the OR for patients aged ≥ 60 years was 0·99 (95% CI 0·77–1·26). The adjusted ORs of developing MI for patients of all ages with ≤ 2 or > 2 prescriptions/year for oral psoriasis treatment were 2·48 (95% CI 0·69–8·91) and 1·39 (95% CI 0·43–4·53), with a similar finding for stroke and TIA. Conclusions The risk of developing a cardiovascular outcome was not materially elevated for patients with early psoriasis overall. In subanalyses, however, there was a suggestion of an increased (but low absolute) MI risk for patients with psoriasis aged < 60 years, mainly with severe disease. [ABSTRACT FROM AUTHOR]

Background Several case reports have associated use of beta-blockers with an increased risk of psoriasis or psoriasiform drug eruptions. Objectives To study the association between use of beta-blockers and other antihypertensive drugs and the risk of developing a first-time diagnosis of psoriasis. Methods We conducted a case–control analysis on the U.K.-based General Practice Research Database. We identified cases with an incident psoriasis diagnosis between 1994 and 2005 and matched them to one control patient on age, sex, general practice, calendar time (same index date) and years of history in the database. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of developing a first-time psoriasis diagnosis in relation to previous exposure to antihypertensive drugs, stratified by exposure timing (current vs. past use) and exposure duration based on the number of prescriptions. Results The study encompassed 36 702 cases with a first-time psoriasis diagnosis and the same number of matched controls. Adjusted ORs for current use of 1–4, 5–19 or ≥ 20 prescriptions for beta-blockers, as compared with nonuse, were 0·93 (95% CI 0·76–1·13), 1·10 (95% CI 0·97–1·24), and 1·10 (95% CI 1·01–1·20), respectively. The risk estimates for current use of other antihypertensives at any exposure duration were all close to 1·0. Conclusions This large population-based case–control analysis does not support the current proposition that beta-blocker use is associated with an increased risk of psoriasis, nor did we find evidence for a substantially altered psoriasis risk for other antihypertensive drugs. [ABSTRACT FROM AUTHOR]

Population-based data on migraine incidence and comorbidity are scarce. We therefore aimed to quantify incidence rates and comorbidity of diagnosed migraine and health resource utilization (HRU) in migraineurs in the UK primary care setting. We conducted a follow-up study with a nested case-control analysis on the General Practice Research Database. The study encompassed 51,688 patients with a first-time diagnosis of migraine between 1994 and 2001, and the same number of matched controls. The migraine incidence rate was 3.69 (95% confidence interval 3.66, 3.73) cases per 1000 person-years. It was around 2.5 times higher in women. Most chronic diseases were slightly more prevalent in migraineurs than in controls. Triptan users had higher health resource utilization than other migraineurs. This study shows that migraine is a common diagnosis in general practice and associated with a high prevalence of comorbidity. The increased HRU in triptan users suggests greater migraine severity. [ABSTRACT FROM AUTHOR]

Background and objective: Drug-interaction alert systems are commonly used in community pharmacies to identify potential drug–drug interactions. However, depending on the software default setting, pharmacists may override alerts because they are too numerous. We explored the handling of drug-interaction alerts by community pharmacies in Switzerland. Methods: Data were collected by 15 trained pharmacy students in 15 Swiss community pharmacies. The medication history and the drug-interaction alerts of 600 patients who had ≥2 drugs on prescription were assessed, and the pharmacists in charge were interviewed about their management of drug-interaction alerts. Results: In the 15 pharmacies studied, the computer systems were programmed to flag only ‘severe’ drug interactions in four, ‘severe or moderate’ in six or ‘severe, moderate or minor’ in five pharmacies. The median frequency of drug-interaction alerts increased with decreasing default severity level from 0.5 to 40, respectively, to 76 per 40 patient visits and pharmacy. Because of these default settings, 277 (35·2%) of 787 potential drug-interaction alerts on new or repeated prescriptions were overridden by the computer systems. Only 256 (32·5%) of 787 potential drug interactions emerged from new prescriptions. The alert systems produced 656 alerts of which 146 were irrelevant because of multiple alerting of the same interaction or of drug combinations currently no longer taken. Of the 510 remaining relevant drug-interaction alerts, 289 (56·7%) were overridden by community pharmacists without any action taken. If the pharmacist took care of a patient's prescription him- or herself (as opposed to just controlling a prescription after a technician took care of the patient), fewer drug-interaction alerts were overridden by the pharmacist [Odds ratio (OR) 0·6, 95% confidence interval (CI) 0·42–0·98; P = 0·042). Technical overrides (by default settings) and pharmacists’ overrides together accounted for 71·9% (566 of 787 potential drug interactions). Of the remaining 211 interactions alerts, 87 (41·2%) were checked more closely by consulting the literature, contacting the prescribing physician or discussion with the patient. This led to 55 (63·2%) interventions (close monitoring, adjustment of dose or ingestion time, therapy stop or switching to alternative therapy). Determinants associated with action taken after an interaction alert were potential high severity (severe or moderate) (OR 3·34, 95% CI 1·77–6·31; P < 0·001) and alert flagged for the first time (OR 3·76, 95% CI 1·98–7·14; P < 0·001). All severe potential drug interactions ( n = 10) generated an alert and all caused an intervention. Conclusions: Pharmacists override a substantial proportion of drug-interaction alerts of minor or moderate potential severity by ignoring them or by programming the system to only flag drug interactions of potentially high severity. More sophisticated systems with improved sensitivity and specificity are required. Until these become available, it is important to ensure that at least potentially severe drug interactions are not missed; a goal that seems to be largely achieved. [ABSTRACT FROM AUTHOR]

Background: There is growing interest in the role of infections in the aetiology of acute myocardial infarction (AMI). We undertook a large, population-based study to explore the association between risk of AMI and recent acute respiratory-tract infection.Methods: We used data from general practices in the UK (General Practice Research Database). Potential cases were people aged 75 years or younger, with no history of clinical risk factors, who had a first-time diagnosis of AMI between Jan 1, 1994, and Oct 31, 1996. Four controls were matched to each case on age, sex, and the practice attended. The date of the AMI in the case was defined as the index date. For both cases and controls the date of the last respiratory-tract infection before the index date was identified. We also did a case-crossover analysis of cases who had an acute respiratory-tract infection either before the index date or before an arbitrarily chosen date (1 year before AMI).Findings: In the case-control analysis of 1922 cases and 7649 matched controls, significantly more cases than controls had an acute respiratory-tract infection in the 10 days before the index date (54 [2.8%] vs 72 [0.9%]). The odds ratios, adjusted for smoking and body-mass index, for first-time AMI in association with an acute respiratory-tract infection 1-5, 6-10, 11-15, or 16-30 days before the index date (compared with participants who had no such infection during the preceding year) were 3.6 (95% CI 2.2-5.7), 2.3 (1.3-4.2), 1.8 (1.0-3.3), and 1.0 (0.7-1.6); (test for trend p<0.01). The case-crossover analysis showed a relative risk of 2.7 (1.6-4.7) for AMI in relation to an acute respiratory-tract infection in the 10 days before the index date.Interpretation: Our findings suggest that in people without a history of clinical risk factors for AMI, acute respiratory-tract infections are associated with an increased risk of AMI for a period of about 2 weeks. We cannot, however, completely exclude the possibility of misdiagnosis bias, if prodromal symptoms of AMI were mistaken for respiratory-tract infection. [ABSTRACT FROM AUTHOR]

Background: Previous studies have been interpreted as suggesting an increase in risk of cancer among users of calcium-channel blockers compared with users of beta-blockers. To explore this issue further, we studied a large group of hypertensive patients to investigate the relation of calcium-channel blockers and cancer. Methods: In cohorts of users of calcium-channel blockers, angiotensin-converting-enzyme (ACE) inhibitors, and beta-blockers, we identified all cases of cancer diagnosed in 1995. We used a nested case-control analysis to estimate the risk of cancer among users of calcium-channel blockers and ACE inhibitors, with users of beta-blockers as a reference group. The study was based on information taken from the General Practice Research Database, and the study population was restricted to patients with at least 4 years of medical history recorded on computer. Findings: The study was based on 446 cases of cancer and 1750 controls. The relative risk estimates for all cancers combined were 1.27 (95% CI 0.98-1.63) and 0.79 (0.58-1.06) for users of calcium-channel blockers and ACE inhibitors, respectively, relative to users of beta-blockers. There was little difference in risk estimates with duration of use of calcium-channel blockers of less than 1.0 year (relative risk 1.46), 1.0-3.9 years (1.26), and 4.0 years or more (1.23). Interpretation: The small positive association between calcium-channel blockers and risk of cancer is unlikely to be causal since there is no increase in risk with increasing duration of calcium-channel blocker use. [ABSTRACT FROM AUTHOR]