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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]

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]

Background: There is concern about an increase in deaths from respiratory causes in asthma patients using long acting beta agonists. According to the guidelines of the British Thoracic Society, long acting beta agonists, ipratropium bromide, and theophylline should be used to treat patients with increasing asthma severity who are already receiving treatment with short acting beta agonists and inhaled steroids. A study was therefore undertaken to compare the characteristics and short term respiratory mortality rates in first time users of one of these three drugs.Methods: An open cohort study with a nested case-control analysis was performed on the UK based General Practice Research Database (GPRD). First time users of either salmeterol (n = 8386), ipratropium bromide (n = 4305), or theophylline (n = 4228) between 1 January 1992 and 30 April 1995 were identified and followed for 16 weeks. Drug usage patterns, predictors for respiratory mortality, and the number of deaths at 16 weeks in the three drug groups were compared.Results: The three asthma drugs were most often prescribed to patients with severe asthma. Age, a concomitant diagnosis of chronic obstructive pulmonary disease or emphysema, number of asthma drug prescriptions, number of visits to the general practitioner, and whether or not the patient had been admitted to hospital due to the respiratory disease in the 12 months prior to the start of the new drug therapy were strong predictors for asthma mortality. After adjusting for several risk factors, the relative risk estimates of a respiratory death for ipratropium bromide and theophylline users compared with salmeterol users were 1.8 (95% CI 0.4 to 9.6) and 3.0 (95% CI 0.4 to 22.4), respectively.Conclusions: In the UK population studied, salmeterol, ipratropium bromide and theophylline are regularly used to treat patients with asthma of increasing severity. Salmeterol use was not associated with an increase in short term mortality compared with ipratropium bromide and theophylline. [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]

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., Competing Interests: Declaration of competing interest The authors have no relevant personal or financial conflicts of interests to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (© 2021 British Association of Dermatologists.)

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., (Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Hydroxymethyl glutaryl coenzyme A inhibitors ("statins") are carcinogenic in rodents and an increased incidence of breast cancer was reported among pravastatin users in one randomised trial. We conducted a case-control study in the General Practice Research Database to evaluate the risk of breast cancer among 50- to 79-year old women treated with statins for hyperlipidaemia. Case and control women were matched by age, general practice, duration of prescription history in the General Practice Research Database, and index date. Adjusting for history of benign breast disease, body mass index, and use of hormone replacement therapy, women currently treated with statins had an estimated relative risk for breast cancer of 1.0 (95% confidence interval 0.6-1.6) compared to women without hyperlipidaemia. Untreated hyperlipidaemia was associated with an increased risk of breast cancer (estimated relative risk 1.6; 95% confidence interval 1.1-2.5). The estimated relative risk among women currently receiving only non-statin lipid-lowering drugs was similar to that of women with untreated hyperlipidaemia (1.8; 95% confidence interval 0.9-3.4). We found no evidence for an increasing trend in breast cancer risk with increasing duration of statin use (median duration 1.8 years, maximum 8.6 years)., (Copyright 2002 Cancer Research UK)

Background: Studies in dogs showed that some hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are associated with cataract when administered in excessive doses. Clinical safety data of statins regarding cataract development in humans have been of limited value so far., Objective: To determine whether long-term use of statins is associated with an increased risk of cataract., Methods: We conducted a case-control analysis using data from the United Kingdom-based General Practice Research Database. The main outcome was a first-time diagnosis of cataract and/or cataract extraction in patients aged 40 to 79 years. Controls were matched to cases on age, sex, practice, calendar time, and duration of medical history in the database. Use of statins, fibrates, or other lipid-lowering drugs was compared with nonuse of any lipid-lowering drug, stratified by exposure duration and dose., Results: We identified 7405 cases and 28 327 controls. Long-term use of statins (eg, > or =30 prescriptions) was not associated with an increased cataract risk (adjusted odds ratio [OR], 0.9; 95% confidence interval [CI], 0.5-1.6), nor was use of fibrates or of other lipid-lowering drugs (adjusted OR, 0.5; 95% CI, 0.3-1.1; and OR, 0.7; 95% CI, 0.1-5.6, respectively). We found evidence that concomitant use of simvastatin and erythromycin, a potent inhibitor of simvastatin metabolism, is associated with an increased cataract risk (adjusted odds ratio, 2.2; 95% confidence interval, 1.2-4.1)., Conclusions: Our study provides evidence that long-term use of therapeutic statin doses does not increase the risk of developing cataract. Concomitant use of erythromycin and simvastatin may increase the cataract risk.

Aims: Selective serotonin reuptake inhibitors (SSRIs) have been associated with serotonin depletion in platelets, potentially leading to abnormal aggregation and prolonged bleeding time. In view of the importance of serotonin in coronary thrombosis, and decreased platelet serotonin concentrations associated with SSRIs, the present study was performed to test the hypothesis of a decreased risk of acute myocardial infarction (AMI) associated with SSRIs., Methods: We conducted a population-based case-control analysis using the UK General Practice Research Database (GPRD). A total of 3319 patients aged 75 years or younger free of clinical conditions predisposing to ischaemic heart disease, with a first-time diagnosis of AMI between 1992 and 1997, and 13 139 controls without AMI matched to cases for age, sex, general practice attended, and calendar time were included. Conditional logistic regression was used to estimate relative risks., Results: Adjusted odds ratios (with 95% CI) for current use of SSRIs, non-SSRIs, or other antidepressants, compared to the group of nonusers of antidepressants were 0.9 (95% CI 0.5,1.8), 0.9 (95% CI 0.7,1.2), and 1.3 (95% CI 0.6,2.8), respectively. As compared with nonuse of SSRIs, current use (regardless of any other antidepressants used) resulted in an adjusted OR of 1.1 (95% CI 0.7,1.6)., Conclusions: The current analysis provides evidence that SSRI exposure does not substantially decrease the risk of developing first-time AMI in patients free of factors predisposing to ischaemic heart disease. However, due to relatively small numbers of exposed subjects and the resulting wide confidence intervals, further studies may be needed to document a lack of effect of SSRIs in subjects without pre-existing diseases predisposing to AMI.

Context: Recent animal studies have suggested that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) increase bone formation, volume, and density. It is unknown whether use of statins is associated with a decreased risk of fractures in humans., Objective: To determine whether exposure to statins, fibrates, or other lipid-lowering drugs is associated with reduced bone fracture risk., Design: Population-based, nested case-control analysis., Setting: The UK-based General Practice Research Database (GPRD), comprising some 300 practices, with data collection from the late 1980s until September 1998., Subjects: Within a base population of 91,611 individuals aged at least 50 years (28,340 individuals taking lipid-lowering drugs, 13,271 untreated individuals with a diagnosis of hyperlipidemia, and 50,000 randomly selected individuals without diagnosis of hyperlipidemia), we identified 3940 case patients who had a bone fracture and 23,379 control patients matched for age (+/-5 years), sex, general practice attended, calendar year, and years since enrollment in the GPRD., Main Outcome Measures: Use of statins, fibrates, or other lipid-lowering drugs in case patients vs control patients., Results: After controlling for body mass index, smoking, number of physician visits, and corticosteroid and estrogen use, current use of statins was associated with a significantly reduced fracture risk (adjusted odds ratio [OR], 0.55; 95% confidence interval [CI], 0.44-0.69) compared with nonuse of lipid-lowering drugs. Current use of fibrates or other lipid-lowering drugs was not related to a significantly decreased bone fracture risk (adjusted OR, 0.87; 95% CI, 0.70-1.08 and adjusted OR, 0.76; 95% CI, 0.41-1.39, respectively)., Conclusions: This study suggests that current exposure to statins is associated with a decreased risk of bone fractures in individuals age 50 years and older. This finding has a potentially important public health impact and should be confirmed further in controlled prospective trials. JAMA. 2000;283:3205-3210

Seroepidemiology, pathology, and animal studies provide evidence for a possible association between Chlamydia pneumoniae infections and atherosclerosis, coronary heart disease, and myocardial infarction. If this association exists, then exposure to certain antibiotics may positively affect the clinical course after an acute ischemic cardiac event (secondary prevention) and affect the risk of developing a first-time myocardial infarction (primary prevention). Preliminary evidence from clinical trials suggests that treatment with new macrolide antibiotics may improve outcome after ischemic events, and evidence from a large case-control analysis indicates that exposure to tetracyclines or quinolones may reduce the risk of developing a first-time myocardial infarction. However, antibiotics for the treatment or prevention of ischemic heart disease must not be recommended yet. This review of published studies briefly summarizes the currently available literature on the effects of antibiotics on the risk of developing coronary heart disease and myocardial infarction.

Background: The use of angiotensin-converting enzyme (ACE) inhibitors has been linked to a decreased risk of developing cancer, and longer-term use of calcium channel blockers (CCBs) has been associated with an increased risk of developing cancer in general and breast cancer in particular., Methods: Using data from the General Practice Research Database, we conducted a large case-control analysis. Previous exposure to ACE inhibitors, CCBs, and beta-blockers was compared between 3706 postmenopausal women who were diagnosed with incident breast cancer between 1992 and 1997 and 14155 matched-control women., Results: Compared with nonusers of antihypertensive drugs, women who used ACE inhibitors (odds ratio [OR], 1.0; 95% confidence interval [CI], 0.7-1.5), CCBs (OR, 0.9; 95% CI, 0.7-1.2), or beta-blockers (OR, 1.0; 95% CI, 0.8-1.2) for 5 or more years were not at an increased or decreased risk of developing breast cancer (adjusted for smoking and body mass index [calculated as weight in kilograms divided by the square of height in meters]). The risk of breast cancer did not differ between users of different ACE inhibitors or different CCBs (dihydropyridines, diltiazem hydrochloride, and verapamil hydrochloride) or between users of short-acting (OR, 1.0; 95% CI, 0.7-1.4) or sustained-release (OR, 1.0; 95% CI, 0.8-1.3) nifedipine preparations., Conclusion: The findings of this large case-control analysis do not support the hypothesis that longer-term use of ACE inhibitors or CCBs affects the risk of developing breast cancer.

Background: Minocycline has increasingly been associated with different adverse auto-immune reactions including drug-induced lupus., Objective: To identify the scope of minocycline-induced lupus and to characterise its typical features., Methods: Comprehensive Medline and Embase search of the English and non-English literature for case reports of minocycline-induced lupus., Results: We included 57 cases of minocycline-induced lupus (mean age +/- SD at onset: 21.6+/-8.6 years, median time of exposure: 19 months, range 3 days to 6 years). All patients showed the clinical features of polyarthralgia/polyarthritis often accompanied by liver abnormalities. Twelve patients had evidence of dermatological manifestations (i.e rash, livedo reticularis, oral ulceration, subcutaneous nodules, alopecia). The ANA test was positive in all patients., Conclusion: Long-term exposure to minocycline may be associated with drug-induced lupus. Baseline and periodic liver function and ANA tests accompanied by appropriate clinical monitoring are suggested for patients receiving long-term minocycline therapy., (Copyright 2000 S. Karger AG, Basel.)

Cardiovascular diseases, particularly coronary heart disease (CHD) and myocardial infarction (MI), are among the leading causes for morbidity and mortality in industrialized countries [2, 77]. During the past decades, various clinical or lifestyle risk factors for myocardial infarction such as hyperlipidemia, hypertension, obesity, lack of physical exercise and smoking have been identified. However, it is also recognized that these well-documented risk factors do not sufficiently account for all new cases of myocardial infarction [77]. Many patients with myocardial infarction have only a borderline risk profile or even lack known risk factors. The question arises: What additional risk factors may play a role in the etiology of atherosclerosis and ischemic heart disease?

Background: Recently several case reports described the association between minocycline and lupuslike syndrome. Minocycline, one of the tetracyclines, is widely used to treat acne. We aimed to examine the association of exposure to minocycline and other tetracyclines with the development of lupuslike syndrome., Methods: We conducted a nested case-control study in a cohort of 27 688 acne patients aged 15 to 29 years, using data automatically recorded on general practitioners' office computers in the United Kingdom. Controls were matched to cases on age, sex, and practice. The main outcome was lupuslike syndrome defined as the occurrence of polyarthritis or polyarthralgia of unknown origin, with negative rheumatoid factor or latex agglutination test, positive or unmeasured antinuclear factor, elevated or unmeasured erythrocyte sedimentation rate, and absence of or unmeasured antinative DNA antibody levels., Results: We identified 29 cases and selected 152 controls. Current single use of minocycline was associated with an 8.5-fold (95% confidence interval [CI], 2.1-35) increased risk of developing lupuslike syndrome compared with non-users and past users of tetracyclines combined. The risk of past exposure to any of the tetracyclines was closely similar to nonuse (relative risk, 1.3; 95% CI, 0.5-3.3). Current use of doxycycline, oxytetracycline, or tetracycline combined was associated with a 1.7-fold (95% CI, 0.4-8.1) increase of risk. The risk increased with longer use., Conclusion: Current use of minocycline increased the risk of developing lupuslike syndrome 8.5-fold in the cohort of young acne patients. The effect was stronger in longer-term users. However, the absolute risk of developing lupuslike syndrome seems to be relatively low.

Context: Increasing evidence supports the hypothesis of a causal association between certain bacterial infections and increased risk of developing acute myocardial infarction. If such a causal association exists, subjects who used antibiotics active against the bacteria, regardless of indication, might be at lower risk of developing acute myocardial infarction than nonusers., Objective: To determine whether previous use of antibiotics decreases the risk of developing a first-time acute myocardial infarction., Design: Population-based case-control analysis., Setting: The United Kingdom-based General Practice Research Database comprising 350 general practices., Patients: A total of 3315 case patients aged 75 years or younger with a diagnosis of first-time acute myocardial infarction between 1992 and 1997 and 13139 controls without myocardial infarction matched to cases for age, sex, general practice attended, and calendar time., Main Outcome Measures: Use of antibiotics among those who did or did not have a first-time acute myocardial infarction., Results: Cases were significantly less likely to have used tetracycline antibiotics (adjusted odds ratio [OR], 0.70; 95% confidence interval [CI], 0.55-0.90) or quinolones (adjusted OR, 0.45; 95% CI, 0.21-0.95). No effect was found for previous use of macrolides (primarily erythromycin), sulfonamides, penicillins, or cephalosporins., Conclusions: The findings from this large case-control analysis provide further, albeit indirect, evidence for an association between bacterial infections with organisms susceptible to tetracycline or quinolone antibiotics and the risk of acute myocardial infarction. These results of preliminary nature should stimulate more research to further explore the role of infections in the etiology of acute myocardial infarction.

Background: Recent case reports suggest that a combination of the appetite suppressants fenfluramine and phentermine is associated with an increased risk of cardiac-valve regurgitation. There are also reports of valvular disorders in persons taking fenfluramine or dexfenfluramine alone, particularly for more than three months., Methods: We conducted a population-based follow-up study and a nested case-control analysis of 6532 subjects who received dexfenfluramine, 2371 who received fenfluramine, and 862 who received phentermine to assess the risk of a subsequent clinical diagnosis of a valvular disorder of uncertain origin. For comparison, we identified a group of 9281 obese subjects who had not taken appetite suppressants who were matched to the treated subjects for age, sex, and weight. All subjects were free of diagnosed cardiovascular disease at the start of follow-up. The average duration of follow-up for all subjects was about four years., Results: There were 11 cases of newly diagnosed idiopathic valvular disorders, 5 after the use of dexfenfluramine and 6 after the use of fenfluramine. There were six cases of aortic regurgitation, two cases of mitral regurgitation, and three cases of combined aortic and mitral regurgitation. There were no cases of idiopathic cardiac-valve abnormalities among the subjects who had not taken appetite suppressants or among those who took only phentermine. The five-year cumulative incidence of idiopathic cardiac-valve disorders was 0 per 10,000 subjects among those who had not taken appetite suppressants (95 percent confidence interval, 0 to 15.4) and among those who took phentermine alone (95 percent confidence interval, 0 to 76.6), 7.1 per 10,000 subjects among those who took either fenfluramine or dexfenfluramine for less than four months (95 percent confidence interval, 3.6 to 17.8; P=0.02 for the comparison with subjects who had not taken appetite suppressants), and 35.0 per 10,000 subjects among those who received either of these medications for four or more months (95 percent confidence interval, 16.4 to 76.2; P<0.001)., Conclusions: The use of fenfluramine or dexfenfluramine, particularly for four months or longer, is associated with an increased risk of newly diagnosed cardiac-valve disorders, particularly aortic regurgitation.

Objective: There is evidence that estrogens play a role in the etiology of systemic lupus erythematosus (SLE), but this has not yet been shown for discoid lupus. We examined the association of postmenopausal estrogen use with the development of SLE and discoid lupus., Methods: We did a case-control evaluation, using the UK based General Practice Research Database. We analyzed 41 cases with SLE, 34 cases with discoid lupus, and 295 age, sex and practice matched controls, and estimated relative risk estimates (odds ratios) in relation to estrogen exposure duration as well as total cumulative dose and estrogen type (alone or combined with progestogens)., Results: While short term estrogen exposure was not associated with increased risk, the risk of developing SLE (adjusted OR 2.8; 95% CI 0.9-9.0) or discoid lupus (adjusted OR 2.8; 95% CI 1.0-8.3) was significantly increased among current users who were exposed for 2 or more years. The adjusted RR estimate comparing longer term estrogen users and nonusers for all cases (SLE and discoid lupus combined) was 2.8 (95% CI 1.3-5.8; p < 0.01). A difference was found between longterm users of estrogens alone (OR 5.3; 95% CI 1.5-18.6) and those who used estrogens combined with progestogens (OR 2.0; 95% CI 0.8-5.0), compared to nonusers., Conclusion: Our findings suggest that longer term use of postmenopausal estrogens plays a role in the etiology of both SLE and discoid lupus. There is a suggestion that progestogens may reduce the effect of estrogens on these autoimmune disorders.

Aims: To evaluate a possible positive association between tamoxifen treatment and the risk of developing idiopathic venous thromboembolism (VTE) in women with breast cancer in the absence of clinical risk factors for venous thromboembolism other than breast cancer itself., Methods: Using information from the large UK-based General Practice Research Database, we identified, within a cohort of more than 10000 women with breast cancer, all women who developed a first-time diagnosis of deep vein thrombosis or pulmonary embolism of uncertain cause between January 1, 1991 and December 31, 1996. In a case-control analysis, we compared their tamoxifen exposure experience prior to the thromboembolic event with that of a randomly selected group of control women with breast cancer who were matched to cases on age, year of the breast cancer diagnosis and calendar time., Results: We identified 25 cases of idiopathic VTE and 172 controls, all of whom had breast cancer, but were otherwise free from other risk factors for VTE. Past tamoxifen exposure was not materially associated with an elevated risk of developing VTE, and we therefore combined never and past users as reference group. The relative risk estimate of VTE for current tamoxifen exposure, as compared with never and past use combined, was 7.1 (95% CI 1.5-33), adjusted for body mass index, smoking status and hysterectomy status. High body mass index was an independent predictor of VTE itself., Conclusions: Our study provides evidence that current use of tamoxifen increases the risk of idiopathic venous thromboembolism.