Statin use and risk of first-time psoriasis diagnosis.

BACKGROUND: Statins have been suggested as a potential treatment for psoriasis because of their anti-inflammatory properties. However, evidence on the benefits of statins is scarce. OBJECTIVE: We sought to study the association between use of statins or other lipid-lowering agents and the risk of developing psoriasis. METHODS: We conducted a case-control analysis using the United Kingdom-based General Practice Research Database. We identified patients with an incident psoriasis diagnosis between 1994 and 2005 and matched one control subject to each patient on age, sex, general practice, calendar time, and years of history in the database. We estimated odds ratios (ORs) with 95% confidence intervals (CIs), stratified exposure by timing and duration, and adjusted the ORs for potential confounders. RESULTS: We identified 36,702 incident psoriasis cases and the same number of matched controls. Adjusted ORs for current use (last prescription <30 days before index date) of 1 to 4, 5 to 19, or greater than or equal to 20 prescriptions for statins, as compared with nonuse, were 0.60 (95% CI 0.45-0.80), 1.00 (95% CI 0.84-1.18), and 1.08 (95% CI 0.92-1.28), respectively. The ORs for recent and past use (last prescription 30-89 days and ≥90 days ago, respectively) were around 1, except for past use of 1 to 4 prescriptions (OR 1.39; 95% CI 1.09-1.78). LIMITATIONS: Potential of residual confounding as a result of retrospective study design is a limitation. CONCLUSIONS: This large case-control study does not provide evidence for an altered risk of developing psoriasis in association with long-term use of statins. The reduced psoriasis risk for current short-term statin users is interesting, but whether the association is indeed causal needs further investigation.

Diabetes mellitus and the risk of cholecystectomy.

BACKGROUND: Whether diabetes mellitus is associated with an increased risk of cholecystectomy remains controversial. AIMS: To explore the association between diabetes mellitus and the risk of cholecystectomy. METHODS: Population-based case-control analysis using UK-based General Practice Research Database. Cases of cholecystectomy and up to four controls per case, matched on age, sex, BMI, general practice, calendar time, and years of history in the database were identified between 1994 and 2008. Conditional logistic regression was used to estimate the risk of cholecystectomy in diabetics compared to non-diabetics. Odds ratios (ORs) were calculated, adjusted for smoking, alcohol consumption, statin use, and additional confounders. RESULTS: Amongst 22,574 cases with cholecystectomy and 72,476 controls, 1068 (4.7%) and 3270 (4.5%) had diabetes, respectively, yielding an adjusted OR for developing gallstone disease followed by cholecystectomy of 0.88, 95% CI 78-1.00, p=0.05) in association with diabetes mellitus. Neither glycaemic control, nor increasing diabetes duration or oral antidiabetic therapies were associated with an altered risk of cholecystectomy. Use of statins was protective in patients with (adj. OR 0.66, 95% CI 0.54-0.80, p<0.0001) or without diabetes (adj. OR 0.70, 95% CI 0.62-0.78, p<0.0001). CONCLUSIONS: Diabetes mellitus was not associated with an altered risk of cholecystectomy.

Use of depot medroxyprogesterone acetate and fracture risk.

CONTEXT: Depot medroxyprogesterone acetate (DMPA), which has a high rate of use among teenagers in Europe and the United States, has been associated with impaired bone mineral acquisition during adolescence and accelerated bone loss in later life. Studies on the association between DMPA use and fracture risk are limited. OBJECTIVE: We aimed at evaluating the relationship between use of hormonal contraceptives, specifically DMPA, and fracture risk. DESIGN: We conducted a case-control analysis using the United Kingdom-based General Practice Research Database. SETTING AND PARTICIPANTS: Participants were females aged 20-44 yr with an incident fracture diagnosis between 1995 and 2008. MAIN OUTCOME MEASURES: Odds ratios (OR) with 95% confidence intervals (CI) of incident fracture in relation to exposure to DMPA or combined oral contraceptives were assessed. Adjustments were made for smoking, body mass index, and additional potential confounders. RESULTS: We identified 17,527 incident fracture cases and 70,130 control patients (DMPA exposure: 11 and 8%, respectively). Compared with nonuse, current use of one to two, three to nine, or 10 or more DMPA prescriptions yielded adjusted OR for fractures of 1.18 (95% CI = 0.93-1.49), 1.36 (95% CI = 1.15-1.60), and 1.54 (95% CI = 1.33-1.78), respectively. Fracture risk was highest after longer treatment duration (>2-3 yr), and there was no difference in patients below and above the age of 30 yr. For users of combined estrogen-containing oral contraceptives, the OR were around 1. CONCLUSIONS: This population-based study suggests that use of DMPA is associated with a slightly increased risk of fractures.

Statin use and risk of gallstone disease followed by cholecystectomy.

CONTEXT: Gallstone disease is a leading cause of morbidity in western countries and carries a high economic burden. Statins decrease hepatic cholesterol biosynthesis and may therefore lower the risk of cholesterol gallstones by reducing the cholesterol concentration in the bile. Data on this association in humans are scarce. OBJECTIVE: To study the association between the use of statins, fibrates, or other lipid-lowering agents and the risk of incident gallstone disease followed by cholecystectomy. DESIGN, SETTING, AND PARTICIPANTS: Case-control analysis using the UK-based General Practice Research Database. Incident patients between 1994 and 2008 and 4 controls per each patient were identified and matched on age, sex, general practice, calendar time, and years of history in the database. The study population was 76% women and the mean (SD) age was 53.4 (15.0) years at the index date. Conditional logistic regression was used to estimate the odds ratio (OR) of developing gallstones followed by cholecystectomy in relation to exposure to lipid-lowering agents, stratified by exposure timing and duration. The ORs and 95% confidence intervals (CIs) were adjusted for smoking, body mass index, ischemic heart disease, stroke, and estrogen use. MAIN OUTCOME MEASURE: The adjusted OR (AOR) for developing gallstone disease followed by cholecystectomy in relation to exposure to lipid-lowering agents. RESULTS: A total of 27,035 patients with cholecystectomy and 106,531 matched controls were identified, including 2396 patients and 8868 controls who had statin use. Compared with nonuse, current statin use (last prescription recorded within 90 days before the first-time diagnosis of the disease) was 1.0% for patients and 0.8% for controls (AOR, 1.10; 95% CI, 0.95-1.27) for 1 to 4 prescriptions; 2.6% vs 2.4% (AOR, 0.85; 95% CI, 0.77-0.93) for 5 to 19 prescriptions, and 3.2% vs 3.7% (AOR, 0.64; 95% CI, 0.59-0.70) for 20 or more prescriptions. The AORs for current use of statins defined as 20 or more prescriptions were similar (around 0.6) across age, sex, and body mass index categories, and across the statin class. CONCLUSION: Long-term use of statins was associated with a decreased risk of gallstones followed by cholecystectomy.

Lithium, antipsychotics, and risk of psoriasis.

BACKGROUND: Observations in controlled trials and case reports have linked lithium exposure to induction or exacerbation of psoriasis. A causal relationship between lithium exposure and incident psoriasis has been questioned, and observational studies are lacking. METHODS: We conducted a case-control analysis using the United Kingdom-based General Practice Research Database to study the association between the use of lithium or antipsychotics and the risk of developing an incident diagnosis of psoriasis. We identified cases with an incident diagnosis of psoriasis between 1994 and 2005, and controls were matched to the cases on age, sex, general practice, calendar time, and years of history in the database. We used conditional logistic regression to estimate the risk of developing a first-time diagnosis of psoriasis in relation to previous exposure to lithium and antipsychotic drugs, stratified by exposure timing and duration. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) adjusted for smoking, body mass index, and additional potential confounders. RESULTS: We identified 36,702 incident cases of psoriasis and the same number of matched controls. Compared with nonuse, current use of 5 or more prescriptions for lithium and atypical antipsychotics yielded adjusted ORs of 1.68 (95% CI, 1.18-2.39; P < 0.01) and 0.76 (95% CI, 0.55-1.06; P = 0.11), respectively. The OR for olanzapine was 0.50 (95% CI, 0.28-0.89, P = 0.02). CONCLUSIONS: Long-term use of lithium was associated with a small increase in risk of incident psoriasis. There was a suggestion of a possible reduced psoriasis risk associated with the use of atypical antipsychotics, mainly olanzapine, a finding that needs further evaluation.

Psoriasis and risk of incident cancer: an inception cohort study with a nested case-control analysis.

Psoriasis has been associated with lymphohematopoietic and solid cancers; however, reports have been inconsistent. Cancer incidence was compared between psoriasis and psoriasis-free patients, and the roles of psoriasis duration and treatment were explored in this observational study using the UK General Practice Research Database. Among 67,761 patients, 1,703 patients had incident cancer; of whom 54% had a history of psoriasis. Incidence rate ratios for lymphohematopoietic and pancreatic cancers were 1.81 (95% confidence interval (CI) 1.35-2.42) and 2.20 (95% CI 1.18-4.09), respectively. In a nested case-control analysis, adjusted odds ratios (ORs) for cancer overall were 1.50 (95% CI 1.30-1.74) for psoriasis of >or=4 years duration and 1.53 (95% CI 0.97-2.43) for patients receiving systemic treatment (marker of disease severity). Lymphohematopoietic malignancy risk was highest in patients with systemic treatment. The OR for patients without systemic treatment was 1.59 (95% CI 1.01-2.50) for psoriasis of <2 years and 2.12 (95% CI 1.45-3.10) for that of >or=2 years duration. Risks of bladder/kidney and colorectal cancers were increased with longer-duration psoriasis. Psoriasis patients may have an increased overall risk of incident cancer (mainly lymphohematopoietic and pancreatic). Longer-term psoriasis and more severe disease may increase the risk of some cancers. These observations need further confirmation, particularly because of the potential of findings by chance in observational studies with subgroup analyses.

A fatal tick bite occurring during the course of tick-borne encephalitis vaccination.

In Western Europe tick-borne encephalitis virus infections with fatal outcome are rare, especially in children. We report the case of an adolescent who died of meningoencephalitis after a tick bite that occurred between the first 2 tick-borne encephalitis vaccinations. The case demonstrates the difficulty of differentiating possible adverse events associated with the immunization from symptoms of simultaneous infection with tick-borne encephalitis virus.

Association between use of thiazolidinediones or other oral antidiabetics and psoriasis: A population based case-control study.

BACKGROUND: Small clinical trials suggest that thiazolidinediones may exert a beneficial effect on skin lesions of patients with psoriasis. Little is known about other classes of antidiabetic drugs and the psoriasis risk. OBJECTIVE: We sought to study the association between use of thiazolidinediones, sulfonylureas, biguanides, or acarbose and the risk of developing a first-time diagnosis of psoriasis. METHODS: We conducted a case-control analysis on the United Kingdom-based General Practice Research Database. We identified patients with an incident psoriasis diagnosis from 1994 to 2005 and matched one control subject to each patient on age, sex, general practice, calendar time, and years of history in the database. Conditional logistic regression was used to estimate the odds ratio with 95% confidence intervals (CI) of developing a first-time psoriasis diagnosis in relation to previous exposure to antidiabetic drugs, stratified by exposure timing and duration of use and adjusted for a variety of potential confounders. RESULTS: We identified 36,702 patients with a first-time psoriasis diagnosis and the same number of matched control subjects. As compared with no use, the adjusted odds ratio for current use of 1 to 4 prescriptions or greater than or equal to 5 prescriptions for thiazolidinediones were 1.01 (95% CI 0.34-3.01) and 0.33 (95% CI 0.16-0.66), respectively. Current use of greater than or equal to 15 prescriptions for metformin or sulfonylureas yielded adjusted odds ratio of 0.77 (95% CI 0.62-0.96) and 1.07 (95% CI 0.88-1.31), respectively. LIMITATIONS: The findings are based on a small number of patients exposed to thiazolidinediones (100 in total, 48 current users of >or=5 prescriptions). CONCLUSIONS: The findings of this large observational study provide further evidence for a potentially beneficial effect of thiazolidinediones on psoriasis. While current long-term use of metformin was also associated with a suggestion of a reduced psoriasis risk, no such effect was seen for use of other oral antidiabetics.

Undetectable phenytoin serum levels by an automated particle-enhanced turbidimetric inhibition immunoassay in a patient with monoclonal IgM lambda.

INTRODUCTION: Phenytoin is a drug used for the treatment of different types of seizures. Its variable pharmacokinetics, mainly a consequence of variable bioavailability, saturable protein binding and saturable hepatic metabolism, predisposes the drug to therapeutic drug monitoring. Several methods to analyze the drug in serum exist with immunoassays being the method of choice for routine measurements. Immunoassays are specific and sensitive, but cross-reactivity, possibly leading to erroneous serum levels, is a concern. We report a patient with falsely undetectable phenytoin serum levels. CASE REPORT: This 73-year old woman was treated with intravenous phenytoin due to epilepsia partialis continua in the context of a bilateral cerebrovascular insult. Anamnestically, a chronic lymphatic leukemia was known. In this patient, serum phenytoin levels became only detectable by the particle enhanced turbidimetric inhibition immunoassay used after precipitation of serum proteins. Protein electrophoresis revealed a monoclonal immunoglobulin, identified as IgMlambda. With other methods such as HPLC and fluorescence depolarization immunoassay, phenytoin was detectable. CONCLUSION: We propose interference between the monoclonal IgMlambda and/or other serum proteins and the particle-enhanced turbidimetric inhibition immunoassay, rendering phenytoin falsely undetectable in samples of this patient. In such patients, alternative methods such as HPLC should be used to prevent dosage errors.