Use of methimazole and risk of acute pancreatitis: A case–control study in Taiwan

Objective:

Some cases of acute pancreatitis have been reported to be associated with use of methimazole. The aim of this study was to investigate the relationship between use of methimazole and risk of acute pancreatitis on the basis of a systematic analysis.

Methods:

This was a population-based case–control study analyzing the database of the Taiwan National Health Insurance Program. There were 5764 individuals aged 20–84 years with a first attack of acute pancreatitis from 1998 to 2011 as the cases and 23,056 randomly selected sex- and age-matched individuals without acute pancreatitis as the controls. Use of methimazole was categorized as “never use” and “ever use.” We estimated the relative risk of acute pancreatitis associated with the use of methimazole by calculating the odds ratio (OR) with 95% confidence interval (CI) using a multivariable logistic regression model.

Results:

After adjustment for confounding factors, the OR of acute pancreatitis was 0.91 in individuals with ever use of methimazole, when compared with individuals with never use of methimazole (95% CI, 0.60–1.38). Unlike methimazole use, alcohol-related disease, biliary stone, cardiovascular disease, chronic obstructive pulmonary disease, diabetes mellitus, hepatitis B, hepatitis C, and hypertriglyceridemia were factors significantly associated with acute pancreatitis.

Conclusions:

Our study does not detect a substantial association between the use of methimazole and risk of acute pancreatitis on the basis of systematic analysis. There appears to be a discrepancy between case reports and our systematic analysis about the association between the use of methimazole and risk of acute pancreatitis.KEY WORDS: Acute pancreatitis, alcoholism, biliary stone, diabetes mellitus, methimazole     

Effects of glutathione-S-transferase polymorphisms on the risk of breast cancer: A population-based case–control study in Pakistan

Cancer is widely accepted as one of the major health issues. Diet composition and exposure to environmental genotoxic and carcinogenic agents such as polycyclic aromatic hydrocarbons (PAHs) are among the causative factors for various types of cancers, including breast cancer. Low penetrance genes including glutathione S transferases (GST) in association with environmental factors can contribute greatly in the development of breast cancer. We were interested to investigate the association of the polymorphisms of GSTM1, GSTT1, GSTP1 and GSTO2 with the risk of breast cancer in the Pakistani population. One hundred women visiting the Department of Radiology and Oncology, Nishter Hospital, Multan with pathologically confirmed breast cancer, and 100 healthy volunteers from central Pakistan were enrolled in the present study. The strength of the association of various factors with breast cancer was measured by calculating odd ratios (ORs) which were determined by logistic regression. All P values cited are two-sided; differences resulting in a P value of less or equal to 0.05 were declared statistically significant. The Hardy Weinberg equilibrium was tested for the genotype proportions in the control group, as a measure of quality control. Those aged 36–45, in menopause or with a history of cancer in the family had a significantly higher prevalence of breast cancer compared with controls. The frequency of GSTM1 and GSTT1 was similar in both control and patients suggesting no association with the risk of cancer development, however GSTM1 and GSTT1 were significantly linked with the risk of breast cancer in smokers and in women with a history of breast cancer in the family respectively. Similarly women homozygous for GSTP1 or GSTO2 and with a history of breast cancer, or in menopause, were at greater risk of breast cancer than wild type or heterozygotes. Our data suggest that genetic differences in some GST genes may be linked with an increased susceptibility to breast cancer. Furthermore it also gives an insight into the interaction between the GST polymorphisms and pre-menopausal diagnosis of breast cancer.     

Misinterpretation of categorical rate ratios and inappropriate exposure–response model fitting can lead to biased estimates of risk: Ethylene oxide case study

There are pitfalls associated with exposure–response modeling of human epidemiological data based on rate ratios (RRs). Exposure–response modeling is best based on individual data, when available, rather than being based on summary results of that data such as categorical RRs. Because the data for the controls (or the lowest exposure interval if there are not enough controls) are random and not known with certainty a priori, any exposure–response model fit to RRs should estimate the intercept rather than fixing it equal to one. Evaluation of a model’s goodness-of-fit to the individual data should not be based on the assumption that summary RRs describe the true underlying exposure–response relationship. These pitfalls are illustrated by Monte Carlo simulation examples with known underlying models. That these pitfalls are a practical concern is illustrated by the need for U.S. EPA to reconsider its most recent evaluation of ethylene oxide. If they had avoided these pitfalls, their exposure–response modeling would have been in better agreement with the log-linear model fit to the individual data.     

Benefit–risk assessment of plant sterols in margarine: A QALIBRA case study

This paper presents the benefit–risk assessment of adding plant sterols to margarine as an illustration of the QALIBRA method and software. With the QALIBRA tool health effects, risks as well as benefits are expressed in a common metric (DALY) which allows quantitative balancing of benefits and risks of food intake. The QALIBRA software can handle uncertainties in a probabilistic simulation. This simple case study illustrates the data need and assumptions that go into a quantitative benefit–risk assessment. The assessment shows that the benefits of plant sterols added to margarine outweigh the risks, if any.     

Pharmacists’ advice and clinical reasoning in relation to cardiovascular disease risk factors – A vignette case study

BackgroundPharmacists are increasingly providing public health services like the screening and monitoring for cardiovascular disease risk factors. Information on risk factors should be integrated into an assessment of absolute cardiovascular disease risk. Limited information is available on how pharmacists interpret test results and information related to cardiovascular disease risk factors.ObjectiveTo investigate the potential advice to clients featured in vignette case studies and reasoning of pharmacists in relation to multiple cardiovascular disease risk factors.MethodsThree vignette case studies representing clients with varying degrees of absolute cardiovascular disease risk who requested blood pressure and cholesterol level testing and related advice were designed and distributed to practicing pharmacists. Vignettes contained all necessary information for absolute cardiovascular disease risk assessment. Two open ended questions asked what advice pharmacists would provide and what influenced their decisions to give specific advice. Responses were analysed using content analysis and assessed for appropriateness in relation to cardiovascular guidelines.ResultsReplies of twenty-nine pharmacists were analysed. Advice to hypothetical clients was mainly appropriate when it concentrated on lifestyle modifications. Pharmacists’ reasoning indicated a focus on individual risk factors in their decision making on advice rather than consideration of absolute cardiovascular disease risk, which resulted in inappropriate recommendations of referral and follow up.ConclusionAdvice provided in relation to case studies and underlying clinical reasoning indicate potential knowledge gaps, anchoring bias and a framing effect in how pharmacists interpret multiple cardiovascular disease risk factors.     

Statins are associated with a reduced risk of cholangiocarcinoma: a population-based case–control study

Aims

Cholangiocarcinoma (CCA) is the second most common primary liver cancer in the world. Due to the lack of effective treatments, the survival rate of CCA is low and it is usually considered difficult to diagnose early. To date, no effective strategies for the prevention of CCA have been developed. Statins are cholesterol-lowering agents which possess pleiotropic properties and the use of statins may reduce cancer risk. The aim of the study was to investigate the effect of statin use on the risk of CCA.

Methods

We used nationwide insurance data to perform a case–control study including 3174 CCA patients diagnosed in 2002–2011 and 3174 propensity score matched controls. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated to assess the association between CCA risk and statin use by type of statin and dose.

Results

Patients with CCA were slightly younger than controls with mean ages of 67.4 (SD 12.3) and 68.5 (SD 13.2) years (P = 0.001), respectively, and had less users of statins (22.7 vs. 26.5%, P < 0.001). The overall adjusted OR of statin use associated CCA was 0.80 (95% CI 0.71, 0.90) and lowered for those with longer medications. The OR ranged from 0.65 to 0.77. Stronger dose–response association was seen when using lovastatin.

Conclusions

Statin use is associated with reduced risk of CCA and there is a dose–response relationship between the use of statins and risk of CCA.     

Use of read-across and tiered exposure assessment in risk assessment under REACH – A case study on a phase-in substance

REACH requests the exploration of alternative strategies for hazard identification before resorting to (in vivo) testing. Here, we combined read-across as non-testing strategy with a tiered exposure assessment for the risk characterisation of 1-methoxypropan-2-ol (PGME) as a representative for phase-in substances to be registered under REACH. Read-across from the selected source substances provided data which were comparable with experimental data available for target substance PGME, resulting in a realistic starting point for both qualitative and quantitative risk assessment. Greater variability was observed in the exposure estimates from a first Tier model (ECETOC TRA) or less conservative further Tier models (Stoffenmanager; RISKOFDERM), when these results were compared with results from a data-rich approach using measured data.     

Social and economic inequalities in fatal opioid and cocaine related overdoses in Luxembourg: A case–control study

BackgroundTo investigate social and economic inequalities in fatal overdose cases related to opioid and cocaine use, recorded in Luxembourg between 1994 and 2011.MethodsCross-examination of national data from law enforcement and drug use surveillance sources and of forensic evidence in a nested case–control study design. Overdose cases were individually matched with four controls, when available, according to sex, year of birth, drug administration route and duration of drug use. 272 cases vs 1056 controls were analysed. Conditional logistic regression analysis was performed to assess the respective impact of a series of socioeconomic variables.ResultsBeing professionally active [OR = 0.66 (95% CI 0.45–0.99)], reporting salary as main legal income source [OR = 0.42 (95% CI 0.26–0.67)] and education attainment higher than primary school [OR = 0.50 (95% CI 0.34–0.73)] revealed to be protective factors, whereas the professional status of the father or legal guardian of victims was not significantly associated to fatal overdoses.ConclusionsSocioeconomic inequalities in drug users impact on the occurrence of fatal overdoses. Compared to their peers, users of illicit drugs with lower socioeconomic profiles show increased odds of dying from overdose. However, actual and self-referred socioeconomic characteristics of drug users, such as educational attainment and employment, may have a greater predictive value of overdose mortality than the parental socioeconomic status. Education, vocational training and socio-professional reintegration should be part of drug-related mortality prevention policies.     

Drug interactions with phenprocoumon and the risk of serious haemorrhage: a nested case–control study in a large population-based German database

Purpose  

Phenprocoumon is the most frequently used vitamin K antagonist in Germany. The aim of this study was to estimate the risk of serious bleeding as a result of the use of drugs with potential interaction with phenprocoumon.     

Fibromyalgia as a cause of uncontrolled asthma: a case–control multicenter study

Background: Fibromyalgia can affect the control of asthma when both diseases are present in a single patient.

Objectives: To characterize asthma in patients with concomitant fibromyalgia to assess whether fibromyalgia is an independent factor of asthma severity that influences poor asthma control. We also evaluated how dyspnea is perceived by patients in order to demonstrate that alterations in the perception of airway obstruction may be responsible for poor asthma control.

Methods: This was a cross-sectional case–control multicenter study, in which 56 patients in the asthma and fibromyalgia group were matched to 36 asthmatics by sex, approximate age, and asthma severity level. All patients were women. Study variables included the Asthma Control Test (ACT), the Mini Asthma Quality of Life Questionnaire (MiniAQLQ), the Nijmegen hyperventilation syndrome questionnaire, the Hospital Anxiety and Depression Scale, and perception of dyspnea after acute bronchoconstriction.

Results: Although patients in both study groups showed similar asthma severity and use of anti-asthmatic drugs, patients in the asthma and fibromyalgia group showed lower scores on the ACT and MiniAQLQ questionnaires, and higher scores of anxiety and depression as well as hyperventilation compared to asthma patients without fibromyalgia. All these differences were statistically significant.

Conclusions: Fibromyalgia in patients with asthma influences poor control of the respiratory disease and is associated with altered perception of dyspnea, hyperventilation syndrome, high prevalence of depression and anxiety, and impaired quality of life.

Clinical implications: Fibromyalgia may be considered a risk factor for uncontrolled asthma in patients suffering from asthma and fibromyalgia concomitantly.