Severe irritability associated with statin cholesterol-lowering drugs.

BACKGROUND: As use of a drug becomes widespread, the full spectrum of its effects becomes clearer. Although a link has been suggested between low or lowered cholesterol and irritability/aggression, less is known about possible links between irritability and statins. AIM: To assess the possible connection of statin usage to severe irritability. DESIGN: Case series. METHODS: Six patients referred or self-referred with irritability and short temper on statin cholesterol-lowering drugs completed a survey providing information on character of behavioural effect, time-course of onset and recovery, and factors relevant to drug adverse effect causality. RESULTS: In each case the personality disruption, once evident, was sustained until statin use was discontinued; and resolved promptly with drug cessation. In four patients, re-challenge with statins occurred, and led to recrudescence of the problem. All patients experienced other recognized statin adverse effects while on the drug. Manifestations of severe irritability included homicidal impulses, threats to others, road rage, generation of fear in family members, and damage to property. DISCUSSION: Case series invariably raise more questions than they can answer. These case reports suggest that severe irritability may occur in some statin users. Although this adverse effect may be rare, potentially life-threatening adverse effects of drugs must be taken seriously.

Logistic regression in the medical literature: standards for use and reporting, with particular attention to one medical domain.

Logistic regression (LR) is a widely used multivariable method for modeling dichotomous outcomes. This article examines use and reporting of LR in the medical literature by comprehensively assessing its use in a selected area of medical study. Medline, followed by bibliography searches, identified 15 peer-reviewed English-language articles with original data, employing LR, published between 1985 and 1999, pertaining to patient interest in genetic testing for cancer susceptibility. Articles were examined for each of 10 criteria for proper use and reporting of LR models. Substantial shortcomings were found in both use of LR and reporting of results. For many studies, the ratio of the number of outcome events to predictor variables (events per variable) was sufficiently small to call into question the accuracy of the regression model. Additionally, no studies reported validation analysis, regression diagnostics, or goodness-of-fit measures. It is recommended that authors, reviewers, and editors pay greater attention to guidelines concerning the use and reporting of LR models.

A review of health-related quality-of-life measures in stroke.

The objective of this review was to evaluate health-related quality of life (HR-QOL) measures for use with patients with stroke. HR-QOL measures are increasingly used for assessment in many health conditions; these measures may serve an important role in evaluating the impact of stroke and of stroke interventions. HR-QOL measures used in patients with stroke should: (i) cover the domains of HR-QOL that may be affected by stroke; (ii) have administration characteristics suitable for use in patients with stroke; and (iii) have undergone reliability and validity assessment in patients with stroke. The present study evaluates HR-QOL measures with reference to these requirements. A systematic literature review was conducted to identify and evaluate HR-QOL measures of potential use in studies of patients with stroke. Identified measures were assessed with regard to stroke-relevant domains covered, measure characteristics (e.g. self-administration versus administration by an interviewer, interviewer time to complete) and psychometric properties of reliability and validity. The measures evaluated vary widely on domains covered, and limited assessment of the performance of HR-QOL measures has been conducted in patients with stroke. No existing measure comprehensively covers all relevant domains or addresses fully the issues of obtaining and combining HR-QOL assessments in patients and proxies in many stroke populations. Additional psychometric testing in stroke populations is needed for existing HR-QOL measures. In addition, stroke-targeted HR-QOL measures need to be developed and evaluated with patients with stroke.

Low cholesterol and violent crime.

BACKGROUND: Community cohort studies and meta-analyses of randomized trials have shown a relation between low or lowered cholesterol and death by violence (homicide, suicide, accident); in primates, cholesterol reduction has been linked to increased behavioral acts of aggression (Kaplan J, Manuck S. The effects of fat and cholesterol on aggressive behaviour in monkeys. Psychosom. Med 1990;52:226-7; Kaplan J, Shively C, Fontenot D, Morgan T, Howell S, Manuck S et al. Demonstration of an association among dietary cholesterol, central serotonergic activity, and social behaviour in monkeys. Psychosom. Med 1994;56:479-84.). In this study we test for the first time whether cholesterol level is related to commission of violent crimes against others in a large community cohort. METHODS: We merged one-time cholesterol measurements on 79,777 subjects enrolled in a health screening project in Varmland, Sweden with subsequent police records for arrests for violent crimes in men and women aged 24-70 at enrollment; and with information on covariates. We performed a nested case control comparison of cholesterol in violent criminals - defined as those with two or more crimes of violence against others - to cholesterol in nonoffenders matched on age, enrollment year, sex, education and alcohol, using variable-ratio matching, with a nonparametric sign test. RESULTS: One hundred individuals met criteria for criminal violence. Low cholesterol (below the median) was strongly associated with criminal violence in unadjusted analysis (Men: risk ratio 1.94, P=0.002; all subjects risk ratio 2.32, P<0.001). Age emerged as a strong confounder. Adjusting for covariates using a matching procedure, violent criminals had significantly lower cholesterol than others identical in age, sex, alcohol indices and education, using a nonparametric sign test (P=0.012 all subjects; P=0.035 men). CONCLUSIONS: Adjusting for other factors, low cholesterol is associated with increased subsequent criminal violence.

The role of psychiatrists in primary care of patients with severe mental illness.

OBJECTIVE: This study sought to identify health conditions for which a primary care psychiatrist would be an appropriate treatment provider in an integrated model of health care delivery for persons with serious mental illness. A primary care psychiatrist is a psychiatrist with primary care training who is supervised by an on-site internist. METHODS: Rating methods for health conditions were adapted from those jointly developed by Rand and the University of California, Los Angeles. A consensus panel of 14 hospital administrators, internists, psychiatrists, and nursing service representatives from three southern California Veterans Affairs health care systems was convened. Eleven physician-panelists, including five psychiatrist, five internists, and a medical specialist, rated whether a general psychiatrist, a primary care psychiatrist, an internist, or a medical specialist could reasonably provide evaluation, treatment, or preventive care for uncomplicated instances of each of 344 physical health conditions or procedures. RESULTS: A primary care psychiatrist, with supervision by an internist, was rated as an appropriate treatment provider for most of the 344 conditions. The conditions included many of those cited by patients as the most common reasons for ambulatory care visits. Panelists identified some intrusive elements of primary care, such as a pelvic examination, as potentially injurious to the psychiatrist-patient relationship and inappropriate for performance by psychiatrists. CONCLUSIONS: This study took the first essential step in evaluating the integration of primary care into the psychiatric setting. Further research is needed to determine whether use of primary care psychiatrists will increase access to primary care by persons with serious mental illness and improve outcomes.

Epidemiologic aspects of lipid abnormalities.

Existing cholesterol guidelines aimed at preventing cardiovascular disease emphasize the role of total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol in lipid management decisions, with a subsidiary role for high-density lipoprotein (HDL) cholesterol in guiding treatment and little role for triglycerides. In this article, epidemiologic evidence is reviewed relating to the independent value of lipid factors in prediction of cardiovascular disease risk, including TC, LDL cholesterol, HDL cholesterol, very-low-density lipoprotein (VLDL) cholesterol and triglycerides, LDL particle size ("pattern B"), and the TC/HDL-cholesterol ratio. Several observations are highlighted. Triglycerides appear to be an independent risk factor in specific populations. Postprandial triglycerides may be superior to fasting triglycerides as a predictor of risk. LDL particle size does not have independent predictive value after adjustment for triglycerides. Particular emphasis is placed on the observation that the single most predictive lipid factor is the TC/HDL-cholesterol ratio, which implicitly incorporates information on both LDL and triglycerides in the numerator. This is the best predictor both of outcome and of treatment benefit, and its predictive value appears to be maintained into older age. It is concluded that increasing emphasis should be placed on the TC/HDL cholesterol ratio in epidemiologic analyses and in monitoring patients on therapy for dyslipidemia.

Cholesterol and violence: is there a connection?

PURPOSE: To determine whether the seeming relation between low or lowered cholesterol levels and violence is consistent with causality according to Hill's criteria and whether construct validity is supported by convergence of findings across different types of studies. DATA SOURCES: Search of the MEDLINE database for English-language articles published between 1965 and 1995 was supplemented by searches of the PsycINFO and Current Contents databases and bibliographies of relevant articles. STUDY SELECTION: Peer-reviewed observational and experimental articles and meta-analyses that presented original research; related cholesterol levels to behaviorally defined violence; and, if experimental, had single-factor (lipid-only) intervention. DATA EXTRACTION: Studies were grouped according to type. Data on the relation of violence to cholesterol levels from each study were recorded. DATA SYNTHESIS: Observational studies (including cohort, case-control, and cross-sectional studies) consistently showed increased violent death and violent behaviors in persons with low cholesterol levels. Some meta-analyses of randomized trials found excess violent deaths in men without heart disease who were randomly assigned to receive cholesterol-lowering therapy. Experimental studies showed increased violent behaviors in monkeys assigned to low-cholesterol diets. Human and animal research indicates that low or lowered cholesterol levels may reduce central serotonin activity, which in turn is causally linked to violent behaviors. Many trials support a significant relation between low or lowered cholesterol levels and violence (P < 0.001). CONCLUSIONS: A significant association between low or lowered cholesterol levels and violence is found across many types of studies. Data on this association conform to Hill's criteria for a causal association. Concerns about increased risk for violent outcomes should figure in risk-benefit analyses for cholesterol screening and treatment.