This study shows that the different measures used are broadly comparable when four or more cases per combination have been collected.

OBJECTIVES:To study the effectiveness of haloperidol prophylaxis on incidence, severity, and duration of postoperative delirium in elderly hip-surgery patients at risk for delirium. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Large medical school-affiliated general hospital in Alkmaar, the Netherlands. PARTICIPANTS: A total of 430 hip-surgery patients aged 70 and older at risk for postoperative delirium. INTERVENTION: Haloperidol 1.5 mg/d or placebo was started preoperatively and continued for up to 3 days postoperatively. Proactive geriatric consultation was provided for all randomized patients. MEASUREMENTS: The primary outcome was the incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria). Secondary outcomes were the severity of delirium (Delirium Rating Scale, revised version-98 (DRS-R-98)), the duration of delirium, and the length of hospital stay. RESULTS: The overall incidence of postoperative delirium was 15.8%. The percentage of patients with postoperative delirium in the haloperidol and placebo treatment condition was 15.1% and 16.5%, respectively (relative risk 5 0.91, 95% confidence interval (CI) 5 0.6-1.3); the mean highest DRS-R-98 score AE standard deviation was 14.4 AE 3.4 and 18.4 AE 4.3, respectively (mean difference 4.0, 95% CI 5 2.0-5.8; Po.001); delirium duration was 5.4 versus 11.8 days, respectively (mean difference 6.4 days, 95% CI 5 4.0-8.0; Po.001); and the mean number of days in the hospital was 17.1 AE 11.1 and 22.6 AE 16.7, respectively (mean difference 5.5 days, 95% CI 5 1.4-2.3; Po.001). No haloperidol-related side effects were noted. CONCLUSION: Low-dose haloperidol prophylactic treatment demonstrated no efficacy in reducing the incidence of postoperative delirium. It did have a positive effect on the severity and duration of delirium. Moreover, haloperidol reduced the number of days patients stayed in the hospital, and the therapy was well tolerated.

This observational study suggests that statins may have a protective effect against cancer.

Objective: To assess whether use of oral glucocorticoids is associated with cardiovascular and cerebrovascular morbidity. Design and setting: Nested case-control study within a cohort of patients (> 50 years old) with at least one prescription for oral or non-systemic glucocorticoids. Data were from the general practice research database. Patients: 50 656 patients were identified with a first record for ischaemic heart disease (International classification of diseases, ninth revision (ICD-9) codes 410, 411, 413, and 414), ischaemic stroke or transient ischaemic attack (ICD-9 codes 430-436), or heart failure (ICD-9 code 428) between 1988 and 1998. One control was matched to each case by sex, age, general practice, underlying disease, and calendar time. Main outcome measure: Odds ratio (OR) of cardiovascular or cerebrovascular events in patients using oral glucocorticoids compared with non-users.Results: There was a significant association between ever use of oral glucocorticoids and any cardiovascular or cerebrovascular outcome (adjusted OR 1.25, 95% confidence interval (CI) 1.21 to 1.29). The association was stronger for current use of oral glucocorticoids than for recent or past use. Among current users, the highest ORs were observed in the group with the highest average daily dose, although the dose-response relation was not continuous. Current use was associated with an increased risk of heart failure (adjusted OR 2.66, 95% CI 2.46 to 2.87), which was consistent between patients with rheumatoid arthritis, patients with chronic obstructive pulmonary disease, and patients without either of the two conditions. Also, current use was associated with a smaller increased risk of ischaemic heart disease (OR 1.20, 95% CI 1.11 to 1.29). Conclusions: Oral glucocorticoid use was identified as a risk factor for heart failure. However, the evidence remains observational and only a randomised controlled trial of glucocorticoid treatment versus other disease modifying agents is likely to distinguish the importance of the underlying disease activity from its treatment in predicting cardiovascular outcomes. G lucocorticoids are widely prescribed drugs in modern medicine. Data from the UK suggest that nearly 1% of the total adult population use oral glucocorticoids.

No abstract

The driving performance is easily impaired as a consequence of the use of alcohol and/or licit and illicit drugs. However, the role of drugs other than alcohol in motor vehicle accidents has not been well established. The objective of this study was to estimate the association between psychoactive drug use and motor vehicle accidents requiring hospitalisation. A prospective observational case-control study was conducted in the Tilburg region of The Netherlands from May 2000 to August 2001. Cases were car or van drivers involved in road crashes needing hospitalisation. Demographic and trauma related data was collected from hospital and ambulance records. Urine and/or blood samples were collected on admission. Controls were drivers recruited at random while driving on public roads. Sampling was conducted by researchers, in close collaboration with the Tilburg police, covering different days of the week and times of the day. Respondents were interviewed and asked for a urine sample. If no urine sample could be collected, a blood sample was requested. All blood and urine samples were tested for alcohol and a number of licit and illicit drugs. The main outcome measures were odds ratios (OR) for injury crash associated with single or multiple use of several drugs by drivers. The risk for road trauma was increased for single use of benzodiazepines (adjusted OR 5.1 (95% Cl: 1.8-14.0)) and alcohol (blood alcohol concentrations of 0.50-0.79 g/l, adjusted OR 5.5 (95% Cl: 1.3-23.2) and >or=0.8 g/l, adjusted OR 15.5 (95% Cl: 7.1-33.9)). High relative risks were estimated for drivers using combinations of drugs (adjusted OR 6.1 (95% Cl: 2.6-14.1)) and those using a combination of drugs and alcohol (OR 112.2 (95% Cl: 14.1-892)). Increased risks, although not statistically significantly, were assessed for drivers using amphetamines, cocaine, or opiates. No increased risk for road trauma was found for drivers exposed to cannabis. The study concludes that drug use, especially alcohol, benzodiazepines and multiple drug use and drug-alcohol combinations, among vehicle drivers increases the risk for a road trauma accident requiring hospitalisation.

Background Intravenous-busulfan (IV-busulfan) combined with therapeutic drug monitoring to guide dosing improves outcomes after allogeneic hematopoietic cell transplantation (allo-HCT). The best method to estimate busulfan exposure and the optimal exposure in children/young adults remains unclear. We therefore evaluated three approaches to estimate IV-Bu exposure (expressed as cumulative-area-under-the-curve; AUC) and associated busulfan-AUC with clinical outcomes in children/young adults undergoing allo-HCT. Methods In this retrospective analysis, patients (0.1–30.4 years) receiving busulfan-based conditioning regimen from 15 centers were included. Cumulative AUC was calculated by numerical integration using non-linear mixed effect modeling (AUCNONMEM), non-compartmental analysis (AUC0-infinity and AUC to the end of the dose interval AUC0-tau) and by individual centers using a variety of approaches (AUCcenter). Main outcome of interest was event-free survival (EFS). Other outcomes of interest were overall survival, graft-failure, relapse, transplantation related mortality (TRM), acute toxicity (veno-occlusive disease (VOD) and/or acute graft versus-host disease (aGvHD), chronic GvHD (cGvHD) and cGVHD-free event-free survival (GEFS). Propensity score adjusted cox proportional hazard models, Weibull models, and Fine-Gray competing risk regressions were used. Results 674 patients were included (41% malignant, 59% non-malignant) Estimated 2-year EFS was 69.7%. The median busulfan AUCNONMEM was 74.4 mg*h/L (CI95% 31.1–104.6 mg*h/L). The median AUCNONMEM correlated poorly with AUCcenter (R2 = 0.254). Patients with optimal IV-busulfan AUC of 78–101 mg*h/L showed 81% EFS at 2 years compared to 66.1% and 49.5% in the low (<78 mg*h/L) and high (>101 mg*h/L) busulfan AUC group respectively (P=0.011). Graft-failure/relapse occurred more frequently in the low AUC group (HR=1.75 P<0.001). Acute toxicity, cGvHD and TRM was significantly higher in the high AUC group (HR 1.69, 2.99 and 1.30), independent of indication. Interpretation These results demonstrate that improved clinical outcomes may be achieved by targeting the busulfan-AUC to 78–101 mg*h/L using a new validated pharmacokinetic-model for all indications.

Objective. To design and validate a new questionnaire for identifying patients with methotrexate (MTX) intolerance, and to determine the prevalence of MTX intolerance in patients with juvenile idiopathic arthritis (JIA) using this questionnaire.Methods. The MTX Intolerance Severity Score (MISS) questionnaire was constructed, consisting of 5 domains: stomach ache, nausea, vomiting, sore mouth, and behavioral symptoms. The domains each consisted of 3 questions pertaining to the presence of a symptom upon, prior to (anticipatory), and when thinking of (associative) MTX intake. The MISS questionnaire was validated in 86 patients by determining its discriminative power between patients with and those without MTX intolerance, identified as such by a gold standard (physician's opinion). Using the MISS questionnaire, the prevalence of MTX intolerance was determined in 297 JIA patients.Results. The MISS questionnaire discriminated well between MTX-intolerant and MTX-tolerant patients. A cutoff score of 6 yielded the best sensitivity (88%) and specificity (80%). MTX intolerance was found in 150 (50.5%) of 297 patients. Of 220 patients receiving oral MTX, 98 (44.5%) experienced MTX intolerance, whereas 67.5% of 77 patients receiving parenteral MTX experienced intolerance to the drug (P ‫؍‬ 0.001).Conclusion. Our findings indicate that the MISS questionnaire is a highly sensitive and specific tool for the diagnosis of MTX intolerance, and that there is a high prevalence of MTX intolerance among JIA patients. The prevalence of intolerance in patients receiving parenteral MTX exceeds that in patients receiving oral MTX. The frequent occurrence of anticipatory and associative symptoms suggests that classic conditioning plays an important role in MTX intolerance.