Multivariable analysis of total cholesterol levels in male Swiss Armed Forces conscripts 2006-2012 (N = 174,872)

BACKGROUND: Cholesterol is an important contributor to morbidity and mortality risks due to its association with obesity, cardiovascular disease, and cancer. A system of mandatory military conscription is a useful tool for disease-risk monitoring in a given male population. Swiss military conscription data are representative for more than 90% of a given male birth cohort (with Swiss citizenship). The medical examination also includes voluntary laboratory testing, for which approximately 65% of the young men present at conscription give consent. METHODS: Here we present the temporal and subgroup analyses of total serum cholesterol levels (TCL) among Swiss conscripts from 2006 to 2012 (N = 174,872; mean age = 19.75 years). The voluntary blood samples were tested by a central laboratory (Viollier AG) with identical measurement standards and strict quality control. To test differences in TCL by socioeconomic occupational status, sports test performance, Body Mass Index (BMI), age, and place of residence of the conscripts we used a multivariable regression model with TCL as dependent variable. RESULTS: Mean TCL decreased significantly, by 0.125 mmol/l (95% CI 0.108-0.142, p < 0.001) from 4.225 mmol/l (95% CI 4.210-4.240) in 2006 to 4.100 mmol/l (95% CI 4.091-4.109) in 2012. Similarly, the prevalence of conscripts with an elevated TCL ≥ 5.17 mmol/l decreased from ≥ 10.2% prior to 2011 to 6.9% in 2011 and 8.2% in 2012. Multivariate regression showed an association between elevated TCL and lower socioeconomic occupational status, lower sports test performance, higher BMI, higher age, and area of residence. There was no longer a significant increase in mean TCL among the three grades of obesity (BMI ≥ 30.0 kg/m2) as defined by the WHO. Within the BMI categories of normal weight and overweight, TCL was stratified by sports performance (better sports performance = lower TCL). CONCLUSION: Decreasing TCL in 2011 and 2012 fits the known pattern of conscripted persons' stabilizing BMI and sports test performance of the conscripts in recent years. However, small temporal drifts within the laboratory analyses cannot be ruled out as confounding factors. In conclusion, identifying subgroups with unfavorable lipid profiles will contribute to the continuing success of intensified public health programs

Corticosteroid treatment for community-acquired pneumonia--the STEP trial: study protocol for a randomized controlled trial

BACKGROUND Community-acquired pneumonia (CAP) is the third-leading infectious cause of death worldwide. The standard treatment of CAP has not changed for the past fifty years and its mortality and morbidity remain high despite adequate antimicrobial treatment. Systemic corticosteroids have anti-inflammatory effects and are therefore discussed as adjunct treatment for CAP. Available studies show controversial results, and the question about benefits and harms of adjunct corticosteroid therapy has not been conclusively resolved, particularly in the non-critical care setting. METHODS/DESIGN This randomized multicenter study compares a treatment with 7 days of prednisone 50 mg with placebo in adult patients hospitalized with CAP independent of severity. Patients are screened and enrolled within the first 36 hours of presentation after written informed consent is obtained. The primary endpoint will be time to clinical stability, which is assessed every 12 hours during hospitalization. Secondary endpoints will be, among others, all-cause mortality within 30 and 180 days, ICU stay, duration of antibiotic treatment, disease activity scores, side effects and complications, value of adrenal function testing and prognostic hormonal and inflammatory biomarkers to predict outcome and treatment response to corticosteroids. Eight hundred included patients will provide an 85% power for the intention-to-treat analysis of the primary endpoint. DISCUSSION This largest to date double-blind placebo-controlled multicenter trial investigates the effect of adjunct glucocorticoids in 800 patients with CAP requiring hospitalization. It aims to give conclusive answers about benefits and risks of corticosteroid treatment in CAP. The inclusion of less severe CAP patients will be expected to lead to a relatively low mortality rate and survival benefit might not be shown. However, our study has adequate power for the clinically relevant endpoint of clinical stability. Due to discontinuing glucocorticoids without tapering after seven days, we limit duration of glucocorticoid exposition, which may reduce possible side effects. TRIAL REGISTRATION 7 September 2009 on ClinicalTrials.gov: NCT00973154

Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial

BACKGROUND Clinical trials yielded conflicting data about the benefit of adding systemic corticosteroids for treatment of community-acquired pneumonia. We assessed whether short-term corticosteroid treatment reduces time to clinical stability in patients admitted to hospital for community-acquired pneumonia. METHODS In this double-blind, multicentre, randomised, placebo-controlled trial, we recruited patients aged 18 years or older with community-acquired pneumonia from seven tertiary care hospitals in Switzerland within 24 h of presentation. Patients were randomly assigned (1:1 ratio) to receive either prednisone 50 mg daily for 7 days or placebo. The computer-generated randomisation was done with variable block sizes of four to six and stratified by study centre. The primary endpoint was time to clinical stability defined as time (days) until stable vital signs for at least 24 h, and analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00973154. FINDINGS From Dec 1, 2009, to May 21, 2014, of 2911 patients assessed for eligibility, 785 patients were randomly assigned to either the prednisone group (n=392) or the placebo group (n=393). Median time to clinical stability was shorter in the prednisone group (3·0 days, IQR 2·5-3·4) than in the placebo group (4·4 days, 4·0-5·0; hazard ratio [HR] 1·33, 95% CI 1·15-1·50, p<0·0001). Pneumonia-associated complications until day 30 did not differ between groups (11 [3%] in the prednisone group and 22 [6%] in the placebo group; odds ratio [OR] 0·49 [95% CI 0·23-1·02]; p=0·056). The prednisone group had a higher incidence of in-hospital hyperglycaemia needing insulin treatment (76 [19%] vs 43 [11%]; OR 1·96, 95% CI 1·31-2·93, p=0·0010). Other adverse events compatible with corticosteroid use were rare and similar in both groups. INTERPRETATION Prednisone treatment for 7 days in patients with community-acquired pneumonia admitted to hospital shortens time to clinical stability without an increase in complications. This finding is relevant from a patient perspective and an important determinant of hospital costs and efficiency. FUNDING Swiss National Science Foundation, Viollier AG, Nora van Meeuwen Haefliger Stiftung, Julia und Gottfried Bangerter-Rhyner Stiftung