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.

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.

Unexpected high prevalence of metabolic disorders and chronic disease among young male draftees--the Swiss Army XXI experience.

QUESTIONS: What are the benefits of laboratory screening examinations entailed in the new army recruitment concept (Swiss Army XXI)? PRINCIPLES/METHODS: Between January 1 and June 30, 2004, a total of 7714 of 11,322 (68%) draftees from 6 Swiss army recruitment centres underwent clinical examination and laboratory testing. RESULTS: In 1.7% of the draftees we found elevated levels of the C-reactive protein (CRP) as evidence of infection or inflammation. Although we found no case of acute hepatitis, 16 draftees had active hepatitis B and 1 patient had active hepatitis C. Diseases, which were found by laboratory screening, and which forbid service in the army, included Crohn's disease, terminal renal insufficiency and essential thrombocytosis. In conditions such as anaemia (0.1%) or latent iron deficiency (7.2%), the cause may have to be elucidated before the start of military training. In other draftees (9.8%), we found elevated alanine-amino-transferase (ALAT) levels as a hint to possible alcohol abuse, which might impair the ability to serve in special units of the army. Finally, elevated levels of ferritin (0.1%), glucose (0.4%), and cholesterol (1.4%) may indicate iron overload/haemochromatosis, impaired glucose tolerance or even overt diabetes mellitus and hypercholesterolaemia. CONCLUSIONS: The results of our studies indicate that laboratory evaluation may confirm findings of the medical examination and may help to explain unspecific symptoms. Draftees with severe diseases and conditions caused by serious underlying disease can be excluded from military services early on the basis of laboratory testing. Future cost benefit analyses will have to show whether laboratory screening and consecutive early preventive measures are also advantageous to society as a whole and will reduce public health costs.

Progesterone increase under DHEA-substitution in males.

Two case reports of men suffering from excessive fatigue and depression are presented, both treated with 50 or 25 mg DHEA per day over a period of 1 year. Under DHEA treatment one subject reported being less tired and the other experienced improved well-being without depressive episodes and an increase in libido. Investigations of sex hormone parameters in plasma before and under treatment revealed a decrease of testosterone and an increase of progesterone in both, possibly dose-dependent to DHEA application. It is hypothesised that the increase of progesterone is parallel to an increase of its metabolite allopregnanolone (which was not determined), that might explain the improvement in well-being. The increase of progesterone under DHEA supplementation in males should receive further attention.

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.