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.

Subclinical hypothyroidism: summary of evidence in 2014

Subclinical hypothyroidism, which is defined as elevated thyroid-stimulating hormone (TSH) levels with free thyroxine concentrations within the reference range, is a common disorder that increases with age and affects up to 18% of the elderly, with a higher prevalence in women compared to men. Prospective data have shown an increased risk of coronary heart disease events, heart failure, and cardiovascular mortality among affected adults. Conflicting results have been found on the association between subclinical hypothyroidism and cognitive impairment, depression and the risk of fractures. Management strategies including screening and treatment of subclinical hypothyroidism are still controversial, while the ongoing European randomised controlled trial "TRUST" targets to solve these uncertainties. This narrative review aims to assess current evidence on the clinical aspects, as well as screening and treatment recommendations in adults with subclinical hypothyroidism.

Le Synhedrin ou Grand conseil de Jérusalem : son origine et son histoire

Felix Blum

Low statin use in adults hospitalized with acute coronary syndrome.

OBJECTIVE To assess recommended and actual use of statins in primary prevention of cardiovascular disease (CVD) based on clinical prediction scores in adults who develop their first acute coronary syndrome (ACS). METHOD Cross-sectional study of 3172 adults without previous CVD hospitalized with ACS at 4 university centers in Switzerland. The number of participants eligible for statins before hospitalization was estimated based on the European Society of Cardiology (ESC) guidelines and compared to the observed number of participants on statins at hospital entry. RESULTS Overall, 1171 (37%) participants were classified as high-risk (10-year risk of cardiovascular mortality ≥5% or diabetes); 1025 (32%) as intermediate risk (10-year risk <5% but ≥1%); and 976 (31%) as low risk (10-year risk <1%). Before hospitalization, 516 (16%) were on statins; among high-risk participants, only 236 of 1171 (20%) were on statins. If ESC primary prevention guidelines had been fully implemented, an additional 845 high-risk adults (27% of the whole sample) would have been eligible for statins before hospitalization. CONCLUSION Although statins are recommended for primary prevention in high-risk adults, only one-fifth of them are on statins when hospitalized for a first ACS.

Subclinical thyroid dysfunction and fracture risk: a meta-analysis.

IMPORTANCE Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. OBJECTIVE To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. DATA SOURCES AND STUDY SELECTION The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. DATA EXTRACTION Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH <0.45 mIU/L), and subclinical hypothyroidism (TSH ≥4.50-19.99 mIU/L) with normal thyroxine concentrations. MAIN OUTCOME AND MEASURES The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. RESULTS Among 70,298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762,401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56,471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25,901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21,722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20,328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk. CONCLUSIONS AND RELEVANCE Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures.

Variation in treatment strategies of Swiss general practitioners for subclinical hypothyroidism in older adults.

QUESTIONS UNDER STUDY As the best management of subclinical hypothyroidism is controversial, we aimed to assess variations in treatment strategies depending on different Swiss regions, physician and patient characteristics. METHODS We performed a case-based survey among general practitioners (GPs) in different Swiss regions, which consisted of eight hypothetical cases presenting a female patient with subclinical hypothyroidism and nonspecific complaints differing by age, vitality status and thyroid-stimulating hormone (TSH) concentration. RESULTS A total of 262 GPs participated in the survey. There was considerable variation in the levothyroxine starting dose chosen by GPs, ranging from 25 µg to 100 µg. Across the Swiss regions, GPs in the Bern region were significantly more inclined to treat, with a higher probability of initiating treatment (60%, p = 0.01) and higher mean starting doses (45 µg, p <0.01) compared with the French-speaking region (44%, 36 µg); the Zurich region had intermediate values (52%, 39 µg). We found no association between treatment rate and other physician characteristics. GPs were more reluctant to initiate treatment in 85-year-old than in 70-year-old women (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.63-0.94), and more likely to treat women with a TSH of 15 mU/l than those with a TSH of 6mU/l (OR 8.71, 95% CI 6.21-12.20). CONCLUSIONS There are strong variations in treatment strategies for elderly patients with subclinical hypothyroidism across different Swiss regions, including use of higher starting doses than the recommended 25 µg in the Swiss guidelines, which recommend a starting dose of 25 µg. These variations likely reflect the current uncertainty about the benefits of treatment, which arise from the current lack of evidence from adequately powered clinical trials.

Eine Verhandlung des deutschen Vaterlands-Vereins zu Leipzig, in der Versammlung vom 30. Mai 1848

Boberach: Eine lebhafte Debatte, an der sich der Verleger Reclam, der Historiker Wuttke, Robert Blum und J. G. Günther MdNV beteiligen, führt zu dem Ergebnis, daß der Verein sich zur Zeit nicht offen für die Republik aussprechen, aber regelmäßig über die Staatsform diskutieren soll

Sind indirecte Wahlen zur constituirenden Deutschen Nationalversammlung erlaubt und zweckmäßig? Als in der zweiten Sitzung der Frankfurter Versammlung deutscher Volksmänner ...

Boberach: Wie bereits Blum im Vorparlament dargelegt hat, können indirekte Wahlen den Volkswillen verfälschen

Des deutschen Volkes Erhebung im Jahre 1848, sein Kampf um freie Institutionen und sein Siegesjubel : ein Volks- und Erinnerungsbuch für die Mit- und Nachwelt

Boberach: Behandelt werden die Märzereignisse und Mißstände vor der Revolution, insbesondere die Bürokratie, kommunistische und sozialistische Bestrebungen, die Lichtfreunde, Itzstein und die badischen Kammern, der Hungertyphus in Oberschlesien, die Entwicklung in Hannover, Sachsen und Württemberg und von den Politikern besonders Blum, Jacoby und Gagern. - Welsch (Projektbearbeiter): Mit lithographischen Porträts der Politiker Bassermann, Camphausen, Simon, von Itzstein, Graf von Schwerin, von Auerswald, Braun, von Vincke, Hansemann, von Beckerath, Welcker, Jordan, Erzherzog Johann, Robert Blum, Todt, Jacoby, Dittmer, Uhland, von Soiron sowie von Gagern

Die Blutzeugen der deutschen Volkserhebung, oder Scenen aus dem tragischen Ende der neu'sten Volksaufstände in Deutschland

Boberach: Knappen Darstellungen der Ereignisse in Baden, der Pfalz und Dresden 1849 und der Wiener Oktoberrevolution 1848 folgen Beiträge über Max Dortu, Gustav Schlöffel, Blum, August Bernigau, Messenhäuser [sic!], Lamartine, Bem, Graf Batthyani, Struve, Greiner, P. Fries, Reichard, Hepp, Hanitz, Nikolaus Schmitt, Cullmann [sic!], Goldmark, d'Ester, Franz Umbscheiden, Blenker, Raquillet [sic!], Sznayder [sic!], Zitz, Eisenstuck, Crzeriak, Fr. Ludwig Krahn, Dr. Sander, Jodokus Temme, Schulze-Delitzsch, Carl Vogt; eingefügt sind Briefe und Aufzeichnungen über die Prozesse in Rastatt, die Prager Unruhen im Juni 1848, die Kämpfe in Ungarn und die Lage der Emigranten, ferner Gedichte, u.a. von Herwegh

Devisen der Transparente, welche bei der festlichen Illumination Frankfurts am 1. April 1848 zu Ehren der deutschen Volksmänner ausgestellt waren

Boberach: Wiedergegeben sind 216 Texte im Umfang zwischen einem (z.B. "Einigkeit macht stark") und 16 Versen und die Beschreibungen von zugehörigen und von vier nur bildlichen Darstellungen (z.B.: "Eine geharnischte Jungfrau - Germania -, die einen Drachen besiegt."). Die meisten Texte fordern zur Einigkeit auf, einige wenden sich gegen das überwundene System Metternichs. Als Vorkämpfer der liberalen Bewegung werden u.a. Jahn, Arndt, Blum, Gagern genannt, als Aussteller lediglich einmal "Sämtliche Gesellen des Schreinerhandwerks"

Zeitgenossen in Biographieen und Porträts : ein Volksbuch

Boberach: Behandelt werden Alexander Freiherr von Soiron, Jakob Venedey, Oskar von Wydenbrugk, Gottlieb Christian Schüler, Heinrich Freiherr von Gagern, Ernst Moritz Arndt, Carl Theodor Welcker, Friedrich Ludwig Jahn, Franz Schuselka, Friedrich Siegmund Jucho, Johann Gustav Moritz Heckscher, Felix Fürst von Lichnowsky, Friedrich Christoph Dahlmann, Anton Ritter von Schmerling, Franz Raveaux, Heinrich Simon, Johann Jacoby, Robert Blum, Johann Erzherzog von Österreich, Louis Cavaignac, Friedrich Hecker, Friedrich von Wrangel, Joseph Wenzel Graf Radetzky, Joseph Freiherr Jellachich von Buszin, Hermann Rollett, Alphonse de Lamartine, Georg Jung, Louis Napoleon, Ernst Alfred Fürst zu Windischgrätz, Ferdinand Freiligrath, Ludwig Kossuth, Emanuel Geibel