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Purpose Recently, non-osmotic tests such as glucagon, arginine or macimorelin stimulation were assessed for the ability to evaluated posterior pituitary function. Results showed that glucagon and arginine, but not macimorelin, stimulate copeptin secretion (as a surrogate marker of vasopressin) and, therefore, provide novel tests to assess the posterior pituitary. The exact underlying mechanism behind the stimulatory effect remain elusive.Methods This study combined data from three diagnostic studies conducted at the University Hospital Basel, Switzerland. In total, 80 healthy adults underwent the glucagon (n=22), arginine (n=30), and macimorelin (n= 28) stimulation test. The primary objective was to investigated glucose dynamics upon glucagon, arginine, and macimorelin stimulation tests and its effect on plasma copeptin release.Results Upon glucagon stimulation, the median [IQR] glucose level at baseline was 5.0 [4.6, 5.2] mmol/l, peaked to 8.1 [7.2, 9.4] mmol/l at 30 minutes and decreased to a minimum of 3.8 [3.5, 4.5] mmol/l at 120 minutes. The median copeptin increased upon glucagon stimulation by 7.6 [2.4, 28.0] pmol/l. Upon arginine, the glucose level at baseline was 4.9 [4.8, 5.5] mmol/l, peaked to 6.0 [5.2, 6.4] mmol/l at 30 minutes and decreased to a minimum of 4.3 [3.8, 4.8] mmol/l at 60 minutes. The median copeptin increased upon arginine stimulation by 4.5 [2.9, 7.5] pmol/l. Upon macimorelin, glucose levels showed no notable dynamics over the 120 minutes, and no major change in copeptin was observed. In the pooled dataset, a decrease in glucose levels was significantly correlated with copeptin increase (ρ= 0.49, pConclusion We demonstrate a similar course in plasma glucose after glucagon and arginine stimulation, while macimorelin had no effect on glucose levels, and show a strong correlation between the decrease in glucose levels and increase in copeptin after glucagon and arginine stimulation.

IL (Interleukin)-1 antagonism decreases blood pressure in obese individuals. The underlying mechanisms are unknown. Based on experimental data, we hypothesized an effect of IL-1 antagonism via modulation of the renin-angiotensin-aldosterone system. In this explorative study, we examined shorter- (2 days) and longer-term effects (4 weeks) of IL-1 antagonism (anakinra/Kineret) on renin-angiotensin system peptide profiles and on hemodynamic parameters assessed by noninvasive measurement in obese (body mass index ≥30 kg/m 2 ) individuals from 2 interventional trials (a prospective interventional trial [n=73] and a placebo controlled-double blinded interventional trial [n=67]). A total of 140 patients were included. Systolic blood pressure decreased after short-term (absolute difference −5.2 mm Hg [95% CI, −8.5 to −1.8]; P =0.0006) and after longer-term treatment with anakinra (absolute difference −3.9 mm Hg [95% CI, −7.59 to −0.21]; P =0.04), with no change in blood pressure in the placebo group. Upon IL-1 antagonism, equilibrium levels of Ang II (angiotensin II), Ang I, aldosterone, and renin remained unchanged. In contrast, Ang (1–7) peptide levels increased after 4 weeks (between-group difference 16.35 pmol/L [95% CI, 1.22–30.17], P =0.03), as well as the Ang (1–7)/Ang II ratio (between-group difference 0.42 [95% CI, 0.17–0.67], P =0.02) in comparison to placebo. Consistently, the stroke systemic vascular resistance index significantly decreased in the anakinra group (between-group difference of −62.65 dyn/sec per cm −5 per m 2 [95% CI, −116.94 to −18.36], P =0.008, consistent with a 25% decrease). IL-1 antagonism increased the vasodilatory Ang (1–7) peptide after 4 weeks of treatment in obese individuals, paralleled by a decrease in peripheral vascular resistance. These findings point to an IL-1 mediated blood pressure-lowering mechanism via modulation of Ang (1–7). Registration— URL: https://www.clinicaltrials.gov . Unique identifiers: NCT02227420 and NCT02672592.

Glucocorticoids are frequently prescribed in inflammatory diseases and have recently experienced a boom in the treatment of COVID‐19. Small studies have shown an effect of glucocorticoids on inflammatory marker levels, but definitive proof is lacking. We investigated the influence of prednisone on inflammatory biomarkers in a previous placebo‐controlled, randomized‐controlled multicenter trial which compared a 7‐day treatment course of 50 mg prednisone to placebo in patients hospitalized with community‐acquired pneumonia (CAP). We compared levels of C‐reactive protein (CRP), procalcitonin (PCT), leukocyte and neutrophil count between patients with and without glucocorticoid treatment at baseline and on days 3, 5, 7, and at discharge by Wilcoxon tests and variance analysis. 356 patient data sets in the prednisone group and 355 in the placebo group were available for analysis. Compared to placebo, use of prednisone was associated with reductions in levels of CRP on days 3, 5, and 7, (mean difference of 46%, p < 0.001 for each time point). For PCT, no such difference was observed. Leukocyte and neutrophil count were higher in the prednisone group at all time points (mean difference of 27% for leukocytes and 33% for neutrophils, p < 0.001 for all time points). We conclude that after administration of glucocorticoids in CAP, patients had lower CRP levels and increased leukocyte and neutrophil count as compared to the placebo group. PCT levels were not different between treatment groups. PCT levels thus may more appropriately mirror the resolution of infection compared to more traditional inflammatory markers. This article is protected by copyright. All rights reserved

Background A previous study found community-acquired pneumonia (CAP) patients with imbalance of high inflammation and discordantly low cortisol levels to benefit most from adjunctive corticosteroid treatment. Our aim was to validate this hypothesis in a preplanned secondary analysis of the randomized controlled STEP trial. Methods Patients included in the STEP trial receiving 50 mg prednisone or placebo for 5 days were categorized based on pro-inflammatory cytokines (Interleukin-6/8/MCP-1), CRP and cortisol levels on admission into four groups (high/low inflammation and high/low cortisol). The primary combined end-point was mortality or ICU admission within 30 days. Results In total, 632 patients (315 prednisone, 317 placebo) were included in this analysis. Prednisone did not significantly reduce the risk for the primary end-point in patients with high cytokines/low cortisol and in any other subgroups. However, we noted some differences in the strength of corticosteroid effect in the different subgroups with stronger effects in patients with high cytokines [OR 0.44 (0.10,1.72)] compared to patients with low cytokines [OR 0.68 (0.30,1.5)] (P-interaction = 0.600). The effects did not differ according to cortisol levels. Conclusion The imbalance of high inflammation state and low cortisol levels did not predict treatment response to corticosteroids in patients with CAP. However, in line to previous research, inflammation as measured by cytokine levels irrespective of cortisol tended to predict treatment response to corticosteroids in CAP. Whether this concept may help to personalize corticosteroids to patients most likely benefitting from this treatment needs to be tested in future intervention trials.

Fibroblast growth factor-21 (FGF21) is elevated in patients with the metabolic syndrome. Although the exact underlying mechanisms remain ill-defined, chronic low-grade inflammation with increased Interleukin-(IL)-1β expression may be responsible. The aim of this study was to investigate effects of two different anti-inflammatory treatments (IL-1 antagonism or high-dose corticosteroids) on FGF21 in patients with the metabolic syndrome. This is a secondary analysis of two interventional studies in patients with obesity and features of the metabolic syndrome. Trial A was an interventional trial (n = 73) investigating short-term effects of the IL-1 antagonist anakinra and of dexamethasone. Trial B was a randomized, placebo-controlled, double-blinded trial (n = 67) investigating longer-term effects of IL-1 antagonism. In total, 140 patients were included in both trials. Median age was 55 years (IQR 44–66), 26% were female and median BMI was 37 kg/m2 (IQR 34–39). Almost half of the patients were diabetic (45%) and had increased c-reactive protein levels of 3.4 mg/L. FGF21 levels correlated with fasting glucose levels, HOMA-index, C-peptide levels, HbA1c and BMI. Short-term treatment with anakinra led to a reduction of FGF21 levels by − 200 pg/mL (95%CI − 334 to − 66; p = 0.004). No effect was detectable after longer-term treatment (between-group difference: − 8.8 pg/mL (95%CI − 130.9 to 113.3; p = 0.89). Acute treatment with dexamethasone was associated with reductions of FGF21 by -175 pg/mL (95%CI − 236 to − 113; p Trial registration: ClinicalTrials.gov Identifiers NCT02672592 and NCT00757276.

Purpose The test with the highest diagnostic accuracy for diabetes insipidus is copeptin measurement after hypertonic saline infusion. However, the procedure is cumbersome and unpleasant due to rapid sodium increase. An oral stimulation test would be highly desirable. Macimorelin, an oral ghrelin agonist, is a newly approved diagnostic test for growth hormone (GH) deficiency, but its effects on copeptin/vasopressin are unknown and the effects on other pituitary hormones only scarcely investigated. Methods In this prospective, interventional, proof-of-concept study Copeptin and anterior pituitary hormones were measured in 28 healthy volunteers on two test days at baseline, 30, 45, 60, 90 and 120 min after a single dose of macimorelin (first visit: 0.5 mg/kg, second visit: 0.75 mg/kg). Results Baseline copeptin levels were 5.26 pmol/L [1.57, 6.81] and did not change after macimorelin intake (0.5 mg/kg: maximal median change 0.40 [− 0.49, 0.65] pmol/L, p = 0.442; 0.75 mg/kg: − 0.13 [− 0.45, 0.17] pmol/L, p = 0.442. Median GH levels increased from 3.67 mU/L with a maximal median change of 94.66 [IQR 56.5; 110.96] mU/L, p Conclusion We confirm an increase of GH upon macimorelin in healthy volunteers. However, macimorelin did not stimulate copeptin and therefore does not provide an oral test alternative for the diagnosis of diabetes insipidus. Additionally, a stimulatory effect was seen for prolactin and fT4, but not for ACTH and gonadotropic hormones. Registration The trial was registered on ClinicalTrials.gov (NCT03844217) on February 18, 2019.

Background Hypernatraemia is common in inpatients and is associated with substantial morbidity. Its differential diagnosis is challenging, and delayed treatment may have devastating consequences. The most important hormone for the regulation of water homeostasis is arginine vasopressin, and copeptin, the C-terminal portion of the precursor peptide of arginine vasopressin, might be a reliable new parameter with which to assess the underlying cause of hypernatraemia. Methods In this prospective, multicentre, observational study conducted in two tertiary referral centres in Switzerland, 92 patients with severe hyperosmolar hypernatraemia (Na+ > 155 mmol/L) were included. After a standardised diagnostic evaluation, the underlying cause of hypernatraemia was identified and copeptin levels were measured. Results The most common aetiology of hypernatraemia was dehydration (DH) (n = 65 [71%]), followed by salt overload (SO) (n = 20 [22%]), central diabetes insipidus (CDI) (n = 5 [5%]) and nephrogenic diabetes insipidus (NDI) (n = 2 [2%]). Low urine osmolality was indicative for patients with CDI and NDI (P

Background Primary polydipsia, characterized by excessive fluid intake, carries the risk of water intoxication and hyponatremia, but treatment options are scarce. Glucagon-like peptide-1 (GLP-1) reduces appetite and food intake. In experimental models, they also play a role in thirst and drinking behavior in. The aim of this trial was to investigate whether GLP-1 receptor agonists reduce fluid intake in patients with primary polydipsia. Methods: In this randomized, double-blind, placebo-controlled, 3-week crossover-trial, 34 patients with primary polydipsia received weekly dulaglutide (Trulicity®) 1.5mg and placebo (0.9% sodium chloride). During the last treatment week, patients attended an 8-hour evaluation visit with free water access. The primary endpoint was total fluid intake during the evaluation visits. The treatment effect was estimated using a linear mixed-effects model. In a subset of 15 patients and matched controls, thirst perception and neuronal activity in response to beverage pictures were assessed by functional MRI. Results Median [IQR] total fluid intake was 2250ml [1600-2600] on dulaglutide versus 2400ml [1850-3400] on placebo. Patients on dulaglutide reduced fluid intake by 490ml [95%-CI -780, -199], p=0.002, corresponding to a relative reduction of 17%. 24-hour urinary output was reduced by -943ml [95%-CI -1473, -413]. Thirst perception in response to beverage pictures was higher in patients with primary polydipsia versus controls and lower on dulaglutide versus placebo, but functional neuronal activity was similar between groups and treatments. Conclusion: GLP-1 receptor agonists reduce fluid intake and thirst perception in patients with primary polydipsia and could therefore be a novel treatment option for these patients.

Background: Interleukin (IL)-1 antagonism led to a decrease of systolic blood pressure (5mmHg) in obese individuals. The underlying mechanism is unknown. Based on experimental data in animals we hypothesised a blood-pressure lowering effect of IL-1-antagonism via modulation of the Renin-Angiotensin-Aldosterone System (RAAS). Methods: In this post-hoc explorative study, we examined short- (2 days) and long-term effects (4 weeks) of IL-1 antagonism (anakinra/Kineret®) on RAAS-peptide-profiles and on hemodynamic parameters assessed by a non-invasive measurement using HOTMAN® system in 128 obese (BMI > 30kg/m2) individuals with at least one feature of the metabolic syndrome from two previous interventional trials (CortIL trial a prospective interventional trial (n= 61) and TestIL trial, a placebo controlled-double blinded interventional trial (n=67)). Results: Upon IL-1 antagonism circulating levels of angiotensin II, angiotensin I, aldosterone and renin remained unchanged after short- and long-term treatment, respectively. In contrast, the vasodilatory angiotensin 1-7 peptide significantly increased after 4 weeks compared to placebo (in between group difference 16.35 pmol/L [1.22 to 30.17], p=0.028), without short-term effect on day 2. Non-invasive hemodynamic measurement revealed a decrease in the stroke systemic vascular resistance index (SSVRI) with an in between group difference of -62.65 dyn.sec.cm-5.m2 [95%CI -116.94 to -18.36], p=0.008 (consistent with a 25%-decrease) after 4 weeks of treatment compared to baseline. Conclusion: IL-1 antagonism in obese individuals with features of the metabolic syndrome led to an increase of the vasodilatory angiotensin 1-7 peptide and a decrease in peripheral vascular resistance, reflected by the SSVRI after 4 weeks of treatment. These findings point to a possible blood pressure lowering mechanism via modulation of the RAAS-system of IL-1 antagonism.

Glucocorticoids have been shown to improve outcome in community-acquired pneumonia (CAP). However, glucocorticoids have potential side-effects, and treatment response may vary. It is thus crucial to select patients with high likelihood to respond favourably. In critical illness, cosyntropin testing is recommended to identify patients in need for glucocorticoids. We investigated whether cosyntropin testing predicts treatment response to glucocorticoids in CAP.Predefined secondary analysis of a randomized controlled trial.Hospitalized patients with CAP.We performed 1 µg cosyntropin tests in a randomized trial comparing prednisone 50 mg for 7 days to placebo. We investigated whether subgroups based on baseline and stimulated cortisol levels responded differently to glucocorticoids with regard to time to clinical stability (TTCS) and other outcomes by inclusion of interaction terms into statistical models.A total of 326 patients in the prednisone and 309 patients in the placebo group were evaluated. Neither basal cortisol nor a Δcortisol250 nmol/L after stimulation nor the combination of basal cortisol and Δcortisol predicted treatment response as measured by TTCS (all P for interaction0.05). Similarly, we found no effect modification with respect to mortality, rehospitalization, antibiotic treatment duration or CAP-related complications (all P for interaction0.05). However, glucocorticoids had a stronger effect on shortening length of hospital stay in patients with a baseline cortisol of ≥938 nmol/L (P for interaction = 0.015).Neither baseline nor stimulated cortisol after low-dose cosyntropin testing at a dose of 1 µg predicted glucocorticoid responsiveness in mild to moderate CAP. A treatment decision for or against adjunct glucocorticoids in CAP should not be made depending on cortisol values or cosyntropin testing results.

Context Hypogonadism is highly prevalent among obese men with metabolic syndrome. Chronic low-grade inflammation is suspected to be a major cause for low testosterone levels in obese individuals. Objectives To test the inflammatory hypothesis of testosterone deficiency in metabolic syndrome. Design, setting, participants, and intervention In this randomized, placebo-controlled, double-blind trial involving men with metabolic syndrome, we randomly assigned 33 patients to receive 100 mg of anakinra (recombinant human IL-1 receptor antagonist) subcutaneously twice daily for 4 weeks and 34 patients to receive placebo. Main outcome measures The primary endpoint was the change from baseline in total testosterone levels after 4 weeks. Results The mean age was 54 years and baseline total testosterone levels were 9.3 nmol/L (95% CI, 8.7 to 10.0). At 4 weeks, total testosterone levels increased by 1.2 nmol/L (95% CI, 0.3 to 2.0; P = 0.01) in the anakinra group as compared with no change in the placebo group (0.01 nmol/L; 95% CI, -0.5 to 0.5; P = 0.99), resulting in a between-group difference of 0.96 nmol/L (95% CI, 0.3 to 1.9; P = 0.04). The effects were most pronounced with baseline C-reactive protein >2 mg/L (between-group difference 2.14 nmol/L; 95% CI, 0.11 to 4.17; P = 0.04) and body mass index >40 kg/m2 (between-group difference 2.64 nmol/L; 95% CI, 0.19 to 5.09; P = 0.04). Anakinra treatment did not exert benefits on fatigue and sexual dysfunction, but it improved grip strength of nondominant hand by 3.5 kg (95% CI 0.23 to 6.81; P = 0.04) and reduced mean arterial blood pressure by 2.9 mm Hg (95% CI, -5.99 to 0.19; P = 0.07). Conclusions Anti-inflammatory treatment with an antagonist of IL-1 led to an increase in testosterone levels in obese men with testosterone deficiency.

In this study, we compared the 2 mg dexamethasone suppression test (DST) with the gold-standard 1 mg DST in obese patients in order to reduce the false-positive rate for Cushing’s syndrome (CS). The primary endpoint was the comparison of serum cortisol levels after 1 mg versus 2 mg DST in patients with a BMI >30 kg/m2 and at least one additional feature of the metabolic syndrome. Secondary endpoints were comparison of salivary cortisol and ACTH levels, respectively. Fifty-four obese patients were included. Median serum cortisol levels after 1 mg DST and 2 mg DST were similar [28 nmol/l (20; 36) vs. 28 nmol/l (20; 38), p=0.53]. Salivary cortisol was 8.2 nmol/l (4.7; 11.7) after the 1 mg DST vs. 6.7 nmol/l (4.2; 9.5) after the 2 mg test, p=0.09. ACTH levels were higher after the 1 mg DST compared to the 2 mg DST [10.0 pg/ml (7.6; 10.7) vs. 5.0 pg/ml (5.0; 5.1), p ClinicalTrials.gov Number: NCT02227420

Context: Increased cortisol levels in obesity may contribute to the associated metabolic syndrome. In obesity, the activated innate immune system leads to increased interleukin (IL)-1β, which is known to stimulate the release of adrenocorticotropin hormone (ACTH). Objectives: We hypothesized that in obesity IL-1 antagonism would result in downregulation of the hypothalamo-pituitary-adrenal axis, leading to decreased cortisol levels. Design and Participants: In this prospective intervention study, we included 73 patients with obesity (body mass index [BMI] ≥30 kg/m2) and at least one additional feature of the metabolic syndrome. Outcome Measures: The primary end point was change in morning cortisol from baseline to after the administration of the IL-1 receptor antagonist (anakinra/Kineret®, total dose 3 × 100 mg). Secondary end points were effects on salivary cortisol and ACTH. Results: Median age was 56 years, 50.7% of patients were female, and median BMI was 36.3 kg/m2. Median morning serum cortisol levels (nmol/L) decreased significantly after IL-1 antagonism [from baseline, 452 to 423; absolute difference, −38.7; 95% confidence interval (CI), −64 to −13.4; P = 0.0019]. Similar effects were found for salivary cortisol levels (−2.8; 95% CI, −4.4 to −1.3; P = 0.0007), ACTH levels (−2.2; 95% CI; −4.2 to −0.1; P = 0.038), systolic blood pressure (−5.2, 95% CI, −8.5 to −1.8; P = 0.0006), and heart rate (−2.9; 95% CI, −4.7 to −1.0; P = 0.0029). Conclusion: IL-1 antagonism in obese individuals with features of the metabolic syndrome leads to a decrease in serum cortisol, salivary cortisol, and ACTH levels along with a reduction in systolic blood pressure and heart rate.

Context: Apelin and arginine vasopressin are antagonists in the regulation of body fluid and osmotic homeostasis. There are no data about apelin levels in patients with polyuria-polydipsia syndrome (PPS). Objective: To investigate plasma apelin levels and plasma apelin to copeptin ratios in patients with PPS and healthy volunteers using copeptin as a surrogate marker for arginine vasopressin. Design, Participants, and Setting: We included 41 patients with PPS in this post hoc analysis of a prospective study performed in tertiary care hospitals in Switzerland and Germany and 113 healthy volunteers as a control group. Outcome Measures: Plasma apelin and copeptin levels were measured in 15 patients with complete central diabetes insipidus (DI), seven patients with complete nephrogenic DI, 19 patients with primary polydipsia (PP), and 113 healthy volunteers. Results: Plasma apelin levels were highest in patients with complete nephrogenic DI (413 pmol/L; interquartile range, 332-504 pmol/L; P = .01) and lower in patients with PP (190 [172-215] pmol/L; P < .001) or complete central DI (209 [174-241] pmol/L; P = .02) as compared to healthy volunteers (254 [225-311] pmol/L). Plasma apelin to copeptin ratio in patients with PP (53 [38-92] pmol/pmol; P > .9) was similar to healthy volunteers (57 [37-102] pmol/pmol). In contrast, the apelin to copeptin ratio was higher in patients with complete central DI (89 [73-135] pmol/pmol; P = .02) and lower in patients with complete nephrogenic DI (7 [6-10] pmol/pmol; P < .001) compared to healthy volunteers. Conclusion: In PP, normal plasma apelin to copeptin ratio attests a normal water homeostasis. In contrast, in patients with central or nephrogenic DI, the increased or decreased apelin to copeptin ratio, respectively, reflects a disturbed osmotic and body fluid homeostasis.

Background and Purpose— An accurate long-term outcome prediction may improve management of stroke patients. We investigated the ability of copeptin to predict 1-year outcome in stroke patients. Methods— In this preplanned post hoc analysis, the National Institutes of Health Stroke Scale score and copeptin levels were measured on admission in a cohort of patients with ischemic stroke. The primary end point was functional outcome (modified Rankin Scale score Results— Of 362 patients, 341 (94.2%) completed the 1-year follow-up, 146 (43%) patients had an unfavorable functional outcome, and 66 (20%) died. Multivariate logistic-regression analysis adjusted for age and National Institutes of Health Stroke Scale score showed that copeptin was an independent predictor of functional outcome (odds ratio=4.00; 95% CI, 1.94–8.19) and death (odds ratio=2.68; 95% CI, 1.24–5.82). The area under the receiver operating characteristic curve of copeptin was 0.72 (95% CI, 0.67–0.77) for functional outcome and 0.74 (95% CI, 0.69–0.78) for mortality. Copeptin improved the area under the receiver operating characteristic curve of the National Institutes of Health Stroke Scale score for functional outcome from 0.70 (95% CI, 0.64–0.74) to 0.76 (95% CI, 0.71–0.82; P =0.002) and for mortality from 0.74 (95% CI, 0.69–0.78) to 0.78 (95% CI, 0.71–0.85; P =0.04). Conclusions— Copeptin levels are a useful, complementary tool to predict functional outcome and mortality 1 year after stroke. Clinical Trial Registration— ISCTRN 00390962; clinicaltrials.gov No. NCT00390962.

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.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.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, p0·0001). 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.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.Swiss National Science Foundation, Viollier AG, Nora van Meeuwen Haefliger Stiftung, Julia und Gottfried Bangerter-Rhyner Stiftung.

Clinical trials yielded conflicting data about the benefit of adding systemic corticosteroids for community-acquired pneumonia (CAP). We evaluated whether short-term corticosteroid treatment reduces time to clinical stability in patients hospitalized for CAP.