***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: CONTEXT AND OBJECTIVE Sepsis and septic shock are very common conditions among critically ill patients that lead to multiple organ dysfunction syndrome ( MODS ) and death . Our purpose was to investigate the efficacy of early administration of dexamethasone for patients with septic shock , with the aim of halting the progression towards MODS and death . DESIGN AND SETTING Prospect i ve , r and omized , double-blind , single-center study , developed in a surgical intensive care unit at Hospital das Clínicas , Faculdade de Medicina da Universidade de São Paulo . METHODS The study involved 29 patients with septic shock . All eligible patients were prospect ively r and omized to receive either a dose of 0.2 mg/kg of dexamethasone ( group D ) or placebo ( group P ) , given three times at intervals of 36 hours . The patients were monitored over a seven-day period by means of the sequential organ failure assessment score . RESULTS Patients treated with dexamethasone did not require vasopressor therapy for as much time over the seven-day period as did the placebo group ( p = 0.043 ) . Seven-day mortality was 67 % in group P ( 10 out of 15 ) and 21 % in group D ( 3 out of 14 ) ( relative risk = 0.31 , 95 % confidence interval 0.11 to 0.88 ) . Dexamethasone enhanced the effects of vasopressor drugs . CONCLUSIONS Early treatment with dexamethasone reduced the seven-day mortality among septic shock patients and showed a trend towards reduction of 28-day mortality Background Recent studies have reported a high prevalence of relative adrenal insufficiency in patients with liver cirrhosis . However , the effect of corticosteroid replacement on mortality in this high-risk group remains unclear . We examined the effect of low-dose hydrocortisone in patients with cirrhosis who presented with septic shock . Methods We enrolled patients with cirrhosis and septic shock aged 18 years or older in a r and omized double-blind placebo-controlled trial . Relative adrenal insufficiency was defined as a serum cortisol increase of less than 250 nmol/L or 9 μg/dL from baseline after stimulation with 250 μg of intravenous corticotropin . Patients were assigned to receive 50 mg of intravenous hydrocortisone or placebo every six hours until hemodynamic stability was achieved , followed by steroid tapering over eight days . The primary outcome was 28-day all-cause mortality . Results The trial was stopped for futility at interim analysis after 75 patients were enrolled . Relative adrenal insufficiency was diagnosed in 76 % of patients . Compared with the placebo group ( n = 36 ) , patients in the hydrocortisone group ( n = 39 ) had a significant reduction in vasopressor doses and higher rates of shock reversal ( relative risk [ RR ] 1.58 , 95 % confidence interval [ CI ] 0.98–2.55 , p = 0.05 ) . Hydrocortisone use was not associated with a reduction in 28-day mortality ( RR 1.17 , 95 % CI 0.92–1.49 , p = 0.19 ) but was associated with an increase in shock relapse ( RR 2.58 , 95 % CI 1.04–6.45 , p = 0.03 ) and gastrointestinal bleeding ( RR 3.00 , 95 % CI 1.08–8.36 , p = 0.02 ) . Interpretation Relative adrenal insufficiency was very common in patients with cirrhosis presenting with septic shock . Despite initial favourable effects on hemodynamic  parameters , hydrocortisone therapy did not reduce mortality and was associated with an increase in adverse effects . ( Current Controlled Trials registry no. IS RCT N99675218 . Background Clinical evidence continues to exp and and is increasingly difficult to overview . We aim ed at conceptualizing a visual assessment tool , i.e. , a matrix for overviewing studies and their data in order to assess the clinical evidence at a glance . Methods A four-step matrix was constructed using the three dimensions of systematic error , r and om error , and design error . Matrix step I ranks the identified studies according to the dimensions of systematic errors and r and om errors . Matrix step II orders the studies according to the design errors . Matrix step III assesses the three dimensions of errors in studies . Matrix step IV assesses the size and direction of the intervention effect . Results The application of this four-step matrix is illustrated with two examples : peri-operative beta-blockade initialized in relation to surgery versus placebo for major non-cardiac surgery , and antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation .  When clinical evidence is deemed both internally and externally valid , the size of the intervention effect is to be assessed . Conclusion The error matrix provides an overview of the validity of the available evidence at a glance , and may assist in deciding which interventions to use in clinical practice BACKGROUND In sub-Saharan Africa , bacterial meningitis is common and is associated with a high mortality .  Adjuvant therapy with corticosteroids reduces mortality among adults in the developed world , but it has not been adequately tested in developing countries or in the context of advanced human immunodeficiency virus ( HIV ) infection . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of dexamethasone ( 16 mg twice daily for 4 days ) and an open-label trial of intramuscular versus intravenous ceftriaxone ( 2 g twice daily for 10 days ) in adults with an admission diagnosis of bacterial meningitis in Blantyre , Malawi . The primary outcome was death at 40 days after r and omization . RESULTS A total of 465 patients , 90 % of whom were HIV-positive , were r and omly assigned to receive dexamethasone ( 233 patients ) or placebo ( 232 patients ) plus intramuscular ceftriaxone ( 230 patients ) or intravenous ceftriaxone ( 235 patients ) . There was no significant difference in mortality at 40 days in the corticosteroid group ( 129 of 231 patients ) as compared with the placebo group ( 120 of 228 patients ) by intention-to-treat analysis ( odds ratio , 1.14 ; 95 % confidence interval [ CI ] , 0.79 to 1.64 ) or when the analysis was restricted to patients with proven pneumococcal meningitis ( 68 of 129 patients receiving corticosteroids vs. 72 of 143 patients receiving placebo ) ( odds ratio , 1.10 ; 95 % CI , 0.68 to 1.77 ) . There were no significant differences between groups in the outcomes of disability and death combined , hearing impairment , and adverse events . There was no difference in mortality with intravenous ceftriaxone ( 121 of 230 patients ) as compared with intramuscular ceftriaxone ( 128 of 229 patients ) ( odds ratio , 0.88 ; 95 % CI , 0.61 to 1.27 ) . CONCLUSIONS Adjuvant therapy with dexamethasone for bacterial meningitis in adults from an area with a high prevalence of HIV did not reduce mortality or morbidity . In this setting , intramuscular administration was not inferior to intravenous administration of ceftriaxone for bacterial meningitis . ( Current Controlled Trials number , IS RCT N31371499 [ controlled-trials.com ] . ) We hypothesize that hydrocortisone infusion in severe community-acquired pneumonia attenuates systemic inflammation and leads to earlier resolution of pneumonia and a reduction in sepsis-related complications . In a multicenter trial , patients admitted to the Intensive Care Unit ( ICU ) with severe community-acquired pneumonia received protocol -guided antibiotic treatment and were r and omly assigned to hydrocortisone infusion or placebo . Hydrocortisone was given as an intravenous 200-mg bolus followed by infusion at a rate of 10 mg/hour for 7 days . Primary end-points of the study were improvement in Pa(O(2)):FI(O(2 ) ) ( Pa(O(2)):FI(O(2 ) ) > 300 or > /= 100 increase from study entry ) and multiple organ dysfunction syndrome ( MODS ) score by Study Day 8 and reduction in delayed septic shock .  Forty-six patients entered the study . At study entry , the  hydrocortisone group had lower Pa(O(2)):FI(O(2 ) ) , and higher chest radiograph score and C-reactive protein level . By Study Day 8 , treated patients had , compared with control subjects , a significant improvement in Pa(O(2)):FI(O(2 ) ) ( p = 0.002 ) and chest radiograph score ( p < 0.0001 ) , and a significant reduction in C-reactive protein levels ( p = 0.01 ) , MODS score ( p = 0.003 ) , and delayed septic shock ( p = 0.001 ) . Hydrocortisone treatment was associated with a significant reduction in length of hospital stay ( p = 0.03 ) and mortality ( p = 0.009 ) Background Thresholds for statistical significance are insufficiently demonstrated by 95 % confidence intervals or P-values when assessing results from r and omised clinical trials . First , a P-value only shows the probability of getting a result assuming that the null hypothesis is true and does not reflect the probability of getting a result assuming an alternative hypothesis to the null hypothesis is true . Second , a confidence interval or a P-value showing significance may be caused by multiplicity . Third , statistical significance does not necessarily result in clinical significance . Therefore , assessment of intervention effects in r and omised clinical trials deserves more rigour in order to become more valid . Methods Several method ologies for assessing the statistical and clinical  significance of intervention effects in r and omised clinical trials were considered . Balancing simplicity and comprehensiveness , a simple five-step procedure was developed . Results For a more valid assessment of results from a r and omised clinical trial we propose the following five-steps : ( 1 ) report the confidence intervals and the exact P-values ; ( 2 ) report Bayes factor for the primary outcome , being the ratio of the probability that a given trial result is compatible with a ‘ null ’ effect ( corresponding to the P-value ) divided by the probability that the trial result is compatible with the intervention effect hypothesised in the sample size calculation ; ( 3 ) adjust the confidence intervals and the statistical significance threshold if the trial is stopped early or if interim analyses have been conducted ; ( 4 ) adjust the confidence intervals and the P-values for multiplicity due to number of outcome comparisons ; and ( 5 ) assess clinical significance of the trial results . Conclusions If the proposed five-step procedure is followed , this may increase the validity of assessment s of intervention effects in r and omised clinical trials RATIONALE Some studies have shown a beneficial effect of corticosteroids in patients with community-acquired pneumonia ( CAP ) , possibly by diminishing local and systemic antiinflammatory host response . OBJECTIVES To assess the efficacy of adjunctive prednisolone treatment in patients hospitalized with CAP . METHODS Hospitalized patients , clinical ly and radiologically diagnosed with CAP using st and ard clinical and radiological criteria , were r and omized to receive 40 mg prednisolone for 7 days or placebo , along with antibiotics . Primary outcome was clinical cure at Day 7 . Secondary outcomes were clinical cure at Day 30 , length of stay , time to clinical stability , defervescence , and C-reactive protein . Disease severity was scored using CURB-65 ( a severity index for community-acquired pneumonia evaluating Confusion , blood Urea nitrogen , Respiratory rate , Blood pressure , and age 65 or older ) and Pneumonia Severity Index . MEASUREMENTS AND MAIN RESULTS We enrolled 213 patients . Fifty-four ( 25.4 % ) patients had a CURB-65 score greater than 2 , and 93 ( 43.7 % ) patients were in Pneumonia Severity Index class IV-V. Clinical cure at Days 7 and 30 was 84/104 ( 80.8 % ) and 69/104 ( 66.3 % ) in the prednisolone group and 93/109 ( 85.3 % ) and 84/109 ( 77.1 % ) in the placebo group ( P = 0.38 and P = 0.08 ) . Patients on prednisolone had faster defervescence and faster decline in serum C-reactive protein levels compared with placebo . Sub analysis of patients with severe pneumonia did not show differences in clinical outcome . Late failure ( > 72 h after admittance ) was more common in the prednisolone group ( 20 patients , 19.2 % ) than in the placebo group ( 10 patients , 6.4 % ; P = 0.04 ) . Adverse events were few and not different between the two groups . CONCLUSIONS Prednisolone ( at 40 mg ) once daily for a week does not improve outcome in hospitalized patients with CAP . A benefit in more severely ill patients can not be excluded . Because of its association with increased late failure and lack of efficacy  prednisolone should not be recommended as routine adjunctive treatment in CAP Objectives : Vasopressin and corticosteroids are both commonly used adjunctive therapies in septic shock . Retrospective analyses have suggested that there may be an interaction between these 
    Output:
    
The effects did not vary according to the degree of sepsis .
TSA showed that many more r and omised patients are needed before definitive conclusions may be drawn .
Conclusion Evidence to support or negate the use of steroids in any dose in sepsis patients is lacking .