The primary outcome for which this RCT was powered was time to clinical stability rather than mortality, and there were only 24 people in total with laboratoryconfirmed influenza. New citation required but conclusions have not changed. Gu L, #27 'clinical study'/de Clinical and prognostic features of patients with pandemic 2009 influenza a (H1N1) virus in the intensive care unit. The majority of studies investigated adults admitted to hospital with pandemic influenza in 2009 and 2010. Volkow P, Data specific to mortality were of very low quality, based predominantly on observational studies, with inconsistent reporting of variables potentially associated with the outcomes of interest, differences between studies in the way in which they were conducted, and with the likelihood of potential confounding by indication. S15 TI steroid* OR AB steroid* Horita N, Pinto R, Wu ZX, Kudo K, MethylPREDNISolone Dose Pack side effects. Corticosteroid therapy in the 90 days prior to hospital admission was independently associated with poor outcome (defined as a composite outcome of ICU admission and death) (adjusted OR 3.37, 95% CI 1.39 to 8.20) in a study of individuals hospitalised with 2009 influenza A H1N1 virus (H1N1pdm09) infection (DelgadoRodriguez 2012). 13 corticoid*.tw,nm. Impact of neuraminidase inhibitor treatment on outcomes of public health importance during the 20092010 influenza A (H1N1) pandemic: a systematic review and metaanalysis in hospitalized patients. Carrara E, Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection. Diaz E, et al. 3 exp Influenzavirus B/ S1 (MH "Influenza+"), (mh:"Influenza, Human" OR influenza$ OR flu OR grippe OR or gripe OR mh:"Influenzavirus A" OR mh:b04.820.545.405$ OR mh:b04.909.777.545.405$ OR mh:"Influenzavirus B" OR mh:b04.820.545.407$ OR mh:b04.909.777.545.407$ OR h1n1 OR h5n1 OR h3n2) AND (mh:"Adrenal Cortex Hormones" OR mh:d06.472.040$ OR corticoesteroides OR corticosterides OR corticoid$ OR corticosteroid$ OR "adrenal cortex hormone" OR "adrenal cortex hormones" OR adrenocorticosteroid$ OR glucocorticoid$ OR hydroxycorticosteroid$ OR mh:glucocorticoids OR glucocorticides OR mh:steroids OR esterides OR mh:d04.808$ OR hydrocortison$ OR hidrocortisona OR mh:prednisolone OR prednisolone OR prednisolona OR mh:prednisone OR prednisone OR prednisona OR mh:dexamethasone OR dexamethasone OR dexametasona OR mh:methylprednisolone OR methylprednisolone OR metilprednisolona) AND db:("LILACS") AND type_of_study:("clinical_trials" OR "case_control" OR "cohort" OR "overview" OR "systematic_reviews"), APACHE: Acute Physiology and Chronic Health Evaluation Two further systematic reviews and metaanalyses did not find an effect of adjuvant corticosteroids on mortality, either overall or in severely ill cases, but both reported decreased length of hospital stay (Chen 2015 (7 RCTs; n = 944); Wan 2016 (9 RCTs; n = 1667 and 6 cohort studies; n = 4095)). Zhang X, In the second study, a large retrospective cohort study from mainland China, there was an increased risk of ICU admission in people admitted with 2009 influenza A H1N1 viral pneumonia and treated with corticosteroids (unadjusted OR 5.13, 95% CI 4.26 to 6.17) (Li 2017). Xiong W, GarnachoMontero J. Characteristics of immunocompromised patients with influenza A virus admitted to the intensive care unit. Fan LC, LopezMedrano F, et al. GutierrezPizarraya A, #21 #19 OR #20 Suarez D, Worldwide clinical data from the influenza A (H1N1) pandemic in 2009 revealed that more than onefifth of hospitalised individuals experienced severe disease requiring admission to an intensive care unit (ICU) (Jain 2009; Muthuri 2013; Richard 2012). Yu HT, We amended the Types of studies to state: "We excluded studies with casecontrol designs due to the inability to determine temporal effects of corticosteroids on the development of nonmortality outcomes. et al. Invasive pulmonary aspergillosis is a frequent complication of critically ill H1N1 patients: a retrospective study. aStratification by 30day mortality was not possible due to heterogeneity between studies in reporting the timing of mortality after hospital admission. In this study outcomes were stratified according to different corticosteroid regimens (high dose and lowtomoderate dose). The populationbased incidence estimate for influenzaassociated critical illness in the USA is 12 per 100,000 personyears; this represents 1.3% of all critical illness hospitalisations, or 3.4% of critical illness hospitalisations during the influenza season (Ortiz 2014). Park MS, Arlt W, Bramley A, Uryu H, Differences between asthmatics and nonasthmatics hospitalised with influenza A infection, SanteonCAP; Dexamethasone in communityacquired pneumonia, clinicaltrials.gov/ct2/show/study/NCT01743755?term=SANTEON&rank=1, Communityacquired pneumonia: evaluation of corticosteroids, clinicaltrials.gov/ct2/show/study/NCT02517489?term=CAPE+COD&rank=3. Wong CK, There were no date, publication, or language restrictions. Xie H, These side effects may go away during treatment as your body adjusts to the medicine. Adhikari NK, et al. Leon Moya C, #7 corticosteroid*:ab,ti If a flow chart was not available, we looked for information in the text of the results to determine whether all participants included in the study had been analysed. Viboud CG, et al. The influence of corticosteroid treatment on the outcome of influenza A (H1N1pdm09)related critical illness. It is used to treat a number of different conditions, such as inflammation (swelling), severe allergies, adrenal problems, arthritis, asthma, blood or bone marrow problems, endocrine problems, eye or vision problems, stomach or bowel problems, lupus, skin conditions, kidney problems, ulcerative colitis, and flare-ups of multiple sclerosis. Adjusted estimates also presented for 60day mortality. Barberio P, Future observational studies investigating corticosteroids for the treatment of influenza should state the precise rationale for the administration of corticosteroid therapy in study participants (such as treatment of complications of influenza, comorbid illness, or use solely as adjunctive therapy). Macrolidebased regimens in absence of bacterial coinfection in critically ill H1N1 patients with primary viral pneumonia. Opal SM, Rhodes A, Twentyone studies were included in the metaanalysis (9536 individuals), of which 15 studied people infected with 2009 influenza A H1N1 virus (H1N1pdm09). Yan XX, Zarychanski R, ARDS: adult respiratory distress syndrome Zhang C, Other recent metaanalyses have also noted an association between adjuvant corticosteroid therapy and decreased mortality in a subset of people with severe communityacquired pneumonia, as well as decreased length of hospital stay and decreased time to clinical stability (Bi 2016 (8 RCTs; n = 528); Horita 2015 (10 RCTs; n = 1780); Marti 2015 (14 RCTs; n = 2077); and Wu 2018 (10 RCTs; n = 729)). Annane D, et al. Peterson J, The pooled analysis of mortality showed high statistical heterogeneity, most likely due to the inclusion of unadjusted estimates of mortality. #35 ('case control' NEXT/1 (study OR studies)):ab,ti JLB undertook consultancy work for the UK Food Standards Agency in 20132015, and for a Breast Milk Substitute manufacturer in 2017, to help them design a healthcare claim trial. IQR: interquartile range Choi W, Pinto R, Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. LeonardiBee J, S5 TI (h1n1 or h5n1 or h3n2 ) OR AB ( h1n1 or h5n1 or h3n2) Hydrocortisone plus fludrocortisone for adults with septic shock. Arisoy A, Wauters J, Women's health is once again the center of a political ping-pong match with evidence-based science on one side and anti-choice advocates on the other. PVS: persistent viral shedding We judged the randomisation method, allocation of concealment, and blinding to be adequate and at low risk of bias in the one included RCT (Wirz 2016). Comparisons between patients with mild and severe pandemic influenza have revealed significantly higher levels of cytokines (especially interleukin6) in the plasma of patients with severe disease (Yu 2011b), and similar findings have been replicated in studies of severe seasonal influenza (Heltzer 2009). PaO2/FiO2: ratio of partial pressure of oxygen in arterial blood to inspired fraction of oxygen Welch V, Du B, Varpula T, et al. Agoritsas T, We analysed data on an intentiontotreat basis. In contrast, an individual patient level metaanalysis of over 29,000 patients with 2009 influenza A H1N1 virus (H1N1pdm09) infection from 78 observational studies across the world found that NI treatment at any time, in comparison to no treatment, was associated with a 19% reduction in mortality risk; early treatment (within two days of symptom onset) was associated with a 52% reduction in mortality risk in comparison to late treatment (Muthuri 2013). The remaining study found no association 30 days after admission (HR 1.81, 95% CI 0.88 to 3.74) (Cao 2016), although corticosteroid use was associated with mortality at 60 days (HR 1.98, 95% CI 1.03 to 3.79). Lee N, Schliephake F, A study of individuals hospitalised with 2009 influenza A H1N1 virus (H1N1pdm09) infection found that corticosteroid therapy was associated with persistent viral shedding (defined as the detection of virus on RTPCR at day 7 after diagnosis on nasopharyngeal swabs) (Giannella 2011). Bellissant E, Hospitalized patients with 2009 H1N1 influenza in the United States, AprilJune 2009. Yang P, The currently available evidence is insufficient to determine the effectiveness of corticosteroids for people with influenza. et al. Clark DV, Duan J, Yang Y, We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 9, searched 3 October 2018), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1946 to October week 1, 2018), Embase (1980 to 3 October 2018), CINAHL (Cumulative Index to Nursing and Allied Health Literature) (1981 to 3 October 2018), LILACS (Latin American and Caribbean Health Science Information database) (1982 to 3 October 2018), and Web of Science (1985 to 3 October 2018). CI: confidence interval The other review authors shared the duplicate data extraction of all included studies. MartinLoeches I, Bordogna AC, characteristics of study (design, setting, country, enrolment period, methodological details including 'Risk of bias' criteria for RCTs and the NewcastleOttawa Scale for nonrandomised trials and comparative observational studies); characteristics of participants (inclusion and exclusion criteria, demographics, comorbid illnesses, disease severity, numbers in each group); characteristics of intervention (type of steroid, route of administration, dose, timing of corticosteroid use (early versus late), and duration of treatment, cointerventions administered); adequacy of the method for generating the randomisation sequence; adequacy of the method for allocation concealment; blinding of participants, clinicians, and outcome assessors with regard to the intervention given; incomplete outcome data (participants lost to followup in each treatment group and reasons for losses reported); analysis of participants in the groups to which they were originally randomised (intentiontotreat principle); selective outcome reporting (all primary outcomes listed in the study protocol that are relevant to this review were reported); daily corticosteroid dose (low versus high; in adults low dose is defined as hydrocortisone 300 mg, dexamethasone 12 mg, prednisolone 75 mg, methylprednisolone 60 mg) (, timing of corticosteroid use (early versus late; early defined as < 4 days of onset of symptoms and late 4 days) (, duration of corticosteroid course (short versus long course; short course defined as < 5 days and long course 5 days) (. We then repeated the MEDLINE search, replacing the randomised trial filter with the Scottish Intercollegiate Guidelines Network (SIGN) filter to identify observational studies (SIGN 2011). Increased odds of hospitalacquired infection related to corticosteroid therapy were found on pooled analysis of seven studies (pooled OR 2.74, 95% CI 1.51 to 4.95; I2 = 90%); all were unadjusted estimates, and we graded the data as of very low certainty. DelgadoRodriguez M, Comparison 1 Corticosteroid therapy versus no corticosteroid therapy, Outcome 2 Mortality following admission, hospitalised participants studies reporting hazard ratios. Although there was overlap in the included studies between this review and the other reviews, our review included several studies that were not included in one or both of the other reviews (Balaganesakumar 2013; Boudreault 2011; DelgadoRodriguez 2012; Han 2011; Jain 2009; Kim 2011; Li 2012; Liem 2009; Linko 2011; Mady 2012; Patel 2013; Sertogullarindan 2011; Wu 2012). We searched for studies comparing additional steroid treatment with no additional steroid treatment in individuals with influenza. Yes. Balk RA, We did not use a fixedeffect model to analyse the data because a) there was a clear rationale for choosing the randomeffects model, and b) there was no concern about the influence of smallstudy effects. Estimates from the UK indicate an influenzaattributable annual general practitioner consultation rate of 2156 per 100,000 population and a corresponding annual hospitalisation rate of 34 per 100,000 population (Cromer 2014). Risk factors for hospitalisation and poor outcome with pandemic A/H1N1 influenza: United Kingdom first wave (MaySeptember 2009). We wish to thank the following domain experts for ensuring that we have identified pertinent studies in our literature search: Frederick Hayden, David Hui, Nelson Lee, and Djillali Annane. Ho Y, et al. RosaZamboni D, List of Approved HIV Antiretroviral Drugs Statin Drugs Statin drugs are used to reduce cholesterol levels and work by blocking a liver enzyme responsible for producing cholesterol. MartinLoeches I, COPD: chronic obstructive pulmonary disease In the first publication of this review we did not identify any RCTs reporting the impact of adjunctive corticosteroids therapy on clinical outcomes in people with influenza, and the available evidence from observational studies was of very low quality, suggesting that corticosteroid therapy might be associated with up to threefold greater odds of mortality. ICU: intensive care unit It can cause cataracts and glaucoma. Avian influenza A (H5N1) infection in humans, WHO guidelines for the pharmacological management of pandemic influenza A(H1N1) 2009 and other influenza viruses, www.who.int/csr/resources/publications/swineflu/h1n1_guidelines_pharmaceutical_mngt.pdf?ua=1, www.who.int/newsroom/factsheets/detail/influenza(seasonal), Efficacy of corticosteroid treatment for severe communityacquired pneumonia: a metaanalysis. Subgroup analysis by individual pathogens not specified in protocol. The analysis in this study supercedes that of a previously included report, Retrospective analysis of Japan Medical Center Database data, Study reporting outcomes according to regular CS use prior to the diagnosis of influenza rather than CS as adjunctive treatment for influenza, Randomised controlled trial of prednisone in communityacquired pneumonia caused by different pathogens, with subgroup analysis of people with confirmed influenza infection. Yazicioglu O, Rudd KE, swelling of your face, tongue, or throat . Williams J, et al. Wu C, 6 or/15 The 'comparability' domain performed the poorest across all the studies in the risk of bias assessment. Complicated influenza (adjusted for age, comorbid illnesses, clinical features, laboratory findings, and CS use), In Chinese language. McGeer A, Heneghan C, Funnel plot of studies reporting mortality. The Cochrane Collaboration, 2011. 2 exp Influenzavirus A/ A more recent subgroup analysis failed to identify credible effect modification with corticosteroid dose, although most studies used hydrocortisone with or without fludrocortisone at a low dose (< 400 mg/day of hydrocortisone equivalent) and over a long duration (> 2 days) (Rochwerg 2018). McIntyre P, Mller MH, Although commonly prescribed for severe influenza, there is uncertainty over their potential benefits or harms. Jacob S, Annane D, Sun WJ, Early treatment defined as < 72 hours from influenzalike illness. Li A, Careers, Unable to load your collection due to an error. Han K, We could not perform subgroup analyses according to corticosteroid regimens and age of study participants as there was an insufficient number of studies reporting outcomes stratified according to these variables. Lytvyn L, Hospital-acquired infection was the main 'side effect' related to steroid treatment reported in the included studies; most studies reported a greater risk of hospital-acquired infection in the group treated with steroids. et al. One single randomised controlled trial of corticosteroid use versus placebo with subgroup analysis of people with confirmed influenza was not powered for this outcome, and the number of participants in each arm was very small. Lu LJ. Shay DK, Subgroup analysis of unadjusted and adjusted OR estimates of mortality showed a similar association with corticosteroid therapy (OR 4.79, 95% CI 2.35 to 9.79; I2 = 67%; Analysis 1.1.1 and OR 2.23, 95% CI 1.54 to 3.24; Analysis 1.1.2; I2 = 0%, respectively). However, it was unclear whether patients with more severe influenza had been selected to receive steroid treatment. et al. 5 (h1n1 or h5n1 or h3n2).tw. Barcan L, Cytokine response patterns in severe pandemic 2009 H1N1 and seasonal influenza among hospitalized adults, Chapter 6: Searching for studies. Vist G, Efficacy and safety of glucocorticoids in the treatment of communityacquired pneumonia: a metaanalysis of randomized controlled trials. Overall, people treated with corticosteroids had greater odds of developing secondary infection than those who did not receive corticosteroids on pooled analysis (unadjusted OR 2.74, 95% CI 1.51 to 4.95; I2 = 90%; 6114 participants; 7 studies; Analysis 1.3; Figure 5). Differential evolution of peripheral cytokine levels in symptomatic and asymptomatic responses to experimental influenza virus challenge. Campins A, Get emergency medical help if you have signs of an allergic reaction: hives ; difficult . Jonathan NguyenVanTam: The University of Nottingham Health Protection Research Group currently holds an unrestricted educational grant for influenza research from F. HoffmannLa Roche. Meersseman P, Any disagreements at either stage were resolved through discussion with a third review author (JNVT). Wang LX, Mar CB, We gave the lowest score of two stars for the 'selection' domain to the following studies: Balaganesakumar 2013 (mortality); Boudreault 2011 (time to death); Huang 2017 (mortality); Li 2012 (mortality); Ono 2016 (hospitalisation); Patel 2013 (mortality); and Yu 2011a (mortality). Two review authors independently extracted data and assessed risk of bias. et al. Marti C, government site. Osterholm M, Takasaki J, Thunga G, CS: corticosteroid Gutierrez Pizarraya A, Lee N, Hien ND, Prednisone side effects Precautions Summary Tylenol (acetaminophen) is commonly used to manage pain and control a fever. Gupte N, Keh D, The majority of individuals with influenza have a fever, headache, and cough and improve without any specific treatment. Canton Bulnes ML, Side effects of topical corticosteroids. All of the review authors of the original version designed and conceived the systematic review. We included an additional 12 studies in this 2018 update. We extracted adjusted outcome measures as ORs or hazard ratios (HRs) with 95% CIs and presented these separately in pooled analyses. Review question. et al. We used the methods and recommendations described in Section 8.5 and Chapter 12 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), employing GRADEpro GDT software (GRADEpro GDT 2014). et al. Beishuizen A, Cohen J, Villarejo F, et al. FalckYtter Y, Tukenmez B, We combined these two searches to give the search results for MEDLINE. Ruokonen E, Mandourah Y, Corey L, Over the same period, the 'Surviving Sepsis Campaign' recommended the use of corticosteroid therapy only in the setting of vasopressordependent septic shock (Dellinger 2013). et al. We downgraded the certainty of the evidence from low (observational data) to very low due to high risk of indication bias (sicker adults with influenza were more likely to receive corticosteroids) and clinical/statistical heterogeneity (unadjusted estimates of odds ratio for hospitalacquired infection were presented in some studies, and the definitions of hospitalacquired infection varied across the studies). However, It was unclear whether patients with more severe influenza, There no... For Systematic Reviews of Interventions Version 5.1.0 [ updated March 2011 ] were steroids for flu side effects viagra plus date, publication, or.. 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