{"corpus_id":6946554,"paper_sha":"f715dd0d86337920ee38fa5da55d59e949b2bfd8","doi":"10.1002/14651858.CD002244.pub4","arxiv_id":null,"pmid":27121755,"pmcid":"4916936","mag_id":2160408047,"dblp_id":null,"acl_id":null,"title":"Corticosteroids for managing tuberculous meningitis","year":2016,"publication_date":"2016-04-01","venue":"Cochrane Database of Systematic Reviews","journal":{"name":"The Cochrane Database of Systematic Reviews","pages":null,"volume":"2016"},"journal_issn":null,"journal_title":null,"publication_types":["Review","MetaAnalysis","JournalArticle"],"pubmed_pub_types":["Journal Article","Meta-Analysis","Research Support, Non-U.S. Gov't","Systematic Review"],"s2_fields_of_study":["Medicine"],"reference_count":59,"citation_count":449,"influential_citation_count":13,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Adult","mj":false,"ui":"D000328"},{"d":"Antitubercular Agents","mj":false,"qs":[{"q":"therapeutic use","mj":true,"ui":"Q000627"}],"ui":"D000995"},{"d":"Chemotherapy, Adjuvant","mj":false,"ui":"D017024"},{"d":"Child","mj":false,"ui":"D002648"},{"d":"Dexamethasone","mj":false,"qs":[{"q":"therapeutic use","mj":false,"ui":"Q000627"}],"ui":"D003907"},{"d":"Glucocorticoids","mj":false,"qs":[{"q":"therapeutic use","mj":true,"ui":"Q000627"}],"ui":"D005938"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Hydrocortisone","mj":false,"qs":[{"q":"therapeutic use","mj":false,"ui":"Q000627"}],"ui":"D006854"},{"d":"Intention to Treat Analysis","mj":false,"ui":"D057194"},{"d":"Prednisolone","mj":false,"qs":[{"q":"therapeutic use","mj":false,"ui":"Q000627"}],"ui":"D011239"},{"d":"Randomized Controlled Trials as Topic","mj":false,"ui":"D016032"},{"d":"Tuberculosis, Meningeal","mj":false,"qs":[{"q":"drug therapy","mj":true,"ui":"Q000188"},{"q":"mortality","mj":false,"ui":"Q000401"}],"ui":"D014390"}],"chemicals":[{"n":"Antitubercular Agents","ui":"D000995","reg":"0"},{"n":"Glucocorticoids","ui":"D005938","reg":"0"},{"n":"Dexamethasone","ui":"D003907","reg":"7S5I7G3JQL"},{"n":"Prednisolone","ui":"D011239","reg":"9PHQ9Y1OLM"},{"n":"Hydrocortisone","ui":"D006854","reg":"WI4X0X7BPJ"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://europepmc.org/articles/pmc4916936?pdf=render","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/f715dd0d86337920ee38fa5da55d59e949b2bfd8","s2_open_access_license":"CCBYNCND","s2_open_access_status":"GREEN","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Abstract Background Tuberculous meningitis is a serious form of tuberculosis (TB) that affects the meninges that cover a person's brain and spinal cord. It is associated with high death rates and with disability in people who survive. Corticosteroids have been used as an adjunct to antituberculous drugs to treat people with tuberculous meningitis, but their role has been controversial. Objectives To evaluate the effects of corticosteroids as an adjunct to antituberculous treatment on death and severe disability in people with tuberculous meningitis. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register up to the 18 March 2016; CENTRAL; MEDLINE; EMBASE; LILACS; and Current Controlled Trials. We also contacted researchers and organizations working in the field, and checked reference lists. Selection criteria Randomized controlled trials that compared corticosteroid plus antituberculous treatment with antituberculous treatment alone in people with clinically diagnosed tuberculous meningitis and included death or disability as outcome measures. Data collection and analysis We independently assessed search results and methodological quality, and extracted data from the included trials. We analysed the data using risk ratios (RR) with 95% confidence intervals (CIs) and used a fixed‐effect model. We performed an intention‐to‐treat analysis, where we included all participants randomized to treatment in the denominator. This analysis assumes that all participants who were lost to follow‐up have good outcomes. We carried out a sensitivity analysis to explore the impact of the missing data. Main results Nine trials that included 1337 participants (with 469 deaths) met the inclusion criteria. At follow‐up from three to 18 months, steroids reduce deaths by almost one quarter (RR 0.75, 95% CI 0.65 to 0.87; nine trials, 1337 participants, high quality evidence). Disabling neurological deficit is not common in survivors, and steroids may have little or no effect on this outcome (RR 0.92, 95% CI 0.71 to 1.20; eight trials, 1314 participants, low quality evidence). There was no difference between groups in the incidence of adverse events, which included gastrointestinal bleeding, invasive bacterial infections, hyperglycaemia, and liver dysfunction. One trial followed up participants for five years. The effect on death was no longer apparent at this time‐point (RR 0.93, 95% CI 0.78 to 1.12; one trial, 545 participants, moderate quality evidence); and there was no difference in disabling neurological deficit detected (RR 0.91, 95% CI 0.49 to 1.69; one trial, 545 participants, low quality evidence). One trial included human immunodeficiency virus (HIV)‐positive people. The stratified analysis by HIV status in this trial showed no heterogeneity, with point estimates for death (RR 0.90, 95% CI 0.67 to 1.20; one trial, 98 participants) and disability (RR 1.23, 95% CI 0.08 to 19.07; one trial, 98 participants) similar to HIV‐negative participants in the same trial. Authors' conclusions Corticosteroids reduce mortality from tuberculous meningitis, at least in the short term. Corticosteroids may have no effect on the number of people who survive tuberculous meningitis with disabling neurological deficit, but this outcome is less common than death, and the CI for the relative effect includes possible harm. However, this small possible harm is unlikely to be quantitatively important when compared to the reduction in mortality. The number of HIV‐positive people included in the review is small, so we are not sure if the benefits in terms of reduced mortality are preserved in this group of patients. 11 April 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (18 Mar, 2016) were included","claims":[{"public_id":"cl_291cbca12c1cbd02f99dd7be31a4fd50","status":"active","text":"Corticosteroids may have little or no effect on disabling neurological deficit in survivors (RR 0.92, 95% CI 0.71 to 1.20; eight trials, 1314 participants, low quality evidence).","confidence":0.85,"contributors":[{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["extraction"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":35,"public_id":"b2adb6bfad","public_label":"Anonymous (b2adb6bfad)","roles":["review"],"url":"https://sah.borca.ai/u/b2adb6bfad"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_291cbca12c1cbd02f99dd7be31a4fd50"},{"public_id":"cl_4570bc094693078332b80a5c1a130be6","status":"active","text":"Corticosteroids reduce mortality from tuberculous meningitis in the short term (RR 0.75, 95% CI 0.65 to 0.87; nine trials, 1337 participants, high quality evidence).","confidence":0.95,"contributors":[{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["extraction"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":35,"public_id":"b2adb6bfad","public_label":"Anonymous (b2adb6bfad)","roles":["review"],"url":"https://sah.borca.ai/u/b2adb6bfad"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_4570bc094693078332b80a5c1a130be6"},{"public_id":"cl_47a5b90e62f8b09912ae41043287deeb","status":"active","text":"In HIV-positive participants, corticosteroids showed no significant heterogeneity in effect on death (RR 0.90, 95% CI 0.67 to 1.20; one trial, 98 participants) or disability (RR 1.23, 95% CI 0.08 to 19.07; one trial, 98 participants) compared to HIV-negative participants.","confidence":0.8,"contributors":[{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["extraction"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":35,"public_id":"b2adb6bfad","public_label":"Anonymous (b2adb6bfad)","roles":["review"],"url":"https://sah.borca.ai/u/b2adb6bfad"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_47a5b90e62f8b09912ae41043287deeb"},{"public_id":"cl_363abfbc35033df83de2af2506aa2c5d","status":"active","text":"The effect of corticosteroids on mortality was no longer apparent at five-year follow-up (RR 0.93, 95% CI 0.78 to 1.12; one trial, 545 participants, moderate quality evidence).","confidence":0.9,"contributors":[{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["extraction"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":35,"public_id":"b2adb6bfad","public_label":"Anonymous (b2adb6bfad)","roles":["review"],"url":"https://sah.borca.ai/u/b2adb6bfad"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_363abfbc35033df83de2af2506aa2c5d"}],"concepts":[{"public_id":"co_07c684dbb4834d553a9c9a43c0e3ac2a","status":"active","name":"antituberculous treatment","description":"Drug therapy for tuberculosis, used as the control arm in the included trials.","types":["therapeutic intervention"],"aliases":["antituberculous drugs"],"contributors":[{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["extraction"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":35,"public_id":"b2adb6bfad","public_label":"Anonymous (b2adb6bfad)","roles":["review"],"url":"https://sah.borca.ai/u/b2adb6bfad"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_07c684dbb4834d553a9c9a43c0e3ac2a"},{"public_id":"co_134444b4a148f09ea5ec971f58cfc128","status":"active","name":"disabling neurological deficit","description":"Severe disability in survivors of tuberculous meningitis, a secondary outcome assessed in the review.","types":["outcome"],"aliases":["disability"],"contributors":[{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["extraction"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":35,"public_id":"b2adb6bfad","public_label":"Anonymous (b2adb6bfad)","roles":["review"],"url":"https://sah.borca.ai/u/b2adb6bfad"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_134444b4a148f09ea5ec971f58cfc128"},{"public_id":"co_49a055cc75ca06733b9d87e7c18cd4f6","status":"active","name":"corticosteroids","description":"Adjunctive steroid therapy used alongside antituberculous treatment for tuberculous meningitis.","types":["therapeutic intervention"],"aliases":["steroids"],"contributors":[{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["extraction"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":35,"public_id":"b2adb6bfad","public_label":"Anonymous (b2adb6bfad)","roles":["review"],"url":"https://sah.borca.ai/u/b2adb6bfad"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_49a055cc75ca06733b9d87e7c18cd4f6"},{"public_id":"co_6fc6bcdffdeff4c27729bb25696bb078","status":"active","name":"HIV-positive","description":"Human immunodeficiency virus positive status of participants in one included trial, used for stratified analysis.","types":["patient subgroup"],"aliases":["HIV-positive people"],"contributors":[{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["extraction"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":35,"public_id":"b2adb6bfad","public_label":"Anonymous (b2adb6bfad)","roles":["review"],"url":"https://sah.borca.ai/u/b2adb6bfad"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_6fc6bcdffdeff4c27729bb25696bb078"},{"public_id":"co_88b471f27e9aaa042de8bdf5174e9c4d","status":"active","name":"five-year follow-up","description":"Long-term follow-up period of five years in one included trial that assessed mortality and disability.","types":["time point"],"aliases":[],"contributors":[{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["extraction"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":35,"public_id":"b2adb6bfad","public_label":"Anonymous (b2adb6bfad)","roles":["review"],"url":"https://sah.borca.ai/u/b2adb6bfad"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_88b471f27e9aaa042de8bdf5174e9c4d"},{"public_id":"co_b24f01efbe7251d151eb8e5fa99c84ea","status":"active","name":"mortality","description":"Death outcome measured in the included trials, the primary endpoint of the review.","types":["outcome"],"aliases":["death"],"contributors":[{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["extraction"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":35,"public_id":"b2adb6bfad","public_label":"Anonymous (b2adb6bfad)","roles":["review"],"url":"https://sah.borca.ai/u/b2adb6bfad"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_b24f01efbe7251d151eb8e5fa99c84ea"},{"public_id":"co_e06735cadeabe59a53f718717354966d","status":"active","name":"randomized controlled trials","description":"Study design of the included trials that compared corticosteroid plus antituberculous treatment versus antituberculous treatment alone.","types":["study design"],"aliases":["RCTs"],"contributors":[{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["extraction"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":35,"public_id":"b2adb6bfad","public_label":"Anonymous (b2adb6bfad)","roles":["review"],"url":"https://sah.borca.ai/u/b2adb6bfad"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_e06735cadeabe59a53f718717354966d"},{"public_id":"co_f4b58004a0405ffec24da2c5a6cfac2f","status":"active","name":"tuberculous meningitis","description":"A serious form of tuberculosis affecting the meninges of the brain and spinal cord.","types":["condition"],"aliases":["TBM"],"contributors":[{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["extraction"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":35,"public_id":"b2adb6bfad","public_label":"Anonymous (b2adb6bfad)","roles":["review"],"url":"https://sah.borca.ai/u/b2adb6bfad"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_f4b58004a0405ffec24da2c5a6cfac2f"},{"public_id":"co_fef8d56f387294b577a09af029e1741e","status":"active","name":"adverse events","description":"Incidence of gastrointestinal bleeding, invasive bacterial infections, hyperglycaemia, and liver dysfunction, reported as safety outcomes.","types":["outcome"],"aliases":[],"contributors":[{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["extraction"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":35,"public_id":"b2adb6bfad","public_label":"Anonymous (b2adb6bfad)","roles":["review"],"url":"https://sah.borca.ai/u/b2adb6bfad"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/concepts/co_fef8d56f387294b577a09af029e1741e"}],"external_ids":{"DOI":"10.1002/14651858.CD002244.pub4","ArXiv":null,"PubMed":27121755,"PubMedCentral":"4916936","MAG":2160408047,"DBLP":null,"ACL":null},"open_access":{"is_open_access":true,"pdf_url":"https://europepmc.org/articles/pmc4916936?pdf=render","landing_url":"https://www.semanticscholar.org/paper/f715dd0d86337920ee38fa5da55d59e949b2bfd8","source":"semantic_scholar","pdf_url_source":"semantic_scholar_open_access_pdf","license":"CCBYNCND","status":"GREEN","reason":null},"reference_availability":{"status":"available","references_indexed":true,"full_text_available":false,"full_text_source":null,"count_basis":"semantic_scholar_metadata","extraction_status":"not_applicable","reason":null},"source":{"provider":"episteme2","base_corpus":"semantic_scholar_dump","freshness_mode":"unknown","basis":["semantic_scholar_metadata","postgres_metadata"],"limits":["paper metadata is based on indexed upstream scholarly datasets","claims and concepts are available only for extracted papers","absence of claims or concepts means no extracted graph data is available in this response"],"status":"available","degraded":false,"degraded_reasons":[],"diagnostics":{"status":"available","degraded":false,"degraded_reasons":[],"metadata_status":"available","graph_status":"available","abstract_status":"available"},"source_flags":5},"paper_id":633158,"paper_uid":"0b9c130a-74df-4f2e-b4be-afb4a161285a","canonical_identity":{"paper_id":633158,"paper_uid":"0b9c130a-74df-4f2e-b4be-afb4a161285a","identity_status":"available","lookup_basis":"semantic_scholar_external_id","compatibility_path":"corpus_id"},"url":"https://sah.borca.ai/papers/6946554"}