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Functional outcomes in adults with tuberculous meningitis admitted to the ICU: a multicenter cohort study.

ABSTRACT: BACKGROUND:Tuberculous meningitis (TBM) is a devastating infection in tuberculosis endemic areas with limited access to intensive care. Functional outcomes of severe adult TBM patients admitted to the ICU in nonendemic areas are not known. METHODS:We conducted a retrospective multicenter cohort study (2004-2016) of consecutive TBM patients admitted to 12 ICUs in the Paris area, France. Clinical, biological, and brain magnetic resonance imaging (MRI) findings at admission associated with a poor functional outcome (i.e., a score of 3-6 on the modified Rankin scale (mRS) at 90 days) were identified by logistic regression. Factors associated with 1-year mortality were investigated by Cox proportional hazards modeling. RESULTS:We studied 90 patients, of whom 61 (68%) had a score on the Glasgow Coma Scale ? 10 at presentation and 63 (70%) required invasive mechanical ventilation. Brain MRI revealed infarction and hydrocephalus in 38/75 (51%) and 25/75 (33%) cases, respectively. A poor functional outcome was observed in 55 (61%) patients and was independently associated with older age (adjusted odds ratio (aOR) 1.03, 95% CI 1.0-1.07), cerebrospinal fluid protein level ? 2 g/L (aOR 5.31, 95% CI 1.67-16.85), and hydrocephalus on brain MRI (aOR 17.2, 95% CI 2.57-115.14). By contrast, adjunctive steroids were protective (aOR 0.13, 95% CI 0.03-0.56). The multivariable adjusted hazard ratio of adjunctive steroids for 1-year mortality (47%, 95% CI 37%-59%) was 0.23 (95% CI 0.11-0.44). Among survivors at 1 year, functional independence (mRS of 0-2) was observed in 27/37 (73%, 95% CI 59%-87%) cases. CONCLUSIONS:A poor functional outcome in adult TBM patients admitted to the ICU in a nonendemic area is observed in 60% of cases and is independently associated with elevated cerebrospinal fluid protein level and hydrocephalus. Our data also suggest a protective effect of adjunctive steroids, with reduced disability and mortality, irrespective of immune status and severity of disease at presentation. One-year follow-up revealed functional independence in most survivors.

SUBMITTER: Cantier M

PROVIDER: S-EPMC6098613 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Functional outcomes in adults with tuberculous meningitis admitted to the ICU: a multicenter cohort study.

Cantier Marie M Morisot Adeline A Guérot Emmanuel E Megarbane Bruno B Razazi Keyvan K Contou Damien D Mariotte Eric E Canet Emmanuel E De Montmollin Etienne E Dubée Vincent V Boulet Eric E Gaudry Stéphane S Voiriot Guillaume G Mayaux Julien J Pène Frédéric F Neuville Mathilde M Mourvillier Bruno B Ruckly Stéphane S Bouadma Lila L Wolff Michel M Timsit Jean-François JF Sonneville Romain R

Critical care (London, England) 20180817 1

<h4>Background</h4>Tuberculous meningitis (TBM) is a devastating infection in tuberculosis endemic areas with limited access to intensive care. Functional outcomes of severe adult TBM patients admitted to the ICU in nonendemic areas are not known.<h4>Methods</h4>We conducted a retrospective multicenter cohort study (2004-2016) of consecutive TBM patients admitted to 12 ICUs in the Paris area, France. Clinical, biological, and brain magnetic resonance imaging (MRI) findings at admission associate ...[more]

PMID: 30119686

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Project description:ImportancePrognostication following ICU admission can often be determined based on known risk factors, including demographics and illness severity; however, little is known about outcomes of patients deemed to be "low-risk" at the time of hospital admission who subsequently are admitted to the ICU.ObjectivesThe objectives of this study were to determine the characteristics, outcomes, and costs for patients requiring ICU admission despite having lower predicted mortality when they were admitted to the hospital.Design setting and participantsIn this historical cohort study, we used a prospectively maintained ICU registry that included all ICU admissions to The Ottawa Hospital for patients 18 years or older from January 2011 to December 2016. We classified patients as low-risk using the Hospital-patient 1-year Mortality Risk at admission score, a hospital admission score validated to predict 1-year mortality.Main outcomes and measuresThe primary outcome was inhospital mortality. Secondary outcomes included adverse events, resource utilization, and costs.ResultsOf the 17,173 total ICU patients, 3,445 (20.1%) were classified as low-risk at hospital admission. Low-risk patients were younger (48.7 vs 67.5 yr; p < 0.001) and had a lower Multiple Organ Dysfunction Score (2.37 vs 4.14; p < 0.001). Mortality for low-risk patients was significantly lower than for non-low-risk patients (4.1% vs 25.4%; p < 0.001). For low-risk patients, multivariable logistic regression showed mortality was independently associated with older age (odds ratio, 1.02 per 1 yr; 95% CI, 1.00-1.03 per 1 yr), Multiple Organ Dysfunction Score (odds ratio, 1.42 per 1 point; 95% CI, 1.31-1.54 per 1 point), fluid management adverse events (odds ratio, 2.84; 95% CI, 1.29-6.25), hospital-acquired infections (odds ratio, 1.60; 95% CI, 1.02-2.51), and mechanical ventilation (odds ratio, 1.98; 95% CI, 1.20-3.26).Conclusions and relevanceDespite their robust premorbid status, low-risk patients admitted to the ICU had significant inhospital mortality. Fluid management adverse events, hospital-associated infections, multiple organ dysfunction, and mechanical ventilation are important prognostic factors for low-risk patients.

Project description:BackgroundWHO recommends Xpert MTB/RIF as initial diagnostic testing for tuberculous meningitis. However, diagnosis remains difficult, with Xpert sensitivity of about 50-70% and culture sensitivity of about 60%. We evaluated the diagnostic performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis.MethodsWe prospectively obtained diagnostic cerebrospinal fluid (CSF) specimens during screening for a trial on the treatment of HIV-associated cryptococcal meningitis in Mbarara, Uganda. HIV-infected adults with suspected meningitis (eg, headache, nuchal rigidity, altered mental status) were screened consecutively at Mbarara Regional Referral Hospital. We centrifuged CSF, resuspended the pellet in 2 mL of CSF, and tested 0·5 mL with mycobacteria growth indicator tube culture, 1 mL with Xpert, and cryopreserved 0·5 mL, later tested with Xpert Ultra. We assessed diagnostic performance against uniform clinical case definition or a composite reference standard of any positive CSF tuberculous test.FindingsFrom Feb 27, 2015, to Nov 7, 2016, we prospectively evaluated 129 HIV-infected adults with suspected meningitis for tuberculosis. 23 participants were classified as probable or definite tuberculous meningitis by uniform case definition, excluding Xpert Ultra results. Xpert Ultra sensitivity was 70% (95% CI 47-87; 16 of 23 cases) for probable or definite tuberculous meningitis compared with 43% (23-66; 10/23) for Xpert and 43% (23-66; 10/23) for culture. With composite standard, we detected tuberculous meningitis in 22 (17%) of 129 participants. Xpert Ultra had 95% sensitivity (95% CI 77-99; 21 of 22 cases) for tuberculous meningitis, which was higher than either Xpert (45% [24-68]; 10/22; p=0·0010) or culture (45% [24-68]; 10/22; p=0·0034). Of 21 participants positive by Xpert Ultra, 13 were positive by culture, Xpert, or both, and eight were only positive by Xpert Ultra. Of those eight, three were categorised as probable tuberculous meningitis, three as possible tuberculous meningitis, and two as not tuberculous meningitis. Testing 6 mL or more of CSF was associated with more frequent detection of tuberculosis than with less than 6 mL (26% vs 7%; p=0·014).InterpretationXpert Ultra detected significantly more tuberculous meningitis than did either Xpert or culture. WHO now recommends the use of Xpert Ultra as the initial diagnostic test for suspected tuberculous meningitis.FundingNational Institute of Neurologic Diseases and Stroke, Fogarty International Center, National Institute of Allergy and Infectious Disease, UK Medical Research Council/DfID/Wellcome Trust Global Health Trials, Doris Duke Charitable Foundation.

Project description:BackgroundAdjunctive glucocorticoids are widely used to treat human immunodeficiency virus (HIV)-associated tuberculous meningitis despite limited data supporting their safety and efficacy.MethodsWe conducted a double-blind, randomized, placebo-controlled trial involving HIV-positive adults (≥18 years of age) with tuberculous meningitis in Vietnam and Indonesia. Participants were randomly assigned to receive a 6-to-8-week tapering course of either dexamethasone or placebo in addition to 12 months of antituberculosis chemotherapy. The primary end point was death from any cause during the 12 months after randomization.ResultsA total of 520 adults were randomly assigned to receive either dexamethasone (263 participants) or placebo (257 participants). The median age was 36 years; 255 of 520 participants (49.0%) had never received antiretroviral therapy, and 251 of 484 participants (51.9%) with available data had a baseline CD4 count of 50 cells per cubic millimeter or less. Six participants withdrew from the trial, and five were lost to follow-up. During the 12 months of follow-up, death occurred in 116 of 263 participants (44.1%) in the dexamethasone group and in 126 of 257 participants (49.0%) in the placebo group (hazard ratio, 0.85; 95% confidence interval, 0.66 to 1.10; P = 0.22). Prespecified analyses did not reveal a subgroup that clearly benefited from dexamethasone. The incidence of secondary end-point events, including cases of immune reconstitution inflammatory syndrome during the first 6 months, was similar in the two trial groups. The numbers of participants with at least one serious adverse event were similar in the dexamethasone group (192 of 263 participants [73.0%]) and the placebo group (194 of 257 participants [75.5%]) (P = 0.52).ConclusionsAmong HIV-positive adults with tuberculous meningitis, adjunctive dexamethasone, as compared with placebo, did not confer a benefit with respect to survival or any secondary end point. (Funded by the Wellcome Trust; ACT HIV ClinicalTrials.gov number, NCT03092817.).

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Functional outcomes in adults with tuberculous meningitis admitted to the ICU: a multicenter cohort study.

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Functional outcomes in adults with tuberculous meningitis admitted to the ICU: a multicenter cohort study.

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