BackgroundThe incidence, manifestations, outcome and clinical predictors of paradoxical TB-IRIS in patients with HIV and culture confirmed pulmonary tuberculosis (PTB) in India have not been studied prospectively.MethodsHIV+ patients with culture confirmed PTB started on anti-tuberculosis therapy (ATT) were followed prospectively after anti-retroviral therapy (ART) initiation. Established criteria for IRIS diagnosis were used including decline in plasma HIV RNA at IRIS event. Pre-ART plasma levels of interleukin (IL)-6 and C-reactive protein (CRP) were measured. Univariate and multivariate logistic regression models were used to evaluate associations between baseline variables and IRIS.ResultsOf 57 patients enrolled, 48 had complete follow up data. Median ATT-ART interval was 28 days (interquartile range, IQR 14–47). IRIS events occurred in 26 patients (54.2%) at a median of 11 days (IQR: 7–16) after ART initiation. Corticosteroids were required for treatment of most IRIS events that resolved within a median of 13 days (IQR: 9–23). Two patients died due to CNS TB-IRIS. Lower CD4+ T-cell counts, higher plasma HIV RNA levels, lower CD4/CD8 ratio, lower hemoglobin, shorter ATT to ART interval, extra-pulmonary or miliary TB and higher plasma IL-6 and CRP levels at baseline were associated with paradoxical TB-IRIS in the univariate analysis. Shorter ATT to ART interval, lower hemoglobin and higher IL-6 and CRP levels remained significant in the multivariate analysis.ConclusionParadoxical TB–IRIS frequently complicates HIV-TB therapy in India. IL-6 and CRP may assist in predicting IRIS events and serve as potential targets for immune interventions.

The benefit of daily over thrice-weekly antituberculosis therapy among HIV-positive patients with pulmonary tuberculosis (TB) who are receiving antiretroviral therapy remains unproven. OBJECTIVE To compare the efficacy and safety of daily, part-daily, and intermittent antituberculosis therapy regimens in the treatment of HIV-associated pulmonary TB. DESIGN, SETTING, AND PARTICIPANTS This open-label, randomized clinical trial was conducted by the National Institute for Research in Tuberculosis, south India. Adults infected with HIV with newly diagnosed, culture-positive, pulmonary TB were enrolled between September 14, 2009, and January 18, 2016. INTERVENTIONS Patients were randomized to daily, part-daily, and intermittent antituberculosis therapy regimens, stratified by baseline CD4 lymphocyte count and sputum smear grade. Antiretroviral therapy was initiated as per national guidelines. Clinical and sputum microbiological examinations of patients were performed monthly until 18 months after randomization. Adverse events were recorded using standard criteria. MAIN OUTCOMES AND MEASURES The primary outcome was favorable response, defined as treatment completion with all available sputum cultures negative for Mycobacterium tuberculosis during the last 2 months of treatment. Unfavorable responses included treatment failures, dropouts, deaths, and toxic effects among regimens. RESULTS Of 331 patients (251 [76%] male; mean [SD] age, 39 [9] years; mean [SD] HIV viral load, 4.9 [1.2] log 10 copies/mL; and median [interquartile range] CD4 lymphocyte count, 138 [69-248] cells/μL), favorable responses were experienced by 91% (89 of 98), 80% (77 of 96), and 77% (75 of 98) in the daily, part-daily, and intermittent regimens, respectively. With the difference in outcome between daily and intermittent regimens crossing the O'Brien-Fleming group sequential boundaries and acquired rifampicin resistance emergence (n = 4) confined to the intermittent group, the data safety monitoring committee halted the study. A total of 18 patients died and 18 patients dropped out during the treatment period in the 3 regimens. Six, 4, and 6 patients in the daily, part-daily, and intermittent regimens, respectively, had TB recurrence. CONCLUSIONS AND RELEVANCE Among HIV-positive patients with pulmonary TB receiving antiretroviral therapy, a daily anti-TB regimen proved superior to a thrice-weekly regimen in terms of efficacy and emergence of rifampicin resistance. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00933790

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Background:Swallowing changes are common in Parkinson's disease (PD). Early identification is essential to avoid complications of aspiration.Objectives:To evaluate the swallowing ability of the PD patients and to correlate it with the indicators of disease progression.Materials and Methods:A total of 100 PD patients (70 males and 30 females) aged between 50 years and 70 years with varying stage, duration, and severity were enrolled in a cross-sectional study carried out between January and May 2012. A simple bedside water swallowing test was performed using standard 150 ml of water. Swallowing process was assessed under three categories-swallowing speeds (ml/s), swallowing volume (ml/swallow) and swallowing duration (s/swallow). Equal number of age and sex matched controls were also evaluated.Results:All of them completed the task of swallowing. A mean swallowing speed (27.48 ml/s), swallowing volume (28.5 ml/s), and swallowing duration (1.05 s/swallow) was established by the control group. The PD patients showed decreased swallowing speed (7.15 ml/s in males and 6.61 ml/s in females), decreased swallowing volume (14.59 ml/swallow and 14 ml/swallow in females), and increased swallowing duration (2.37 s/swallow and 2.42 s/swallow) which are statistically significant. There was a significant positive correlation between the severity, duration, and staging of the disease with the swallowing performance and a poor correlation between the subjective reports of dysphagia and the objective performance on water swallow test.Conclusion:The water swallowing test is a simple bedside test to identify the swallowing changes early in PD. It is recommended to do the test in all PD Patients to detect dysphagia early and to intervene appropriately.

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