Analysing the relationship between polysomnographic measures of sleep with measures of physical and cognitive fatigue in people with multiple sclerosis.

OBJECTIVES: We aimed to determine whether there was a relationship between objective measures of sleep measured by polysomnography and measures of physical and cognitive fatigue in patients with Multiple Sclerosis (MS). METHODS: People with MS of age 18-50 years of any subtype attending the OPD satisfying the revised 2010 McDonald criteria were recruited. Modified Fatigue Impact Scale (MFIS) and the Fatigue Severity Scale (FSS) were used to assess physical fatigue. Cognitive fatigue was measured with modified versions of the Stroop test, modified Symbol Digit Modalities Test, Serial Addition Test, and with latency and amplitude of the P300 evoked potential. Percentage of N1, N2, N3 and REM sleep stages, Sleep onset latency, Sleep efficiency, Wake after sleep onset, Respiratory event index, Periodic limb movement index were the measures recorded with polysomnography. RESULTS: Among 113 patients, 43 (38.05%) complained of disturbed sleep and 88 (77.88%) complained of increased fatigability and tiredness. Mean MFIS score of the sample was 42.34 ±â€¯9.09. Mean FSS score was 19.12 ±â€¯9.42. Polysomnographic measures of sleep showed a significant correlation with objective measures of cognitive fatigue and did not show any significant correlation with measures of physical fatigue. CONCLUSIONS: Sleep impairment is a very common problem in people with MS justifying routine polysomnographic evaluation. We have found evidence that though sleep impairment is not related to physical fatigue, it is strongly related to cognitive fatigue.

Daily vs Intermittent Antituberculosis Therapy for Pulmonary Tuberculosis in Patients With HIV: A Randomized Clinical Trial.

Importance: 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] log10 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.

Predicting falls in multiple sclerosis: Do electrophysiological measures have a better predictive accuracy compared to clinical measures?

BACKGROUND: The risk of falls in people with Multiple Sclerosis (MS) is much greater than that of the general population due to impaired coordination, gait, sensation, muscle tone, strength, and cognition. These MS related falls hamper the day to day living of these individuals and are one of the prime factors aggravating the disease related morbidity. The fear of falling itself may make these individuals more dependent and hinder their professional and leisurely activities. Hence, the significance of identifying individuals who are at risk of falling and instituting preventive counter-measures cannot be overemphasized. Various simple clinical tests and questionnaires have been recommended for this purpose, but are far from ideal. OBJECTIVE: The objective was to find accurate measures to predict a future fall in MS patients. We also aimed to enquire about the prevalence of falls in MS population and its clinical profile which included detailed history about the past falls, Expanded disability status scale (EDSS) scores, Timed 25 foot walk (T25FW) scores, Activities specific balance confidence (ABC) scores, Falls efficacy scale international (FESI) scores, Multiple Sclerosis Walking Scale 12 (MSWS12) questionnaire. DESIGN/METHODS: This was a prospective cohort study conducted at the Institute of Neurology, Chennai from January 2015 to August 2017. MS patients of any subtype attending Neurology OPD satisfying revised 2010 McDonald criteria were recruited. 134 subjects with MS consented to participate in this study and 113 of them who met the criteria were included. Baseline history was obtained about the number of falls in the previous year. EDSS, T25FW, ABC, FESI, and MSWS12 scores were obtained at the baseline. VEMP and SEP tests were done and the baseline P13/N23 cVEMP latencies, N10 oVEMP latency, and P37 lower limb SEP latency were obtained. These subjects were followed up for one year and were enquired if they had fallen during that period and the number of falls was recorded. Logistic regression models were used to compute the area under receiver operating characteristic curve (AUC) for each variable tested. Pearson correlation coefficients were calculated for each variable with the number of future falls. RESULTS: Among the 113 patients, 72% (n = 81) had one or more falls during follow-up. Among all variables tested P13 cervical VEMP latency had the highest predictive accuracy (AUC = 0.820) followed by N10 ocular VEMP latency (AUC = 0.794) and P37 SEP latency (AUC = 0.732). P13 latency also had the highest correlation coefficient (R = 0.689, R2 = 0.475) with the number of future falls. CONCLUSION: P13, N10 and P37 latencies were the most accurate in predicting a future fall when compared to clinical measures.