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      Early Mortality during Initial Treatment of Tuberculosis in Patients Co-Infected with HIV at the Yaoundé Central Hospital, Cameroon: An 8-Year Retrospective Cohort Study (2006-2013)

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          Abstract

          Background

          Understanding contributors to mortality during the initial phase of tuberculosis (TB) treatment in patients co-infected with HIV would guide targeted interventions to improve survival. The aim of this study was to ascertain the incidence of death during the initial 2 months (new cases) and 3 months (retreatment cases) of TB treatment and to assess correlates of mortality in HIV co-infected patients.

          Methods

          We conducted a hospital-based retrospective cohort study from January 2006 to December 2013 at Yaoundé Central Hospital, Cameroon. We reviewed medical records to identify co-infected TB/HIV inpatients aged 15 years and older who died during TB treatment. Death was defined as any death occurring during TB treatment, as per World Health Organization recommendations. We collected socio-demographic, clinical and laboratory data. We conducted multivariable logistic binary regression analysis to identify factors associated with death during the intensive phase of TB treatment. Magnitudes of associations were expressed by adjusted odds ratio (a OR) with 95% confidence interval. A p value < 0.05 was considered statistically significant.

          Results

          The 99 patients enrolled had a mean age of 39.5 (standard deviation 10.9) years and 53% were male. Patients were followed for 276.3 person-months of observation (PMO). Forty nine patients were died during intensive phase of TB treatment. Death incidence during the intensive phase of TB treatment was 32.2 per 100 PMO. Having a non-AIDS comorbidity (a OR 2.47, 95%CI 1.22-5.02, p = 0.012), having extra-pulmonary TB (a OR 1.89, 95%CI 1.05-3.43, p = 0.035), and one year increase in duration of known HIV infection (aOR 1.23, 95%CI 1.004-1.49) were independently associated with death during the intensive phase of TB treatment.

          Conclusions

          Mortality incidence during intensive phase of TB treatment was high among TB/HIV co-infected patients during TB treatment; and strongly associated with extra pulmonary TB suggesting advanced stage of immunosuppression and non-AIDS comorbidities. Early HIV diagnosis and care and good management of non-comorbidities can reduce this incidence.

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          Most cited references21

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          Dosing Frequency and Medication Adherence in Chronic Disease

          BACKGROUND: Prior research has shown a decrease in medication adherence as dosing frequency increases; however, meta-analyses have not been able to demonstrate a significant inverse relationship between dosing frequency and adherence when comparing twice-daily versus once-daily dosing. OBJECTIVES: To determine the effect of scheduled dosing frequency on medication adherence in patients with chronic diseases. METHODS: A systematic literature search of Medline and Embase from January 1986 to December 2011 and a hand search of references were performed to identify eligible studies. Randomized and observational studies were included if they utilized a prospective design, assessed adult patients with chronic diseases, evaluated scheduled oral medications taken 1 to 4 times daily, and measured medication adherence for at least 1 month using an electronic monitoring device. Manual searches of reference sections of identified studies and systematic reviews were also performed to find other potentially relevant articles. Standard definitions for medication taking, regimen, and timing adherence were used and evaluated. Studies were pooled using a multivariate linear mixed-model method to conduct meta-regression accounting for both random and fixed effects, weighted 
by the inverse of the variance of medication adherence. RESULTS: Fifty-one studies, comprising 65, 76, and 47 dosing frequency arms for the taking, regimen, and timing adherence endpoints were included. Unadjusted adherence estimates were highest when the least stringent definition, taking adherence, was used (range for dosing frequencies: 80.1%-93.0%) and lowest when the most stringent definition, timing adherence, was used (range for dosing frequencies: 18.8%-76.9%). In multivariate meta-regression analyses, the adjusted weighted mean percentage adherence rates for all regimens dosed more frequently than once per day were significantly lower compared with once-daily regimens (for 2-times, 3-times, and 4-times daily regimens, respectively: differences for taking adherence: –6.7%, –13.5%, and –19.2%; regimen adherence: –13.1%, –24.9%, and –23.1%; and timing adherence: –26.7%, –39.0%, and –54.2%). CONCLUSIONS: Patients with chronic diseases appear to be more adherent with once-daily compared with more frequently scheduled medication regimens. The use of more stringent definitions of adherence magnified these findings.
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            Effect of medication dosing frequency on adherence in chronic diseases.

            To systematically review available data on the effect of daily medication dosing frequency on medication adherence in chronic disease states, as assessed by precise medication event monitoring systems (MEMS). Systematic review of relevant literature published between January 1986 and August 2007. Four electronic databases were searched to identify appropriate studies. Study selection criteria included prospective study design, patient population with quiescent chronic disease, medication intervention prescribed to each treatment arm for at least 6 weeks, and the use of MEMS to measure adherence. Data were extracted on the chronic disease being treated, the frequency of medication dosing, and the proportion of days with correct number of doses. Twenty studies met the selection criteria. All studies reported higher adherence rates in patients using less frequently dosed medications, and these differences were statistically significant (P <.05) in 75% (15 of 20) of studies. For 5 of 6 studies comparing once-daily versus thrice-daily dosing, patients receiving once-daily dosing had 22% to 41% more adherent days compared with patients receiving thrice-daily dosing. For studies comparing once-daily versus twice-daily dosing, patients receiving once-daily dosing had 2% to 44% more adherent days compared with patients receiving twice-daily dosing, with most studies clustering around 13% to 26%. Patients are more compliant with once-daily compared with twice-daily or thrice-daily treatment regimens.
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              Mortality and causes of death in adults receiving highly active antiretroviral therapy in Senegal: a 7-year cohort study.

              To evaluate survival and investigate causes of death among HIV-1 infected adults receiving HAART in Senegal. An observational prospective cohort. Mortality was assessed in the first patients enrolled between August 1998 and April 2002 in the Senegalese antiretroviral drug access initiative. First-line regimen combined two nucleoside reverse transcriptase inhibitors and either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor. The most likely causes of death were ascertained through medical records or post-mortem interviews (verbal autopsy). Four hundred and four patients (54.7% women) were enrolled in the study and were followed for a median of 46 months (interquartile range: 32-57 months) after HAART initiation. At baseline, 5% were antiretroviral therapy (ART) non-naive, 39 and 55% were respectively at CDC stage B and C, median age, CD4 cell count and viral load were 37 years, 128 cells/microl and 5.2 log cp/ml, respectively. Ninety-three patients died during follow-up and the overall incidence rate of death was 6.3/100 person-years [95% confidence interval (CI), 5.2-7.7]. During the first year after HAART initiation, 47 patients died and seven were lost to follow-up, yielding to a probability of dying of 11.7% (95% CI, 8.9-15.3%). The death rate, which was highest during the first year after HAART initiation, decreased with time yielding a cumulative probability of dying of 17.4% (95% CI, 13.9-21.5%) and 24.6% (95% CI, 20.4-29.4%) at 2 and 5 years. Causes of death were ascertained in 76 deaths. Mycobacterial infections, neurotropic infections and septicaemia were the most frequent likely causes of death. This study underlines the early mortality pattern after HAART initiation and highlights the leading role of mycobacterial infections in the causes of death.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                27 July 2015
                2015
                : 10
                : 7
                : e0132394
                Affiliations
                [1 ]Department of Epidemiology and Public Health, Pasteur Center of Cameroon, Yaoundé, Cameroon
                [2 ]Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa
                [3 ]Medical Diagnosis Center, Yaoundé, Cameroon
                [4 ]Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, Yaoundé, Cameroon
                [5 ]Department of Medicine, NYU-Langone Medical Center, New York, New York, United States of America
                [6 ]National AIDS control committee, Ministry of Public Health, Yaoundé, Cameroon
                [7 ]Faculty of Medicine and Pharmaceutic Sciences, University of Douala, Douala, Cameroon
                [8 ]Infectious Diseases Unit, Yaoundé Central Hospital, Yaoundé, Cameroon
                Chinese Academy of Medical Sciences and Peking Union Medical College, CHINA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JJRB. Performed the experiments: AAA SK-S. Analyzed the data: JJRB APRA. Contributed reagents/materials/analysis tools: JJRB JJNN CSP SCB APRA. Wrote the paper: JJRB CSP. Critical revision and review of the manuscript: JJNN AAA CSP SCB APRA SK-S.

                Article
                PONE-D-15-04086
                10.1371/journal.pone.0132394
                4516239
                26214516
                ad556ba1-797b-4434-9d85-a19a90931b00
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 29 January 2015
                : 12 June 2015
                Page count
                Figures: 2, Tables: 3, Pages: 13
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Custom metadata
                The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper as Supporting Information file S1 Data.

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