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      Patients with MDR-TB on domiciliary care in programmatic settings in Myanmar: Effect of a support package on preventing early deaths

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          Abstract

          Background

          The community-based MDR-TB care (CBMDR-TBC) project was implemented in 2015 by The Union in collaboration with national TB programme (NTP) in 33 townships of upper Myanmar to improve treatment outcomes among patients with MDR-TB registered under NTP. They received community-based support through the project staff, in addition to the routine domiciliary care provided by NTP staff. Each project township had a project nurse exclusively for MDR-TB and a community volunteer who provided evening directly observed therapy (in addition to morning directly observed therapy by NTP).

          Objectives

          To determine the effect of CBMDR-TBC project on death and unfavourable outcomes during the intensive phase of MDR-TB treatment.

          Methods

          In this cohort study involving record review, all patients diagnosed with MDR-TB between January 2015 and June 2016 in project townships and initiated on treatment till 31 Dec 2016 were included. CBMDR-TBC status was categorized as “receiving support” if project initiation in patient’s township was before treatment initiation, “receiving partial support” if project initiation was after treatment initiation, and “not receiving support” if project initiation was after intensive phase treatment outcome declaration. Time to event analysis (censored on 10 April 2017) and cox regression was done.

          Results

          Of 261 patients initiated on treatment, death and unfavourable outcomes were accounted for 13% and 21% among “receiving support (n = 163)”, 3% and 24% among “receiving partial support (n = 75)” and 13% and 26% among “not receiving support (n = 23)” respectively. After adjusting for other potential confounders, the association between CBMDR-TBC and unfavourable outcomes was not statistically significant. However, when compared to “not receiving support”, those “receiving support” and “receiving partial support” had 20% [aHR (0.95 CI: 0.8 (0.2–3.1)] and 90% lower hazard [aHR (0.95 CI: 0.1 (0.02–0.9)] of death, respectively. This was intriguing. Implementation of CBMDR-TBC coincided with implementation of decentralized MDR-TB centers at district level. Hence, patients that would have generally not accessed MDR-TB treatment before decentralization also started receiving treatment and were also included under CBMDR-TBC “received support” group. These patients could possibly be expected to sicker at treatment initiation than patients in other CBMDR-TBC groups. This could be the possible reason for nullifying the effect of CBMDR-TBC in “receiving support” group and therefore similar survival was found when compared to “not receiving support”.

          Conclusion

          CBMDR-TBC may prevent early deaths and has a scope for expansion to other townships of Myanmar and implications for NTPs globally. However, future studies should consider including data on extent of sickness at treatment initiation and patient level support received under CBMDR-TBC.

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          Most cited references3

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          Unfavourable outcomes among patients with MDR-TB on the standard 24-month regimen in Maharashtra, India.

          Setting: Patients with multidrug-resistant tuberculosis (MDR-TB) registered for treatment (2011-2012 cohort) using the standard 24-month regimen, under the Revised National TB Control Programme's programmatic management of drug-resistant TB (PMDT), Maharashtra, India. Objectives: To assess the treatment outcomes and the timing and risk factors for unfavourable treatment outcomes, with a focus on death and loss to follow-up (LTFU). Method: This was a retrospective cohort study involving a review of PMDT records. Treatment outcomes were reported on 31 December 2014. Results: Of 4024 patients, treatment success was recorded in 1168 (29%). Unfavourable outcomes occurred in 2242 (56%), of whom 857 (21%) died and 768 (19%) were lost to follow-up. Treatment outcomes were missing on record review for 375 (9%) patients, and 239 (6%) were still undergoing treatment. Half of LTFU occurred within 3 months, and more than four fifths of deaths occurred after 6 months of treatment. Human immunodeficiency virus infection, being underweight, age ⩾ 15 years, male sex and pulmonary TB were the main risk factors for death, LTFU or other unfavourable treatment outcomes. Conclusion: The study found poor treatment outcomes in patients with MDR-TB registered for treatment in Maharashtra, India. Interventions are required to address the high rates of LTFU and death.
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            The effect of early versus late treatment initiation after diagnosis on the outcomes of patients treated for multidrug-resistant tuberculosis: a systematic review

            Background Globally it is estimated that 480 000 people developed multidrug-resistant tuberculosis (MDR-TB) in 2014 and 190 000 people died from the disease. Successful treatment outcomes are achieved in only 50 % of patients with MDR-TB, compared to 86 % for drug susceptible disease. It is widely held that delay in time to initiation of treatment for MDR-TB is an important predictor of treatment outcome. The objective of this review was to assess the existing evidence on the outcomes of multidrug- and extensively drug-resistant tuberculosis patients treated early (≤4 weeks) versus late (>4 weeks) after diagnosis of drug resistance. Methods Eight sources providing access to 17 globally representative electronic health care databases, indexes, sources of evidence-based reviews and grey literature were searched using terms incorporating time to treatment and MDR-TB. Two-stage sifting in duplicate was employed to assess studies against pre-specified inclusion and exclusion criteria. Only those articles reporting WHO-defined treatment outcomes were considered for inclusion. Articles reporting on fewer than 10 patients, published before 1990, or without a comparison of outcomes in patient groups experiencing different delays to treatment initiation were excluded. Results The initial search yielded 1978 references, of which 1475 unique references remained after removal of duplicates and 28 articles published pre-1990. After title and abstract sifting, 64 papers underwent full text review. None of these articles fulfilled the criteria for inclusion in the review. Conclusions Whilst there is an inherent logic in the theory that treatment delay will lead to poorer treatment outcomes, no published evidence was identified in this systematic review to support this hypothesis. Reports of programmatic changes leading to reductions in treatment delay exist in the literature, but attribution of differences in outcomes specifically to treatment delay is confounded by other contemporaneous changes. Further primary research on this question is not considered a high priority use of limited resources, though where data are available, improved reporting of outcomes by time to treatment should be encouraged. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1524-0) contains supplementary material, which is available to authorized users.
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              Impact of rapid molecular diagnostic tests on time to treatment initiation and outcomes in patients with multidrug-resistant tuberculosis, Tamil Nadu, India

              India is replacing culture and drug sensitivity testing (CDST) with rapid molecular tests for diagnosing MDR-TB. We assessed the impact of rapid tests on time to initiation of treatment and outcomes in patients with MDR-TB compared with CDST.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                20 December 2017
                2017
                : 12
                : 12
                : e0187223
                Affiliations
                [1 ] International Union against Tuberculosis and Lung Disease (The Union), Mandalay, Myanmar
                [2 ] International Union against Tuberculosis and Lung Disease (The Union), South-East Asia Office, New Delhi, India
                [3 ] National Tuberculosis Programme, Ministry of Health and Sports, Myanmar
                [4 ] Department of Medical Research (Pyin oo Lwin Branch), Ministry of Health and Sports, Myanmar
                Instituto de Diagnostico y Referencia Epidemiologicos, MEXICO
                Author notes

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

                Author information
                http://orcid.org/0000-0002-8232-6260
                Article
                PONE-D-17-24402
                10.1371/journal.pone.0187223
                5737886
                29261669
                6bc73b72-eb24-4466-9614-52ea7b53e24c
                © 2017 Wai et al

                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
                : 28 June 2017
                : 11 October 2017
                Page count
                Figures: 3, Tables: 9, Pages: 18
                Funding
                The training programme within which this paper was developed were funded by the Department for International Development (DFID), UK. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Tuberculosis
                Multi-Drug-Resistant Tuberculosis
                Medicine and Health Sciences
                Tropical Diseases
                Tuberculosis
                Multi-Drug-Resistant Tuberculosis
                Medicine and Health Sciences
                Pharmaceutics
                Drug Therapy
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Tuberculosis
                Medicine and Health Sciences
                Tropical Diseases
                Tuberculosis
                Medicine and Health Sciences
                Diagnostic Medicine
                Tuberculosis Diagnosis and Management
                Medicine and Health Sciences
                Hematology
                Anemia
                People and Places
                Geographical Locations
                Asia
                Myanmar
                People and Places
                Population Groupings
                Professions
                Medical Personnel
                Nurses
                Medicine and Health Sciences
                Health Care
                Health Care Providers
                Nurses
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Mucus
                Sputum
                Medicine and Health Sciences
                Anatomy
                Body Fluids
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                Sputum
                Biology and Life Sciences
                Physiology
                Body Fluids
                Mucus
                Sputum
                Medicine and Health Sciences
                Physiology
                Body Fluids
                Mucus
                Sputum
                Custom metadata
                The dataset and programme file in STATA format contain potentially identifying participant information. Therefore, they are available to all interested researchers upon request. Please contact the corresponding author to request these underlying data.

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