Summary of risk of bias in included studies assessed using New Castle Ottawa quality assessment scale for cohort studies [37].

<p>Summary of risk of bias in included studies assessed using New Castle Ottawa quality assessment scale for cohort studies [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0186697#pone.0186697.ref037" target="_blank">37</a>].</p

Effect of glycemic control and type of diabetes treatment on unsuccessful TB treatment outcomes among people with TB-Diabetes: A systematic review

<div><p>Background</p><p><b>S</b>tringent glycemic control by using insulin as a replacement or in addition to oral hypoglycemic agents (OHAs) has been recommended for people with tuberculosis and diabetes mellitus (TB-DM). This systematic review (PROSPERO 2016:CRD42016039101) analyses whether this improves TB treatment outcomes.</p><p>Objectives</p><p>Among people with drug-susceptible TB and DM on anti-TB treatment, to determine the effect of i) glycemic control (stringent or less stringent) compared to poor glycemic control and ii) insulin (only or with OHAs) compared to ‘OHAs only’ on unsuccessful TB treatment outcome(s). We looked for unfavourable TB treatment outcomes at the end of intensive phase and/or end of TB treatment (minimum six months and maximum 12 months follow up). Secondary outcomes were development of MDR-TB during the course of treatment, recurrence after 6 months and/or after 1 year post successful treatment completion and development of adverse events related to glucose lowering treatment (including hypoglycemic episodes).</p><p>Methods</p><p>All interventional studies (with comparison arm) and cohort studies on people with TB-DM on anti-TB treatment reporting glycemic control, DM treatment details and TB treatment outcomes were eligible. We searched electronic databases (EMBASE, PubMed, Google Scholar) and grey literature between 1996 and April 2017. Screening, data extraction and risk of bias assessment were done independently by two investigators and recourse to a third investigator, for resolution of differences.</p><p>Results</p><p>After removal of duplicates from 2326 identified articles, 2054 underwent title and abstract screening. Following full text screening of 56 articles, nine cohort studies were included. Considering high methodological and clinical heterogeneity, we decided to report the results qualitatively and not perform a meta-analysis. Eight studies dealt with glycemic control, of which only two were free of the risk of bias (with confounder-adjusted measures of effect). An Indian study reported 30% fewer unsuccessful treatment outcomes (aOR (0.95 CI): 0.72 (0.64−0.81)) and 2.8 times higher odds of ‘no recurrence’ (aOR (0.95 CI): 2.83 (2.60−2.92)) among patients with optimal glycemic control at baseline. A Peruvian study reported faster culture conversion among those with glycemic control (aHR (0.95 CI): 2.2 (1.1,4)). Two poor quality studies reported the effect of insulin on TB treatment outcomes.</p><p>Conclusion</p><p>We identified few studies that were free of the risk of bias. There were limited data and inconsistent findings among available studies. We recommend robustly designed and analyzed studies including randomized controlled trials on the effect of glucose lowering treatment options on TB treatment outcomes.</p></div

Characteristics of the studies excluded from the systematic review^*.

<p>Characteristics of the studies excluded from the systematic review^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0186697#t002fn001" target="_blank">*</a>}.</p

PRISMA flow diagram through different phases of the systematic review [39].

<p>PRISMA flow diagram through different phases of the systematic review [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0186697#pone.0186697.ref039" target="_blank">39</a>].</p

Effect of glucose lowering treatment on unfavourable TB treatment outcomes, summarized as unadjusted relative risk (RR)^* [47,48].

<p>Effect of glucose lowering treatment on unfavourable TB treatment outcomes, summarized as unadjusted relative risk (RR)^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0186697#t004fn001" target="_blank">*</a>} [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0186697#pone.0186697.ref047" target="_blank">47</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0186697#pone.0186697.ref048" target="_blank">48</a>].</p

Effect of glycemic control (stringent or less stringent) on unfavourable TB treatment outcomes, summarized as unadjusted relative risk (RR)^* [40–47].

<p>Effect of glycemic control (stringent or less stringent) on unfavourable TB treatment outcomes, summarized as unadjusted relative risk (RR)^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0186697#t003fn001" target="_blank">*</a>} [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0186697#pone.0186697.ref040" target="_blank">40</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0186697#pone.0186697.ref047" target="_blank">47</a>].</p

Comparison of PPTCT and general population surveys (GPS) in select districts of Karnataka, 2006–09.

<p>N, total number of individuals tested.</p><p>p-value for HIV prevalence comparison.</p>*<p>Only for Bagalkot, Jamkhandi and Mudhol sub-district areas.</p

Comparison of HSS-ANC and PPTCT data sets in three high-prevalence South Indian states, 2008.

<p>Comparison of HSS-ANC and PPTCT data sets in three high-prevalence South Indian states, 2008.</p

HIV prevalence among ANC women tested in PPTCT centers at district (Andhra Pradesh, Karnataka, Maharashtra, and Tamil Nadu) and sub-district levels (Karnataka), 2009.

<p>HIV Prevalence ranges are indicated by color. Lines indicate boundaries at district (graph on right) and sub-district (graph on left) levels.</p

HIV prevalence trends using HSS-ANC and PPTCT data sets.

<p>Prevalence of HIV among pregnant women from the HSS-ANC (green lines) and PPTCT data sets (red lines). Diamonds are prevalence (95% CI). P indicates p-value for trend.</p