Search

Background: India accounts for about one-quarter of people contracting tuberculosis (TB) disease annually and nearly one-third of TB deaths globally. Many Indians do not navigate all care cascade stages to receive TB treatment and achieve recurrence-free survival. Guided by a population/exposure/comparison/outcomes (PECO) framework, we report findings of a systematic review to identify factors contributing to unfavorable outcomes across each care cascade gap for TB disease in India. Methods and findings: We defined care cascade gaps as comprising people with confirmed or presumptive TB who did not: start the TB diagnostic workup (Gap 1), complete the workup (Gap 2), start treatment (Gap 3), achieve treatment success (Gap 4), or achieve TB recurrence-free survival (Gap 5). Three systematic searches of PubMed, Embase, and Web of Science from January 1, 2000 to August 14, 2023 were conducted. We identified articles evaluating factors associated with unfavorable outcomes for each gap (reported as adjusted odds, relative risk, or hazard ratios) and, among people experiencing unfavorable outcomes, reasons for these outcomes (reported as proportions), with specific quality or risk of bias criteria for each gap. Findings were organized into person-, family-, and society-, or health system-related factors, using a social-ecological framework. Factors associated with unfavorable outcomes across multiple cascade stages included: male sex, older age, poverty-related factors, lower symptom severity or duration, undernutrition, alcohol use, smoking, and distrust of (or dissatisfaction with) health services. People previously treated for TB were more likely to seek care and engage in the diagnostic workup (Gaps 1 and 2) but more likely to suffer pretreatment loss to follow-up (Gap 3) and unfavorable treatment outcomes (Gap 4), especially those who were lost to follow-up during their prior treatment. For individual care cascade gaps, multiple studies highlighted lack of TB knowledge and structural barriers (e.g., transportation challenges) as contributing to lack of care-seeking for TB symptoms (Gap 1, 14 studies); lack of access to diagnostics (e.g., X-ray), non-identification of eligible people for testing, and failure of providers to communicate concern for TB as contributing to non-completion of the diagnostic workup (Gap 2, 17 studies); stigma, poor recording of patient contact information by providers, and early death from diagnostic delays as contributing to pretreatment loss to follow-up (Gap 3, 15 studies); and lack of TB knowledge, stigma, depression, and medication adverse effects as contributing to unfavorable treatment outcomes (Gap 4, 86 studies). Medication nonadherence contributed to unfavorable treatment outcomes (Gap 4) and TB recurrence (Gap 5, 14 studies). Limitations include lack of meta-analyses due to the heterogeneity of findings and limited generalizability to some Indian regions, given the country's diverse population. Conclusions: This systematic review illuminates common patterns of risk that shape outcomes for Indians with TB, while highlighting knowledge gaps—particularly regarding TB care for children or in the private sector—to guide future research. Findings may inform targeting of support services to people with TB who have higher risk of poor outcomes and inform multicomponent interventions to close gaps in the care cascade. Tulip A. Jhaveri and team report findings of a systematic review to identify factors contributing to unfavorable outcomes across each care cascade gap for tuberculosis disease in India. Author summary: Why was this study done?: India has the highest tuberculosis (TB) incidence, accounting for about one-quarter of people with TB disease and nearly one-third of TB deaths globally. Many Indians with TB do not traverse all care stages needed to receive treatment and achieve an optimal long-term outcome, with serial losses of people across these stages referred to as the "care cascade." Understanding why losses of people with TB disease occur across the care cascade is crucial to inform interventions to prevent unfavorable outcomes. What did the researchers do and find?: We conducted 3 systematic searches to identify papers published from 2000 to 2023. We extracted information from these studies on risk factors for unfavorable outcomes for each care cascade gap, as well as reasons reported by people with TB who experienced unfavorable outcomes and were surveyed by researchers. Some factors contributed to losses at multiple care cascade stages, including male sex, older age, poverty-related factors, history of prior TB treatment, lower symptom severity or duration, undernutrition, alcohol use, smoking, and dissatisfaction with health services. Other barriers included: lack of TB knowledge and transportation barriers to clinic contributing to lack of care-seeking (Gap 1), poor accessibility of testing and failure to identify people eligible for testing contributing to non-completion of the diagnostic workup (Gap 2), early deaths from diagnostic delays and poor recording of contact information contributing to losses of people before treatment (Gap 3), lack of TB knowledge and depression contributing to unfavorable treatment outcomes (Gap 4), and medication nonadherence contributing to unfavorable treatment outcomes and TB recurrence (Gaps 4 and 5). What do these findings mean?: Reasons for losses of people with TB disease across the care cascade are complex, vary by care cascade gap, and involve patient- and health system-related barriers. India's TB program should target additional services to people with higher risk of poor outcomes and develop multicomponent interventions to address the diverse challenges faced by people with TB. Study limitations include lack of meta-analyses (i.e., estimation of the average effect of each risk factor by combining findings across studies), and caution is required when applying findings across India's diverse population. [ABSTRACT FROM AUTHOR]

Background: Diabetes control is poor globally and leads to burdensome microvascular and macrovascular complications. We aimed to assess post hoc between-group differences in sustained risk factor control and macrovascular and microvascular endpoints at 6.5 years in the Center for cArdiovascular Risk Reduction in South Asia (CARRS) randomized trial. Methods and findings: This parallel group individual randomized clinical trial was performed at 10 outpatient diabetes clinics in India and Pakistan from January 2011 through September 2019. A total of 1,146 patients with poorly controlled type 2 diabetes (HbA1c ≥8% and systolic BP ≥140 mm Hg and/or LDL-cholesterol ≥130 mg/dl) were randomized to a multicomponent quality improvement (QI) strategy (trained nonphysician care coordinator to facilitate care for patients and clinical decision support system for physicians) or usual care. At 2.5 years, compared to usual care, those receiving the QI strategy were significantly more likely to achieve multiple risk factor control. Six clinics continued, while 4 clinics discontinued implementing the QI strategy for an additional 4-year follow-up (overall median 6.5 years follow-up). In this post hoc analysis, using intention-to-treat, we examined between-group differences in multiple risk factor control (HbA1c <7% plus systolic BP <130 mm Hg and/or LDL-cholesterol <100 mg/dl) and first macrovascular endpoints (nonfatal myocardial infarction, nonfatal stroke, death, revascularization [angioplasty or coronary artery bypass graft]), which were coprimary outcomes. We also examined secondary outcomes, namely, single risk factor control, first microvascular endpoints (retinopathy, nephropathy, neuropathy), and composite first macrovascular plus microvascular events (which also included amputation and all-cause mortality) by treatment group and whether QI strategy implementation was continued over 6.5 years. At 6.5 years, assessment data were available for 854 participants (74.5%; n = 417 [intervention]; n = 437 [usual care]). In terms of sociodemographic and clinical characteristics, participants in the intervention and usual care groups were similar and participants at sites that continued were no different to participants at sites that discontinued intervention implementation. Patients in the intervention arm were more likely to exhibit sustained multiple risk factor control than usual care (relative risk: 1.79; 95% confidence interval [CI], 1.45, 2.20), p < 0.001. Cumulatively, there were 233 (40.5%) first microvascular and macrovascular events in intervention and 274 (48.0%) in usual care patients (absolute risk reduction: 7.5% [95% CI: −13.2, −1.7], p = 0.01; hazard ratio [HR] = 0.72 [95% CI: 0.61, 0.86]), p < 0.001. Patients in the intervention arm experienced lower incidence of first microvascular endpoints (HR = 0.68 [95% CI: 0.56, 0.83), p < 0.001, but there was no evidence of between-group differences in first macrovascular events. Beneficial effects on microvascular and composite vascular outcomes were observed in sites that continued, but not sites that discontinued the intervention. Conclusions: In urban South Asian clinics, a multicomponent QI strategy led to sustained multiple risk factor control and between-group differences in microvascular, but not macrovascular, endpoints. Between-group reductions in vascular outcomes at 6.5 years were observed only at sites that continued the QI intervention, suggesting that practice change needs to be maintained for better population health of people with diabetes. Trial registration: ClinicalTrials.govNCT01212328. Nikhil Tandon and colleagues explore the impact of a quality improvement strategy for patients with type 2 diabetes 6.5 years after its implementation for the CARRS randomised trial. Author summary: Why was this study done?: Data on whether improvements in diabetes care goal achievement can be sustained (>5 years) with quality improvement (QI) strategies are lacking from low- and middle-income countries (LMICs). Prior studies of QI strategies to improve care goal achievement among people with diabetes from high-income countries reported modest benefits in blood glucose, blood pressure, and lipids, but the effects of these improvements on reducing vascular complications and deaths related to diabetes are unknown. What did the researchers do and find?: In the Center for cArdiovascular Risk Reduction in South Asia (CARRS) randomised trial of 1,146 patients with type 2 diabetes attending 10 diverse diabetes clinics in India and Pakistan, the QI strategy was associated with benefits on diabetes care goals (HbA1c <7% plus systolic BP <130 mm Hg and/or LDL-cholesterol <100 mg/dl) at 2.5 years after randomization. Four clinics discontinued implementation, while 6 clinics continued to implement the QI strategy for an additional 4 years. This report assesses whether benefits were sustained and reduced vascular complications and deaths associated with diabetes at 6.5 years. Patients receiving the QI strategy, compared to those receiving usual care, experienced sustained benefits on diabetes care goals and less microvascular endpoints (eye, kidney, and nerve diseases) at 6.5 years after randomization. Total macrovascular and microvascular events were also lower in those receiving the QI strategy, and this was only observed at sites that continued implementation of the QI strategy for 6.5 years. What do these findings mean?: These findings add to our knowledge of the long-term effects of multicomponent QI strategies in sustaining multiple risk factor control and reducing combined vascular events compared to usual care in resource-limited settings. In view of these findings, clinical decision support and trained nonphysician health workers may be important QI strategies to consider integrating into India's healthcare system to improve diabetes care quality and reduce morbidity and mortality. One limitation of the study is that the tertiary care facilities included in the CARRS trial may not be generalizable across LMICs. [ABSTRACT FROM AUTHOR]

Background: Micronutrient deficiencies are widespread in India. Soil-transmitted helminth (STH) infections are acquired by interaction with soil and water contaminated by human feces and lead to blood loss and poor micronutrient absorption. The current recommendation for control of STH-related morbidity is targeted deworming, yet little is known about the effectiveness of deworming on micronutrient status in varying sanitation contexts. Ranging between 1% and 40% prevalence across Indian states, open defecation (OD) remains high despite India's investments at elimination by promoting community-wide sanitation. This variation provides an opportunity to study the relationship between deworming, micronutrient status, and OD at-scale. Methods and findings: Cross-sectional datasets that were representative for India were obtained the Comprehensive National Nutrition Survey in 2016 to 2018 (n = 105,060 individuals aged 1 to 19 years). Consumption of deworming medication was described by age and community OD level. Logistic regression models were used to examine the relationship between deworming, cluster OD, and their interactions, with anemia and micronutrient deficiencies (iron, zinc, vitamin A, folate, and vitamin B12), controlling for age, sex, wealth, diet, and seasonality. These regression models further allowed us to identify a minimum OD rate after which deworming becomes ineffective. In sensitivity analyses, the association between deworming and deficiencies were tested in subsamples of communities classified into 3 OD levels based on statistical tertiles: OD free (0% of households in the community practicing OD), moderate OD (>0% and <30%), or high OD (at least 30%). Average deworming coverage and OD prevalence in the sample were 43.4% [IQR 26.0, 59.0] and 19.1% [IQR 0, 28.5], respectively. Controlling for other determinants of nutritional status, adolescents living in communities with higher OD levels had lower coverage of deworming and higher prevalence of anemia, zinc, vitamin A, and B12 deficiencies. Compared to those who were not dewormed, dewormed children and adolescents had lower odds of anemia (adjusted odds ratio 0.72, (95% CI [0.67, 0.78], p < 0.001) and deficiencies of iron 0.78, (95% CI [0.74, 0.82], p < 0.001) and folate 0.69, (95% CI [0.64,0.74], p<0.001)) in OD free communities. These protective effects remained significant for anemia but diminished for other micronutrient deficiencies in communities with moderate or high OD. Analysis of community OD indicated a threshold range of 30% to 60%, above which targeted deworming was no longer significantly associated with lower anemia, iron, and folate deficiency. The primary limitations of the study included potential for omitted variables bias and inability to capture longitudinal effects. Conclusions: Moderate to high rates of OD significantly modify the association between deworming and micronutrient status in India. Public health policy could involve sequencing interventions, with focus on improving deworming coverage in communities that have achieved minimum thresholds of OD and re- triggering sanitation interventions in high OD communities prior to deworming days, ensuring high coverage for both. The efficacy of micronutrient supplementation as a complementary strategy to improve nutritional outcomes alongside deworming and OD elimination in this age group needs further study. Using data from India, Chakrabarti and colleagues evaluate whether higher open defecation levels diminished the protection provided by deworming against anaemia or micronutrient deficiencies. Author summary: Why was this study done?: Deworming is recommended to tackle soil-transmitted worm infections in low- and middle-income countries (LMICs), but the effectiveness of deworming provided on a large scale varies significantly. Sanitation levels across communities are likely to influence the impact of deworming in populations due to high rates of reinfection, but no studies have investigated these links. Despite well-intended programs intended to eliminate open defecation in India, this behavior persists in certain communities. This study was done to test whether higher open defecation levels diminished the protection provided by deworming against anemia or micronutrient deficiencies among Indian children and adolescents. What did the researchers do and find?: We used a cross-sectional dataset (sample size 105,060 individuals) representative of Indian children and adolescents to look at links between open defecation, deworming, anemia, and micronutrient deficiencies. We found that deworming coverage remains low in India, especially among young children and adolescents out of school, indicating the need for enhanced and expanded deworming interventions. After accounting for the influence of age, sex, wealth, education, diet, and season, dewormed children in areas without open defecation had lower rates of anemia (28% lower), iron deficiency (22% lower), and folate deficiency (31% lower); however, in communities with open defecation, dewormed children showed similar deficiency levels as those not dewormed. What do these findings mean?: Our findings suggest that open defecation diminishes the protection provided by deworming medication against anemia and micronutrient deficiencies in India. The findings highlight the importance of sequencing sanitation interventions such as behavior change campaigns before deworming initiatives in high open defecation communities. This study cannot establish causation because the statistical models were based on observing associations at a single point in time rather than tracking changes over time. [ABSTRACT FROM AUTHOR]