Periodontal Inflammation and Dysbiosis Relate to Microbial Changes in the Gut.

Periodontal disease (PerioD) is a chronic inflammatory disease of dysbiotic etiology. Animal models and few human data showed a relationship between oral bacteria and gut dysbiosis. However, the effect of periodontal inflammation and subgingival dysbiosis on the gut is unknown. We hypothesized that periodontal inflammation and its associated subgingival dysbiosis contribute to gut dysbiosis even in subjects free of known gut disorders. We evaluated and compared elderly subjects with Low and High periodontal inflammation (assessed by Periodontal Inflamed Surface Area (PISA)) for stool and subgingival derived bacteria (assayed by 16S rRNA sequencing). The associations between PISA/subgingival dysbiosis and gut dysbiosis and bacteria known to produce short-chain fatty acid (SCFA) were assessed. LEfSe analysis showed that, in Low PISA, species belonging to Lactobacillus, Roseburia, and Ruminococcus taxa and Lactobacillus zeae were enriched, while species belonging to Coprococcus, Clostridiales, and Atopobium were enriched in High PISA. Regression analyses showed that PISA associated with indicators of dysbiosis in the gut mainly reduced abundance of SCFA producing bacteria (Radj = -0.38, p = 0.03). Subgingival bacterial dysbiosis also associated with reduced levels of gut SCFA producing bacteria (Radj = -0.58, p = 0.002). These results suggest that periodontal inflammation and subgingival microbiota contribute to gut bacterial changes.

One Health Risk and Disease (OHRAD): a tool to prioritise the risks for epidemic-prone diseases from One Health perspective.

BACKGROUND: The rise in epidemic-prone diseases daily poses a serious concern globally. Evidence suggests that many of these diseases are of animal origin and contribute to economic loss. Considering the limited time and other resources available for the animal and human health sectors, selecting the most urgent and significant risk factors and diseases is vital, even though all epidemic-prone diseases and associated risk factors should be addressed. The main aim of developing this tool is to provide a readily accessible instrument for prioritising risk factors and diseases that could lead to disease emergence, outbreak or epidemic. METHODS: This tool uses a quantitative and semi-quantitative multi-criteria decision analysis (MCDA) method that involves five steps: Identifying risk factors and diseases, Weighting the criteria, Risk and disease scoring, Calculating risk impact and disease burden score, and Ranking risks and diseases. It is intended to be implemented through a co-creation workshop and involves individual and group activities. The last two steps are automated in the MS Excel score sheet. RESULTS: This One Health Risk and Disease (OHRAD) prioritisation tool starts with an individual activity of identifying the risks and diseases from the more extensive list. This, then, leads to a group activity of weighing the criteria and providing scores for each risk and disease. Finally, the individual risk and disease scores with the rankings are generated in this tool. CONCLUSIONS: The outcome of this OHRAD prioritisation tool is that the top risks and diseases are prioritised for the particular context from One Health perspective. This prioritised list will help experts and officials decide which epidemic-prone diseases to focus on and for which to develop and design prevention and control measures.

Risk Assessment Tools from the One Health Perspective: A Narrative Review.

Background: 61% of the infections around the world that have emerged to date are zoonotic. Evidence warns that the threat posed by zoonoses is on the rise, and the risk of a new pandemic is higher now than ever. Early identification of risk, populations at risk, and risk of transmission are essential steps towards a prevention, preparation and response to outbreaks. This review aims to look at the tools available for identifying and estimating risks and threats from one health perspective and finally propose a list of indicators which could assess the risk of transmission of disease at the humans, animals and the environment intersection. Methods: The databases like PubMed, google scholar, Embase and Scopus were used to extract the relevant articles. A search was carried out using a keyword. A total of 1311 articles were listed initially after the search and reviewed. Out of 1311, only 26 tools which assessed the risk of diseases mainly infectious or were relevant to risk of transmission of any infectious diseases were included in the review. Results: The tools included in this review involve risk assessment at the environmental, animal and human dimensions. The tools are used to evaluate the contamination of the environment due to chemicals or toxins or the risk of transmission of infection due to environmental factors like air contamination, to identify the animal diseases like bovine respiratory disease and foot and mouth disease and to estimate the human health risk at the community or individual levels. Conclusion: Risk assessment tools are an essential part of the prevention of pandemics. These tools are helpful in assessing the risk of transmission of infections either from human to human, between human and animals, between animals and animals and so on. Thus this review gives us an insight into the existing risk assessment tools and the need for a One Health risk assessment tools to prevent outbreaks in future. It also provides a list of factors that can be included in a one health risk assessment tool.

Incidence of Sudden Cardiac Death in Low- and Middle-Income Countries: A Systematic Review of Cohort Studies.

Sudden cardiac death (SCD) is a leading cause of mortality worldwide and, in recent years, has become an urgent public health concern in low- and middle-income countries (LMICs). Data from LMICs, however, remains limited. As such, the aim of this article is to systematically review the current literature on the incidence of SCD in LMICs to inform policymakers and identify potential research gaps. A search of PubMed and Embase was utilized to capture the targeted condition, outcome, and setting. Only peer-reviewed cohort studies in LMICs reporting SCD incidence estimates in the general population of individuals aged ≥1 year were eligible for selection. Papers providing incidence data for specific types of SCD, including sudden coronary death or death from sudden cardiac arrest, were also included. After deduplication, 1941 citations were identified and screened. Seven studies representing four countries-Cameroon, China, India, and Iran-met the criteria for inclusion and were considered in our analysis. The crude incidence rate for SCD ranged from 19.9 to 190 cases per 100,000 person-years, while age-adjusted rates ranged from 33.6 to 230 cases per 100,000 person-years. There was notable variability in methods utilized to ascertain SCD cases. These findings suggest that the incidence of all-cause SCD in LMICs and may exceed that of high-income countries; however, observed disparities may be partly attributable to differences in case ascertainment methods. Additional research is needed to better understand the true incidence of SCD in developing countries. It is crucial that future studies across regions utilize standard diagnostic criteria and methodology for identifying SCD, which would provide a framework by which to compare outcomes between settings.

Socio-Economic and Health Consequences of COVID-19 on Indian Migrants: A Landscape Analysis.

The COVID-19 pandemic has hugely affected the world and human lives, the economy, and lifestyles. The pandemic control measures, such as lockdowns, forced many people to migrate from their destination to their source in various states, leading to increased vulnerability of migrants. The present review aimed to explore the different health, economic, and social impacts on internal migrants of India during the pandemic. The publications on internal migration and COVID-19 from India were retrieved from PubMed and Google Scholar using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 159 articles were extracted, of which 28 were reviewed. The articles published after March 1, 2020, were included in the review, irrespective of the design. Out of 28 articles, only half were original studies; the rest were either perspective, opinion, and review studies or editorial and commentary papers. Depression, anxiety, and stress due to job loss and lockdown were the major health issues documented. There was livelihood disturbance due to loss of income, such as inability to pay rent, loans, borrowing from relatives, and fear of its consequences. The migrants also faced stigma and discrimination from the villagers. The review also highlighted that although the government implemented various schemes to help the migrants, the majority were left out due to the non-availability of identity proof and ration cards. The safeguarding measures for these unregistered migrants must be facilitated to access health, economic, and social protection. Although various publications have focused on the mental health of the migrants, the socio-ecological aspects have been least explored, which calls for further studies. The literature on the impact of COVID-19 on other vulnerable populations like women and children and access to healthcare services is also scant, which needs to be explored further.

Bridging the Gap: A Strategic Approach to Upscale Knowledge Among Diverse Healthcare Providers for Effective Tuberculosis Management in Gujarat, India.

INTRODUCTION: Tuberculosis (TB) remains a global health challenge, particularly in low- and middle-income countries. Knowledge gaps among healthcare providers (HCPs) significantly impact TB management, hindering timely care-seeking and effective interventions. OBJECTIVE: The primary objective was to assess knowledge gaps among 3086 HCPs engaged in the National Tuberculosis Elimination Program (NTEP) implementation in Gujarat, India. The study provided a platform to develop and implement cadre-specific training modules to address identified knowledge deficiencies and enhance TB management. METHODOLOGY: The study was conducted in two phases. Phase one was designed as a cross-sectional assessment to identify the knowledge gaps. Phase two involved the development of cadre-specific training modules based on identified deficiencies in the knowledge, crafted with collaboration from an expert panel. The training impact will be evaluated after completion of the training of all cadres through a comprehensive assessment. RESULTS: Out of 3086 assessed HCPs, 26% scored below the passing benchmark, revealing significant knowledge gaps. The variations were observed among and within the same cadres, with the accredited social health activists (ASHAs) and community health workers showing higher proficiency while pharmacists and medical officers showed lower proficiency. The cadre-specific training modules and training cascade were designed to address these gaps and improve TB-related knowledge and skills. CONCLUSION: The study underscores the critical need for targeted interventions to address knowledge gaps among HCPs involved in TB control. The customized HCP-specific training programs are recommended to enhance knowledge, improve TB management, and contribute to national TB elimination goals.

Estimation of the Parasitic Burden of Soil-Transmitted Helminths Among Pregnant Women in the Maharashtra State of India Using qPCR: A Community-Based Study.

Background: Soil-transmitted helminth (STH) infections are widespread in developing countries with inadequate sanitation facilities. These infections can lead to malnutrition, anemia, and other complications that can negatively impact both the mother's and fetus's health during pregnancy. This study aimed to estimate the burden of STH by Kato-Katz microscopy and quantitative polymerase chain reaction (qPCR) in pregnant women from rural India. The diagnostic accuracy of these two methods was also compared. Material and Methods: A community-based cross-sectional study was conducted in rural areas of Wardha district of Maharashtra state. We randomly selected and interviewed 688 pregnant women. A total of 534 (77.61%) participants gave stool samples. Two containers (60 mL) labeled with a unique identification number were given to pregnant women to collect stool samples for Kato-Katz microscopy and qPCR. Stool specimens were transported to an accredited lab and examined within 24 hours. Suitable examinations were conducted to compare sensitivity between two tests. Results: The results are presented for 534 participants who gave stool samples. The prevalence of any STH by Kato-Katz stool microscopy was 6.55% (95%CI 4.46-12.19), and that by qPCR was 20.41 (95%CI 17.53-29.40). The sensitivity of Kato-Katz microscopy was 29.17% compared to sensitivity of 90.83% by qPCR (P = 0.001). Pregnant women with STH infection have a significantly lower weight gain during pregnancy, and the majority were either mild or moderate anemic compared to those without STH. Conclusion: The study highlighted significant differences in prevalence of STH among pregnant women by Kato-Katz microscopy and qPCR. The sensitivity of qPCR for detecting STH was higher than that of Kato-Katz microscopy.

Effect of IV ferric carboxy maltose for moderate/severe anemia: a systematic review and meta-analysis.

Introduction: Anemia remains a prevalent global health issue with varying severity. Intravenous iron supplementation, particularly with ferric carboxymaltose (FCM), has appeared as a possible therapeutic intervention for individuals with moderate to severe anemia. The study aimed to assess the efficacy and safety of ferric carboxymaltose (FCM) in reducing anemia. Methods: We searched electronic databases, registries, websites, e-libraries, reference lists of reviews, citations, etc. We included randomized control trials (RCTs), non-RCTs, and single-arm studies, while observational studies, case series, and case studies were excluded. Two reviewers independently screened the studies and extracted the data. We included studies of moderate-to-severely anemic Indians and excluded Indians with other comorbidities. We assessed the risk of bias and the overall quality of evidence (QoE) using GRADE GDT. Result: We identified 255 studies and included 14 studies (11 RCT, one non-RCT, and two single-arm studies) with 1,972 participants for qualitative analysis and 10 studies in the meta-analysis. All the included studies detailed the use of FCM for anemia. The primary outcomes assessed in the included studies were anemia, hemoglobin, and adverse events. The outcomes assessed ranged from 2 weeks to 12 weeks. The risk of bias varied across different studies with different outcomes. FCM is consistent with a fewer number of adverse events as compared to other interventions and provides "moderate" to "very low" QoE. Conclusion: A slow single infusion of 1 gram of FCM is well-tolerated, safe, and effective in treating iron deficiency anemia (IDA) and surpasses other interventions (Iron Sucrose Complex (ISC), Iron sucrose, and ferrous ascorbate) in elevating hemoglobin levels and replenishing iron stores. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=459363, CRD42023459363.

Understanding the role of household hygiene practices and foodborne disease risks in child stunting: a UKRI GCRF Action Against Stunting Hub protocol paper.

INTRODUCTION: Environmental hygiene and food safety are important determinants of child stunting. This research aims to explore the relationship between child stunting and household hygiene practices and behaviours, including the availability of water, sanitation and hygiene (WASH) facilities; the use of safe food and good quality drinking water (especially when used for complementary feeding); hygienic practices in food transport, storage and preparation and the control of cross-contamination from animals, their produce and waste. METHODS AND ANALYSIS: This study is part of a wider observational study which aims to investigate the interdisciplinary factors contributing to child stunting using a 'whole child' paradigm. The observational study recruits women during pregnancy in Hyderabad, India, Lombok, Indonesia and Kaffrine, Senegal, and dyads (ie, 500 mother-infant pairs per country) are followed longitudinally up to 24 months after birth. Within the interdisciplinary niche, the study here has developed tools to investigate the potential exposure pathways to environmental pathogen contamination of foods and water. Holistic WASH and food safety data collection tools have been developed to explore exposure pathways at the household level, including: (1) survey questionnaires; (2) spot-checks; (3) biological sampling of drinking water, food and domestic surfaces and (4) direct observation. An integrated analytical approach will be used to triangulate the evidence in order to examine the relationships between child stunting, WASH and food safety behaviours. ETHICS AND DISSEMINATION: Ethical approval of the study was granted by the ethics committee of the LSHTM, RVC, ILRI, ICMR, IIPHG, SEAMEO-RECFON, University of Cheikh Anta Diop. Findings of the study will be disseminated through publication in peer-reviewed journals, relevant international conferences, public engagement events, and policy-maker and stakeholder events.

Impact of SARS-CoV-2 infection and mitigation strategy during pregnancy on prenatal outcome, growth and development in early childhood in India: a UKRI GCRF Action Against Stunting Hub protocol paper.

INTRODUCTION: The COVID-19 pandemic has offset some of the gains achieved in global health, particularly in relation to maternal, child health and nutrition. As pregnancy is a period of plasticity where insults acting on maternal environment have far-reaching consequences, the pandemic has had a significant impact on prenatal outcomes, intrauterine and postnatal development of infants. This research will investigate both the direct and indirect impacts of the COVID-19 pandemic during pregnancy on prenatal outcomes, growth and development in early childhood. METHODS AND ANALYSIS: Community and hospital data in Hyderabad and Gujarat, India will be used to recruit women who were pregnant during the COVID-19 pandemic and contracted SARS-CoV-2 infection. In comparison with women who were pregnant around the same time and did not contract the virus, the study will investigate the impact of the pandemic on access to healthcare, diet, nutrition, mental health and prenatal outcomes in 712 women (356 per study arm). Children born to the women will be followed prospectively for an 18-month period to investigate the impact of the pandemic on nutrition, health, growth and neurocognition in early childhood. ETHICS AND DISSEMINATION: Ethics approval was granted from the institutional ethics committees of the Indian Institute of Public Health Gandhinagar (SHSRC/2021/2185), Indian Council of Medical Research-National Institute of Nutrition (EC/NEW/INST/2021/1206), and London School of Hygiene and Tropical Medicine (72848). The findings of the study will be disseminated to policy and research communities through engagements, scientific conferences, seminars, and open-access, peer-reviewed publication.

Cost-effectiveness analysis of parenteral iron therapy compared to oral iron supplements in managing iron deficiency anemia among pregnant women.

OBJECTIVE: This study compared the clinical efficacy and cost-effectiveness of parenteral iron, using intravenous iron sucrose (IVIS) therapy against the standard regimen of oral iron (OI) therapy for managing iron-deficiency anemia (IDA) among pregnant women in a natural primary care setting in Gujarat. DESIGN: A prospective cost-effectiveness study was conducted in natural programme setting wherein 188 pregnant women in their 14 to 18 weeks with moderate and severe anemia women enrolled from two districts of Gujarat, and 142 were followed up until the post-partum phase. The intervention group comprised of 82 participants who were administered IVIS, while the comparison group comprised of 106 participants who were put on OI therapy. Hemoglobin (Hb) levels were measured at periodic intervals, first during enrollment and then during each month of pregnancy period and finally on the 42nd day of the post-natal period. OUTCOME MEASURES: Change in mean Hb level from baseline was the primary outcome, while the incidence of morbidity and mortality was a secondary outcome measure. RESULTS: The intervention group showed a significant incremental mean change in Hb level from 8.2 g/dl to 11.45 g/dl at the fourth follow-up, while the control group's mean Hb level reduced from 9.99 g/dl to 9.55 g/dl. The discounted cost per beneficiary for IVIS was US$ 87, while that for OI was US$ 49. The incremental cost-effectiveness ratio (ICER) was US$ 9.84, which is 0.049% of India's per capita GDP. CONCLUSION: IVIS therapy was more clinically effective and cost-effective than OI therapy among pregnant women for management of moderate and severe anemia.

Exploring private sector perspectives on barriers and facilitators in availing tuberculosis care cascade services: a qualitative study from the Indian state.

INTRODUCTION: The private sector plays an important role in tuberculosis (TB) elimination by providing access to quality TB care services like diagnosis and treatment, advocacy for preventive measures, innovation to address challenges in TB elimination, vaccines etc. The study aims to understand the perspectives of private practitioners on patients' TB care cascade to reinforce existing interventions by assuring the quality of care to TB patients. METHODS: The study utilized a qualitative design through in-depth interviews of private practitioners and was conducted in Ranchi and Purbi Singhbhum District of Jharkhand State from March-August 2021. The pilot-tested, semi-structured, open-ended interview guide questionnaire collected information from private practitioners on various aspects of the TB care cascade. The data from the provider interviews were transcribed into multiple codes and themes on the TB program. An inductive analysis was carried out with a focus on content credibility to eliminate bias. Ethical approval was received from the Institutional Ethics Committee of the Indian Institute of Public Health Gandhinagar (IIPHG), India. Written consent was taken from the private practitioners involved in the study. RESULT: In-depth interviews of 17 private practitioners reveal various factors contributing to delays in TB care cascades, especially delay in access to TB diagnosis and TB Care, delay in providing treatment once after diagnosis and poor adherence to the TB treatment. According to the perception of private practitioners, there was an array of client, provider and system side factors affecting the TB care cascade gaps positively and negatively. Positive aspects mainly emerged from interviews: strong governance, consistent supply chain management, innovative PPP models and financial schemes reducing out-of-pocket expenditure (OOPE). Various factors affecting the TB care cascade negatively include awareness among the patient, socio-economic status, approach and decision-making power of providers, adverse effects of drugs, staff capacity building, etc. CONCLUSIONS: Engaging private practitioner in TB elimination efforts is critical to achieving global targets and reducing the burden of TB. The study helps to determine geography-specific barriers and facilitators of the TB care cascade to achieve the aim of providing universal access to TB healthcare with the inclusion of private practitioners.

A novel SUCNR1 inhibitor alleviates dysbiosis through inhibition of host responses without direct interaction with host microbiota.

Type 2 diabetes (T2D) is a chronic metabolic disorder in which insulin resistance and impaired insulin secretion result in altered metabolite balance, specifically elevated levels of circulating glucose and succinate, which increases the risk of many pathologies, including periodontitis. Succinate, a tricarboxylic acid (TCA) cycle intermediate, can be produced and metabolized by both host cells and host microbiota, where elevated levels serve as an inflammation and pathogen threat signal through activating the succinate G protein-coupled receptor, SUCNR1. Modulating succinate-induced SUCNR1 signaling remains a promising therapeutic approach for pathologies resulting in elevated levels of succinate, such as T2D and periodontitis. Here, we demonstrate hyperglycemia and elevated intracellular succinate in a T2D mouse model and determine gut microbiome composition. Drawing on previous work demonstrating the ability of a novel SUCNR1 antagonist, compound 7a, to block inflammation and alleviate dysbiosis in a mouse model, we examined if compound 7a has an impact on the growth and virulence gene expression of bacterial and fungal human microbiota in vitro, and if 7a could reduce bone loss in a periodontitis-induced mouse model. T2D mice harbored a significantly different gut microbiome, suggesting the altered metabolite profile of T2D causes shifts in host-microbial community structure, with enrichment in succinate producers and consumers and mucin-degrading bacteria. Bacterial and fungal cultures showed that 7a did not influence growth or virulence gene expression, suggesting the therapeutic effects of 7a are a direct result of 7a interacting with host cells and that alterations in microbial community structure are driven by reduced host SUCNR1 signaling. This work further suggests that targeting SUCNR1 signaling is a promising therapeutic approach in metabolic, inflammatory, or immune disorders with elevated succinate levels.

Impact of ambient air pollution and socio-environmental factors on the health of children younger than 5 years in India: a population-based analysis.

Background: Ambient air pollution and household environmental factors affect child health, particularly in low-income and middle-income countries. This study aimed to investigate the association between ambient air pollution (PM2·5) levels, socio-environmental factors (including household wealth, housing quality measures, smoking status), and the occurrence of respiratory illness in Indian children. Methods: In this retrospective and observational study, we analysed data from India's National Family Health Survey (NFHS-5, 2019-2021) combined with NASA's Global Annual PM2·5 Grids database. Bivariate and multivariable generalized additive models were employed to examine associations between key social-environmental factors and respiratory illness in children younger than 5 years. Findings: We analysed data from 224,214 children younger than 5 years, representing 165,561 families from 29,757 geographic clusters. Our results showed extremely high annual PM2·5 levels throughout India (median 63·4·g/m3, IQR 41·9-81·6), with higher exposure for rural and impoverished families. In bivariate analyses, PM2·5 was significantly associated with reported respiratory illness (p < 0·001). Using generalized additive models and after accounting for key social and environmental factors, a monotonic increasing and non-linear relationship was observed between PM2·5 and respiratory illness (p < 0·001), with increased likelihood of illness observed even at values near and below India's National Ambient Air Quality Standards of 40 µg/m3. Interpretation: The study highlights the significant association of social-environmental conditions with health outcomes among young children in India. Efforts specifically targeting ambient air pollution and child health during monsoon season could have significant health benefits among this population and help achieve the goal of ending preventable deaths of children younger than 5 years. Funding: National Institutes of Health (NIH T-32-HL139443-3).

A Community Trial in Coastal Karnataka using Life Style Modifications to Assess its Impact on Hypertension and Diabetes.

Introduction: In the management of hypertension and diabetes mellitus, a systematic response like modifications in lifestyles is needed along with the medication. The study was conducted to determine the impact of comprehensive lifestyle modifications on hypertension and diabetes and to compare it with that of physical activity alone as a health education intervention. Materials and Method: A risk factor-based community intervention trial was conducted for one year in 3 villages in coastal Karnataka. The sample of 305 was calculated depending on the expected change in blood pressure and an equal sample size was drawn from each of the villages using a systematic random sampling method. Baseline data on blood pressure level, random blood sugar, and HbA1c levels were recorded. After 1 year of intervention, all the parameters were further recorded along with the adherence to medication for these non-communicable diseases. Results: The mean difference between the groups suggested that participants with physical activity intervention reported a statistically significant reduction in systolic blood pressure. In the comprehensive lifestyle modification group, there was a significant reduction in both diastolic blood pressure and glycated hemoglobin levels (21 mmHg and 2.1%; p < 0.001). Conclusion: The study indicates that in the management of hypertension and diabetes mellitus, the impact of comprehensive lifestyle modifications was more significant compared to physical activity alone.

Deaths among tuberculosis patients of the western state of India: A secondary record based analytical study on its determinants.

INTRODUCTION: India has a significant TB burden, and ongoing attempts are being made to eradicate the disease. Globally, the number of TB deaths is declining, but not quickly enough to meet the End TB Goals. The National Strategic Plan (NSP) 2017-2025 in India set in motion an ambitious effort to expand the scope and efficacy of the National Tuberculosis Elimination Program (NTEP). METHODS: A descriptive retrospective study based on secondary data was conducted on information obtained from the electronic TB notification register for 2019, abstracted from Ni-kshay. Further, descriptive analysis was undertaken to identify the factors associated with deaths and successful treatment outcomes. The binomial logistic regression model estimates the crude relative risk and a 95% confidence interval to describe the association between predictor variables and TB treatment outcomes. RESULTS: After applying the eligibility criteria for the study population, a total of 1,44,643 (88%) TB patients were included in the study. 1,35,934 (94%) TB patients had completed the treatment and survived, while 8709 (6%) TB patients died. A significant association of treatment outcomes was observed in age, gender, key population, site of diseases, type of case, type of health facilities, HIV and Diabetes. When a logistic regression was applied, the model showed the association of the independent variables with the risk of death in TB patients. CONCLUSION: The epidemiological factors associated with treatment outcomes among TB patients should be audited systematically. A structure of TB death surveillance and response system should be established with a mortality audit, including a community-based death review (CBDR) and a facility-based medical audit (FBMA) in case the patient is hospitalized or discharged from a hospital.

Design-redesign, implementation, and evaluation of effectiveness of maternal nutrition and responsive parenting program on child development at 2 years of age from rural India: a cluster RCT.

Background: To promote early childhood development (ECD), we require information not only on what needs to be addressed and on what effects can be achieved but also on effective delivery methods that can be adapted to local context. We describe design, implementation, and evaluation of a complex intervention to strengthen nurturing environment for young children. Methods: Study participants were pregnant women and their children from birth to 2 years. We used design and redesign, implementation, and evaluation approaches for the study. We co-created curriculum and delivery plan with stakeholders, based on the theoretical framework, findings from formative research, and our preliminary work. We recruited 656 pregnant women and newborns, 326 (49.69%) from intervention and 330 (50.30%) from the control group. We conducted a cluster randomized controlled trial to evaluate the program's effectiveness. The outcomes of children were assessed at 12 and 24 months. Findings: At recruitment, study participants from both the study arms were similar in sociodemographic characteristics. We conducted 6,665 home visits, 25 toy-making workshops, and 65 caregiver-meetings. The initial examination of program data revealed gaps in quality and coverage of interventions. The intervention was redesigned based on feedback from stakeholders in community meetings. At recruitment, participants in both study groups had similar socio-demographics. We conducted 6,665 home visits, 25 toy workshops, and 65 caregiver meetings. Initial program data showed intervention quality and coverage gaps, leading to a redesign program based on community and stakeholder feedback. Post-re-designing, session quality improved, with program coverage rising from 32 to 98%. Male participation in home visits increased from 4.3 to 32.65%, and data errors reduced from 270 to 140 per month on average. At 24 months, program showed moderate-mild impact on ECD - cognitive (0.31, 95%CI: 0.13-0.48), language (0.2, 95%CI: 0.01-0.39), and socioemotional-development (0.19, 95%CI: 0.01-0.37), moderate effect on home-environment and mother-child interaction. 96% of women initiated breastfeed within one-hour of delivery, and exclusive-breastfeeding rate of 89.80%. Interpretations: The study provides an evidence-based community centered ECD curriculum and implementation strategies to enhance service providers, and caregivers' knowledge and skills for promoting ECD in low-resource settings with the potential to scale within existing Government Program. Funding: The trial was funded by the Saving Brains Round 5 Initiative of Grand Challenges Canada (Grant no. SB-1707-05084), and we are grateful for their ongoing support through online sessions and orientation workshops. The trial was also supported by the Indian Council of Medical Research (File No: 5/7/1693/CH/Adhoc/RBMCH-2020).

Getting off tract: contributions of intraorgan microbiota to cancer in extraintestinal organs.

The gastrointestinal ecosystem has received the most attention when examining the contributions of the human microbiome to health and disease. This concentration of effort is logical due to the overwhelming abundance of microbes in the gut coupled with the relative ease of sampling compared with other organs. However, the intestines are intimately connected to multiple extraintestinal organs, providing an opportunity for homeostatic microbial colonisation and pathogenesis in organs traditionally thought to be sterile or only transiently harbouring microbiota. These habitats are challenging to sample, and their low microbial biomass among large amounts of host tissue can make study challenging. Nevertheless, recent findings have shown that many extraintestinal organs that are intimately linked to the gut harbour stable microbiomes, which are colonised from the gut in selective manners and have highlighted not just the influence of the bacteriome but that of the mycobiome and virome on oncogenesis and health.